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  • 1.
    Bannbers, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kask, Kristiina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Risbrough, Victoria
    Department of Psychiatry, University of California, San Diego, CA, USA.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Patients with premenstrual dysphoric disorder have increased startle modulation during anticipation in the late luteal phase period in comparison to control subjects2011In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 36, no 8, p. 1184-1192Article in journal (Refereed)
    Abstract [en]

    The acoustic startle response (ASR) is a withdrawal reflex to sudden or noxious auditory stimuli and, most importantly, an unbiased measure of emotional processing of appetitive and aversive stimuli. By exposing subjects to fearful situations, such as aversive pictures, the ASR may be enhanced, suggesting that amygdala modulates the startle circuit during threat situations. As one previous study, investigating affective modulation of the ASR in women with premenstrual dysphoric disorder (PMDD), discovered no difference during picture viewing it is possible that the mood changes observed in PMDD relate to anxious anticipation rather than to direct stimulus responding. Hence we sought to examine the effects of PMDD on picture anticipation and picture response.

    Sixteen PMDD patients and 16 controls watched slide shows containing pleasant and unpleasant pictures and positive and negative anticipation stimuli during the follicular and luteal phase of the menstrual cycle. Simultaneously, semi-randomized startle probes (105dB) were delivered and the ASR was assessed with electromyography.

    Compared with control subjects, PMDD patients displayed an enhanced startle modulation by positive and negative anticipation stimuli in the luteal phase of the menstrual cycle. This finding was mainly driven by increased modulation in the luteal phase in comparison to the follicular phase among PMDD patients but also by an increased modulation in patients compared to controls during luteal phase. This suggests that the neural circuits underlying response to emotional anticipation are more sensitive during this period and emphasize the need of examining the neural correlates of anticipatory processes in women with PMDD.

  • 2.
    Bannbers, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kask, Kristiina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Lower levels of prepulse inhibition in luteal phase cycling women in comparison with postmenopausal women2010In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 35, no 3, p. 422-429Article in journal (Refereed)
    Abstract [en]

    Menopause denotes the end of the reproductive period in a woman's life and is characterized by gradually declining plasma levels of ovarian hormones. Mounting evidence suggests that prepulse inhibition (PPI) is sensitive to fluctuations in estradiol and progesterone. Deficits in PPI are associated with conditions characterized by increased levels of ovarian steroids, such as the mid-luteal phase of the menstrual cycle and the third trimester of pregnancy. The aim of the current study was to further elucidate ovarian steroid-related effects on PPI by examining 43 women with regular menstrual cycles, 20 healthy postmenopausal women without hormone replacement treatment (HRT) and 21 healthy postmenopausal women with ongoing estradiol-only or estradiol and progesterone therapy (EPT). Cycling women were tested during the late luteal phase of the menstrual cycle while postmenopausal women were tested on any arbitrary day. The PPI was measured by electromyography. Cycling women exhibited lower levels of PPI than postmenopausal women (p<0.05). There were no differences in PPI between postmenopausal HRT users and non-users. However, postmenopausal women with estradiol serum concentrations in the cycling range had lower PPI than postmenopausal women with low estradiol concentrations (groupxPPI interaction, p<0.05). In conclusion, the results further suggest a role for the ovarian steroids in PPI regulation as PPI is increased in postmenopausal women in comparison to regularly menstruating women examined during the late luteal phase. Furthermore, postmenopausal women with estradiol levels in the cycling range had lower PPI than postmenopausal women with low estradiol levels.

  • 3. Bengtsson, Sara K. S.
    et al.
    Nyberg, Sigrid
    Hedstrom, Helena
    Zingmark, Elisabeth
    Jonsson, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Backstrom, Torbjorn
    Bixo, Marie
    Isoallopregnanolone antagonize allopregnanolone-induced effects on saccadic eye velocity and self-reported sedation in humans2015In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 52, p. 22-31Article in journal (Refereed)
    Abstract [en]

    Allopregnanolone (AP) is an endogenous neurosteroid. It modulates the effect of gamma-amino-butyric acid (GABA) on the GABA type A (GABA(A)) receptor, which leads to increased receptor activity. Since the GABA-system is mainly inhibitory, increased AP activity leads to modulation of neuronal activity. In vitro studies of GABA(A) receptor activity and in vivo animal studies of sedation have shown that AP-induced effects can be inhibited by another endogenous steroid, namely isoallopregnanolone (ISO). In this study we investigated if ISO can antagonize AP-induced effects in healthy female volunteers, via measurements of saccadic eye velocity (SEV) and self-rated sedation. With a single-blind cross-over design, 12 women were studied on three separate occasions; given AP alone or AP in combination with one of two ISO doses. Congruent with previous reports, AP administration decreased SEV and induced sedation and these effects were diminished by simultaneous ISO administration. Also, the ISO effect modulation was seemingly stronger for SEV than for sedation. These effects were observed already at an ISO dose exposure that was approximately half of that of AP. In conclusion, ISO antagonized AP-induced decrease in SEV and self-reported sedation, probably in a non-competitive manner. (C) 2014 Elsevier Ltd. All rights reserved.

  • 4.
    Bixo, Marie
    et al.
    Umea Univ, Dept Clin Sci, SE-90185 Umea, Sweden..
    Ekberg, Karin
    Asarina Pharma AB, Fogdevreten 2, SE-17165 Solna, Sweden..
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hirschberg, Angelica Linden
    Karolinska Inst, Dept Womens & Childrens Hlth, SE-17176 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Obstet & Gynecol, SE-17176 Stockholm, Sweden..
    Jonasson, Aino Fianu
    Karolinska Univ Hosp, Kvinnoforskningsenheten, SE-14146 Huddinge, Sweden..
    Andreen, Lotta
    Sundsvall Hosp, Dept Obstet & Gynecol, SE-85186 Sundsvall, Sweden..
    Timby, Erika
    Umea Univ, Dept Clin Sci, SE-90185 Umea, Sweden..
    Wulff, Marianne
    Slottsstadens Lakarhus Malmo, Fagelbacksgatan 11, SE-21744 Malmo, Sweden..
    Ehrenborg, Agneta
    Specialistlakarna Kungsbacka Qvinnolivet, Sodra Torggatan 18, SE-43430 Kungsbacka, Sweden..
    Bäckström, Torbjörn
    Umea Univ, Dept Clin Sci, SE-90185 Umea, Sweden..
    Treatment of premenstrual dysphoric disorder with the GABA(A) receptor modulating steroid antagonist Sepranolone (UC1010)-A randomized controlled trial2017In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 80, p. 46-55Article in journal (Refereed)
    Abstract [en]

    Context: Allopregnanolone is a metabolite from progesterone and a positive modulator of the GABA(A) receptor. This endogenous steroid may induce negative mood in sensitive women when present in serum levels comparable to the premenstrual phase. Its endogenous isomer, isoallopregnanolone, has been shown to antagonize allopregnanolone effects in experimental animal and human models.

    Objective: The objective was to test whether inhibition of allopregnanolone by treatment with the GABA(A) modulating steroid antagonist (GAMSA) Sepranolone (UC1010) during the premenstrual phase could reduce symptoms of the premenstrual dysphoric disorder (PMDD). The pharmacokinetic parameters of UC1010 when given as a subcutaneous injection were measured in healthy women prior to the study in women with PMDD.

    Design: This was an explorative randomized, double-blind, placebo-controlled study.

    Setting: Swedish multicentre study with 10 centers.

    Participants: Participants were 26 healthy women in a pharmacokinetic phase I study part, and 126 women with PMDD in a phase II study part. Diagnosis followed the criteria for PMDD in DSM-5 using Daily Record of Severity of Problems (DRSP) and Endicott's algorithm.

    Intervention: Subjects were randomized to treatment with UC1010 (10 or 16 mg) subcutaneously every second day during the luteal phase or placebo during one menstrual cycle.

    Outcome measures: The primary outcome measure was the sum of all 21 items in DRSP (Total DRSP score). Secondary outcomes were Negative mood score i.e. the ratings of the 4 key symptoms in PMDD (anger/irritability, depression, anxiety and lability) and impairment (impact on daily life).

    Results: 26 healthy women completed the pharmacokinetic phase I study and the dosing in the following trial was adjusted according to the results. 106 of the 126 women completed the phase II study. Within this group, a significant treatment effect with UC1010 compared to placebo was obtained for the Total DRSP score (p = 0.041) and borderline significance (p = 0.051) for the sum of Negative mood score. Nineteen participants however showed symptoms during the follicular phase that might be signs of an underlying other conditions, and 27 participants had not received the medication as intended during the symptomatic phase. Hence, to secure that the significant result described above was not due to chance, a post hoc sub-group analysis was performed, including only women with pure PMDD who completed the trial as intended (n =60). In this group UC1010 reduced Total DRSP scores by 75% compared with 47% following placebo; the effect size 0.7 (p = 0.006), and for sum of Negative mood score (p=0.003) and impairment (p =0.010) with the effect size 0.6. No severe adverse events were reported during the treatment and safety parameters (vital signs and blood chemistry) remained normal during the study.

    Conclusions: This explorative study indicates promising results for UC1010 as a potential treatment for PMDD. The effect size was comparable to that of SSRIs and drospirenone containing oral contraceptives. UC1010 was well tolerated and deemed safe.

  • 5.
    Borgström, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kask, Kristiina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Gulinello, Maria
    Odlind, Viveca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Patients with adverse mood effects from combined oral contraceptives have lower levels of prepulse inhibition than healthy controls2008In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 33, no 4, p. 487-496Article in journal (Refereed)
    Abstract [en]

    Background: Negative mood symptoms remain one of the major reasons for discontinuation of oral contraceptive pills. The aim of this study was to compare acoustic startle response and prepulse inhibition (PPI) in women with different experience of oral contraceptive pills. Methods: Thirty women currently on combined oral contraceptives (COCs) with no reports of adverse mood symptoms, 28 women currently on COCs and experiencing mood-related side effects from treatment, 27 women who had discontinued COC use for reasons other than adverse mood symptoms and 32 women who had discontinued COC use due to adverse mood effects were included. The eyeblink component of the acoustic startle reflex was assessed using electromyographic measurements of musculus Orbicularis Oculi. Twenty pulse-alone trials (115dB 40 ms broad-band white noise) and 40 prepulse-pulse trials were presented. The prepulse stimuli consisted of a 115dB 40 ms noise burst preceded at a 100 ms interval by 20 ms prepulses that were 72, 74, 78, or 86 dB. Results: Patients with adverse mood effects of COCs exhibited lower levels of PPI with 86dB prepulse compared to COC users with no adverse effects of COCs (p<0.05). There was no difference in PPI between the two groups of prior COC users. No significant difference was found between the groups regarding acoustic startle response. Conclusion: Relative to COC users with no reports of adverse mood symptoms, subjects suffering from COC-induced negative mood displayed deficits in PPI of acoustic startle. The fact that there was no difference in PPI between the two groups of prior COC users indicates that deficient PPI is related to adverse mood effects caused by COCs.

  • 6.
    Breedh, Julia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comasco: Neuropsychopharmacology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Comasco, Erika
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comasco: Neuropsychopharmacology.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Papadopoulos, Fotios C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Hypothalamic-pituitary-adrenal axis responsiveness, startle response, and sensorimotor gating in late pregnancy2019In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 106, p. 1-8Article in journal (Refereed)
    Abstract [en]

    During pregnancy, the hypothalamic-pituitary-adrenal (HPA) axis, the main regulator of the stress response, undergoes dramatic changes. The acoustic startle response (ASR) and the prepulse inhibition (PPI) of the startle response are neurophysiological research tools and objective measures of an individual's response to an emotional context or stressor. The ASR and PPI are influenced by psychiatric diseases characterized by anxiety symptoms and are sensitive to cortisol. Hence, the ASR and the PPI can be used to investigate the effects of pregnancy-induced endocrine changes and their contribution to affective disorders. The present study sought to investigate the association between measures of HPA-axis responsiveness, startle reactivity and sensorimotor gating during pregnancy that to date remains unknown. The eye-blink component of the ASR, and its prepulse inhibition, were measured in 107 late third trimester pregnant women. Saliva samples were collected to assess the cortisol awakening response (CAR), a measure of HPA-axis activity. Blood was sampled to measure serum levels of cortisol, cortisone and the cortisone to cortisol ratio. Ongoing anxiety disorders, sleep duration, smoking, and age were considered as potential confounders in the statistical analyses. CAR reactivity, measured as area under the curve (AUC) increase and above baseline, was positively associated with baseline startle magnitude [Cohen's d = 0.27; F (1, 105) = 4.99; p = 0.028, and Cohen's d = 0.30; F (1, 105) = 6.25; p = 0.014, respectively] as well as PPI at 86 dB [Cohen's d = 0.29; F (1, 105) = 5.93; p = 0.017; and Cohen's d = 0.34; F (1, 105) = 8.38; p = 0.005, respectively]. The observed positive correlation between startle magnitude in pregnant women and greater increase in cortisol during the awakening response may be interpreted as heightened neurophysiological reactivity, likely associated with dysregulation of the stress system.

  • 7.
    Bränn, Emma
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Papadopoulos, Fotios
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Fransson, Emma
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.; Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden .
    White, Richard
    Norwegian Inst Publ Hlth, Oslo, Norway.
    Edvinsson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kamali-Moghaddam, Masood
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Boström, Adrian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Inflammatory markers in late pregnancy in association with postpartum depression-A nested case-control study.2017In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 79, p. 146-159Article in journal (Refereed)
    Abstract [en]

    Recent studies indicate that the immune system adaptation during pregnancy could play a significant role in the pathophysiology of perinatal depression. The aim of this study was to investigate if inflammation markers in a late pregnancy plasma sample can predict the presence of depressive symptoms at eight weeks postpartum. Blood samples from 291 pregnant women (median and IQR for days to delivery, 13 and 7-23days respectively) comprising 63 individuals with postpartum depressive symptoms, as assessed by the Edinburgh postnatal depression scale (EPDS≥12) and/or the Mini International Neuropsychiatric Interview (M.I.N.I.) and 228 controls were analyzed with an inflammation protein panel using multiplex proximity extension assay technology, comprising of 92 inflammation-associated markers. A summary inflammation variable was also calculated. Logistic regression, LASSO and Elastic net analyses were implemented. Forty markers were lower in late pregnancy among women with depressive symptoms postpartum. The difference remained statistically significant for STAM-BP (or otherwise AMSH), AXIN-1, ADA, ST1A1 and IL-10, after Bonferroni correction. The summary inflammation variable was ranked as the second best variable, following personal history of depression, in predicting depressive symptoms postpartum. The protein-level findings for STAM-BP and ST1A1 were validated in relation to methylation status of loci in the respective genes in a different population, using openly available data. This explorative approach revealed differences in late pregnancy levels of inflammation markers between women presenting with depressive symptoms postpartum and controls, previously not described in the literature. Despite the fact that the results do not support the use of a single inflammation marker in late pregnancy for assessing risk of postpartum depression, the use of STAM-BP or the novel notion of a summary inflammation variable developed in this work might be used in combination with other biological markers in the future.

  • 8.
    Cedernaes, Jonathan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Fanelli, Flaminia
    Univ Bologna, S Orsola Malpighi Hosp, Endocrinol Unit, Dept Med & Surg Sci, Bologna, Italy.;Univ Bologna, S Orsola Malpighi Hosp, Ctr Appl Biomed Res, Bologna, Italy..
    Fazzini, Alessia
    Univ Bologna, S Orsola Malpighi Hosp, Endocrinol Unit, Dept Med & Surg Sci, Bologna, Italy.;Univ Bologna, S Orsola Malpighi Hosp, Ctr Appl Biomed Res, Bologna, Italy..
    Pagotto, Uberto
    Univ Bologna, S Orsola Malpighi Hosp, Endocrinol Unit, Dept Med & Surg Sci, Bologna, Italy.;Univ Bologna, S Orsola Malpighi Hosp, Ctr Appl Biomed Res, Bologna, Italy..
    Broman, Jan-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Vogel, Heike
    German Inst Human Nutr Potsdam Rehbrucke, Dept Expt Diabetol, Nuthetal, Germany..
    Dickson, Suzanne L.
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol Endocrinol, Gothenburg, Sweden..
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Sleep restriction alters plasma endocannabinoids concentrations before but not after exercise in humans2016In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 74, p. 258-268Article in journal (Refereed)
    Abstract [en]

    Following binding to cannabinoid receptors, endocannabinoids regulate a variety of central nervous system processes including appetite and mood. Recent evidence suggests that the systemic release of these lipid metabolites can be altered by acute exercise and that their levels also vary across the 24-h sleep wake cycle. The present study utilized a within-subject design (involving 16 normal-weight men) to determine whether daytime circulating endocannabinoid concentrations differ following three nights of partial sleep deprivation (4.25-h sleep opportunity, 2:45-7 a.m. each night) vs. normal sleep (8.5-h sleep opportunity, 10:30 p.m.-7 a.m. each night), before and after an acute bout of ergometer cycling in the morning. In addition, subjective hunger and stress were measured. Pre-exercise plasma concentrations of 2-arachidonoylglycerol (2AG) were 80% higher 1.5 h after awakening (vs. normal sleep, p< 0.05) when participants were sleep-deprived. This coincided with increased hunger ratings (+25% vs. normal sleep, p < 0.05). Moreover, plasma 2AG was elevated 15 min post-exercise (+44%, p <0.05). Sleep duration did not however modulate this exercise-induced rise. Finally, subjective stress was generally lower on the day after three nights of short sleep vs. normal sleep, especially after exercise (p < 0.05). Given that activation of the endocannabinoid system has been previously shown to acutely increase appetite and mood, our results could suggest that behavioral effects of acute sleep loss, such as increased hunger and transiently improved psychological state, may partially result from activation of this signaling pathway. In contrast, more pronounced exercise-induced elevations of endocannabinoids appear to be less affected by short sleep duration.

  • 9.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Olivier, Jocelien D A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Supraphysiological hormonal status, anxiety disorders, and COMT Val/Val genotype are associated with reduced sensorimotor gating in women2015In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 60, p. 217-23Article in journal (Refereed)
    Abstract [en]

    Pregnancy is a period characterized by a supraphysiological hormonal status, and greater anxiety proneness, which can lead to peripartum affective symptoms with dramatic consequences not only for the woman but also for the child. Clinical psychiatry is heavily hampered by the paucity of objective and biology-based intermediate phenotypes. Prepulse inhibition (PPI) of the startle response, a neurophysiological measure of sensorimotor gating, has been poorly investigated in relation to anxiety and in pregnant women. In the present study, the PPI of healthy non-pregnant women (n=82) and late pregnant women (n=217) was investigated. Age, BMI, depression and anxiety symptoms, tobacco use, and antidepressant medication were considered. We investigated and provided evidence of lower PPI: (i) in healthy pregnant women compared to healthy non-pregnant controls, (ii) in pregnant women with anxiety disorders compared to healthy pregnant women, (iii) in pregnant women with anxiety disorders using SSRI compared to un-medicated pregnant women with anxiety disorders, and (iv) in healthy pregnant women carrying the COMT Val158Met Val/Val genotype compared to Met carriers. Altogether, a reduced sensorimotor gating as an effect of supraphysiological hormonal status, anxiety disorders, SSRIs, and catecholaminergic genotype, implicate the putative relevance of lower PPI as an objective biological correlate of anxiety proneness in pregnant women. These findings call for prospective studies to dissect the multifactorial influences on PPI in relation to mental health of pregnant women.

  • 10.
    Edvinsson, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Bränn, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Freyhult, Eva
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    White, Richard
    Norwegian Inst Publ Hlth, Oslo, Norway..
    Kamali-Moghaddam, Masood
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Olivier, Jocelien
    Univ Groningen, Groningen Inst Evolutionary Life Sci, Unit Behav Neurosci, Dept Neurobiol, Groningen, Netherlands..
    Bergquist, Jonas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Boström, Adrian E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Cunningham, Janet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Lower inflammatory markers in women with antenatal depression brings the M1/M2 balance into focus from a new direction2017In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 80, p. 15-25Article in journal (Refereed)
    Abstract [en]

    Background: Antenatal depression and use of serotonin reuptake inhibitors (SSRI) in pregnancy have both been associated with an increased risk of poor pregnancy outcomes, such as preterm birth and impaired fetal growth. While the underlying biological pathways for these complications are poorly understood, it has been hypothesized that inflammation may be a common physiological pathway. The aim of the present study was to assess peripheral inflammatory markers in healthy women, women with antenatal depression, and in women using SSRI during pregnancy.

    Methods: 160 healthy pregnant controls, 59 women with antenatal depression and 39 women on treatment with SSRIs were included. The relative levels of 92 inflammatory proteins were analyzed by proximity extension assay technology.

    Results: Overall, 23 of the inflammatory markers were significantly lower in women with antenatal depression and in women on treatment with SSRIs in comparison with the healthy controls. No difference in any of the inflammatory markers was observed between women with antenatal depression and those who were using SSRI. Top three inflammatory markers that were down-regulated in women with antenatal depression were TNF-related apoptosis-inducing ligand (TRAIL), p = 0.000001, macrophage colony-stimulating factor 1 (CSF-1), p = 0.000004, and fractalkine (CX3CL1), p =0.000005. Corresponding inflammatory markers in SSRI users were CSF-1, p = 0.000011, vascular endothelial growth factor A (VEGF-A), p =0.000016, and IL-15 receptor subunit alpha (IL-15RA), p = 0.000027. The inflammatory markers were negatively correlated with cortisone serum concentrations in controls, but not in the cases. Differential DNA methylation of was found for seven of these inflammatory markers in an independent epigenetics cohort.

    Conclusion: Women with antenatal depression or on SSRI treatment have lower levels of a number of peripheral inflammatory markers than healthy pregnant controls. Hypothetically, this could be due to dysregulated switch to the pro-M2 milieu that characterizes normal third trimester pregnancy. However, longitudinal blood sampling is needed to elucidate whether the presumably dysregulated M2 shift is driving the development of antenatal depression or is a result of the depression.

  • 11.
    Engman, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA..
    Linnman, Clas
    Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA.;Harvard Univ, Boston Childrens Hosp, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Boston, MA USA..
    Van Dijk, Koene R. A.
    Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.;Harvard Univ, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA..
    Milad, Mohammed R.
    Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA..
    Amygdala subnuclei resting-state functional connectivity sex and estrogen differences2016In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 63, p. 34-42Article in journal (Refereed)
    Abstract [en]

    The amygdala is a hub in emotional processing, including that of negative affect. Healthy men and women have distinct differences in amygdala responses, potentially setting the stage for the observed sex differences in the prevalence of fear, anxiety, and pain disorders. Here, we examined how amygdala subnuclei resting-state functional connectivity is affected by sex, as well as explored how the functional connectivity is related to estrogen levels. Resting-state functional connectivity was measured using functional magnetic resonance imaging (fMRI) with seeds placed in the left and right laterobasal (LB) and centro-medial (CM) amygdala. Sex differences were studied in 48 healthy men and 48 healthy women, matched for age, while the association with estrogen was analyzed in a subsample of 24 women, for whom hormone levels had been assessed. For the hormone analyses, the subsample was further divided into a lower and higher estrogen levels group based on a median split. We found distinct sex differences in the LB and CM amygdala resting-state functional connectivity, as well as preliminary evidence for an association between estrogen levels and connectivity patterns. These results are potentially valuable in explaining why women are more afflicted by conditions of negative affect than are men, and could imply a mechanistic role for estrogen in modulating emotion.

  • 12.
    Eriksson, Olle
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Bäckström, Torbjörn
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hammarlund-Udenaes, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Differential response to estrogen challenge test in women with and without premenstrual dysphoria2006In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 31, no 4, p. 415-427Article in journal (Refereed)
    Abstract [en]

    This study tested the hypothesis that brain sensitivity to normal fluctuations in gonadal hormones is increased in women with premenstrual dysphoria. For this purpose, the effect of a common gonadal hormonal challenge on the sensitivity of the brain was investigated in 13 women with premenstrual dysphoria and 12 asymptomatic controls. The estrogen challenge test, comprising estradiolbenzoate 0.04 mg/kg, was given as an intramuscular gluteal injection between 0700 and 1000h on day 3 or 4 of the menstrual cycle; blood was sampled at 0, 0.6, 6.5, 24, 32, 48, 56, 72, 96, 120, and 144h and analyzed for estradiol, FSH and LH. Serum estradiol levels after the injection and the corresponding FSH responses were similar between the study groups; however, the LH responses were significantly different. Women with premenstrual dysphoria had a relatively stronger negative feedback response (p=0.014) up to the point of nadir LH levels (maximal negative feedback), but displayed higher LH levels at the nadir (p=0.01), more LH surge-like reactions (p=0.047), and a 50% higher area under the curve (AUC) for LH (p=0.03) than controls. The LH response in women with premenstrual dysphoria was related to the VAS-rated symptoms; the negative increment (AOC) correlated to luteal phase "bloating" (r(s)=0.73; p=0.0069) whereas the AUC of LH correlated to "irritability" (r(s)=0.58; p=0.040). A significant interaction term between study group and changes in LH during the negative feedback phase (32-0h), with regard to luteal phase "irritability" was found (test for interaction p=0.005). For the premenstrual dysphoria group, ratings of "depressed mood"were related to baseline FSH levels (r(s)=0.60; p=0.034), and to the AUC of FSH during the negative feedback phase (r(s)=0.58; p=0.043). Women with premenstrual dysphoria displayed a gonadotrophin response to estradiol challenge that differed from that of controls, and was correlated to symptom severity.

  • 13.
    Eriksson, Olle
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Landén, Mikael
    Section of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Gothenburg University, Sweden.
    Sundblad, Charlotta
    Department of Pharmacology, Institute of Physiology and Pharmacology, Gothenburg University, Sweden.
    Holte, Jan
    Carl von Linné Clinic, Uppsala Science Park, Sweden.
    Eriksson, Elias
    Department of Pharmacology, Institute of Physiology and Pharmacology, Gothenburg University, Sweden.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Ovarian morphology in premenstrual dysphoria2012In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 37, no 6, p. 742-751Article in journal (Refereed)
    Abstract [en]

    Ovarian cyclicity is a prerequisite for premenstrual dysphoria (PMD), as illustrated by the fact that this condition is effectively eliminated by ovariectomy or by treatment with a GnRH agonist. Despite the possibility of differences in ovarian function between women with and without PMD, no study comparing ovarian morphology in these two groups has ever been published. Fifty-two women were recruited for this study; 26 had premenstrual dysphoria, fulfilling criteria slightly modified from those of the premenstrual dysphoric disorder, and 26 were asymptomatic age-matched controls. Ovarian morphology was assessed using transvaginal 7MHz ultrasonography on day 5 after the start of menses, and venous blood was sampled for hormone analysis on days 3 and 8, the expected day of ovulation, and day -4 of the menstrual cycle. There were no significant differences between the groups with respect to the prevalence of polycystic ovaries (PCO), the total number of follicles, the total ovarian volume or serum levels of androgen hormones. In addition, serum free testosterone levels in late premenstrual phase showed an inverse association to premenstrual symptoms of irritability and a similar inverse association trend to symptoms of depressed mood. Unexpectedly, the prevalence of ovaries with fewer than five antral or growing follicles was significantly higher in women with PMD than in controls (p=0.016). While the results do not support a role for PCO or androgen hormones in eliciting late luteal phase irritability, the possible relationship between oligofollicular ovaries and PMD deserves further study.

  • 14.
    Georgakis, Marios K.
    et al.
    Univ Athens, Med Sch, Dept Hyg Epidemiol & Med Stat, 75M Asias Str, Athens 11745, Greece;Ludwig Maximilians Univ Munchen, Univ Hosp, Inst Stroke & Dementia Res ISD, Munich, Germany;Ludwig Maximilians Univ Munchen, Grad Sch System Neurosci GSN, Munich, Germany;LMU, Univ Hosp, Inst Stroke & Dementia Res, Feodor Lynen Str 17, D-81377 Munich, Germany.
    Beskou-Kontou, Theano
    Univ Athens, Med Sch, Dept Hyg Epidemiol & Med Stat, 75M Asias Str, Athens 11745, Greece.
    Theodoridis, Ioannis
    Univ Athens, Med Sch, Dept Hyg Epidemiol & Med Stat, 75M Asias Str, Athens 11745, Greece.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Petridou, Eleni Th.
    Univ Athens, Med Sch, Dept Hyg Epidemiol & Med Stat, 75M Asias Str, Athens 11745, Greece.
    Surgical menopause in association with cognitive function and risk of dementia: A systematic review and meta-analysis2019In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 106, p. 9-19Article, review/survey (Refereed)
    Abstract [en]

    Introduction: Experimental and epidemiological studies suggest female sex hormones to have long-lasting neuroprotective and anti-ageing properties. Surgically-induced menopause leads to a premature cessation of exposure to female sex hormones and could thus impact late-life cognitive function. Yet, evidence remains controversial. Methods: We systematically reviewed literature for articles investigating the association of surgical menopause (defined as bilateral oophorectomy before the onset of menopause) with risk of dementia, cognitive performance, cognitive decline, and Alzheimer's disease neuropathological indices later in life. We evaluated study quality with the Newcastle-Ottawa scale and performed random-effects meta-analyses. Results: We identified 11 eligible studies (N = 18,867). Although surgical menopause at any age was not associated with risk of dementia (4 studies; HR: 1.16, 95%CI: 0.96-1.43), early surgical menopause (<= 45 years of age) was associated with a statistically significantly higher risk (2 studies; HR: 1.70, 95%CI: 1.07-2.69). Surgical menopause at any age was associated with faster decline in verbal memory, semantic memory, and processing speed, whereas early surgical menopause was further associated with faster global cognitive decline. No heterogeneity was noted. Among women undergoing surgical menopause, a younger age at surgery was associated with faster decline in global cognition, semantic and episodic memory, worse performance in verbal fluency and executive function, and accumulation of Alzheimer's neuropathology. Conclusions: Current evidence is limited, but suggests surgical menopause induced by bilateral oophorectomy at <= 45 years of age to be associated with higher risk of dementia and cognitive decline. Additional large-scale cohort studies are necessary to replicate these findings.

  • 15.
    Georgakis, Marios K.
    et al.
    Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, 75 Mikras Asias Str, Athens 11527, Greece..
    Kalogirou, Eleni I.
    Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, 75 Mikras Asias Str, Athens 11527, Greece..
    Diamantaras, Andreas-Antonios
    Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, 75 Mikras Asias Str, Athens 11527, Greece.;Charite, Program Med Neurosci, D-10117 Berlin, Germany..
    Daskalopoulou, Stella S.
    McGill Univ, Fac Med, Dept Med, Div Internal Med, Montreal, PQ H3G 1A4, Canada..
    Munro, Cynthia A.
    Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA..
    Lyketsos, Constantine G.
    Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA..
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Petridou, Eleni Th.
    Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, 75 Mikras Asias Str, Athens 11527, Greece..
    Age at menopause and duration of reproductive period in association with dementia and cognitive function: A systematic review and meta-analysis2016In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 73, p. 224-243Article, review/survey (Refereed)
    Abstract [en]

    Introduction: The preponderance of dementia among postmenopausal women compared with same-age men and the female sex hormones neuroprotective properties support a tentative role of their deficiency in the dementia pathogenesis. Methods: Pairs of independent reviewers screened 12,323 publications derived from a search strategy for MEDLINE to identify articles investigating the association of age at menopause/reproductive period with (i) dementia and (ii) cognitive function; a snowball of eligible articles and reviews was conducted and authors were contacted for additional information. Random-effect models were used for the meta analysis. Results: Age at menopause (13 studies; 19,449 participants) and reproductive period (4 studies; 9916 participants) in the highest categories were not associated with odds of dementia (effect size [ES]: 0.97 [0.78-1.21]) and Alzheimer's disease (ES: 1.06 [0.71-1.58]). Significant heterogeneity was however noted in both analyses (12: 63.3%, p = 0.003 and 12: 72.6%, p = 0.01, respectively). Subgroup analyses by outcome assessment, study design, level of adjustment and study quality did not materially change the findings. In 9/13 studies assessing cognitive function, advanced age at menopause/longer reproductive period was significantly associated with better cognitive performance/lower decline. Due to statistical differences, no meta-analysis was possible for cognitive function. Conclusions: Existing evidence does not support an association between indices of prolonged exposure to female hormones and lower dementia risk. There are indications, however, for better cognitive performance and delayed cognitive decline, supporting a link between female hormone deficiency and cognitive aging. Current literature limitations, indicated by the heterogeneous study-set, point towards research priorities in this clinically relevant area.

  • 16.
    Gingnell, Malin
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Frick, Andreas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Moby, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Oral contraceptive use changes brain activity and mood in women with previous negative affect on the pill: A double-blinded, placebo-controlled randomized trial of a levonorgestrel-containing combined oral contraceptive2013In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 38, no 7, p. 1133-1144Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    Most women on combined oral contraceptives (COC) report high levels of satisfaction, but 4-10% complain of adverse mood effects. The aim of this randomized, double-blinded, placebo-controlled trial was to investigate if COC use would induce more pronounced mood symptoms than placebo in women with previous history of COC-induced adverse mood. A second aim was to determine if COC use is associated with changes in brain reactivity in regions previously associated with emotion processing.

    METHODS:

    Thirty-four women with previous experience of mood deterioration during COC use were randomized to one treatment cycle with a levonorgestrel-containing COC or placebo. An emotional face matching task (vs. geometrical shapes) was administered during functional magnetic resonance imaging (fMRI) prior to and during the COC treatment cycle. Throughout the trial, women recorded daily symptom ratings on the Cyclicity Diagnoser (CD) scale.

    RESULTS:

    During the last week of the treatment cycle COC users had higher scores of depressed mood, mood swings, and fatigue than placebo users. COC users also had lower emotion-induced reactivity in the left insula, left middle frontal gyrus, and bilateral inferior frontal gyri as compared to placebo users. In comparison with their pretreatment cycle, the COC group had decreased emotion-induced reactivity in the bilateral inferior frontal gyri, whereas placebo users had decreased reactivity in the right amygdala.

    CONCLUSION:

    COC use in women who previously had experienced emotional side effects resulted in mood deterioration, and COC use was also accompanied by changes in emotional brain reactivity. These findings are of relevance for the understanding of how combined oral contraceptives may influence mood. Placebo-controlled fMRI studies in COC sensitive women could be of relevance for future testing of adverse mood effects in new oral contraceptives.

  • 17.
    Gustafsson, Per E
    et al.
    Umeå universitet, Allmänmedicin.
    Janlert, Urban
    Umeå universitet, Epidemiologi och global hälsa.
    Theorell, Töres
    Stress Research Institute, Stockholm University, Stockholm, Sweden.
    Hammarström, Anne
    Umeå universitet, Allmänmedicin.
    Life-course socioeconomic trajectories and diurnal cortisol regulation in adulthood2010In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 35, no 4, p. 613-623Article in journal (Refereed)
    Abstract [en]

    Although the health risk of socioeconomic disadvantage over the life-course is fairly established, the mechanisms are less studied. One candidate pathway is long-term dysregulation of cortisol. This study assesses whether socioeconomic trajectories from adolescence to adulthood influences the regulation of cortisol in mid-adulthood, and further investigates the importance of adolescence as a critical period and of accumulation of socioeconomic disadvantage. Participants were drawn from a 27-year prospective cohort study (n = 732, 68% of the original cohort). Information on socioeconomic status (SES) was collected at the ages of 16 (based on parental occupation), 21, 30 and 43 (based on own occupation) years, and at 43 years participants collected one-day salivary cortisol samples at awakening, after 15 min, before lunch and at bedtime. We found that the cortisol awakening response (CAR) differed with respect to SES trajectory; those with stable low or early low/upwardly mobile SES tended to display higher CAR than those with early high/downwardly mobile, highly mobile or stable high trajectories. Further analyses revealed that early low SES was related to higher CAR, and in women low SES was related to lower bedtime cortisol, independently of later SES and potential confounders. We found no support for a linear effect of accumulation of socioeconomic disadvantage. In conclusion, our study gives support for an independent effect of low socioeconomic status early in life, on the regulation of cortisol in adulthood.

  • 18.
    Gustafsson, Per E.
    et al.
    Umeå universitet, Allmänmedicin.
    Janlert, Urban
    Umeå universitet, Epidemiologi och global hälsa.
    Virtanen, Pekka
    Hammarström, Anne
    Umeå universitet, Allmänmedicin.
    The association between long-term accumulation of temporary employment, the cortisol awakening response and circadian cortisol levels2012In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 37, no 6, p. 789-800Article in journal (Refereed)
    Abstract [en]

    Temporary employment is an increasingly common contract type, which has not been investigated in a psychoneuroendocrinological context despite previous observations of associations between adverse work and employment conditions and hypothalamic-pituitary-adrenal (HPA) axis dysregulations. The present study aims to examine whether the 12-year accumulation of temporary employment is related to circadian cortisol levels, and if any association is independent of current employment conditions. Participants were drawn from the prospective Northern Swedish Cohort (n = 791, 74% of the original cohort). At age 43 years, retrospective reports of employments over the last 12 years and of current social conditions were collected by questionnaire, and one-day salivary cortisol profile was measured (at awakening, +15 min post-awakening, pre-lunch, bedtime). Results indicated a gradually higher magnitude of the cortisol awakening response (CAR) in subjects with no (0 months in temporary employment; mean CAR = 34%), moderate (1-25 months in temporary employment; mean CAR = 41%) and heavy (>25 months in temporary employment; mean CAR = 51%) exposure (p = .020), remaining after adjustment for potential confounders and for current employment conditions (p = .028). The higher CAR was explained by lower awakening rather than higher post-awakening cortisol levels. Cortisol levels at all times of the day except post-awakening displayed tendencies to negative relations to temporary employment; as indicated by a lower Area Under of Curve (regression coefficient = 5.0%, p = .038 after adjustment). This study thus suggests that the long-term exposure to temporary employment might confer HPA dysregulations in the form of increased dynamics of the CAR and circadian suppression. (C) 2011 Elsevier Ltd. All rights reserved.

  • 19.
    Han, Laura K. M.
    et al.
    Vrije Univ Amsterdam, Amsterdam UMC, Amsterdam Publ Hlth Res Inst, Dept Psychiat, Oldenaller 1, Netherlands;Vrije Univ Amsterdam, Amsterdam UMC, Amsterdam Neurosci, Dept Psychiat, Boelelaan 1117, Amsterdam, Netherlands.
    Verhoeven, Josine E.
    Vrije Univ Amsterdam, Amsterdam UMC, Amsterdam Publ Hlth Res Inst, Dept Psychiat, Oldenaller 1, Netherlands.
    Tyrka, Audrey R.
    Brown Univ, Butler Hosp, Providence, RI 02912 USA;Brown Univ, Warren Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02912 USA.
    Penninx, Brenda W. J. H.
    Vrije Univ Amsterdam, Amsterdam UMC, Amsterdam Publ Hlth Res Inst, Dept Psychiat, Oldenaller 1, Netherlands;Vrije Univ Amsterdam, Amsterdam UMC, Amsterdam Neurosci, Dept Psychiat, Boelelaan 1117, Amsterdam, Netherlands.
    Wolkowitz, Owen M.
    Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA USA;Univ Calif San Francisco, Sch Med, Weill Inst Neurosci, San Francisco, CA USA.
    Månsson, Kristoffer N.T.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden;Stockholm Univ, Dept Psychol, Stockholm, Sweden;.
    Lindqvist, Daniel
    Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA USA;Lund Univ, Dept Clin Sci, Fac Med, Psychiat, Lund, Sweden;Psychiat Clin, Div Psychiat, Lund, Sweden.
    Boks, Marco P.
    Univ Med Ctr Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands.
    Revesz, Dora
    Tilburg Univ, Dept Med & Clin Psychol, Ctr Res Psychol Somat Dis CoRPS, Tilburg, Netherlands.
    Mellon, Synthia H.
    Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA USA;Univ Calif San Francisco, Sch Med, Weill Inst Neurosci, San Francisco, CA USA.
    Picard, Martin
    Columbia Univ, Med Ctr, Div Behav Med, Dept Psychiat, New York, NY 10027 USA;Columbia Univ, Med Ctr, Columbia Translat Neurosci Initiat, Dept Neurol,H Houston Merritt Ctr, New York, NY USA;Columbia Univ, Columbia Aging Ctr, New York, NY USA.
    Accelerating research on biological aging and mental health: Current challenges and future directions2019In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 106, p. 293-311Article in journal (Refereed)
    Abstract [en]

    Aging is associated with complex biological changes that can be accelerated, slowed, or even temporarily reversed by biological and non-biological factors. This article focuses on the link between biological aging, psychological stressors, and mental illness. Rather than comprehensively reviewing this rapidly expanding field, we highlight challenges in this area of research and propose potential strategies to accelerate progress in this field. This effort requires the interaction of scientists across disciplines - including biology, psychiatry, psychology, and epidemiology; and across levels of analysis that emphasize different outcome measures - functional capacity, physiological, cellular, and molecular. Dialogues across disciplines and levels of analysis naturally lead to new opportunities for discovery but also to stimulating challenges. Some important challenges consist of 1) establishing the best objective and predictive biological age indicators or combinations of indicators, 2) identifying the basis for inter-individual differences in the rate of biological aging, and 3) examining to what extent interventions can delay, halt or temporarily reverse aging trajectories. Discovering how psychological states influence biological aging, and vice versa, has the potential to create novel and exciting opportunities for healthcare and possibly yield insights into the fundamental mechanisms that drive human aging.

  • 20.
    Hannerfors, Anna-Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Schijven, Dick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Iliadis, Stavros I.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Olivier, Jocelien D. A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Treatment with serotonin reuptake inhibitors during pregnancy is associated with elevated corticotropin-releasing hormone levels2015In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 58, p. 104-113Article in journal (Refereed)
    Abstract [en]

    Treatment with serotonin reuptake inhibitors (SSRI) has been associated with an increased risk of preterm birth, but causality remains unclear. While placental CRH production is correlated with gestational length and preterm birth, it has been difficult to establish if psychological stress or mental health problems are associated with increased CRH levels. This study compared second trimester CRH serum concentrations in pregnant women on SSRI treatment (n=207) with untreated depressed women (n=56) and controls (n=609). A secondary aim was to investigate the combined effect of SSRI treatment and CRH levels on gestational length and risk for preterm birth. Women on SSRI treatment had significantly higher second trimester CRH levels than controls, and untreated depressed women. CRH levels and SSRI treatment were independently associated with shorter gestational length. The combined effect of SSRI treatment and high CRH levels yielded the highest risk estimate for preterm birth. SSRI treatment during pregnancy is associated with increased CRH levels. However, the elevated risk for preterm birth in SSRI users appear not to be mediated by increased placental CRH production, instead CRH appear as an independent risk factor for shorter gestational length and preterm birth.

  • 21.
    Hellgren, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Edvinsson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Olivier, Jocelien D.
    Univ Groningen, Groningen Inst Evolutionary Life Sci, Dept Neurobiol, Unit Behav Neurosci, NL-9700 AB Groningen, Netherlands..
    Fornes, Romina
    Karolinska Inst, Dept Physiol & Pharmacol, S-10401 Stockholm, Sweden..
    Stener-Victorin, Elisabet
    Karolinska Inst, Dept Physiol & Pharmacol, S-10401 Stockholm, Sweden..
    Ubhayasekera, S. J. Kumari A.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Tandem mass spectrometry determined maternal cortisone to cortisol ratio and psychiatric morbidity during pregnancy-interaction with birth weight2016In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 69, p. 142-149Article in journal (Refereed)
    Abstract [en]

    Maternal serum cortisol has been suggested to be influenced by psychiatric morbidity, and may also influence fetal growth. However, several studies found equal cortisol levels in depressed and healthy pregnant women. Placental 11-beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2) shields the fetus from maternal cortisol by conversion to cortisone, a function that may be compromised by maternal stress. We aimed to compare the serum ratio of cortisone to cortisol, in women with and without psychiatric morbidity during pregnancy. A secondary aim was to investigate whether fetal growth, approximated by infant birth weight, was associated with the cortisone to cortisol ratio. We performed tandem mass spectrometry analysis of serum cortisol and cortisone in late pregnancy in 94 women with antenatal psychiatric morbidity and 122 controls (cohort 1). We also compared the placental gene expression of HSD11B1 and 2 in another group of 69 women with psychiatric morbidity and 47 controls (cohort 2). There were no group differences in cortisol to cortisone ratio, absolute levels of cortisone and cortisol (cohort 1), or expression of HSD11B1 or 2 (cohort 2). However, cortisone to cortisol ratio was positively associated with birth weight in women with psychiatric morbidity, also after adjustment for gestational length, fetal sex, maternal height, smoking, SSRI use, and time of blood sampling (standardized beta = 0.35, p < 0.001), with no association in the healthy controls Thus, the maternal serum cortisone to cortisol ratio does not seem to be affected by psychiatric morbidity, but psychiatric morbidity may increase fetal exposure to cortisol or other metabolic factors influencing fetal growth.

  • 22.
    Hellgren, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Cortisol awakening response in late pregnancy in women with previous or ongoing depression2013In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 38, no 12, p. 3150-54Article in journal (Other academic)
    Abstract [en]

    Pregnancy involves an increase in basal cortisol, and a decrease in the hypothalamic-pituitary-adrenal (HPA) axis reactivity. The cortisol awakening response is a measure of HPA axis reactivity which has been reported to be altered in patients with an ongoing depressive episode, as well as in individuals with remitted depression.

    This study aimed to use the cortisol awakening response to study the HPA axis reactivity in relation to previous and ongoing depression in women during the third trimester of pregnancy. Based on structured interviews, and repeated questionnaires during pregnancy, 134 women were included in one of three groups: never depressed (n=57), depressed prior to the current pregnancy (n=39), and depressed during the current pregnancy (n=38). The hypothesis was that the women with ongoing, or previous, depression would have a higher cortisol awakening response than women who have never suffered from depression.

    Linear mixed models analysis revealed no group differences in the absolute cortisol levels or in the shape of the cortisol awakening response. We conclude that the difference in cortisol awakening response between women with and without experience of a depressive episode is not evident in late pregnancy.

  • 23.
    Hellgren, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Cortisol awakening response in late pregnancy in women with previous or ongoing depression2013In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 38, no 12, p. 3150-3154Article in journal (Refereed)
    Abstract [en]

    Pregnancy is associated with increased basal cortisol levels, and decreased hypothalamic-pituitary-adrenal (HPA) axis reactivity. The cortisol awakening response (CAR) is a measure of HPA-axis reactivity which has been reported to be increased in patients with ongoing depressive disorder and in individuals with remitted depression. In this study, we investigated HPA-axis reactivity in pregnant women with ongoing or previous depression. The CAR was assessed by measurement of salivary cortisol at awakening and 15, 30, and 45min post-awakening. Based on structured psychiatric interviews and repeated measurements of depressive symptoms during pregnancy, 134 women were included in one of the three groups: never depressed (n=57), depressed prior to the current pregnancy (n=39), and depressed during the current pregnancy (n=38). Given the prior findings of increased CAR in non-pregnant depressed subjects, we hypothesized that an ongoing or previous depression would result in a higher CAR. Contrary to our hypothesis, a mixed models analysis failed to yield significant group differences. Thus, our results suggest that never depressed pregnant women and women with depression during pregnancy have similar cortisol awakening responses. Furthermore, our findings suggest that the cortisol awakening response does not differ between currently healthy women with and without experience of a depressive episode during late pregnancy.

  • 24. Herzog, Nina
    et al.
    Jauch-Chara, Kamila
    Hyzy, Franziska
    Richter, Annekatrin
    Friedrich, Alexia
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Oltmanns, Kerstin M.
    Selective slow wave sleep but not rapid eye movement sleep suppression impairs morning glucose tolerance in healthy men2013In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 38, no 10, p. 2075-2082Article in journal (Refereed)
    Abstract [en]

    Shortened nocturnal sleep impairs morning glucose tolerance. The underlying mechanism of this effect is supposed to involve a reduced fraction of slow wave sleep (SWS). However, it remains unanswered if impaired glucose tolerance occurs due to specific SWS reduction or a general disturbance of sleep. Sixteen healthy men participated in three experimental conditions in a crossover design: SWS suppression, rapid eye movement (REM)-sleep disturbance, and regular sleep. Selective sleep stage disturbance was performed by means of an acoustic tone (532 Hz) with gradually rising sound intensity. Blood concentrations of glucoregulatory parameters were measured upon an oral glucose tolerance test the next morning. Our data show that morning plasma glucose and serum insulin responses were significantly increased after selective SWS suppression. Moreover, SWS suppression reduced postprandial insulin sensitivity up to 20%, as determined by Matsuda Index. Contrastingly, disturbed REM-sleep did not affect glucose homeostasis. We conclude that specifically SWS reduction is critically involved in the impairment of glucose tolerance associated with disturbed sleep. Therefore, glucose metabolism in subjects predisposed to reduced SWS (e.g. depression, aging, obstructive sleep apnea, pharmacological treatment) should be thoroughly monitored.

  • 25.
    Hogenkamp, Pleunie S
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Nilsson, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Nilsson, Victor C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Chapman, Colin D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Vogel, Heike
    Lundberg, Lina S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Zarei, Sanaz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Rångtell, Frida H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Broman, Jan-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Dickson, Suzanne L
    Brunström, Jeffrey M
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Acute sleep deprivation increases portion size and affects food choice in young men2013In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 38, no 9, p. 1668-1674Article in journal (Refereed)
    Abstract [en]

    Acute sleep loss increases food intake in adults. However, little is known about the influence of acute sleep loss on portion size choice, and whether this depends on both hunger state and the type of food (snack or meal item) offered to an individual. The aim of the current study was to compare portion size choice after a night of sleep and a period of nocturnal wakefulness (a condition experienced by night-shift workers, e.g. physicians and nurses). Sixteen men (age: 23 ± 0.9 years, BMI: 23.6 ± 0.6 kg/m2) participated in a randomized within-subject design with two conditions, 8-h of sleep and total sleep deprivation (TSD). In the morning following sleep interventions, portion size, comprising meal and snack items, was measured using a computer-based task, in both fasted and sated state. In addition, hunger as well as plasma levels of ghrelin were measured. In the morning after TSD, subjects had increased plasma ghrelin levels (13%, p = 0.04), and chose larger portions (14%, p = 0.02), irrespective of the type of food, as compared to the sleep condition. Self-reported hunger was also enhanced (p < 0.01). Following breakfast, sleep-deprived subjects chose larger portions of snacks (16%, p = 0.02), whereas the selection of meal items did not differ between the sleep interventions (6%, p = 0.13). Our results suggest that overeating in the morning after sleep loss is driven by both homeostatic and hedonic factors. Further, they show that portion size choice after sleep loss depend on both an individual's hunger status, and the type of food offered.

  • 26. Holmer, Helene
    et al.
    Svensson, Johan
    Rylander, Lars
    Johannsson, Gudmundur
    Rosen, Thord
    Bengtsson, Bengt-Ake
    Thoren, Marja
    Hoybye, Charlotte
    Degerblad, Marie
    Bramnert, Margareta
    Hagg, Erik
    Engström, Britt Edén
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Ekman, Bertil
    Erfurth, Eva-Marie
    Psychosocial health and levels of employment in 851 hypopituitary Swedish patients on long-term GH therapy2013In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 38, no 6, p. 842-852Article in journal (Refereed)
    Abstract [en]

    Context: The psychosocial health and working capacity in hypopituitary patients receiving long-term growth hormone (GH) therapy are unknown. Objective: Psychosocial health and levels of employment were compared between GH deficient (GHD) patients on long-term replacement and the general population. Design and participants: In a Swedish nationwide study, 851 GHD patients [101 childhood onset (CO) and 750 adult onset (AO)] and 2622 population controls answered a questionnaire regarding current living, employment and educational level, alcohol consumption and smoking habits. The median time on GH therapy for both men and women with CO GHD was 9 years and for AO GHD 6 years, respectively. Results: As compared to the controls, the GHD patients were less often working full time, more often on sick leave/disability pension, and to a larger extent alcohol abstainers and never smokers (all; P < 0.05). Predominantly CO GHD women and men, but to some extent also AO GHD women and men, lived less frequently with a partner and more often with their parents. Particularly AO GHD craniopharyngioma women used more antidepressants, while AO GHD men with a craniopharyngioma used more analgesics. Conclusions: A working capacity to the level of the general population was not achieved among hypopituitary patients, although receiving long-term GH therapy. Patients were less likely to use alcohol and tobacco. The CO GHD population lived a less independent life.

  • 27.
    Iliadis, Stavros
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sylvén, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Jocelien, Olivier
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Hannefors, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Elfström, Dick
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Corticotropin-releasing hormone and postpartum depression: A longitudinal study2015In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 61, p. 61-61Article in journal (Other academic)
  • 28.
    Isaksson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry. Karolinska Inst, Ctr Neurodev Disorders, Karolinska Inst KIND, Dept Womens & Childrens Hlth,Pediat Neuropsychiat, S-17177 Stockholm, Sweden.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Åslund, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Rehn, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Tuvblad, Catherine
    Department of Psychology, University of Southern California, CA 90089-1061, USA;School of Law, Psychology and Social Work, Örebro University, 701 82 Örebro, Sweden.
    Andershed, Henrik
    School of Law, Psychology and Social Work, Örebro University, 701 82 Örebro, Sweden.
    Nilsson, Kent W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Associations between the FKBP5 haplotype, exposure to violence and anxiety in females2016In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 72, p. 196-204Article in journal (Refereed)
    Abstract [en]

    The gene that encodes the FK506-binding protein 5 (FKBP5) is regarded as a candidate for investigating how negative life events interact with a genetic predisposition to stress-related disorders, such as depression and anxiety. Given the role of FKBP5 as an important regulator of stress responses, we aimed to investigate if single-nucleotide polymorphisms (SNPs) in FKBP5-in the presence/absence of exposure to violence-are associated with symptoms of depression and anxiety. Data from two community-based samples of adolescents (n=1705) and young adults (n=1800) regarding ratings on depression, anxiety, exposure to violence and FKBP5 genotype were collected. A risk haplogenotype including the minor alleles of seven common SNPs in the FKBP5 (rs3800373, rs9296158, rs7748266, rs1360780, rs9394309, rs9470080 and rs4713916) conferred higher ratings on anxiety among females, but not males, in the presence of violence. Exposure to violence and female sex were associated with higher ratings on both depression and anxiety, with the exception of ratings on depression among young adults, on which sex had no effect. Ratings on depression were not associated with the haplogenotype. These findings may correspond to differences in the regulation of the HPA axis and with the higher vulnerability to anxiety in females.

  • 29.
    Jokinen, Jussi
    et al.
    Karolinska Inst, Dept Clin Neurosci Psychiat, Stockholm, Sweden.;Umea Univ, Dept Clin Sci Psychiat, Umea, Sweden..
    Boström, Adrian E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Chatzittofis, Andreas
    Karolinska Inst, Dept Clin Neurosci Psychiat, Stockholm, Sweden.;Univ Cyprus, Sch Med, Nicosia, Cyprus..
    Ciuculete, Diana-Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Oberg, Katarina Gorts
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Flanagan, John N.
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Arver, Stefan
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Methylation of HPA axis related genes in men with hypersexual disorder2017In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 80, p. 67-73Article in journal (Refereed)
    Abstract [en]

    Hypersexual Disorder (HD) defined as non-paraphilic sexual desire disorder with components of compulsivity, impulsivity and behavioral addiction, and proposed as a diagnosis in the DSM 5, shares some overlapping features with substance use disorder including common neurotransmitter systems and dysregulated hypothalamic-pituitary-adrenal (HPA) axis function. In this study, comprising 67 HD male patients and 39 male healthy volunteers, we aimed to identify HPA-axis coupled CpG-sites, in which modifications of the epigenetic profile are associated with hypersexuality. The genome-wide methylation pattern was measured in whole blood using the Illumina Infinium Methylation EPIC BeadChip, measuring the methylation state of over 850 K CpG sites. Prior to analysis, the global DNA methylation pattern was pre-processed according to standard protocols and adjusted for white blood cell type heterogeneity. We included CpG sites located within 2000 bp of the transcriptional start site of the following HPA-axis coupled genes: Corticotropin releasing hormone (CRH), corticotropin releasing hormone binding protein (CRHBP), corticotropin releasing hormone receptor I (CRHR1), corticotropin releasing hormone receptor 2 (CRHR2), FKBP5 and the glucocorticoid receptor (NR3C1). We performed multiple linear regression models of methylation M-values to a categorical variable of hypersexuality, adjusting for depression, dexamethasone non-suppression status, Childhood Trauma Questionnaire total score and plasma levels of TNF-alpha and IL-6. Of 76 tested individual CpG sites, four were nominally significant (p<0.05), associated with the genes CRH, CRHR2 and NR3C1. Cg23409074-located 48 bp upstream of the transcription start site of the CRH gene - was significantly hypomethylated in hypersexual patients after corrections for multiple testing using the FDR-method. Methylation levels of cg23409074 were positively correlated with gene expression of the CRH gene in an independent cohort of 11 healthy male subjects. The methylation levels at the identified CRH site, cg23409074, were significantly correlated between blood and four different brain regions. CRH is an important integrator of neuroendocrine stress responses in the brain, with a key role in the addiction processes. Our results show epigenetic changes in the CRH gene related to hypersexual disorder in men.

  • 30.
    Kask, Kristiina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Bäckström, Torbjörn
    Gulinello, Maria
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Lower levels of prepulse inhibition of startle response in pregnant women compared to postpartum women2008In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 33, no 1, p. 100-107Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: During the postpartum period, estradiol and progesterone levels decline from very high levels during late pregnancy to low levels within 48h of parturition. This period is associated with dysphoric states such as the postpartum blues. Animal studies have suggested an enhanced acoustic startle response and deficient prepulse inhibition (PPI) of startle response following progesterone withdrawal and during the postpartum period. The aim of the current study was to compare acoustic startle response and PPI in healthy third trimester pregnant women and healthy postpartum women. METHODS: Twenty-eight healthy pregnant and 21 healthy postpartum women (examined between 48h and 1 week after delivery) were recruited for the study. In addition, to evaluate the time-course of postpartum changes 11 early postpartum women (examined within 48h following delivery) were included in the study. The eyeblink component of the acoustic startle reflex was assessed using electromyographic measurements of m. Orbicularis Oculi. Twenty pulse-alone trials (115dB 40ms broad-band white noise) and 40 prepulse-pulse trials were presented. The prepulse stimuli consisted of a 115dB 40ms noise burst preceded at a 100ms interval by 20ms prepulses that were 72, 74, 78 or 86dB. RESULTS: Pregnant women exhibited lower levels of PPI compared to late postpartum women, p<0.05. There was no difference between pregnant women and postpartum women examined within 48h of delivery. There was no difference in startle response or habituation to startle response between pregnant women and either of the two groups of postpartum women. CONCLUSION: Healthy women display lower levels of PPI during late pregnancy when estradiol and progesterone levels are high compared to the late postpartum period when ovarian steroid levels have declined.

  • 31. Lennartsson, Anna-Karin
    et al.
    Theorell, Tores
    Kushnir, Mark M.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bergquist, Jonas
    Jonsdottir, Ingibjorg H.
    Perceived stress at work is associated with attenuated DHEA-S response during acute psychosocial stress2013In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 38, no 9, p. 1650-1657Article in journal (Refereed)
    Abstract [en]

    Background: Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) have been suggested to play a protective role during acute psychosocial stress, because they act as antagonists to the effects of the stress hormone cortisol. This study aims to investigate whether prolonged psychosocial stress, measured as perceived stress at work during the past week, is related to the capacity to produce DHEA and DHEA-S during acute psychosocial stress. It also aims to investigate whether prolonged perceived stress affects the balance between production of cortisol and DHEA-S during acute psychosocial stress. Method: Thirty-six healthy subjects (19 men and 17 women, mean age 37 years, SD 5 years), were included. Perceived stress at work during the past week was measured by using the Stress-Energy (SE) Questionnaire. The participants were divided into three groups based on their mean scores; Low stress, Medium stress and High stress. The participants underwent the Trier Social Stress Test (TSST) and blood samples were collected before, directly after the stress test, and after 30 min of recovery. General Linear Models were used to investigate if the Medium stress group and the High stress group differ regarding stress response compared to the Low stress group. Results: Higher perceived stress at work was associated with attenuated DHEA-S response during acute psychosocial stress. Furthermore, the ratio between the cortisol production and the DHEA-S production during the acute stress test were higher in individuals reporting higher perceived stress at work compared to individuals reporting low perceived stress at work. There was no statistical difference in DHEA response between the groups. Conclusions: This study shows that prolonged stress, measured as perceived stress at work during the past week, seems to negatively affect the capacity to produce DHEA-S during acute stress. Given the protective functions of DHEA-S, attenuated DHEA-S production during acute stress may Lead to higher risk for adverse effects on psychological and physiological health, particularly if stress exposure continues.

  • 32.
    Lundin, Cecilia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Danielsson, Kristina Gemzell
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Bixo, Marie
    Umea Univ, Dept Clin Hlth Obstet & Gynecol, Umea, Sweden..
    Moby, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Bengtsdotter, Hanna
    Univ Orebro, Dept Obstet & Gynecol, Orebro, Sweden..
    Jawad, Izabella
    Univ Orebro, Dept Obstet & Gynecol, Orebro, Sweden..
    Marions, Lena
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden..
    Brynhildsen, Jan
    Linkoping Univ, Dept Obstet & Gynaecol, Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Malmborg, Agota
    Linkoping Univ, Dept Obstet & Gynaecol, Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Lindh, Ingela
    Gothenburg Univ, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Obstet & Gynecol, Gothenburg, Sweden..
    Poromaa, Inger Sundström
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Combined oral contraceptive use is associated with both improvement and worsening of mood in the different phases of the treatment cycle - A double-blind, placebo-controlled randomized trial2017In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 76, p. 135-143Article in journal (Refereed)
    Abstract [en]

    Objective: Ever since the introduction of combined oral contraception (COC), one of the major reasons for discontinuing the pill use has been mood-related side effects. Moreover, women who discontinue the pill turn to less effective methods whereby the probability of an unintended conception increases. Approximately 4-10% of COC users complain of depressed mood, irritability or increased anxiety, but drug-related causality has been difficult to prove. Given the lack of randomized controlled trials in this area, we aimed to prospectively estimate the severity of adverse mood in COC users that would be as representative of general users as possible.

    Methods: This investigator-initiated, multi-center, randomized, double-blinded, placebo-controlled study included 202 healthy women. Women were randomized to a COC (1.5 mg estradiol and 2.5 mg nomegestrolacetate) or placebo for three treatment cycles. Main outcome measure was the Daily Record of Severity of Problems (DRSP), which was filled out daily during one baseline cycle and the final treatment cycle.

    Results: Results from 84 women in the COC group and 94 women in the placebo group were analysed. COC use was associated with small, but statistically significant, increases in mean anxiety (0.22; 95% CI: 0.07-0.37, p = 0.003), irritability (0.23; 95% CI: 0.07-0.38, p = 0.012), and mood swings scores (0.15; 95% CI: 0.00-0.31, p = 0.047) during the intermenstrual phase, but a significant premenstrual improvement in depression (-0.33; 95% CI: -0.62 to -0.05, p = 0.049). Secondary analyses showed that women with previous adverse hormonal contraceptive experience reported significantly greater mood worsening in the intermenstrual phase in comparison with healthy women, p <0.05. The proportion of women who reported a clinically relevant mood deterioration did not differ between those allocated to COC (24.1%) or placebo (17.0%), p = 0.262.

    Conclusion: COC use is associated with small but statistically significant mood side effects in the inter menstrual phase. These findings are driven by a subgroup of women who clearly suffer from COC-related side effects. However, positive mood effects are noted in the premenstrual phase and the proportion of women with clinically relevant mood worsening did not differ between treatment groups.

  • 33.
    Olivo, Gaia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Gour, Shaili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Low neuroticism and cognitive performance are differently associated to overweight and obesity: A cross-sectional and longitudinal UK Biobank study.2019In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 101, p. 167-174Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A growing body of research has linked personality traits to cognitive performance. This relationship might play a role in the predisposition toward obesity. Neuroticism and executive function seem to be particularly involved, and reduced executive function has been proposed to underlie the association of neuroticism with sedentary behaviors and fatty food consumption. Despite the link between neuroticism, cognitive functions and obesity has been largely reported, conflicting evidence exists. Moreover, information regarding other cognitive domains, and studies on overweight individuals, are still scarce.

    METHODS: We examined cross-sectional associations of neuroticism and cognitive function with overweight and obesity in a sample of 170 310 individuals from the UK Biobank cohort, adjusted for sociodemographic and life-style factors. Measures on fluid intelligence (FI) (reasoning ability), trail making test (TMT) (executive function), numeric memory test and pairs matching (PM) task (short-term memory) were extracted from the database. Correlations between neuroticism and cognitive performance were explored. Moreover, we investigated whether neuroticism and executive function could predict BMI variability over time.

    RESULTS: Reduced FI and short-term memory were associated with overweight and obesity, while reduced executive function was associated with obesity but not with overweight. Low neuroticism was associated with being overweight rather than lean or obese independently of gender and life-style. Furthermore, baseline neuroticism scores could predict BMI variations over 5-10 years follow-up, and high neuroticism correlated with lower cognitive performance.

    CONCLUSIONS: Lower cognitive performance is associated with both overweight and obesity, except for executive function, which was only related to obesity. Neuroticism correlated with performance on most of the cognitive domains tested, supporting the link between personality and cognition. Our findings also support the role of neuroticism in leading to greater weight variability over time, rather than to overweight/obesity itself.

  • 34.
    Skalkidou, Alkistis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Iliadis, Stavros I.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Huizink, Anja C.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Freyhult, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Stress-related genetic polymorphisms in association with peripartum depression symptoms and stress hormones: A longitudinal population-based study2019In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 103, p. 296-305Article in journal (Refereed)
    Abstract [en]

    Individual differences in the response of the stress system to hormonal changes during pregnancy and the postpartum period render some women susceptible to developing depression. The present study sought to investigate peripartum depression and stress hormones in relation to stress-related genotypes. The Edinburgh Postnatal Depression Scale was used to assess peripartum depressive symptoms in a sample of 1629 women, followed from pregnancy week seventeen to six months postpartum. Genotypes of ninety-four haplotype-tag single nucleotide polymorphisms (SNPs) in sixteen genes of the hypothalamus-pituitary-adrenal axis pathway were analyzed and data on psychosocial and demographic factors was collected. In sub-studies, salivary cortisol awakening response in gestational week 35-39, salivary evening cortisol levels in gestational week 36 and postpartum week 6, and blood cortisol and cortisone levels in gestational week 35-39 were analyzed. SNP-set kernel association tests were performed at the gene-level, considering psychosocial and demographic factors, followed by post-hoc analyses of SNPs of significant genes. Statistically significant findings at the 0.05 p-level included SNPs in the hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1) gene in relation to self-rated depression scores in postpartum week six among all participants, and serpin family A member 6 (SERPINA6) gene at the same time-point among women with de novo onset of postpartum depression. SNPs in these genes also associated with stress hormone levels during pregnancy. The present study adds knowledge to the neurobiological basis of peripartum depression by systematically assessing SNPs in stress-regulatory genes and stress-hormone levels in a population-based sample of women.

  • 35.
    Skalkidou, Alkistis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sylvén, Sara M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Papadopoulos, Fotios C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Risk of postpartum depression in association with serum leptin and interleukin-6 levels at delivery: a nested case-control study within the UPPSAT cohort2009In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 34, no 9, p. 1329-1337Article in journal (Refereed)
    Abstract [en]

    Although postpartum depression (PPD) is a common condition, it often goes undiagnosed and untreated, with devastating consequences for the woman's ability to perform daily activities, to bond with her infant and to relate to the infant's father. Leptin, a protein synthesised in the adipose tissue and involved in regulation of food intake and energy expenditure has been related to depressive disorders, but studies report conflicting results. The aim of this study was to evaluate the association between serum leptin levels at the time of delivery and the subsequent development of postpartum depression in women, using data from a population-based cohort of delivering women in Uppsala, Sweden. Three hundred and forty seven women from which serum was obtained at the time of delivery filled out at least one of three structured questionnaires containing the Edinburgh Scale for Postnatal Depression (EPDS) at five days, six weeks and six months after delivery. Mean leptin levels at delivery did not significantly differ between the 67 cases of PPD and the 280 controls. Using linear regression analysis and adjusting for maternal age, body-mass index, smoking, interleukin-6 levels, duration of gestation and gender of the newborn, the EPDS scores at six weeks and six months after delivery were found to be negatively associated with leptin levels at delivery (p<0.05). Serum leptin levels at delivery were found to be negatively associated with self-reported depression during the first six months after delivery. No such association was found concerning serum IL-6 levels at delivery. If these finding are replicated by other studies, leptin levels at delivery could eventually serve as a biological marker for the prediction of postpartum depression.

  • 36. Stenius, Fredrik
    et al.
    Swartz, Jackie
    Lindblad, Frank
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Pershagen, Göran
    Scheynius, Annika
    Alm, Johan
    Theorell, Thöres
    Low salivary cortisol levels in infants of families with an anthroposophic lifestyle2010In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 35, no 10, p. 1431-1437Article in journal (Refereed)
    Abstract [en]

    The anthroposophic lifestyle implies environmental conditions for the infant aimed at reducing negative stress stimulation and is also related to a lower prevalence of allergic diseases in children. One aim of this prospective birth cohort study was to assess stress levels in infants with an anthroposophic lifestyle. A total of 330 infants from families with anthroposophic or more conventional lifestyles were followed from pregnancy of their mothers until the age of 6 months. Information on lifestyle factors was obtained from questionnaires. Salivary samples from 210 6-month olds and their parents were collected on three occasions during 1 day for analysis of cortisol. Infants from families with an anthroposophic lifestyle had significantly lower cortisol levels on all three sampling occasions compared to other infants. In the morning, the geometric means of salivary cortisol concentration (with 95% confidence limits) were 8.8 nmol/l (6.7-11.5), 11.3 nmol/l (9.3-13.7) and 14.9 nmol/l (11.3-19.6) in infants classified as anthroposophic, partly anthroposophic and non-anthroposophic, respectively (p = 0.018). On the other hand, there was no difference in cortisol levels between the parents in the different groups. Several lifestyle factors differed significantly between the groups, but none of them independently explained the difference in cortisol levels. However, living on a farm during pregnancy was significantly associated with low saliva cortisol level in the infant. It can be concluded that low salivary cortisol levels in infants from anthroposophic families may be related to an environment with a lower degree of exposure to stress, which could influence the development of allergic diseases.

  • 37. Stenius, Fredrik
    et al.
    Theorell, Töres
    Lilja, Gunnar
    Scheynius, Annika
    Alm, Johan
    Lindblad, Frank
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Comparisons between salivary cortisol levels in six-months-olds and their parents2008In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 33, no 3, p. 352-9Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There is a close relation between the psychosocial environment of the infant--including the perception of maternal behaviour--and cortisol levels of the infant. One previous study has also demonstrated a correlation between mother and infant mean cortisol levels. In this study, this relation was further explored, also including father cortisol levels. METHODS: Saliva cortisol samples were collected from 51 six-months-olds and their parents on the same day in the morning, afternoon and evening. Analyses were performed with a radioimmunoassay technique. All mothers were at home with their child at this age and 47/51 mothers were breast feeding. RESULTS: Strong correlations were found between mother and child levels on all sampling occasions whereas weaker correlations were found between father and child levels and only in the afternoon and the evening samples. There was also a strong relation between waking up/bedtime-difference in mother and child and a weaker relation between the corresponding measure in father and child. CONCLUSIONS: The stronger mother-infant than father-infant cortisol level correlations probably mirror that mother and infant not only have genetic similarities but also have been exposed to similar environmental conditions to a higher degree than father and infant.

  • 38.
    Swenne, Ingemar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Rosling, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    Do thyroid hormones mediate the effects of starvation on mood in adolescent girls with eating disorders?2010In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 35, no 10, p. 1517-1524Article in journal (Refereed)
    Abstract [en]

    In the eating disorders (ED) comorbid depression is common and clinical experience suggests that it is partly related to starvation. Starvation affects thyroid hormone status and thyroid hypofunction is in turn associated with depressed mood. We have therefore investigated the possibility that thyroid hormones and starvation are associated with mood in ED. Two-hundred and thirty-nine adolescent girls were examined at presentation of an ED. Analyses of thyroid hormones, documentation of weight and weight changes, self-reports of depressive symptomatology and clinical diagnoses of ED and depression were used in the analyses. Of the 239 girls 100 were diagnosed with depression. The girls with and without depression did not differ in age, weight, height, body mass index (BMI), weight loss or duration of disease. Plasma free thyroxine concentrations were lower in depressed girls (11.9 +/- 1.7 versus 12.8 +/- 1.9 pmol/L; p < 0.01). Plasma triodothyronine and thyroid-stimulating hormone concentrations did not differ between groups. In a logistic regression analysis the odds ratio for depression was 41.1 (95% confidence interval 4.18-405; p = 0.001) for a 10 pmol/L change of plasma free thyroxine after correction for BMI, weight loss, duration of disease, rate of weight loss, plasma triodothyronine and an interaction between BMI and plasma free thyroxine. BMI did not predict depression. Low circulating thyroxine concentrations may provide a link between starvation and depression in adolescent girls with ED.

  • 39.
    Sylvén, Sara M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Elenis, Evangelia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Michelakos, Theodoros
    Department of Hygiene and Epidemiology, Athens Medical School, Athens, Greece.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Thyroid function tests at delivery and risk for postpartum depressive symptoms2013In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 38, no 7, p. 1007-1013Article in journal (Refereed)
    Abstract [en]

    Postpartum depression (PPD) is a common childbirth complication, which can have negative effects on both the newly delivered woman and her family. This condition is underdiagnosed and inadequately treated, while a biological diagnostic test is not yet available. Furthermore, postpartum thyroid dysfunction is common among new mothers, and some evidence point to an association between PPD and thyroid function disturbances. The aim of this study was to evaluate the possible association between serum levels of thyroid hormones at the time of delivery, and the later development of depressive symptoms, using data from a population based cohort of Swedish women. Blood samples were collected during delivery from 347 participating women, delivering at Uppsala University Hospital. The participating women filled in at least one of three structured questionnaires, containing the Edinburgh Postnatal Depression Scale (EPDS), at five days, six weeks and six months postpartum. A cut-off of 12 or more was applied on the EPDS, to identify cases of self-reported PPD and controls. Using a binary logistic regression model (adjusting for previous psychiatric contact, smoking during pregnancy, pre-pregnancy body mass index (BMI) and sleep), having a thyroid stimulating hormone (TSH) level over the clinical cut-off level of 4.0mU/L was associated with increased risk for depressive symptoms at six months postpartum (OR 11.30, 95% CI 1.93-66.11). A ROC analysis revealed that the predictive variable (PV) had significant predictive ability for PPD at 6 months postpartum, given that the AUC was 0.764, and at a PV cut-off value of 6.33, the sensitivity and specificity were 76.2% and 69.4%, respectively. If these findings are replicated in future studies, they can have important clinical implications, since TSH determination is an inexpensive routine blood test, and its inclusion in a biological screening test for PPD involving other parameters would be tempting.

  • 40.
    Tan, Xiao
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Lack of association between self-reported insomnia symptoms and clamp-derived insulin sensitivity in elderly men2019In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 102, p. 256-260Article in journal (Refereed)
    Abstract [en]

    Insomnia-related sleep disruptions, such as short and disturbed sleep, have been tied to systemic insulin resistance in young adult populations. We therefore sought to confirm these findings in a cohort of elderly men. To this aim, we utilized variables from 980 men who participated in the investigation at age 70 of the Uppsala Longitudinal Study of Adult Men. Self-reported insomnia symptoms were assessed by questions about difficulty initiating sleep, early final awakening, and regular use of hypnotics. All participants also underwent the gold standard hyperinsulinemic-euglycemic clamp technique to assess the insulin sensitivity index (M/I). Finally, fasting blood was collected to measure free fatty acids (FFAs) and adiponectin. Differences in blood parameters between men with and those without insomnia were determined by ANCOVA, and were adjusted for lifestyle and cardio-metabolic risk factors. Our analysis yielded no differences in M/I, FFAs, and adiponectin between men with and those without insomnia symptoms. Analyses in non-diabetic and diabetic subsamples confirmed these negative findings. Our cross-sectional results therefore suggest that insomnia symptoms may have a minimal effect, if any, on measures of insulin sensitivity in elderly men. Given the observational design of our study, future studies are needed to determine whether experimental sleep manipulations influence systemic insulin sensitivity in elderly humans, as has previously been shown in young adult populations.

  • 41.
    Toffoletto, Simone
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Lanzenberger, Rupert
    Gingnell, Malin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Emotional and cognitive functional imaging of estrogen and progesterone effects in the female human brain: A systematic review2014In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 50, p. 28-52Article, review/survey (Refereed)
    Abstract [en]

    Ovarian hormones are pivotal for the physiological maintenance of the brain function as well as its response to environmental stimuli. There is mounting evidence attesting the relevance of endogenous ovarian hormones as well as exogenous estradiol and progesterone for emotional and cognitive processing. The present review systematically summarized current knowledge on sex steroid hormonal modulation of neural substrates of emotion and cognition revealed by functional magnetic resonance imaging (fMRI). Twenty-four studies of healthy naturally cycling and combined oral contraceptives (COC) user women, or women undergoing experimental manipulations, during their reproductive age, were included. Furthermore, six studies of premenstrual dysphoric disorder (PMDD), a hormonally based mood disorder, and three of gender dysphoria (GD), which provides an intriguing opportunity to examine the effect of high-dose cross-sex hormone therapy (CSHT) on brain functioning, were included. Globally, low (early follicular and the entire follicular phase for estrogen and progesterone, respectively) and high (COC, CSHT, late follicular and luteal phase for estrogen; COC, mid- and late-luteal phase for progesterone) hormonal milieu diversely affected the response of several brain regions including the amygdala, anterior cingulate cortex, and inferior frontal gyrus, but their functional recruitment across groups and domains was scattered. The constellation of findings provides initial evidence of the influence of sex steroid hormones on cortical and subcortical regions implicated in emotional and cognitive processing. Further well-powered and multimodal neuroimaging studies will be needed to identify the neural mechanism of functional brain alterations induced by sex steroid hormones.

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