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Gingnell, Malin
Publications (10 of 39) Show all publications
Frick, A., Engman, J., Alaie, I., Björkstrand, J., Gingnell, M., Larsson, E.-M., . . . Furmark, T. (2020). Neuroimaging, genetic, clinical, and demographic predictors of treatment response in patients with social anxiety disorder. Journal of Affective Disorders, 261, 230-237
Open this publication in new window or tab >>Neuroimaging, genetic, clinical, and demographic predictors of treatment response in patients with social anxiety disorder
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2020 (English)In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 261, p. 230-237Article in journal (Refereed) Published
Abstract [en]

Background: Correct prediction of treatment response is a central goal of precision psychiatry. Here, we tested the predictive accuracy of a variety of pre-treatment patient characteristics, including clinical, demographic, molecular genetic, and neuroimaging markers, for treatment response in patients with social anxiety disorder (SAD).

Methods: Forty-seven SAD patients (mean +/- SD age 33.9 +/- 9.4 years, 24 women) were randomized and commenced 9 weeks' Internet-delivered cognitive behavior therapy (CBT) combined either with the selective serotonin reuptake inhibitor (SSRI) escitalopram (20 mg daily [10 mg first week], SSRI+CBT, n= 24) or placebo (placebo+CBT, n= 23). Treatment responders were defined from the Clinical Global Impression-Improvement scale (CGI- I <= 2). Before treatment, patients underwent functional magnetic resonance imaging and the Multi-Source Interference Task taxing cognitive interference. Support vector machines (SVMs) were trained to separate responders from nonresponders based on pre-treatment neural reactivity in the dorsal anterior cingulate cortex (dACC), amygdala, and occipital cortex, as well as molecular genetic, demographic, and clinical data. SVM models were tested using leave-one-subject-out cross-validation.

Results: The best model separated treatment responders (n= 24) from nonresponders based on pre-treatment dACC reactivity (83% accuracy, P= 0.001). Responders had greater pre-treatment dACC reactivity than nonresponders especially in the SSRI+CBT group. No other variable was associated with clinical response or added predictive accuracy to the dACC SVM model.

Limitations: Small sample size, especially for genetic analyses. No replication or validation samples were available.

Conclusions: The findings demonstrate that treatment outcome predictions based on neural cingulate activity, at the individual level, outperform genetic, demographic, and clinical variables for medication-assisted Internet-delivered CBT, supporting the use of neuroimaging in precision psychiatry.

Keywords
Social phobia, SSRI, CBT, Personalized medicine, SVM, Pattern recognition
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-402003 (URN)10.1016/j.jad.2019.10.027 (DOI)000499616400031 ()31655378 (PubMedID)
Funder
Swedish Research CouncilRiksbankens JubileumsfondForte, Swedish Research Council for Health, Working Life and Welfare
Available from: 2020-01-20 Created: 2020-01-20 Last updated: 2020-01-20Bibliographically approved
Frick, A., Engman, J., Wahlstedt, K., Gingnell, M., Fredrikson, M. & Furmark, T. (2018). Anterior cingulate cortex activity as a candidate biomarker for treatment selection in social anxiety disorder. BJPsych bulletin, 4(3)
Open this publication in new window or tab >>Anterior cingulate cortex activity as a candidate biomarker for treatment selection in social anxiety disorder
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2018 (English)In: BJPsych bulletin, ISSN 2056-4694, E-ISSN 2056-4708, Vol. 4, no 3Article in journal (Refereed) Published
Abstract [en]

We aimed to identify biomarkers to guide the decision to add selective serotonin reuptake inhibitors (SSRI) to psychological treatment for social anxiety disorder (SAD). Forty-eight patients with SAD underwent functional magnetic resonance imaging and collection of clinical and demographic variables before treatment with cognitive–behavioural therapy, combined on a double-blind basis with either escitalopram or placebo for 9 weeks. Pre-treatment neural reactivity to aversive faces in the dorsal anterior cingulate cortex (ACC), but not clinical/demographic variables, moderated clinical outcomes. Cross-validated individual-level predictions accurately identified 81% of responders/non-responders. Dorsal ACC reactivity is thus a potential biomarker for SAD treatment selection.

Place, publisher, year, edition, pages
Cambridges Institutes Press, 2018
Keywords
Functional magnetic resonance imaging, anxiety, prediction, selective serotonin reuptake inhibitors, cognitive–behavioural therapy, social phobia
National Category
Psychology Psychiatry
Identifiers
urn:nbn:se:uu:diva-353596 (URN)10.1192/bjo.2018.15 (DOI)000436933400012 ()29922481 (PubMedID)
Funder
Swedish Research CouncilRiksbankens JubileumsfondThe Swedish Brain FoundationForte, Swedish Research Council for Health, Working Life and WelfareSwedish Society for Medical Research (SSMF)
Available from: 2018-06-14 Created: 2018-06-14 Last updated: 2018-09-26Bibliographically approved
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
Note

Original Article; Supplementary information available for this article at http://www.nature.com/npp/journal/vaop/ncurrent/suppinfo/npp2017157s1.html

Available from: 2017-11-16 Created: 2017-11-16 Last updated: 2019-09-24Bibliographically approved
Luders, E., Gingnell, M., Sundström Poromaa, I., Engman, J., Kurth, F. & Gaser, C. (2018). Potential Brain Age Reversal after Pregnancy: Younger Brains at 4–6 Weeks Postpartum. Neuroscience, 386, 309-314
Open this publication in new window or tab >>Potential Brain Age Reversal after Pregnancy: Younger Brains at 4–6 Weeks Postpartum
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2018 (English)In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 386, p. 309-314Article in journal (Refereed) Published
Abstract [en]

Pregnancy is accompanied by complex biological adaptations, including extreme hormonal fluctuations. Moreover, changes on the endocrine level are accompanied by changes in cerebral anatomy, such as reductions in brain or gray matter volume. Since declining brain and tissue volumes are characteristic for normal aging, the question arises of whether such pregnancy-induced anatomical effects are permanent or transient. To answer this question, we acquired high-resolution brain image data of 14 healthy women in their mid-twenties to late thirties at two time points: within 1–2 days of childbirth (early postpartum) and at 4–6 weeks after childbirth (late postpartum). At both time points, we estimated the brain ages for each woman using a well-validated machine learning approach based on pattern recognition. Ultimately, this algorithm – designed to identify anatomical correlates of age across the entire brain – reveals a single score for each individual: the BrainAGE index. Comparing the BrainAGE indices between both time points, female brains at late postpartum were estimated to be considerably younger than at early postpartum. On average, that difference was about five years (mean ± SD: 5.4 ± 2.4 years). These findings suggest a substantial restoration/rejuvenation effect after giving birth, which is evident already within the first couple of months.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
aging, brain, estradiol, pregnancy, progesterone
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-356715 (URN)10.1016/j.neuroscience.2018.07.006 (DOI)000440325500025 ()30017956 (PubMedID)
Funder
Swedish Research Council, K2014-54X-20642-07-4
Available from: 2018-08-04 Created: 2018-08-04 Last updated: 2018-11-12Bibliographically approved
Edvinsson, Å., Skalkidou, A., Hellgren, C., Gingnell, M., Ekselius, L., Willebrand, M. & Sundström Poromaa, I. (2017). Different patterns of attentional bias in antenatal and postpartum depression. Brain and Behavior, 7(11), Article ID e00844.
Open this publication in new window or tab >>Different patterns of attentional bias in antenatal and postpartum depression
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2017 (English)In: Brain and Behavior, ISSN 2162-3279, E-ISSN 2162-3279, Vol. 7, no 11, article id e00844Article in journal (Refereed) Published
Abstract [en]

BackgroundBiased information processing in attention, memory, and interpretation is proposed to be central cognitive alterations in patients with major depressive disorder, but studies in women with peripartum depression are scarce. Because of the many similarities with depression in nonperipartum states as regards symptom profile and risk factors, we hypothesized that women with antenatal and postpartum depression would display attentional bias to negatively and positively valenced words. MethodsOne hundred and seventy-seven pregnant and 157 postpartum women were included. Among these, 40 suffered from antenatal depressive disorder and 33 from postpartum depressive disorder. An emotional Stroop task with neutral, positive, negative, and negatively valenced obstetric words was used. ResultsNo significant difference in emotional interference scores was noted between women with antenatal depression and nondepressed pregnant women. In contrast, women with postpartum depression displayed shorter reaction times to both positive (p=.028) and negative (p=.022) stimuli, compared with neutral words. Pregnant women on antidepressant treatment displayed longer reaction times to negatively valenced obstetric words in comparison with untreated depressed women (p=.012), and a trend toward greater interference in comparison with controls (p=.061). ConclusionsIn contrast with the hypothesis, we found no evidence of attentional bias to emotionally valenced stimuli in women with untreated peripartum depression. However, the shorter reaction times to emotional stimuli in women with postpartum depression may indicate emotional numbing, which in turn, is a functional impairment that may have repercussions for child development and well-being. Our findings emphasize the need to identify and treat women with postpartum depression at the earliest possible time point to ensure swift recovery and support for the family.

Keywords
antenatal depression, attentional bias, emotional Stroop, postpartum depression, pregnancy, women
National Category
Obstetrics, Gynecology and Reproductive Medicine Psychiatry
Identifiers
urn:nbn:se:uu:diva-342913 (URN)10.1002/brb3.844 (DOI)000416063200009 ()29201545 (PubMedID)
Funder
Swedish Research Council
Available from: 2018-02-26 Created: 2018-02-26 Last updated: 2018-12-05Bibliographically 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: 2020-03-06Bibliographically 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
Åhs, F., Gingnell, M., Furmark, T. & Fredrikson, M. (2017). Within-session effect of repeated stress exposure on extinction circuitry function in social anxiety disorder. Psychiatry Research: Neuroimaging, 261, 85-90
Open this publication in new window or tab >>Within-session effect of repeated stress exposure on extinction circuitry function in social anxiety disorder
2017 (English)In: Psychiatry Research: Neuroimaging, ISSN 0925-4927, E-ISSN 1872-7506, Vol. 261, p. 85-90Article in journal (Refereed) Published
Abstract [en]

Anxiety reduction following repeated exposure to stressful experiences is generally held to depend on neural processes involved in extinction of conditioned fear. We predicted that repeated exposure to stressful experiences would change activity throughout the circuitry serving extinction, including ventromedial prefrontal cortex (vmPFC), the hippocampus and the amygdala. To test this prediction, 36 participants diagnosed with SAD performed two successive speeches in front of an observing audience while regional cerebral blood flow (rCBF) was recorded using positron emission tomography. To control for non-anxiolytic effects of repeated exposure, rCBF was also measured during repeated presentations of neutral and angry facial expressions. Results showed that anxiety ratings and heart rate decreased from the first to the second speech, indicating an anxiolytic effect of repeated exposure. Exposure attenuated rCBF in the amygdala whereas no change in rCBF was observed in the vmPFC or hippocampus. The rCBF-reductions in the amygdala were greater following repetition of the speech task than repetition of face exposure indicating that they were specific to anxiety attenuation and not due to a reduced novelty. Our findings suggest that amygdala-related attenuation processes are key to understanding the working mechanisms of exposure therapy.

Place, publisher, year, edition, pages
ELSEVIER IRELAND LTD, 2017
Keywords
Extinction, Social phobia, Cognitive behavior therapy, Amygdala, Hippocampus, VmPFC
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-320032 (URN)10.1016/j.pscychresns.2017.01.009 (DOI)000395958900012 ()28167379 (PubMedID)
Funder
Swedish Research CouncilThe Swedish Brain Foundation
Available from: 2017-04-13 Created: 2017-04-13 Last updated: 2017-11-29Bibliographically approved
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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