| 1. |
- Faria, Vanda, et al.
(författare)
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Do You Believe It? Verbal Suggestions Influence the Clinical and Neural Effects of Escitalopram in Social Anxiety Disorder : A Randomized Trial
- 2017
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 24, s. 179-188
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Tidskriftsartikel (refereegranskat)abstract
- 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 18 years 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(20 mg 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%; χ2(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.
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| 2. |
- Frick, Andreas, Docent, et al.
(författare)
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Neuroimaging, genetic, clinical, and demographic predictors of treatment response in patients with social anxiety disorder
- 2020
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Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 261, s. 230-237
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Gingnell, Malin, 1982-
(författare)
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Ovarian Steroid Hormones, Emotion Processing and Mood
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- It is known that some psychiatric disorders may deteriorate in relation to the menstrual cycle. However, in some conditions, such as premenstrual dysphoric disorder (PMDD), symptomatology is triggered mainly by the variations in ovarian steroid hormones. Although symptoms induced by fluctuations in ovarian steroids often are affective, little is known about how emotion processing in women is influenced by variations, or actual levels, of ovarian steroid hormones.The general aim of this thesis was to evaluate menstrual cycle effects on reactivity in emotion generating and controlling areas in the corticolimbic system to emotional stimulation and anticipation, in healthy controls and women with PMDD. A second aim was to evaluate corticolimbic reactivity during long-term administration of exogenous ovarian steroids.In study I, III and IV effects of the menstrual cycle on emotional reactivity in women with PMDD was studied. In study I, women with PMDD in displayed higher amygdala reactivity than healthy controls to emotional faces, not in the luteal phase as was hypothesised, but in the follicular phase. No difference between menstrual cycle phases was obtained in women with PMDD, while healthy controls had an increased reactivity in the luteal phase. The results of study I was further elaborated in study III, where women with PMDD were observed to have an increased anticipatory reactivity to negative emotional stimuli. However, no differences in amygdala reactivity to emotional stimuli were obtained across the menstrual cycle. Finally, in study IV the hypothesis that amygdala reactivity increase in the luteal phase in women with PMDD is linked to social stimuli rather than generally arousing stimuli was suggested, tested and supported.In study II, re-exposure to COC induced mood symptoms de novo in women with a previous history of COC-induced adverse mood. Women treated with COC reported increased levels of mood symptoms both as compared to before treatment, and as compared to the placebo group. There was a relatively strong correlation between depressive scores before and during treatment. The effects of repeated COC administration on subjective measures and brain function were however dissociated with increased aversive experiences accompanied by reduced reactivity in the insular cortex.
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| 4. |
- Bengtsson, Johan, et al.
(författare)
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Autonomic modulation networks in schizophrenia : The relationship between heart rate variability and functional and structural connectivity in the brain
- 2020
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Ingår i: Psychiatry Research. - : Elsevier BV. - 0925-4927 .- 1872-7506. ; 300
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Tidskriftsartikel (refereegranskat)abstract
- Heart rate variability (HRV), a measurement of autonomic nervous system (ANS) activity, has been found reduced in schizophrenia. The anterior cingulate cortex (ACC), which is important in regulating the ANS, is structurally and functionally affected in schizophrenia. We investigate the relationship between HRV and functional and structural connectivity of the ACC in patients with schizophrenia and healthy controls. Ten patients with a diagnosis of schizophrenia and ten healthy controls were recruited. Heart rate was monitored in a naturalistic out-of-clinic setting. Magnetic resonance imaging (MRI) was performed, including resting-state functional MRI and diffusion tensor imaging. Patients with schizophrenia had significantly lower HRV compared to controls. A positive correlation between ACC connectivity with the bilateral cerebellum and HRV was found in the patients. HRV was also positively correlated with amplitude of low frequency fluctuations (ALFF) in the cerebellum, and with axial diffusivity in the middle cerebellar peduncle, in the patients. There was a significant negative relationship between antipsychotic medication dosage, HRV and all neuroimaging measures related to HRV. We conclude that ACC connectivity seems to be affected in schizophrenia, both structurally and functionally, and that the ACC-cerebellum connectivity, as well as cerebellar function, is associated with ANS regulation in patients with schizophrenia.
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| 5. |
- Bengtsson, Johan, et al.
(författare)
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Blinding integrity of dorsomedial prefrontal intermittent theta burst stimulation in depression
- 2023
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Ingår i: International Journal of Clinical and Health Psychology. - : Elsevier BV. - 1697-2600 .- 2174-0852. ; 23:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: The antidepressant effect of repetitive transcranial magnetic stimulation (rTMS) is partly placebo, making blinding integrity important. Blinding of high-frequency rTMS and intermittent theta burst stimulation (iTBS) has been reported as successful at study end. However, blinding integrity at study start is rarely reported. The aim of this study was to investigate blinding integrity during a treatment course of iTBS over the dorsomedial prefrontal cortex (DMPFC) in depression.Methods: Forty-nine patients with depression from a double-blind-designed randomized controlled trial (NCT02905604) were included. Patients received either active or sham iTBS over the DMPFC with a placebo coil. The sham group received iTBS-synchronized transcutaneous electrical nerve stimulation.Results: After one session, 74% of participants were able to correctly guess their treatment allocation. This was above chance level (p = 0.001). The percentage dropped to 64% and 56% after the fifth and last sessions. Belong-ing to the active group influenced the choice to guess "active" (odds ratio: 11.7, 95% CI 2.5-53.7). A higher treat-ment intensity of the sham treatment increased the probability to guess "active", but pain did not influence the choice.Conclusions: Blinding integrity in iTBS trials must be investigated at study start to avoid uncontrolled confounding. Better sham methods are needed.
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| 6. |
- Edvinsson, Åsa, et al.
(författare)
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Different patterns of attentional bias in antenatal and postpartum depression
- 2017
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Ingår i: Brain and Behavior. - : Wiley. - 2162-3279. ; 7:11
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Frick, Andreas, et al.
(författare)
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Classifying social anxiety disorder using multivoxel pattern analyses of brain function and structure
- 2014
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 75:9, s. 358S-358S
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Tidskriftsartikel (refereegranskat)abstract
- Functional neuroimaging of social anxiety disorder (SAD) support altered neural activation to threat-provoking stimuli focally in the fear network, while structural differences are distributed over the temporal and frontal cortices as well as limbic structures. Previous neuroimaging studies have investigated the brain at the voxel level using mass-univariate methods which do not enable detection of more complex patterns of activity and structural alterations that may separate SAD from healthy individuals. Support vector machine (SVM) is a supervised machine learning method that capitalizes on brain activation and structural patterns to classify individuals. The aim of this study was to investigate if it is possible to discriminate SAD patients (n = 14) from healthy controls (n = 12) using SVM based on (1) functional magnetic resonance imaging during fearful face processing and (2) regional gray matter volume. Whole brain and region of interest (fear network) SVM analyses were performed for both modalities. For functional scans, significant classifications were obtained both at whole brain level and when restricting the analysis to the fear network while gray matter SVM analyses correctly classified participants only when using the whole brain search volume. These results support that SAD is characterized by aberrant neural activation to affective stimuli in the fear network, while disorder-related alterations in regional gray matter volume are more diffusely distributed over the whole brain. SVM may thus be useful for identifying imaging biomarkers of SAD.
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| 8. |
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| 9. |
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| 10. |
- Gingnell, Malin, 1982-, et al.
(författare)
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The effect of combined hormonal contraceptives use on brain reactivity during response inhibition
- 2016
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Ingår i: European journal of contraception & reproductive health care. - : Informa UK Limited. - 1362-5187 .- 1473-0782. ; 21:2, s. 150-157
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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