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Engman, Jonas
Publications (10 of 57) Show all publications
Engman, J., Sundström Poromaa, I., Moby, L., Wikström, J., Fredriksson, M. & Gingnell, M. (2018). Hormonal Cycle and Contraceptive Effects on Amygdala and Salience Resting-State Networks in Women with Previous Affective Side Effects on the Pill.. Neuropsychopharmacology, 43(3), 555-563
Open this publication in new window or tab >>Hormonal Cycle and Contraceptive Effects on Amygdala and Salience Resting-State Networks in Women with Previous Affective Side Effects on the Pill.
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2018 (English)In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 43, no 3, p. 555-563Article in journal (Refereed) Published
Abstract [en]

The mechanisms linking ovarian hormones to negative affect are poorly characterized, but important clues may come from the examination of the brain's intrinsic organization. Here, we studied the effects of both the menstrual cycle and oral contraceptives (OCs) on amygdala and salience network resting-state functional connectivity using a double-blind, randomized, and placebo-controlled design. Hormone levels, depressive symptoms, and resting-state functional connectivity were measured in 35 healthy women (24.9±4.2 years) who had previously experienced OC-related negative affect. All participants were examined in the follicular phase of a baseline cycle and in the third week of the subsequent cycle during treatment with either a combined OC (30 μg ethinyl estradiol/0.15 mg levonorgestrel) or placebo. The latter time point targeted the midluteal phase in placebo users and steady-state ethinyl estradiol and levonorgestrel concentrations in OC users. Amygdala and salience network connectivity generally increased with both higher endogenous and synthetic hormone levels, although amygdala-parietal cortical connectivity decreased in OC users. When in the luteal phase, the naturally cycling placebo users demonstrated higher connectivity in both networks compared with the women receiving OCs. Our results support a causal link between the exogenous administration of synthetic hormones and amygdala and salience network connectivity. Furthermore, they suggest a similar, potentially stronger, association between the natural hormonal variations across the menstrual cycle and intrinsic network connectivity.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-333689 (URN)10.1038/npp.2017.157 (DOI)000419961500011 ()28741624 (PubMedID)
Funder
Swedish Research Council, 2016-01439Forte, Swedish Research Council for Health, Working Life and Welfare, 2007-1955, 2007-2116
Available from: 2017-11-16 Created: 2017-11-16 Last updated: 2018-02-14Bibliographically approved
Jonasson, M., Appel, L., Danfors, T., Nyholm, D., Askmark, H., Frick, A., . . . Lubberink, M. (2017). Development of a clinically feasible [11C]PE2I PET method for differential diagnosis of parkinsonism using reduced scan duration and automated reference region extraction.. American Journal of Nuclear Medicine and Molecular Imaging, 7(6), 263-274
Open this publication in new window or tab >>Development of a clinically feasible [11C]PE2I PET method for differential diagnosis of parkinsonism using reduced scan duration and automated reference region extraction.
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2017 (English)In: American Journal of Nuclear Medicine and Molecular Imaging, ISSN 2160-8407, Vol. 7, no 6, p. 263-274Article in journal (Refereed) Published
Abstract [en]

[11C]PE2I is a highly selective dopamine transporter PET ligand. Parametric images based on dynamic [11C]PE2I scans, showing dopamine transporter availability (BPND) and relative cerebral blood flow (R1), can be used in differential diagnosis of parkinsonism. This work aimed to investigate a shortened scan duration and automated generation of parametric images which are two prerequisites for routine clinical application. Twelve subjects with parkinsonism and seventeen healthy controls underwent 80 min dynamic [11C]PE2I PET scans. BPND and R1 images were generated using cerebellum reference region defined on a co-registered MRI, as well as a supervised cluster analysis (SVCA)-based reference. Initial 20, 30 and 40 min of the scans were extracted and images of standardized uptake value ratio (SUVR) and R1 were computed using MRI- and SVCA-based reference. Correlation was high between striatal 80 min MRI-based BPND and 40 min SVCA-based SUVR-1 (R2=0.95). High correlation was also found between R1 values in striatal and limbic regions (R2≥0.91) whereas correlation was moderate for cortical regions (R2=0.71). The results indicate that dynamic [11C]PE2I scans can be restricted to 40 min and that SVCA can be used for automatic extraction of a reference region. These outcomes will support routine applications of [11C]PE2I PET in clinical settings.

Keywords
PET, [11C]PE2I, parametric images, parkinsonism, supervised clustering
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-340790 (URN)000419593300003 ()29348981 (PubMedID)
Funder
Swedish Research CouncilSwedish Society for Medical Research (SSMF)
Available from: 2018-02-02 Created: 2018-02-02 Last updated: 2018-02-21Bibliographically approved
Faria, V., Gingnell, M., M. Hoppe, J., Hjorth, O., Alaie, I., Frick, A., . . . Furmark, T. (2017). Do You Believe It? Verbal Suggestions Influence the Clinical and Neural Effects of Escitalopram in Social Anxiety Disorder: A Randomized Trial. EBioMedicine (24), 179-188, Article ID S2352-3964(17)30385-7.
Open this publication in new window or tab >>Do You Believe It? Verbal Suggestions Influence the Clinical and Neural Effects of Escitalopram in Social Anxiety Disorder: A Randomized Trial
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2017 (English)In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, no 24, p. 179-188, article id S2352-3964(17)30385-7Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depression and anxiety, but their efficacy relative to placebo has been questioned. We aimed to test how manipulation of verbally induced expectancies, central for placebo, influences SSRI treatment outcome and brain activity in patients with social anxiety disorder (SAD).

METHODS: We did a randomized clinical trial, within an academic medical center (Uppsala, Sweden), of individuals fulfilling the DSM-IV criteria for SAD, recruited through media advertising. Participants were 18years or older and randomized in blocks, through a computer-generated sequence by an independent party, to nine weeks of overt or covert treatment with escitalopram (20mg daily). The overt group received correct treatment information whereas the covert group was treated deceptively with the SSRI described, by the psychiatrist, as active placebo. The treating psychiatrist was necessarily unmasked while the research staff was masked from intervention assignment. Treatment efficacy was assessed primarily with the self-rated Liebowitz Social Anxiety Scale (LSAS-SR), administered at week 0, 1, 3, 6 and 9, also yielding a dichotomous estimate of responder status (clinically significant improvement). Before and at the last week of treatment, brain activity during an emotional face-matching task was assessed with functional magnetic resonance imaging (fMRI) and during fMRI sessions, anticipatory speech anxiety was also assessed with the Spielberger State-Trait Anxiety Inventory - State version (STAI-S). Analyses included all randomized patients with outcome data at posttreatment. This study is registered at ISRCTN, number 98890605.

FINDINGS: Between March 17th 2014 and May 22nd 2015, 47 patients were recruited. One patient in the covert group dropped out after a few days of treatment and did not provide fMRI data, leaving 46 patients with complete outcome data. After nine weeks of treatment, overt (n=24) as compared to covert (n=22) SSRI administration yielded significantly better outcome on the LSAS-SR (adjusted difference 21.17, 95% CI 10.69-31.65, p<0.0001) with more than three times higher response rate (50% vs. 14%; χ(2)(1)=6.91, p=0.009) and twice the effect size (d=2.24 vs. d=1.13) from pre-to posttreatment. There was no significant between-group difference on anticipatory speech anxiety (STAI-S), both groups improving with treatment. No serious adverse reactions were recorded. On fMRI outcomes, there was suggestive evidence for a differential neural response to treatment between groups in the posterior cingulate, superior temporal and inferior frontal gyri (all z thresholds exceeding 3.68, p≤0.001). Reduced social anxiety with treatment correlated significantly with enhanced posterior cingulate (z threshold 3.24, p=0.0006) and attenuated amygdala (z threshold 2.70, p=0.003) activity.

INTERPRETATION: The clinical and neural effects of escitalopram were markedly influenced by verbal suggestions. This points to a pronounced placebo component in SSRI-treatment of SAD and favors a biopsychosocial over a biomedical explanatory model for SSRI efficacy.

FUNDING RESOURCES: The Swedish Research Council for Working Life and Social Research (grant 2011-1368), the Swedish Research Council (grant 421-2013-1366), Riksbankens Jubileumsfond - the Swedish Foundation for Humanities and Social Sciences (grant P13-1270:1).

Keywords
Expectancies, Neuroimaging, Placebo effect, SSRI, Social anxiety disorder, fMRI
National Category
Psychology General Practice
Identifiers
urn:nbn:se:uu:diva-331755 (URN)10.1016/j.ebiom.2017.09.031 (DOI)000414392900030 ()29033138 (PubMedID)
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2011-1368Swedish Research Council, 421-2013-1366Riksbankens Jubileumsfond, P13-1270:1
Note

Vanda Faria and Malin Gingnell contributed equally

Available from: 2017-10-18 Created: 2017-10-18 Last updated: 2018-02-12Bibliographically approved
Gingnell, M., Toffoletto, S., Wikström, J., Engman, J., Bannbers, E., Comasco, E. & Sundström Poromaa, I. (2017). Emotional anticipation after delivery - a longitudinal neuroimaging study of the postpartum period. Scientific Reports, 7, Article ID 114.
Open this publication in new window or tab >>Emotional anticipation after delivery - a longitudinal neuroimaging study of the postpartum period
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 114Article in journal (Refereed) Published
Abstract [en]

Neuroimaging research has begun to unveil the mechanisms behind emotion processing during the postpartum period, which, in turn, may be of relevance for the development of postpartum depression. The present study sought to longitudinally investigate the neural correlates of emotion anticipation during the postpartum period in healthy women. Functional magnetic resonance imaging was employed to measure the blood oxygen level-dependent signal in the brain in response to anticipation of negative emotional stimuli and during processing of images with positive or negative valence. The participating women were scanned twice: the first scan occurred during the first 48 hours after delivery, and the second was performed 4-6 weeks after delivery. The early postpartum period was characterized by higher anterior cingulate cortex reactivity during anticipation of negative emotional stimuli than the late postpartum period. This was accompanied by a negative relationship with insular reactivity during the early postpartum period and a trend towards an increase in insular reactivity in the late postpartum period. Thus, during the first four weeks of the postpartum period, a diminished top-down regulatory feedback on emotion-related areas of the brain was noted. This finding suggests a physiologically important adaptation during the healthy postpartum period.

National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-319610 (URN)10.1038/s41598-017-00146-3 (DOI)000425860900001 ()28273912 (PubMedID)
Funder
Swedish Research Council, K2014-54-20642-07-4
Available from: 2017-04-06 Created: 2017-04-06 Last updated: 2018-05-04Bibliographically approved
Bas-Hoogendam, J. M., van Steenbergen, H., Pannekoek, J. N., Fouche, J.-P., Lochner, C., Hattingh, C. J., . . . van der Wee, N. J. J. (2017). Sample Size Matters: A Voxel-Based Morphometry Multi-Center Mega-Analysis of Gray Matter Volume in Social Anxiety Disorder. Paper presented at 72nd Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry (SOBP), MAY 18-20, 2017, San Diego, CA. Biological Psychiatry, 81(10), S7-S8
Open this publication in new window or tab >>Sample Size Matters: A Voxel-Based Morphometry Multi-Center Mega-Analysis of Gray Matter Volume in Social Anxiety Disorder
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2017 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 81, no 10, p. S7-S8Article in journal, Meeting abstract (Other academic) Published
Keywords
Social Anxiety Disorder, Voxel Based Morphometry
National Category
Psychology
Identifiers
urn:nbn:se:uu:diva-331803 (URN)10.1016/j.biopsych.2017.02.027 (DOI)000400348700017 ()
Conference
72nd Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry (SOBP), MAY 18-20, 2017, San Diego, CA
Funder
Swedish Research CouncilForte, Swedish Research Council for Health, Working Life and WelfareEU, FP7, Seventh Framework Programme
Available from: 2017-10-19 Created: 2017-10-19 Last updated: 2017-10-19Bibliographically approved
Bas-Hoogendam, J. M., van Steenbergen, H., Pannekoek, J. N., Fouche, J.-P., Lochner, C., Hattingh, C. J., . . . van der Wee, N. J. A. (2017). Voxel-based morphometry multi-center mega-analysis of brain structure in social anxiety disorder. NeuroImage: Clinical, 16, 678-688
Open this publication in new window or tab >>Voxel-based morphometry multi-center mega-analysis of brain structure in social anxiety disorder
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2017 (English)In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 16, p. 678-688Article in journal (Refereed) Published
Abstract [en]

Social anxiety disorder (SAD) is a prevalent and disabling mental disorder, associated with significant psychiatric comorbidity. Previous research on structural brain alterations associated with SAD has yielded inconsistent results concerning the direction of the changes in graymatter (GM) in various brain regions, as well as on the relationship between brain structure and SAD-symptomatology. These heterogeneous findings are possibly due to limited sample sizes. Multisite imaging offers new opportunities to investigate SAD-related alterations in brain structure in larger samples. An international multi-center mega-analysis on the largest database of SAD structural T1-weighted 3T MRI scans to date was performed to compare GM volume of SAD-patients (n = 174) and healthy control (HC)-participants (n = 213) using voxel-based morphometry. A hypothesis-driven region of interest (ROI) approach was used, focusing on the basal ganglia, the amygdala-hippocampal complex, the prefrontal cortex, and the parietal cortex. SAD-patients had larger GM volume in the dorsal striatum when compared to HC-participants. This increase correlated positively with the severity of self-reported social anxiety symptoms. No SAD-related differences in GM volume were present in the other ROIs. Thereby, the results of this mega-analysis suggest a role for the dorsal striatum in SAD, but previously reported SAD-related changes in GM in the amygdala, hippocampus, precuneus, prefrontal cortex and parietal regions were not replicated. Our findings emphasize the importance of large sample imaging studies and the need for meta-analyses like those performed by the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium.

Keywords
Social anxiety disorder, Structural MRI, Voxel-based morphometry, Gray matter, Mega-analysis, Striatum
National Category
Radiology, Nuclear Medicine and Medical Imaging Neurology
Identifiers
urn:nbn:se:uu:diva-340172 (URN)10.1016/j.nicl.2017.08.001 (DOI)000413235100071 ()
Funder
EU, FP7, Seventh Framework ProgrammeSwedish Research CouncilForte, Swedish Research Council for Health, Working Life and Welfare
Available from: 2018-01-26 Created: 2018-01-26 Last updated: 2018-01-26Bibliographically approved
Engman, J., Linnman, C., Van Dijk, K. R. A. & Milad, M. R. (2016). Amygdala subnuclei resting-state functional connectivity sex and estrogen differences. Psychoneuroendocrinology, 63, 34-42
Open this publication in new window or tab >>Amygdala subnuclei resting-state functional connectivity sex and estrogen differences
2016 (English)In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 63, p. 34-42Article in journal (Refereed) Published
Abstract [en]

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

Keywords
Intrinsic connectivity networks, Spontaneous fluctuations, Sex differences, Hormones, Estradiol, Negative affect
National Category
Endocrinology and Diabetes Neurology Psychiatry
Identifiers
urn:nbn:se:uu:diva-274923 (URN)10.1016/j.psyneuen.2015.09.012 (DOI)000367422400005 ()26406106 (PubMedID)
Funder
NIH (National Institute of Health), 1S10RR023043NIH (National Institute of Health), 1S10RR023401
Available from: 2016-01-27 Created: 2016-01-26 Last updated: 2017-11-30Bibliographically approved
Björkstrand, J., Ågren, T., Motilla Hoppe, J., Hjorth, O., Frick, A., Åhs, F., . . . Furmark, T. (2016). Approach behavior to fear conditioned cues is modulated by monetary reward and correlated to serotonin and dopamine transporter binding in the amygdala. In: : . Paper presented at The European Meeting on Human Fear Conditioning, Utrecht, The Netherlands.
Open this publication in new window or tab >>Approach behavior to fear conditioned cues is modulated by monetary reward and correlated to serotonin and dopamine transporter binding in the amygdala
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2016 (English)Conference paper, Poster (with or without abstract) (Other academic)
National Category
Psychology
Identifiers
urn:nbn:se:uu:diva-291323 (URN)
Conference
The European Meeting on Human Fear Conditioning, Utrecht, The Netherlands
Available from: 2016-05-01 Created: 2016-05-01 Last updated: 2016-05-01
Gingnell, M., Bannbers, E., Engman, J., Frick, A., Moby, L., Wikström, J. & Sundström-Poromaa, I. (2016). The effect of combined hormonal contraceptives use on brain reactivity during response inhibition. European journal of contraception & reproductive health care, 21(2), 150-157
Open this publication in new window or tab >>The effect of combined hormonal contraceptives use on brain reactivity during response inhibition
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2016 (English)In: European journal of contraception & reproductive health care, ISSN 1362-5187, E-ISSN 1473-0782, Vol. 21, no 2, p. 150-157Article in journal (Refereed) Published
Abstract [en]

Objectives Cognitive control, which can be described as the ability to moderate impulses, has not previously been investigated in users of combined hormonal contraception (CHC). Given the suggested modulatory role of ovarian steroids in prefrontal dopaminergic function, which in turn taps into cognitive control, this randomised, double-blinded, placebo-controlled oral contraceptive trial set out to investigate the brain activity pattern during response inhibition in CHC users. Methods Thirty-four women were randomised to one treatment cycle with a levonorgestrel-containing CHC or placebo. The women performed a Go/NoGo task to measure brain activity during response inhibition by use of event-related functional magnetic resonance imaging (fMRI) prior to and during the CHC/placebo treatment cycle. Results No differences between CHC and placebo users in number of correct inhibitions were found during treatment, but only women on CHC significantly improved their performance between the baseline and treatment assessments. During the treatment cycle CHC users displayed decreased activity in the right middle frontal gyrus in comparison with placebo users. No other significant activations were evident between treatment groups or within groups. Conclusion Overall, CHC use had marginal effects on brain activity during response inhibition. If anything, the findings of the study may suggest reduced effort or increased efficiency in maintaining orbitofrontal cortex inhibitory cognitive control when using a combined oral contraceptive.

Keywords
Functional magnetic resonance imaging; Go/NoGo; Oestrogen; Oral contraceptives; Progestagen; Randomised clinical trial; Response inhibition
National Category
Obstetrics, Gynecology and Reproductive Medicine Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-265145 (URN)10.3109/13625187.2015.1077381 (DOI)000375025700006 ()26291330 (PubMedID)
Funder
Swedish Research Council
Available from: 2015-10-23 Created: 2015-10-23 Last updated: 2017-12-01Bibliographically approved
Engman, J., Sundström-Poromaa, I., Fredrikson, M. & Gingnell, M. (2015). Amygdala Resting State Functional Connectivity is Affected by Oral Contraceptives and Menstrual Cycle Phase. Paper presented at Oral presentation at the European Society for Magnetic Resonance in Medicine and Biology (ESMRMB) Congress, Edinburgh, Scotland. October 2015.. Magnetic Resonance Materials in Physics, Biology and Medicine, 28(1S), S70-S70
Open this publication in new window or tab >>Amygdala Resting State Functional Connectivity is Affected by Oral Contraceptives and Menstrual Cycle Phase
2015 (English)In: Magnetic Resonance Materials in Physics, Biology and Medicine, ISSN 0968-5243, E-ISSN 1352-8661, Vol. 28, no 1S, p. S70-S70Article in journal, Meeting abstract (Other academic) Published
National Category
Psychology
Identifiers
urn:nbn:se:uu:diva-284491 (URN)
Conference
Oral presentation at the European Society for Magnetic Resonance in Medicine and Biology (ESMRMB) Congress, Edinburgh, Scotland. October 2015.
Available from: 2016-04-18 Created: 2016-04-18 Last updated: 2017-11-30
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