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  • 1.
    af Klinteberg, Britt
    et al.
    Stockholm Univ, Dept Psychol, Stockholm, Sweden.;Stockholm Univ, Karolinska Inst, Ctr Hlth Equ Studies, Sveav 160, SE-10691 Stockholm, Sweden.;Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Johansson, Sven -Erik
    Karolinska Inst, Ctr Family & Community Med, Stockholm, Sweden..
    Levander, Maria
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Alm, Per Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Oreland, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Smoking habits - Associations with personality/behavior, platelet monoamine oxidase activity and plasma thyroid hormone levels2017In: Personality and Individual Differences, ISSN 0191-8869, E-ISSN 1873-3549, Vol. 118, p. 71-76Article in journal (Refereed)
    Abstract [en]

    The objective was to outline results from our scientific studies on the associations among childhood behavior, adult personality, and biochemical factors in smoking habits. The studies consisted of: (1) follow-up of young criminals and controls, subdivided into risk for antisocial behavior groups, based on childhood rating levels of a projective test; and adult smoking habit groups; and (2) a large group of young adults examined on the same inventories. Personality in terms of KSP and EPQ-I scale scores, controlled for intelligence, indicated that the high and very high risk groups displayed significantly higher self-rated impulsiveness, anxiety, and nonconformity, as compared to the low risk group. Further, the very high risk group subjects, found to be overrepresented among subjects with heavy smoking habits, displayed lower mean platelet MAO-B activity and higher thyroid hormone levels than the low risk group. Thus, the higher the childhood risk for antisocial behavior, the clearer the adult personality pattern making subjects more disposed for smoking appeared; and the higher smoking habits, the stronger the relationships with biochemical measures. Results are discussed in terms of possible underlying mechanisms influencing personality and smoking habits. 

  • 2.
    af Klinteberg, Britt
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Farmakologi 1.
    von Knorring, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Psykiatri UAS.
    Oreland, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Farmakologi 1.
    On the psychobiology of impulsivity2004In: On the psychobiology of personality: Essays in honor of Marvin Zuckerman, Elsevier B.V., Amsterdam , 2004, p. 455-478Chapter in book (Refereed)
  • 3. Agnafors, S.
    et al.
    Sydsjö, G.
    Comasco, Erika
    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.
    Bladh, M.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Svedin, C.
    Behaviour problems in children-a longitudinal study of genetic and environmental factors2015In: European Child and Adolescent Psychiatry, ISSN 1018-8827, E-ISSN 1435-165X, Vol. 24, p. S35-S35Article in journal (Other academic)
  • 4.
    Agnafors, Sara
    et al.
    Linkoping Univ, Fac Hlth Sci, IKE, Div Child & Adolescent Psychiat, S-58185 Linkoping, Sweden.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Bladh, Marie
    Linkoping Univ, Div Obstet & Gynecol IKE, Fac Hlth Sci, S-58185 Linkoping, Sweden.
    Sydsjö, Gunilla
    Linkoping Univ, Div Obstet & Gynecol IKE, Fac Hlth Sci, S-58185 Linkoping, Sweden.
    Dekeyser, Linda
    Linkoping Univ, Div Obstet & Gynecol IKE, Fac Hlth Sci, S-58185 Linkoping, Sweden.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Svedin, Carl-Göran
    Linkoping Univ, Fac Hlth Sci, IKE, Div Child & Adolescent Psychiat, S-58185 Linkoping, Sweden.
    Effect of gene, environment and maternal depressive symptoms on pre-adolescence behavior problems: a longitudinal study2013In: Child and Adolescent Psychiatry and Mental Health, ISSN 1753-2000, E-ISSN 1753-2000, Vol. 7, article id 10Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Depression is a common and disabling condition with a high relapse frequency. Maternal mental health problems and experience of traumatic life events are known to increase the risk of behavior problems in children. Recently, genetic factors, in particular gene-by-environment interaction models, have been implicated to explain depressive etiology. However, results are inconclusive.

    METHODS:

    Study participants were members of the SESBiC-study. A total of 889 mothers and their children were followed during the child's age of 3 months to 12 years. Information on maternal depressive symptoms was gathered postpartum and at a 12 year follow-up. Mothers reported on child behavior and traumatic life events experienced by the child at age 12. Saliva samples were obtained from children for analysis of 5-HTTLPR and BDNF Val66Met polymorphisms.

    RESULTS:

    Multivariate analysis showed a significant association between maternal symptoms of depression and anxiety, and internalizing problems in 12-year-old children (OR 5.72, 95% CI 3.30-9.91). Furthermore, carriers of two short alleles (s/s) of the 5-HTTLPR showed a more than 4-fold increased risk of internalizing problems at age 12 compared to l/l carriers (OR 4.73, 95% CI 2.14-10.48). No gene-by-environment interaction was found and neither depressive symptoms postpartum or traumatic experiences during childhood stayed significant in the final model.

    CONCLUSIONS:

    Concurrent maternal symptoms of depression and anxiety are significant risk factors for behavior problems in children, which need to be taken into account in clinical practice. Furthermore, we found a main effect of 5-HTTLPR on internalizing symptoms in 12-year-old children, a finding that needs to be confirmed in future studies.

  • 5. Agnafors, Sara
    et al.
    Svedin, Carl Göran
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Bladh, Marie
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Sydsjö, Gunilla
    A Biopsychosocial Approach to Risk and Resilience on Behavior in Children Followed from Birth to Age 122017In: Child Psychiatry and Human Development, ISSN 0009-398X, E-ISSN 1573-3327, Vol. 48, no 4, p. 584-596Article in journal (Refereed)
    Abstract [en]

    An increasing prevalence of mental health problems calls for more knowledge into factors associated with resilience. The present study used multiple statistical methodologies to examine a biopsychosocial model of risk and resilience on preadolescence behavior. Data from 889 children and mothers from a birth cohort were used. An adversity score was created by combining maternal symptoms of depression, psychosocial risk and children's experiences of life events. The proposed resilience factors investigated were candidate genetic polymorphisms, child temperament, social functioning, and maternal sense of coherence. The l/l genotype of the serotonin transporter linked polymorphic region was associated with lower internalizing scores, but not mainly related to the level of adversity. An easy temperament was associated with resilience for children exposed to high adversity. Social functioning was found to be promotive independent of the risk level. The results support a multiple-level model of resilience indicating effects, though small, of both biological and psychosocial factors.

  • 6.
    Agnafors, Sara
    et al.
    Linkoping Univ, Dept Clin & Expt Med, Fac Hlth Sci, Div Child & Adolescent Psychiat, SE-58185 Linkoping, Sweden..
    Sydsjö, Gunilla
    Linkoping Univ, Div Obstet & Gynaecol, Dept Clin & Expt Med, Fac Hlth Sci, SE-58185 Linkoping, Sweden..
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Bladh, Marie
    Linkoping Univ, Div Obstet & Gynaecol, Dept Clin & Expt Med, Fac Hlth Sci, SE-58185 Linkoping, Sweden..
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Svedin, Carl Göran
    Linkoping Univ, Dept Clin & Expt Med, Fac Hlth Sci, Div Child & Adolescent Psychiat, SE-58185 Linkoping, Sweden..
    Early predictors of behavioural problems in pre-schoolers: a longitudinal study of constitutional and environmental main and interaction effects2016In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 16, article id 76Article in journal (Refereed)
    Abstract [en]

    Background: The early environment is important for child development and wellbeing. Gene-by-environment studies investigating the impact of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the Brain Derived Neurotrophic Factor (BDNF) Val66Met polymorphisms by life events on mental health and behaviour problems have been inconclusive. Methodological differences regarding sample sizes, study population, definitions of adversities and measures of mental health problems obstacle their comparability. Furthermore, very few studies included children. The aim of this study was to examine the associations between a broad range of risk factors covering pregnancy and birth, genetic polymorphism, experience of multiple life events and psychosocial environment, and child behaviour at age 3, using a comparably large, representative, population-based sample. Methods: A total of 1,106 children, and their mothers, were followed from pregnancy to age 3. Information on pregnancy and birth-related factors was retrieved from the Medical Birth Register. Questionnaires on depressive symptoms, child behaviour and child experiences of life events were filled in by the mothers. Child saliva samples were used for genotyping the 5-HTTLPR and BDNF Val66Met polymorphisms. Multiple logistic regression was used to investigate the association between psychological scales and genetic polymorphisms. Results: Symptoms of postpartum depression increased the risk of both internalizing and externalizing problems. Experience of multiple life events was also a predictor of behavioural problems across the scales. No gene-by-environment or gene-by-gene-by-environment interactions were found. Children of immigrants had an increased risk of internalizing problems and parental unemployment was significantly associated with both internalizing and externalizing type of problems. Conclusion: This study shows the importance of the psychosocial environment for psychosocial health in preschool children, and adds to the literature of null-findings of gene-by-environment effects of 5-HTTLPR and BDNF in children.

  • 7. Akkermann, Kirsti
    et al.
    Kaasik, Kadri
    Kiive, Evelyn
    Nordquist, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Harro, Jaanus
    The impact of adverse life events and the serotonin transporter gene promoter polymorphism on the development of eating disorder symptoms2012In: Journal of Psychiatric Research, ISSN 0022-3956, E-ISSN 1879-1379, Vol. 46, no 1, p. 38-43Article in journal (Refereed)
    Abstract [en]

    Adverse life events have been shown to predict weight fluctuations and dietary restraint, as well as eating disorders during adolescence or early adulthood. Since the s-allele carriers of the 5-HTT gene-linked polymorphic region (5-HTTLPR) are biologically more reactive to stress related stimuli, we aimed to explore whether the eating disturbances are predicted by environmental stressors and moderated by the 5-HTTLPR genotype. The sample was based on the younger cohort of the Estonian Children Personality, Behaviour and Health Study and included those participating in its second and third wave. The history of stressful life events was self-reported at age 15. Data on eating behaviour and attitudes, anxiety, impulsivity and depressiveness were collected at age 18. The effect of the adverse life events on binge eating and on drive for thinness was found to be moderated by the 5-HTTLPR. Adolescent girls who at age 15 had reported a history of frequent adverse life events had elevated scores in EDI-2 Bulimia subscale at age 18 if they were carrying the s-allele. The effect of the s-allele on binge eating was even more pronounced when solely the experience of sexual abuse was considered. The interaction effect of the 5-HTTLPR and the past sexual abuse was also observed on drive, for thinness. These data give further support to the idea that adverse life events in childhood may heighten susceptibility to serotonergic dysregulation following stress, and suggest that in individuals vulnerable to eating disorders this may result in disturbed eating behaviours.

  • 8.
    Aniruddha, Todkar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Granholm, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Hodgins, Sheilagh
    Nilsson W., Kent
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Nylander, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Effect of early life stress and ethanol consumption on Pomc and Avp expression in rat hypothalamus2014In: Alcohol, ISSN 0741-8329, E-ISSN 1873-6823, Vol. 48, no 2, p. 193-193Article in journal (Other academic)
  • 9.
    Balciuniene, J
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Emilsson, L
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Oreland, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Pettersson, U
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Jazin, Elena
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Investigation of the functional effect of monoamine oxidase polymorphisms in human brain2002In: Human Genetics, ISSN 0340-6717, E-ISSN 1432-1203, Vol. 110, no 1, p. 1-7Article in journal (Refereed)
  • 10.
    Berggard, Cecilia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Damberg, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Research and Development, Gävleborg.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Brainstem levels of transcription factor AP-2 in rat are changed after treatment with phenelzine, but not with citalopram2005In: BMC Pharmacology, ISSN 1471-2210, Vol. 5, p. 1-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Before therapeutic effect is obtained after treatment with antidepressant drugs, like serotonin selective reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAO-Is) there is an initial lag-period of a few weeks. Neuronal adaptations on a molecular level are supposed to be involved in the initiation of the antidepressant effect. Transcription factor AP-2 is essential for neuronal development and many genes involved in the brainstem monoaminergic systems have binding sites for AP-2 in their regulatory regions. The genotype of the AP-2beta isoform has been associated with e.g. anxiety-related personality traits and with platelet MAO activity. In addition, previous studies have shown that the levels of AP-2alpha and AP-2beta in rat whole brain were decreased after 10 days of treatment with citalopram (SSRI) and imipramine (TCA), and were increased with phenelzine (MAO-I). RESULTS: In the present study, we report that treatment with citalopram for 1, 7 or 21 days did not have effect on the AP-2 levels in rat brainstem. However, after treatment with phenelzine for 1, 7 or 21 days the levels of AP-2alpha and AP-2beta had increased after 7 days, but had returned to control levels at day 21. CONCLUSION: The decrease in AP-2 levels in rat whole brain previously seen after treatment with citalopram does not seem to be localised to the brainstem, it may rather occur in the monoaminergic terminal projection areas. The present data suggest that the increase in AP-2 levels previously seen in rat whole brain after subchronic treatment with phenelzine is located in the brainstem. It cannot, however, be excluded that other brain regions are involved.

  • 11.
    Comasco, Erika
    et al.
    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.
    Hahn, Andreas
    Ganger, Sebastian
    Gingnell, Malin
    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 Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Bannbers, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Epperson, C Neill
    Lanzenberger, Rupert
    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.
    Emotional fronto-cingulate cortex activation and brain derived neurotrophic factor polymorphism in premenstrual dysphoric disorder2014In: Human Brain Mapping, ISSN 1065-9471, E-ISSN 1097-0193, Vol. 35, no 9, p. 4450-4458Article in journal (Refereed)
    Abstract [en]

    Premenstrual dysphoric disorder (PMDD) is the prototypical sex-specific disorder in which symptom onset and offset require a particular hormonal milieu and for which there is moderate heritability. The present study investigated brain emotion processing in PMDD and healthy controls, as well as functional polymorphisms in two candidate genes for PMDD, the serotonin transporter (5-HTT) and brain derived neurotrophic factor (BDNF). The 5-HTT linked polymorphic region (5-HTTLPR) and BDNF Val66Met polymorphisms were genotyped in 31 patients with PMDD and 31 healthy controls. A subset of 16 patients and 15 controls participated in two functional magnetic resonance imaging-sessions performing an emotion processing task; once in the mid-follicular, and once in the late luteal phase which corresponds with maximum severity of mood symptoms. Genotypes were not directly associated with PMDD. A main effect of group was found in the whole brain analysis, with patients having lower activation of the pre-genual anterior cingulate and ventro-medial prefrontal cortex, independent of menstrual cycle phase. Post-hoc functional ROI analyses in the fronto-cingulate cluster showed no effect of 5-HTTLPR genotype but a genotype-by-group-by-phase interaction effect of BDNF Val66Met. Women with PMDD who were carriers of the Met-allele had lower fronto-cingulate cortex activation in the luteal phase compared to Met-allele carrying controls. The results provide suggestive evidence of impaired emotion-induced fronto-cingulate cortex activation in PMDD patients. Although limited by a small sample, the potential influence of BDNF Val66Met in PMDD is in line with preclinical findings. Hum Brain Mapp, 2014. 

  • 12.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Hallberg, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Helander, Anders
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Sundelin Wahlsten, Viveka
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    Alcohol Consumption Among Pregnant Women in a Swedish Sample and Its Effects on the Newborn Outcomes2012In: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277, Vol. 36, no 10, p. 1779-1786Article in journal (Refereed)
    Abstract [en]

    Background Little is known about the effects of low levels of maternal alcohol intake on the neuropsychological development of the child. This study is part of an ongoing investigation on maternal drinking and presents data on demographic variables, maternal alcohol use, and birth outcomes from that study. Methods The sample comprised 2,264 women from a Swedish antenatal clinic. Retrospective self-report data were collected on alcohol consumption before and during pregnancy, using the Alcohol Use Disorders Identification Test (AUDIT), and on nicotine use. Specific alcohol biomarkers for excessive drinking, carbohydrate-deficient transferrin (CDT) in serum and phosphatidylethanol (PEth) in whole blood, were determined during mid-pregnancy in a subsample of the women. Data on labor and early characteristics of the child were also assessed. Results Before pregnancy, 89% of the women regularly consumed alcohol and 49% reported occasional or frequent binge drinking. Nicotine was used by 15% before and by 5% during pregnancy. During pregnancy, 12% continued using alcohol and 5% also admitted binge drinking. However, all alcohol biomarker values were below the reporting limits (CDT = 1.7% disialotransferrin; total PEth < 0.1 mu mol/L). Self-reported drinking during pregnancy was associated with a higher AUDIT score before pregnancy, nicotine use at the time of the first prenatal visit, older age, and previous legal abortions. Conclusions The AUDIT questionnaire and 2 specific alcohol biomarkers were used in routine maternity care to collect information about drinking during pregnancy and thereby to identify children at risk for alcohol-related complications. While the AUDIT results suggested that a significant number of women continued using alcohol during pregnancy, implying a risk for fetal disorders, the biomarkers showed negative test values thus indicating only modest drinking levels.

  • 13.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    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.
    Influence of COMT val158met polymorphism on startle response during pregnancy2012In: European psychiatry, ISSN 0924-9338, E-ISSN 1778-3585, Vol. 27, no S1Article in journal (Other academic)
  • 14.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Hodgins, Sheilagh
    Rehn, Mattias
    Todkar, Aniruddha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Granholm, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Nylander, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nilsson, Kent W.
    Clinical and experimental evidence of a link between adrenergic genes, early life stress and alcohol-related phenotypes2014In: Alcohol, ISSN 0741-8329, E-ISSN 1873-6823, Vol. 48, no 2, p. 184-184Article in journal (Other academic)
  • 15.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Iliadis, Stavros I
    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, 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.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    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.
    Adipocytokines levels at delivery, functional variation of TFAP2 beta, and maternal and neonatal anthropometric parameters2013In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 21, no 10, p. 2130-2137Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE

    Adipocytokines participate in the regulation of glucose metabolism and foetal development. The transcription factor activating protein 2B (TFAP2β) has been associated with adipocytokine regulation, and gene variations with type 2 diabetes and obesity. This study investigated associations between maternal TFAP2B variation, adipocytokines levels and maternal and neonatal anthropometric characteristics.

    DESIGN AND METHODS

    A population-based sample of women was followed from delivery to six months postpartum. Adiponectin, leptin and interleukin-6 levels at delivery, and maternal as well as neonatal anthropometric variables were assessed. The TFAP2β intron 1 variable number tandem repeat (VNTR) was genotyped.

    RESULTS

    Maternal interleukin-6 correlated positively with leptin at delivery, with peripartum weight changes and weight of newborn males, adjusted for potential confounders. Leptin at delivery was associated with TFAP2β intron 1 VNTR genotype, adjusted for confounders, maternal weight and negatively with birth weight among female neonates. A path model suggested a link between TFAP2β genotype, leptin levels and newborn females' weight.

    CONCLUSIONS

    The present results stress a role for the TFAP2 β in adiposity-related conditions and intrauterine growth. The association between neonatal birth weight and maternal adipocytokine levels, together with the observed sex effect, call for further studies on the mechanisms behind neuro-endocrine foetal programming.

  • 16.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Hallman, Jarmila
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Wallen-Mackenzie, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Haplotype tag single-nucleotide polymorphism analysis of the vesicular glutamate transporter 2 gene in severe alcoholism among women2012In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 22, no S2, p. S397-S397Article in journal (Other academic)
  • 17.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Rangmar, J
    Univ Gothenburg, Dept Psychol, Gothenburg, Sweden.
    Eriksson, Ulf J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Neurological and neuropsychological effects of low and moderate prenatal alcohol exposure2018In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 222, no 1, article id e12892Article in journal (Refereed)
    Abstract [en]

    Several explanations for the diverse results in research on foetal alcohol spectrum disorders or alcohol-related neurodevelopmental disorder might be at hand: timing, amount and patterns of alcohol exposure, as well as complex epigenetic responses. The genetic background of the offspring and its interaction with other prenatal and post-natal environmental cues are likely also of importance. In the present report, key findings about the possible effects of low and moderate doses of maternal alcohol intake on the neuropsychological development of the offspring are reviewed and plausible mechanisms discussed. Special focus is put on the serotonergic system within developmental and gene-environment frameworks. The review also suggests guidelines for future studies and also summarizes some of to-be-answered questions of relevance to clinical practice. Contradictory findings and paucity of studies on the effects of exposure to low alcohol levels during foetal life for the offspring's neuropsychological development call for large prospective studies, as well as for studies including neuroimaging and multi-omics analyses to dissect the neurobiological underpinnings of alcohol exposure-related phenotypes and to identify biomarkers. Finally, it remains to be investigated whether any safe threshold of alcohol drinking during pregnancy can be identified.

  • 18.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Sylvén, Sara M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Papadopoulos, Fotios C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    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.
    Postpartum depressive symptoms and the BDNF Val66Met functional polymorphism: effect of season of delivery:  2011In: Archives of Women's Mental Health, ISSN 1434-1816, E-ISSN 1435-1102, Vol. 14, no 6, p. 453-463Article in journal (Refereed)
    Abstract [en]

    Postpartum depression (PPD) is an often underdiagnosed and undertreated mood disorder, with negative impact on the mother's and infant's health. Seasonal variation has been discussed as a risk factor for PPD. Candidate genes, such as those encoding for the brain-derived neurotrophic factor (BDNF), serotonin transporter (5-HTT), and Period2 (PER2), have been associated with depression and seasonal disorders. The present study is aimed to examine whether functional polymorphic variants, BDNF Val66Met, 5-HTTLPR, or PER2 SNP 10870, are associated with PPD symptoms and whether these genetic polymorphisms interact with season in predicting PPD symptoms. This case-control study comprised of 275 women from a population-based cohort of delivering women in Sweden, who completed a questionnaire containing the Edinburgh postnatal depression scale (EPDS) at 6 weeks and 6 months postpartum. Stressful life events (SLEs) and maternity stressors were also assessed. The results did not reveal any statistically significant overall association between the studied genetic polymorphisms and PPD symptoms. However, a significant association between BDNF Met66 carrier status and development of PPD symptoms at 6 weeks postpartum, even when controlling for prepartum and postpartum environmental risk factors, was evident among mothers delivering during autumn/winter. No gene-gene interactions were found but a cumulative effect was detected with carriers of a greater number of 5-HTTLPR S and BDNFVal66Met Met alleles reporting higher EPDS scores, if delivered during autumn/winter. Our findings propose a role of the BDNF gene in the development of PPD symptoms, potentially mediated by season of delivery.

  • 19.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Vumma, Ravi
    Linnaeus Univ, Fac Hlth & Life Sci, Dept Chem & Biomed Sci, Kalmar, Sweden..
    Toffoletto, Simone
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Johansson, Jessica
    Orebro Univ, Sch Hlth & Med Sci, Dept Clin Med, SE-70182 Orebro, Sweden..
    Flyckt, Lena
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden..
    Lewander, Tommy
    Orebro Univ, Sch Hlth & Med Sci, Dept Clin Med, SE-70182 Orebro, Sweden..
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology. Stromstad Acad, Stromstad, Sweden..
    Bjerkenstedt, Lars
    Andreou, Dimitrios
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden..
    Söderman, Erik
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden..
    Terenius, Lars
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden..
    Agartz, Ingrid
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden.;Univ Oslo, KG Jebsen Ctr Psychosis Res, Div Mental Hlth & Addict, NORMENT,Inst Clin Med, Oslo, Norway.;Diakonhjemmet Hosp, Dept Psychiat Res, Oslo, Norway..
    Jönsson, Erik G.
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden.;Univ Oslo, KG Jebsen Ctr Psychosis Res, Div Mental Hlth & Addict, NORMENT,Inst Clin Med, Oslo, Norway..
    Venizelos, Nikolaos
    Orebro Univ, Sch Hlth & Med Sci, Dept Clin Med, SE-70182 Orebro, Sweden..
    Genetic and Functional Study of L-Type Amino Acid Transporter 1 in Schizophrenia2016In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 74, no 2, p. 96-103Article in journal (Refereed)
    Abstract [en]

    Schizophrenia involves neural catecholaminergic dysregulation. Tyrosine is the precursor of catecholamines, and its major transporter, according to studies on fibroblasts, in the brain is the L-type amino acid transporter 1 (LAT1). The present study assessed haplotype tag single-nucleotide polymorphisms (SNPs) of the SLC7A5 /LAT1 gene in 315 patients with psychosis within the schizophrenia spectrum and 233 healthy controls to investigate genetic vulnerability to the disorder as well as genetic relationships to homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), the major catecholamine metabolites in the cerebrospinal fluid (CSF). Moreover, the involvement of the different isoforms of the system in tyrosine uptake and LAT1 tyrosine kinetics were studied in fibroblast cell lines of 10 patients with schizophrenia and 10 healthy controls. The results provide suggestive evidence of individual vulnerability to schizophrenia related to the LAT1 SNP rs9936204 genotype. A number of SNPs were nominally associated with CSF HVA and MHPG concentrations but did not survive correction for multiple testing. The LAT1 isoform was confirmed as the major tyrosine transporter in patients with schizophrenia. However, the kinetic parameters ( maximal transport capacity, affinity of the binding sites, and diffusion constant of tyrosine transport through the LAT1 isoform) did not differ between patients with schizophrenia and controls. The present genetic findings call for independent replication in larger samples, while the functional study seems to exclude a role of LAT1 in the aberrant transport of tyrosine in fibroblasts of patients with schizophrenia.

  • 20.
    Comasco, Erika
    et al.
    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.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Nilsson, Kent W
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Three-way interaction effect of 5-HTTLPR, BDNF Val66Met, and childhood adversity on depression: A replication study2013In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 23, no 10, p. 1300-1306Article in journal (Refereed)
    Abstract [en]

    Both the serotonin transporter linked promoter region (5-HTTLPR) and the brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms have been shown to interact with unfavourable environment in relation to depression symptoms and to depression diagnosis. Several attempts have been made to study a three-way interaction effect of these factors on depression, however with contradictory results. We aimed to test the hypothesis of a three-way interaction effect and to attempt at replication in an independent population-based sample. Family maltreatment, sexual abuse and depression were self-reported by an adolescent population-based cohort (N=1393) from the county of Västmanland, Sweden. DNA was isolated from saliva, and used for genotyping of the 5-HTTLPR and BDNF Val66Met polymorphisms. Neither 5-HTTLPR or BDNF genotypes separately, nor in interaction with each other had any relation to depression, however in an environment adjusted model a two-way interaction and a three-way interaction effect was found. Both 5-HTTLPR and BDNF Val66Met interacted with unfavourable environment in relation to depressive symptoms (Adj R2=0.19). Depressive symptoms and depression were more common among carriers of either the ss/sl+Val/Val or the ll+Met genotypes in the presence of early-life adversities. This three-way effect was more pronounced among girls. The current study, with a virtually similar set-up compared to previous studies, can partially confirm previous findings and their generalizability. The study also shows the importance of genetic plasticity in individuals with different environmental exposure, for different phenotypic expression.

  • 21.
    Furmark, Tomas
    et al.
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Tillfors, Maria
    Garpenstrand, Håkan
    Marteinsdottir, Ina
    Långström, Bengt
    Oreland, Lars
    Fredrikson, Mats
    Serotonin transporter genetic variation, amygdala activity and symptom severity in social phobia.2004In: Biological Psychiatry, 55, Suppl. 8, 2004, p. 69S-Conference paper (Refereed)
  • 22.
    Furmark, Tomas
    et al.
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Tillfors, Maria
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Garpenstrand, Håkan
    Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Marteinsdottir, Ina
    Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Långström, Bengt
    Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Biochemistry and Organic Chemistry. Uppsala Imanet.
    Oreland, Lars
    Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Fredrikson, Mats
    Uppsala University, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Faculty of Social Sciences, Department of Psychology.
    Serotonin transporter polymorphism related to amygdala excitability and symptom severity in patients with social phobia2004In: Neuroscience Letters, Vol. 362, p. 189-192Article in journal (Refereed)
  • 23. Garpenstrand, H
    et al.
    Annas, P
    Ekblom, J
    Oreland, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Fredrikson, M
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Human fear conditioning is related to dopaminergic and serotonergic biological markers2001In: BEHAVIORAL NEUROSCIENCE, ISSN 0735-7044, Vol. 115, no 2, p. 358-364Article in journal (Refereed)
    Abstract [en]

    Biological markers for acquisition and extinction of fear conditioning were studied in 40 individuals selected for displaying either good or poor acquisition of fear conditioning, as estimated by the skin conductance response. Participants with a short se

  • 24. Garpenstrand, Håkkan
    et al.
    Bergqvist, Michael
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enheten för onkologi.
    Brattström, Daniel
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enheten för onkologi.
    Larsson, Anders
    Department of Medical Sciences. klinisk kemi.
    Oreland, Lars
    Hesselius, Patrik
    Wagenius, Gunnar
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enheten för onkologi.
    Serum semicarbazide-sensitive amine oxidase (SSAO) activity correlates with VEGF in non-small-cell lung cancer patients.2004In: Med Oncol, ISSN 1357-0560, Vol. 21, no 3, p. 241-50Article in journal (Refereed)
  • 25.
    Göktürk, C
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Nilsson, J
    Nordquist, J
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Kristensson, M
    Svensson, K
    Söderberg, C
    Israelsson, M
    Garpenstrand, H
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Sjöquist, M
    Department of Medical Cell Biology.
    Oreland, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Forsberg-Nilsson, K
    Department of Medical Biochemistry and Microbiology.
    Overexpression of semicarbazide-sensitive amine oxidase (SSAO) in smotth muscle cells leads an abnormal structure of the aortic elastic laminas2003In: American J of Pathology, Vol. 163, p. 1921-Article in journal (Refereed)
  • 26.
    Göktürk, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Nordquist, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Sugimoto, Haruyo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Forsberg-Nilsson, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Nilsson, Joakim
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Semicarbazide-sensitive amine oxidase in transgenic mice with diabetes2004In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 325, no 3, p. 1013-1020Article in journal (Refereed)
    Abstract [en]

    Semicarbazide-sensitive amine oxidase (SSAO) activity in plasma is increased in diabetes, and in particular, in diabetic patients with vascular complications. It has been speculated that SSAO is involved in the development of such complications due to the production of cytotoxic compounds. In this work, we have induced diabetes in a previously described mouse-model, overexpressing SSAO in smooth muscle cells. SSAO activity was estimated as well as expression of the endogenous mouse gene and human transgene using real-time PCR. Diabetes induced an increase in SSAO activity in serum, kidney, and adipose tissue of transgenic animals. An inverse correlation between SSAO activity and mouse SSAO mRNA levels was observed in transgenic animals with diabetes. These results further support the suggestion of a negative feedback control of the SSAO gene expression. The increased SSAO activity in diabetes is most likely dependent on post-transcriptional modifications or activation of existing inactive enzyme molecules.

  • 27. Harro, J.
    et al.
    Kiive, E.
    Laas, K.
    Vaht, M.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Veidebaum, T.
    MAOA VNTR genotype, psychiatric vulnerability and life course in a population-representative longitudinal study2012In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 22, no S2, p. S360-S360Article in journal (Other academic)
  • 28.
    Harro, Jaanus
    et al.
    Univ Tartu, Estonian Ctr Behav & Hlth Sci, Div Neuropsychopharmacol, Dept Psychol, EE-50411 Tartu, Estonia.;North Estonia Med Ctr, Psychiat Clin, Tallinn, Estonia..
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    The role of MAO in personality and drug use2016In: Progress in Neuro-psychopharmacology and Biological Psychiatry, ISSN 0278-5846, E-ISSN 1878-4216, Vol. 69, p. 101-111Article in journal (Refereed)
    Abstract [en]

    Monoamine oxidases, both MAO-A and MAO-B, have been implicated in personality traits and complex behaviour, including drug use. Findings supporting the involvement of MAO-A and MAO-B in shaping personality and in the development of strategies of making behavioural choices come from a variety of studies that have examined either prevalence of gene variants in clinical groups or population-derived samples, estimates of enzyme activity in blood or, by positron emission tomography, in the brain and, most recently, measurement of methylation of the gene. Most of the studies converge in associating MAO-A and MAO-B with impulsive, aggressive or antisocial personality traits or behaviours, including alcohol-related problems, and for MAO-A available evidence strongly supports interaction with adverse environmental exposures in childhood. What is known about genotype effects, and on expression and activity of the enzyme in the brain and in blood has not yet been possible to unite into a mechanistic model of the role of monoamine systems, but the reason for this low degree of generalization is likely caused by the cross-sectional nature of investigation that has not incorporated the developmental effects of MAO-s in critical time windows, including the foetal period. The "risk variants" of both MAO-s appear to increase behavioural plasticity, as supportive environments may particularly well enhance the hidden potential of their carriers. Importantly, male and female brain and behaviours have been found very different with regard to MAO x life events interaction. Future studies need to take into consideration these developmental aspects and sex/gender, as well as to specify the role of different types of environmental factors.

  • 29. Jansson, Mårten
    et al.
    McCarthy, Shane
    Sullivan, Patrick F
    Dickman, Paul
    Andersson, Björn
    Oreland, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Schalling, Martin
    Pedersen, Nancy L
    MAOA haplotypes associated with thrombocyte-MAO activity.2005In: BMC Genet, ISSN 1471-2156, Vol. 6, p. 46-Article in journal (Refereed)
  • 30.
    Jokinen, Jussi
    et al.
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden.;Umea Univ, Dept Clin Sci, Umea, Sweden..
    Königsson, Johan
    Umea Univ, Dept Clin Sci, Umea, Sweden..
    Moberg, Tomas
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden..
    Jönsson, Erik G.
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden.;Univ Oslo, Inst Clin Med, KG Jebsen Ctr Psychosis Res, NORMENT, Oslo, Norway..
    Tiihonen, Jari
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden.;Univ Eastern Finland, Niuvanniemi Hosp, Dept Forens Psychiat, Kuopio, Finland..
    Nordström, Peter
    Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden..
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Åsberg, Marie
    Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Platelet monoamine oxidase activity and interpersonal violence in male suicide attempters2018In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 260, p. 173-176Article in journal (Refereed)
    Abstract [en]

    Low platelet monoamine oxidase B (MAO-B) activity, proxy of low central serotonergic functions, has been shown to correlate with criminal behavior in adolescents that come from an unfavorable psychosocial environment but not in adolescents from good conditions, indicating a link between environment, MAO-B activity and aggressive behavior. The purpose of this study was to examine the association between MAO-B activity and lifetime interpersonal violence in suicide attempters. The study included a total of 28 suicide attempters (18 men and 10 women). Assessments of childhood exposure to and expressed interpersonal violence during childhood and as an adult were carried out with the Karolinska Interpersonal Violence Scale (KIVS). Platelet MAO-B activity was measured with 2-phenylethylamine (b-PEA) as substrate. Broken down by gender, the correlations between platelet MAO-B activity and both exposure scores to interpersonal violence as a child and expressed lifetime interpersonal violence were significant in male suicide attempters (r = -0.61, p = 0.035; r = - 0.84, p = 0.0005), but not in women. Our finding of significant associations between interpersonal violence and low MAO-B activity need to be replicated in other cohorts of suicide attempters.

  • 31.
    Joost, Urmeli
    et al.
    Univ Tartu, Dept Family Med & Publ Hlth, Fac Med, Tartu, Estonia.
    Villa, Inga
    Univ Tartu, Dept Family Med & Publ Hlth, Fac Med, Tartu, Estonia.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Veidebaum, Toomas
    Natl Inst Hlth Dev, Dept Chron Dis, Tallinn, Estonia.
    Harro, Jaanus
    Univ Tartu, Div Neuropsychopharmacol, Dept Psychol, Estonian Ctr Behav & Hlth Sci, Tartu, Estonia.
    Association between Transcription Factor AP-2B genotype, obesity, insulin resistance and dietary intake in a longitudinal birth cohort study2019In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 43, no 10, p. 2095-2106Article in journal (Refereed)
    Abstract [en]

    Background The development of obesity has a large genetic component, and the gene encoding the transcription factor 2 beta (TFAP2B) has been identified as one of the responsible factors. We investigated the effect of TFAP2B intron 2 variable number tandem repeat (VNTR) genotype on obesity, insulin resistance and dietary intake from 15 to 33 years of age. Methods The sample included both birth cohorts (originally n = 1176) of the longitudinal Estonian Children Personality Behaviour and Health Study. The association between TFAP2B genotype, and anthropometric measurements, glucose metabolism and dietary intake at ages 15, 18 and 25 years was assessed using the linear mixed-effects regression models. Differences in anthropometric measurements, biochemical measures, blood pressure and dietary intake between TFAP2B genotypes at different age, including data of the older cohort at age 33, were assessed by one-way ANOVA. Results Male homozygotes for the TFAP2B 5-repeat allele had significantly higher body weight, body mass index, sum of 5 skinfolds, proportion of body fat, waist circumference, hip circumference, waist-to-hip ratio, waist-to-height ratio, fasting insulin and HOMA index. In female subjects, homozygotes for the TFAP2B 5-repeat allele had significantly larger increase in the rate of change per year in body weight, body mass index and hip circumference between years 15 and 25. By age 33, the findings were similar. A decrease in daily energy intake from adolescence to young adulthood was observed. In males, heterozygotes had significantly smaller decrease in the rate of change per year in daily energy intake. Conclusions The association of TFAP2B with the development of obesity and insulin resistance is present throughout adolescence to young adulthood in males. In females the effect of TFAP2B on obesity appears later, in young adulthood. The TFAP2B effect is rather related to differences in metabolism than energy intake.

  • 32. Kiive, Evelyn
    et al.
    Laas, Kariina
    Akkermann, Kirsti
    Comasco, Erika
    Department of Psychology, Estonian Centre of Behavioural and Health Sciences, University of Tartu, Tiigi 78, Tartu 50410, Estonia .
    Oreland, Lars
    Department of Psychology, Estonian Centre of Behavioural and Health Sciences, University of Tartu, Tiigi 78, Tartu 50410, Estonia .
    Veidebaum, Toomas
    Harro, Jaanus
    Mitigating aggressiveness through education?: The monoamine oxidase A genotype and mental health in general population2014In: Acta Neuropsychiatrica, ISSN 0924-2708, E-ISSN 1601-5215, Vol. 26, no 1, p. 19-28Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Monoamine oxidase A (MAOA) gene promoter region includes a variable number of tandem repeat (VNTR) associated with antisocial behaviour in adverse environment. We have examined the effect of the MAOA-uVNTR on mental health and academic success by using a population representative sample and a longitudinal design.

    METHODS: The data of the older cohort (n = 593, aged 15 years at the original sampling) of the longitudinal Estonian Children Personality, Behaviour and Health Study (ECPBHS) were used. Follow-ups were conducted at ages 18 and 25 years. Aggressiveness, inattention and hyperactivity were reported by class teachers or, at older age, self-reported. Stressful life events, psychological environment in the family and interactions between family members were self-reported. Data of general mental abilities and education were obtained at the age of 25, and lifetime psychiatric disorder assessment was carried out with the Mini-International Neuropsychiatric Interview (MINI) interview.

    RESULTS: MAOA-uVNTR genotype had no independent effect on aggressiveness, hyperactive and inattentive symptoms, and neither was there a genotype interaction with adverse life events. Interestingly, the proportion of male subjects with higher education by the age of 25 was significantly larger among those with MAOA low-activity alleles (χ² = 7.13; p = 0.008). Logistic regression revealed that MAOA low-activity alleles, higher mental abilities, occurrence of anxiety disorders and absence of substance-use disorder were significant independent predictors for higher education in male subjects.

    CONCLUSIONS: In a population representative sample of young subjects, the MAOA-uVNTR 'risk genotype' predicted better life outcomes as expressed in higher level of education.

  • 33.
    Nillson, Kent W.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Sjöberg, Rickard L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Damberg, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Alm, Per Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Öhrvik, John
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Lindström, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Role of the Serotonin Transporter Gene and Family Function in Adolescent Alcohol Consumption2005In: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277, Vol. 29, no 4, p. 564-570Article in journal (Refereed)
    Abstract [en]

    Background: That the extent to which a particular individual will engage in problematic behaviors such as delinquency, violence, or drug abuse is determined by the way psychosocial, situational, and hereditary factors interact is widely accepted. However, only recently have researchers begun to investigate the interactions between specific genotypes and psychosocial factors in relation to behavior. The purpose of the present study was to investigate possible interactions between a polymorphism in the promoter region of the serotonin transporter (5-HTT) gene and family relations on adolescent alcohol consumption.

    Methods: A cross-sectional study with a randomized sample from a total population of 16- and 19-year-old adolescents from a Swedish county was conducted. Eighty-one male and 119 female adolescents, who volunteered to participate after having answered a questionnaire, were randomly selected from quartiles of volunteers representing various degrees of psychosocial risk behavior.

    Results: 5-HTT genotype (p= 0.029) and family relations (p= 0.022) predicted alcohol consumption independently as well as through an interaction with one another (p= 0.05). The model explained 11% of the variance in alcohol consumption. In a binary logistic model, we found that adolescents with the LS variant of the 5-HTT gene and with family relations being “neutral” or “bad” had a 12- to 14-fold increased risk for high intoxication frequency.

    Conclusions: In sum, our results show that a functional polymorphism of the 5-HTT genotype, family relations, and interactions between these variables predict adolescent alcohol consumption in a randomized sample of adolescents.

  • 34.
    Nillson, Kent W.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Sjöberg, Rickard L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Damberg, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Öhrvik, John
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Alm, Per Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Lindström, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Role of Monoamine Oxidase A Genotype and Psychosocial Factors in Male Adolescent Criminal Activity2006In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 2, no 59, p. 121-127Article in journal (Refereed)
    Abstract [en]

    Background

    A number of important sociological, psychological, and biological predictors of adolescent criminal behavior have been identified during the most recent decades. The aim of this study was to replicate recent findings that interactions between a polymorphism in the monoamine oxidase A (MAO-A) gene promoter region and psychosocial factors might predict male adolescent criminal activity.

    Methods

    A cross-sectional study with a randomized sample from the total population of 16- and 19-year-olds from the county of Västmanland, Sweden. Eighty-one male adolescents, who volunteered to participate, were randomly selected from groups representing different degrees of deviant risk behavior.

    Results

    The present study strongly supports the notion that carrying the 3-repeat allele of the MAO-A–gene promoter increases the risk of male adolescent criminal behavior, when interacting with psychosocial factors. No effects at all of the MAO-A genotype on adolescent criminal activity were found when MAO-A genotype was considered alone (i.e., without its psychosocial context). The explained variance of the bio-psychosocial model (controlling for MAO-A) in this study exceeded the psychosocial model by 12%.

    Conclusions

    The findings support the notion that genotype and psychosocial factors interact to precipitate male adolescent criminal behavior.

  • 35.
    Nilsson, Kent W
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Hodgins, Sheilagh
    Oreland, Lars
    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.
    Genotypes do not confer risk for delinquency but rather alter susceptibility to positive and negative environmental factors: Gene-environment interactions of BDNF Val66Met, 5-HTTLPR, and MAOA-uVNTR2015In: International Journal of Neuropsychopharmacology, ISSN 1461-1457, E-ISSN 1469-5111, Vol. 18, no 5Article in journal (Refereed)
    Abstract [en]

    Background. Previous evidence of gene-by-environment interactions associated with emotional and behavioral disorders is contradictory. Differences in findings may result from variation in valence and dose of the environmental factor, and/or failure to take account of gene-by-gene interactions. The present study investigated interactions between the brain-derived neurotrophic factor gene (BDNF Val66Met), the serotonin transporter gene linked polymorphic region (5-HTTLPR), the monoamine oxidase A (MAOA-uVNTR) polymorphisms, family conflict, sexual abuse, the quality of the child-parent relationship, and teenage delinquency.

    Methods. In 2006, as part of the Survey of Adolescent Life in Västmanland, Sweden, 1337 high-school students, aged 17-18 years, anonymously completed questionnaires and provided saliva samples for DNA analyses.

    Results. Teenage delinquency was associated with two-, three-, and four-way interactions of each of the genotypes and the three environmental factors. Significant four-way interactions were found for BDNF Val66Met×5-HTTLPR×MAOA-uVNTR×family conflicts, and for BDNF Val66Met×5-HTTLPR×MAOA-uVNTR×sexual abuse. Further, the two genotype combinations that differed the most in expression levels (BDNF Val66Met Val, 5-HTTLPR LL, MAOA-uVNTR LL (girls) and L (boys) vs BDNF Val66Met Val/Met, 5-HTTLPR S/LS, MAOA-uVNTR S/SS/LS) in interaction with family conflict and sexual abuse were associated with the highest delinquency scores. The genetic variants previously shown to confer vulnerability for delinquency (BDNF Val66Met Val/Met×5-HTTLPR S×MAOA-uVNTR S) were associated with the lowest delinquency scores in interaction with a positive child-parent relationship.

    Conclusions. Functional variants of the MAOA-uVNTR, 5-HTTLPR, and BDNF Val66Met, either alone or in interaction with each other, may be best conceptualized as modifying sensitivity to environmental factors that confer either risk or protection for teenage delinquency.

  • 36.
    Nilsson, Kent W.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Sjöberg, Rickard L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Wargelius, Hanna-Linn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Lindström, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    The monoamine oxidase A (MAO-A) gene, family function and maltreatment as predictors of destructive behaviour during male adolescent alcohol consumption2007In: Addiction, ISSN 0965-2140, E-ISSN 1360-0443, Vol. 102, no 3, p. 389-398Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate possible interactions between a polymorphism in the monoamine oxidase A (MAO-A) gene promoter, family relations and maltreatment/sexual abuse on adolescent alcohol-related problem behaviour among male adolescents. DESIGN, SETTING AND PARTICIPANTS: A cross-sectional study of a randomized sample of 66 male individuals from a total population of 16- and 19-year adolescents from a Swedish county. Boys, who volunteered to participate answering an alcohol-related problem/behaviour questionnaire, were investigated with regard to interactions between such problems, family function, maltreatment and MAO-A genotype. MEASUREMENTS: MAO-A genotype, family relations history, history of being maltreated or abused and alcohol-related problem behaviour. FINDINGS: Boys with the short (three-repeat) variant of the MAO-A gene, who had been maltreated/abused or came from families with poor relations, showed significantly higher scores of alcohol-related problems. We also found that maltreatment/abuse independently showed the strongest relation to alcohol-related problems among boys in our model. CONCLUSIONS: The results suggest that both maltreatment and MAO-A genotype may be useful for the understanding of male adolescent alcohol-related problem behaviour.

  • 37.
    Nilsson, Kent W.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Sonnby, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Nordquist, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Comasco, Erica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Sjöberg, Richard L
    Transcription Factor Activating Protein-2β (TFAP-2β) genotype and symptoms of attention deficit hyperactivity disorder in relation to symptoms of depression in two independent samples2014In: European Child and Adolescent Psychiatry, ISSN 1018-8827, E-ISSN 1435-165X, Vol. 23, no 4, p. 207-217Article in journal (Refereed)
    Abstract [en]

    The Transcription Factor Activating Protein-2β (TFAP-2β) gene has been shown to influence monoaminergic neurotransmission, and several genes important for monoaminergic function have binding sites for TFAP-2β. Familial studies of attention deficit hyperactivity disorder (ADHD) suggest a hereditary-determined subtype of ADHD with comorbid depression. We examined a functional variation of the TFAP-2β gene in the context of co-occurring symptoms of ADHD and depression in two independent population-based samples of adolescents (Group A, n = 175 and Group B, n = 1,506) from Sweden. Results indicated 6.1 to 7.8 % of adolescents screened positively for ADHD and depression symptoms. Symptoms of depression were more common among girls who screened positively for ADHD and did not carry the nine-repeat allele of the TFAP-2β intron 1 Variable Number Tandem Repeat (VNTR) polymorphism. The presence of the nine-repeat variant of the TFAP-2β intron 1 VNTR appears to protect girls with ADHD symptoms from the co-expression of symptoms of depression.

  • 38.
    Nilsson, Kent W.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Åslund, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Gene-environment interaction of monoamine oxidase A in relation to antisocial behaviour: current and future directions.2018In: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 125, no 11, p. 1601-1626Article, review/survey (Refereed)
    Abstract [en]

    Since the pioneering finding of Caspi and co-workers in 2002 that exposure to childhood maltreatment predicted later antisocial behaviour (ASB) in male carriers of the low-activity MAOA-uVNTR allele, frequent replication studies have been published. Two meta-analyses, one in 2006 and the other in 2014, confirmed the original findings by Caspi and co-workers. In the present paper, we review the literature, note some methodological aspects of candidate gene–environment interaction (cG×E) studies and suggest some future directions. Our conclusions are as follows. (1) The direction of the effect in a cG×E model may differ according to the positive and negative environmental background of the population. (2) There is a predictor-intersection problem such that when measuring one type of maltreatment in a person, other kinds of maltreatment often co-occur. Other forms of abuse are implicitly considered in statistical models; therefore, it is difficult to draw conclusions about the effects of timing and the severity of different forms of stressful life events in relation to ASB. (3) There is also an outcome-intersection problem because of the major intersection of ASB and other forms of mental health problems. It is likely that the G×E with MAOA is related to a common unmeasured factor. (4) For the G×E model, in which the effect of the gene on the outcome variable is dependent on other predictor variables, theoretically, hypothesis-driven statistical modelling is needed.

  • 39.
    Nordquist, Jenny
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Farmakologi.
    Bäcklund, Lars B
    Department of Medical Sciences.
    Garpenstrand, Håkan
    Ekblom, Jonas
    Landin, Britta
    Yu, Peter H
    Oreland, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Farmakologi.
    Rosenkvist, Urban
    Department of Public Health and Caring Sciences.
    Follow-up of plasma semicarbazide-sensitive amine oxidase (SSAO) activity and retinopathy in type 2 diabetes mellitus.2001In: J Diabetes Complications, Vol. 15, no 5, p. 250-256Article in journal (Refereed)
  • 40.
    Nordquist, Jenny
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Farmakologi.
    Göktürk, Camilla
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Farmakologi.
    Oreland, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Farmakologi.
    Semicarbazide-sensitive amine oxidase (SSAO) gene expression in alloxan-induced diabetes in mice.2002In: Mol Med, Vol. 8, no 12, p. 824-829Article in journal (Refereed)
  • 41.
    Oreland, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Farmakologi 1.
    Platelet monoamine oxidase, personality and alcoholism: the rise, fall and resurrection2004In: Neurotoxicology, Vol. 25, no 1-2, p. 79-89Article in journal (Refereed)
  • 42.
    Oreland, L
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Farmakologi 1.
    Hallman, J
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Psykiatri UAS.
    Damberg, M
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Farmakologi 1.
    Platelet MAO and personality--function and dysfunction2004In: Curr Med Chem, Vol. 11, no 15, p. 2007-16Article in journal (Refereed)
  • 43.
    Oreland, L
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Hallman, J
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. psykiatir, UAS.
    Furmark, T
    Fredriksson, M
    Nilsson, K
    Sexual Dimorphism, Heterosis and Epistasis Effects in Studies on Associations Between Monomaminergic Candidate Genes and Personality/Behavior2008In: XIV World Congress of Psychiatry, Prague Sept 20-25,2008, 2008Conference paper (Other scientific)
  • 44.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Henrik Sjobring and the concept of individual psychology in psychiatry2015In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 120, no 2, p. 95-103Article in journal (Refereed)
  • 45.
    Oreland, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Hallman, Jarmila
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Åslund, Cecilia
    Nilsson, Kent
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Epistatic Effects of Bdnf, 5Httlpr and Maoa in Interaction with Environmental Adversity on Adolescent Criminality2013In: European psychiatry, ISSN 0924-9338, E-ISSN 1778-3585, Vol. 28, no S1, p. 1022-Article in journal (Other academic)
  • 46.
    Oreland, Lars
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Hallman, Jarmila
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. psykiatri, UAS.
    Nilsson, Kent
    Harro, Jaanus
    Behavior, Sex, Genes, Environment and Personality/Behavior - Association studies in Humans2007In: World Congress of World association for Social Psychiatry (WASP), Prague Oct 21-24, 2007, 2007Conference paper (Other (popular scientific, debate etc.))
  • 47.
    Oreland, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Lagravinese, Gianvito
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Toffoletto, Simone
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Nillson, Kent W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Harro, Jaanus
    Univ Tartu, Div Neuropsychopharmacol, Dept Psychol, Tartu.; North Estonia Med Ctr, Psychiat Clin, Tallinn.
    Robert Cloninger, C.
    Washington Univ, Sch Med, Dept Psychiat, St Louis.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Personality as an intermediate phenotype for genetic dissection of alcohol use disorder.2018In: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 125, no 1, p. 107-130Article, review/survey (Refereed)
    Abstract [en]

    Genetic and environmental interactive influences on predisposition to develop alcohol use disorder (AUD) account for the high heterogeneity among AUD patients and make research on the risk and resiliency factors complicated. Several attempts have been made to identify the genetic basis of AUD; however, only few genetic polymorphisms have consistently been associated with AUD. Intermediate phenotypes are expected to be in-between proxies of basic neuronal biological processes and nosological symptoms of AUD. Personality is likely to be a top candidate intermediate phenotype for the dissection of the genetic underpinnings of different subtypes of AUD. To date, 38 studies have investigated personality traits, commonly assessed by the Cloninger's Tridimensional Personality Questionnaire (TPQ) or Temperament and Character Inventory (TCI), in relation to polymorphisms of candidate genes of neurotransmitter systems in alcohol-dependent patients. Particular attention has been given to the functional polymorphism of the serotonin transporter gene (5-HTTLPR), however, leading to contradictory results, whereas results with polymorphisms in other candidate monoaminergic genes (e.g., tryptophan hydroxylase, serotonin receptors, monoamine oxidases, dopamine receptors and transporter) are sparse. Only one genome-wide association study has been performed so far and identified the ABLIM1 gene of relevance for novelty seeking, harm avoidance and reward dependence in alcohol-dependent patients. Studies investigating genetic factors together with personality could help to define more homogenous subgroups of AUD patients and facilitate treatment strategies. This review also urges the scientific community to combine genetic data with psychobiological and environmental data to further dissect the link between personality and AUD.

  • 48.
    Oreland, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Nilsson, Kent
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland.
    Damberg, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Hallman, Jarmila
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Monoamine oxidases: activities, genotypes and the shaping of behaviour2007In: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 114, no 6, p. 817-822Article in journal (Refereed)
    Abstract [en]

    The importance of an interaction between environment and biological factors for the expression for a particular behaviour is illustrated by results from a series of adolescents in which effects of platelet MAO activity and psychosocial environment on criminality was investigated. In a favourable environment platelet MAO-B activity was not associated with criminality, while a very strong association was found in adolescents from a bad psychosocial environment. Essentially similar findings were obtained when a MAO-A promoter polymorphism was analysed instead of platelet MAO-B activity. In boys, presence of the low functioning allele seemed to be protective against criminal activity in combination with a good environment, while it predisposed for criminality in a bad psycho-social environment. In girls, instead, homozygosity for the high activity MAO-A allele interacted with environment to predict criminality. Possible mechanisms underlying the role of monoamine oxidases for behaviour are discussed.

  • 49.
    Rydman, Eric
    et al.
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, S-11883 Stockholm, SE, Sweden..
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Pettersson, H.
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, S-11883 Stockholm, SE, Sweden..
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Ponzer, S.
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, S-11883 Stockholm, SE, Sweden..
    Ottosson, C.
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, S-11883 Stockholm, SE, Sweden..
    COMT genotype and non-recovery after a whiplash injury in a Northern European population2017In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 18, article id 507Article in journal (Refereed)
    Abstract [en]

    Background: The COMT (Catechol-O-Methyl Transferase) gene may influence a person's vulnerability to develop long-term pain and some COMT single nucleotide polymorphisms (SNPs) may associate with patterns of acute or chronic pain. Many patients with whiplash-associated disorders (WADs) suffer from long-term pain and other related symptoms, but it is less known if genetic factors play a role in the recovery process. The primary aim of this study was to evaluate whether self-reported non-recovery, including pain, was related to COMT genotype in patients with WAD. The secondary aim was to investigate whether or not background factors, including mental health, were related to genotype and non-recovery.

    Methods: A total of 133 patients with neck pain after a whiplash trauma were included. Background factors were collected and blood samples were taken during the acute phase after the accident. DNA was isolated from blood and used to genotype the SNPs rs6269, rs4633, rs4818 and rs4680 in the COMT gene; additionally haplotypes were estimated and haplogenotypes inferred. The patients were followed up after 12 months and asked to rate their recovery including pain, mental health and quality of life.

    Results: The overall reported non-recovery rate at 12 months was 44% with no significant differences in distribution of the COMT haplotypes. High levels of self-reported pain (OR 7.2) and anxiety (OR 4.4) after the accident were associated with non-recovery, but not related to the haplotypes. None of the other background factors were related to the haplotypes or non-recovery.

    Conclusion: No association between self-reported non-recovery or pain levels and COMT haplotypes in patients with acute whiplash injuries could be detected. Independent replications are necessary to discard the hypothesis that COMT haplotypes do not influence non-recovery or pain levels in patients with acute whiplash injuries. High levels of initial pain and anxiety were associated with non-recovery, thereby confirming previously published reports.

  • 50.
    Sjöberg, Rickard L.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Nilsson, Kent W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Wargelius, Hanna-Linn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Lindström, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Adolescent girls and criminal activity: Role of MAOA-LPR genotype and psychosocial factors2007In: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, ISSN 1552-4841, E-ISSN 1552-485X, Vol. 144, no 2, p. 159-164Article in journal (Refereed)
    Abstract [en]

    Recent findings among boys show that interactions between a polymorphism in the monoamine oxidase A gene promoter region (MAOA-LPR) and psychosocial factors predict criminal activity. The objective of this study was to investigate whether this finding could be extended to adolescent girls. One hundred nineteen female adolescents were recruited among respondents to a cross-sectional study of the total population of 16- and 19-year old girls. These girls constituted a randomly selected sub-sample from groups representing different degrees of risk behavior. The subjects filled in a questionnaire and were interviewed and genotyped with regard to MAOA-LPR. The results indicate that the long, (4-repeat) allele confer an increased risk for criminal behavior in the presence of psychosocial risk. Among girls without social risk, MAOA-LPR genotype was of no importance for criminal behavior. The present results suggest that previous observations on adolescent males, which demonstrate that the short MAOA-LPR genotype and psychosocial adversity interact to predict criminal activity, may not be applicable to females.

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  • rtf