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Background: Screening for depression in patients with coronary heart disease (CHD) remains controversial. There is limited data on the actual depression management need in routine care. The aim of this study was to examine the prevalence, treatment rates, prognosis, and management need of clinical and subclinical depression in CHD patients according to the American Heart Association recommendations and the National Institute for Health and Care Excellence (NICE) guideline "Depression in Adults with a Chronic Physical Health Problem".Methods: Patients were recruited at 2 German university clinics between 2012 and 2014. Depressive disorders were assessed according to the DSM-IV and depressive symptom severity at baseline and during follow-up was evaluated with the Patient Health Questionnaire (PHQ-9). Depression management need was determined by the severity and longitudinal course of depression symptoms.Results: Of 1,024 patients (19% women), 12% had clinical depression (depressive disorder) and 45% had subclinical depression (PHQ-9 score ≥5) at baseline. Among those with clinical depression, 46% were in treatment at least once during 12 months; 26% were continuously in treatment during follow-up. Depressive disorder and depressive symptoms were significant risk factor-adjusted predictors of the 12-months mortality (adjusted HR = 3.19; 95% CI 1.32-7.69, and adjusted HR = 1.09; 95% CI 1.02-1.16, respectively). Depressive symptoms persisted in 85% of the clinically depressed and in 47% of the subclinically depressed patients. According to current recommendations, 29% of all CHD patients would require depression management within 1 year.Conclusions: There is a need for enhanced recognition, referral, and continuous and improved clinical management of depression in CHD patients. [ABSTRACT FROM AUTHOR]

Background: Learning by conditioning is a key ability of animals and humans for acquiring novel behavior necessary for survival in a changing environment. Aberrant conditioning has been considered a crucial factor in the etiology and maintenance of panic disorder with agoraphobia (PD/A). Cognitive-behavioral therapy (CBT) is an effective treatment for PD/A. However, the neural mechanisms underlying the effects of CBT on conditioning processes in PD/A are unknown. Methods: In a randomized, controlled, multicenter clinical trial in medication-free patients with PD/A who were treated with 12 sessions of manualized CBT, functional magnetic resonance imaging (fMRI) was used during fear conditioning before and after CBT. Quality-controlled fMRI data from 42 patients and 42 healthy subjects were obtained. Results: After CBT, patients compared to control subjects revealed reduced activation for the conditioned response (CS+ > CS–) in the left inferior frontal gyrus (IFG). This activation reduction was correlated with reduction in agoraphobic symptoms from t1 to t2. Patients compared to control subjects also demonstrated increased connectivity between the IFG and regions of the “fear network” (amygdalae, insulae, anterior cingulate cortex) across time. Conclusions: This study demonstrates the link between cerebral correlates of cognitive (IFG) and emotional (“fear network”) processing during symptom improvement across time in PD/A. Further research along this line has promising potential to support the development and further optimization of targeted treatments. [ABSTRACT FROM AUTHOR]

S100B is a protein which exerts both detrimental and neurotrophic effects, depending on its concentration in brain tissue. An increase of S100B in micromolar concentrations is observed in traumatic brain conditions and is associated with poor outcome. Micromolar levels of extracellular S100B in vitro may have deleterious effects. However, in nanomolar concentrations S100B has multiple neurotrophic effects in vitro may in vivo be regarded as a hallmark of neuroprotective efforts. This pilot study addresses the hypothesis that S100B serum concentrations may be of predictive validity for the response to antidepressant treatment in patients with major depression. S100B plasma levels were determined in 25 patients with major depression and 25 matched healthy controls using an immunofluorimetric sandwich assay. S100B plasma levels were significantly higher in major depressive patients than in healthy controls and positively correlated with treatment response after 4 weeks of treatment. In a linear regression model, a significant predictive effect was found only for S100B and severity of depressive symptoms upon admission. These results suggest that neuroprotective functions of S100B counterbalance neurodegenerative mechanisms that are involved in the pathophysiology of major depression and in the response to antidepressant treatment. [Copyright &y& Elsevier]

Abstract The search for immune patterns in major depression has thus far resulted in ambiguous findings, probably because patient samples are psychiatrically heterogeneous. We therefore focused on a detailed classification of subtypes of major depression, comparing patients with melancholic and non-melancholic major depression. Inpatients suffering from acute major depression were diagnosed and subclassified according to DSM IV criteria. Cell counts were determined by FACS analysis and morphology. Cytokine production (IL-2, IFN-gamma, IL-10) upon mitogen stimulation was measured by ELISA in a whole blood assay. Non-melancholic patients showed increased counts of leukocytes, lymphocytes and NK-cells in the acute stage of disease and after two and four weeks of treatment. Their lymphokine production was unchanged compared to that of healthy controls. Melancholic patients on the other hand demonstrated normal cell counts but a decreased production of IL-2, IFN-gamma and IL-10 during the acute stage of disease followed by a normalization with clinical improvement. Melancholic and non-melancholic patients showed different immune patterns. Classifying melancholic and non-melancholic patients is helpful towards the identification of immune characteristics typical for these diseases. [ABSTRACT FROM AUTHOR]

Background: In the present study, immunological alterations were investigated as one possible factor contributing towards the pathogenesis of schizophrenia. Specifically cellular changes, deviating cytokine production and interfering variables were studied in order to improve our understanding of how these factors interact. Method: 44 acutely ill schizophrenics were compared with matched healthy controls. Cell numbers were determined by flow cytometry and cytokine production by whole blood assay and ELISA. A criss-cross technique was employed for the assessment of interfering serum factors. Results: Cell counts for leukocytes, lymphocytes, pan T cells, activated T cells and the absolute B cell count of the schizophrenic patients were all within normal limits. The absolute and relative monocyte counts, the number of IL-2 receptor carrying T cells and the relative B cell count were slightly elevated. IL-2 and IFN-γ production were increased while IL-10 production, the sIL-2R and cortisol levels remained unchanged. No interfering serum factors were detected. Conclusion: The deficient production of TH-1 cytokines in schizophrenia is not due either to a changed number of immunocompetent cells or to a counterregulation of the TH-2 cytokine IL-10. Serum factors in in vitro testing are not responsible for the deficient cytokine production. [ABSTRACT FROM AUTHOR]

Objective: Specific phobia is a common anxiety disorder, but the literature on associated brain structure alterations exhibits substantial gaps. The ENIGMA Anxiety Working Group examined brain structure differences between individuals with specific phobias and healthy control subjects as well as between the animal and blood-injection-injury (BII) subtypes of specific phobia. Additionally, the authors investigated associations of brain structure with symptom severity and age (youths vs. adults). Methods: Data sets from 31 original studies were combined to create a final sample with 1,452 participants with phobia and 2,991 healthy participants (62.7% female; ages 5–90). Imaging processing and quality control were performed using established ENIGMA protocols. Subcortical volumes as well as cortical surface area and thickness were examined in a preregistered analysis. Results: Compared with the healthy control group, the phobia group showed mostly smaller subcortical volumes, mixed surface differences, and larger cortical thickness across a substantial number of regions. The phobia subgroups also showed differences, including, as hypothesized, larger medial orbitofrontal cortex thickness in BII phobia (N=182) compared with animal phobia (N=739). All findings were driven by adult participants; no significant results were observed in children and adolescents. Conclusions: Brain alterations associated with specific phobia exceeded those of other anxiety disorders in comparable analyses in extent and effect size and were not limited to reductions in brain structure. Moreover, phenomenological differences between phobia subgroups were reflected in diverging neural underpinnings, including brain areas related to fear processing and higher cognitive processes. The findings implicate brain structure alterations in specific phobia, although subcortical alterations in particular may also relate to broader internalizing psychopathology. [ABSTRACT FROM AUTHOR]

Smooth pursuit eye movements are considered a well-established and quantifiable biomarker of sensorimotor function in psychosis research. Identifying psychotic syndromes on an individual level based on neurobiological markers is limited by heterogeneity and requires comprehensive external validation to avoid overestimation of prediction models. Here, we studied quantifiable sensorimotor measures derived from smooth pursuit eye movements in a large sample of psychosis probands (N = 674) and healthy controls (N = 305) using multivariate pattern analysis. Balanced accuracies of 64% for the prediction of psychosis status are in line with recent results from other large heterogenous psychiatric samples. They are confirmed by external validation in independent large samples including probands with (1) psychosis (N = 727) versus healthy controls (N = 292), (2) psychotic (N = 49) and non-psychotic bipolar disorder (N = 36), and (3) non-psychotic affective disorders (N = 119) and psychosis (N = 51) yielding accuracies of 65%, 66% and 58%, respectively, albeit slightly different psychosis syndromes. Our findings make a significant contribution to the identification of biologically defined profiles of heterogeneous psychosis syndromes on an individual level underlining the impact of sensorimotor dysfunction in psychosis. [ABSTRACT FROM AUTHOR]

• Elevated memory T helper cells in depression point to premature immune system aging. • The memory T helper cell elevation is already present in young adults (<30 years). • High suicide risk is linked to high percentages of memory Th and Th17 cells. Previous research has demonstrated a strong link between immune system abnormalities and Major Depressive Disorder (MDD). High suicide risk is a major complication of MDD and has recently been linked to strong (neuro-)immune alterations, but little is known on the link between circulating immune cell composition and suicidal risk status. Here, we assessed percentages of circulating peripheral blood mononuclear cells with focus on T helper cell subsets (memory T helper cells, Th1, Th2, Th17 and T regulatory cells) in a large and well-matched cohort of 153 patients diagnosed with MDD and 153 age and sex matched controls. We explored the association of these cell populations with suicide risk while accounting for age, sex, BMI, depression severity and childhood trauma. Patients with MDD had reduced percentages of NK cells, and higher percentages of B and T cells in line with current literature. Further exploration of T-cells revealed a robustly elevated number of memory T helper cells, regardless of age group. Patients at high risk for suicide had the highest memory T helper cells and additionally showed a robust increase of Th17 cells compared to other suicide risk groups. The higher abundance of memory T helper cells points towards premature aging of the immune system in MDD patients, even during young adulthood. Patients at high risk for suicide show the clearest immune abnormalities and may represent a clinically relevant subtype of depression. [ABSTRACT FROM AUTHOR]

Objective Brain-derived neurotrophic factor (BDNF) supports neurogenesis, angiogenesis, and promotes the survival of various cell types in the brain and the coronary system. Moreover, BDNF is associated with both coronary heart disease (CHD) and depression. The current study aims to investigate whether serum BDNF levels are associated with the course of depressive symptoms in CHD patients. Methods At baseline, N = 225 CHD patients were enrolled while hospitalized. Of these, N = 190 (84%) could be followed up 6 months later. Depressive symptoms were assessed both at baseline and at the 6-months follow-up using the Patient Health Questionnaire (PHQ-9). Serum BDNF concentrations were measured using fluorometric Enzyme-linked immunosorbent assays (ELISA). Results Logistic regression models showed that lower BDNF levels were associated with persistent depressive symptoms, even after adjustment for age, sex, smoking and potential medical confounders. The incidence of depressive symptoms was not related to lower BDNF levels. However, somatic comorbidity (as measured by the Charlson Comorbidity Index) was significantly associated with the incidence of depressive symptoms. Conclusions Our findings suggest a role of BDNF in the link between CHD and depressive symptoms. Particularly, low serum BDNF levels could be considered as a valuable biomarker for the persistence of depressive symptoms among depressed CHD patients. [ABSTRACT FROM AUTHOR]

• First study on patient acceptance of prediction error-based exposure (PeEx). • PeEx is well accepted regarding credibility, satisfaction and engagement. • 42% of patients report any side effect, while 94% report "positive side effects". • Most side effects are minor, transient, or inherent to psychotherapy (e.g., stigma). • Temporally intensified exposure is tolerated despite higher treatment burden. Despite striking empirical support, exposure-based treatments for anxiety disorders are underutilized. This is partially due to clinicians' concerns that patients may reject exposure or experience severe side effects, particularly in intensive forms of exposure. We examined acceptance and side effects of two randomly assigned variants of prediction error-based exposure treatment differing in temporal density (1 vs. 3 sessions/week) in 681 patients with panic disorder, agoraphobia, social anxiety disorder, and multiple specific phobias. Treatment acceptance included treatment satisfaction and credibility, engagement (i.e., homework completion), and tolerability (i.e., side effects, dropout, and perceived treatment burden). Side effects were measured with the Inventory for the Balanced Assessment of Negative Effects of Psychotherapy (INEP). We found treatment satisfaction, credibility, and engagement to be equally high in both variants of exposure-based treatment, despite higher treatment burden (β = 0.25) and stronger side effects (β = 0.15) in intensified treatment. 94.1% of patients reported positive effects in the INEP. 42.2% reported side effects, with treatment stigma (16.6%), low mood (14.8%) and the experience to depend on the therapist (10.9%) being the most frequently reported. The mean intensity of side effects was low. We conclude that prediction error-based exposure treatment is well accepted by patients with different anxiety disorders and that patients also tolerate temporally intensified treatment, despite higher perceived treatment burden and stronger side effects. Clinicians should be aware of the most frequent side effects to take appropriate countermeasures. In sum, temporal intensification appears to be an acceptable strategy to achieve faster symptom reduction, given patients' well-informed consent. [ABSTRACT FROM AUTHOR]

Mitochondria generate energy through oxidative phosphorylation (OXPHOS). The function of key OXPHOS proteins can be altered by variation in mitochondria-related genes, which may increase the risk of mental illness. We investigated the association of mitochondria-related genes and their genetic risk burden with cognitive performance. We leveraged cross-sectional data from 1320 individuals with a severe psychiatric disorder and 466 neurotypical individuals from the PsyCourse Study. The cognitive tests analyzed were the Trail-Making Test, Verbal Digit Span Test, Digit-Symbol Test, and Multiple Choice Vocabulary Intelligence Test. Association analyses between the cognitive tests, and single-nucleotide polymorphisms (SNPs) mapped to mitochondria-related genes, and their polygenic risk score (PRS) for schizophrenia (SCZ) were performed with PLINK 1.9 and R program. We found a significant association (FDR-adjusted p < 0.05) in the Cytochrome C Oxidase Assembly Factor 8 (COA8) gene locus of the OXPHOS pathway with the Verbal Digit Span (forward) test. Mitochondrial PRS was not significantly associated with any of the cognitive tests. Moderate statistical power due to relatively small sample size. COA8 encodes a poorly characterized mitochondrial protein involved in apoptosis. Here, this gene was associated with the Verbal Digit Span (forward) test, which evaluates short-term memory. Our results warrant replication and may lead to better understanding of cognitive impairment in mental disorders. • Mitochondria generate energy through oxidative phosphorylation (OXPHOS) pathway. • Variation in mitochondria-related genes can affect key proteins involved in OXPHOS. • The protein COA8 is associated with cognitive performance. • Mitochondrial genetic risk burden has no clear effects on cognitive function. [ABSTRACT FROM AUTHOR]

In major depressive disorder (MDD), electrophysiological and imaging studies provide evidence for a reduced neural activity in parietal and dorsolateral prefrontal regions. In the present study, neural correlates and temporal dynamics of visual affective perception have been investigated in patients with unipolar depression in a pre/post treatment design using magnetoencephalography (MEG). Nineteen in-patients and 19 balanced healthy controls passed MEG measurement while passively viewing pleasant, unpleasant and neutral pictures. After a 4-week treatment with electroconvulsive therapy or 4-week waiting period without intervention respectively, 16 of these patients and their 16 corresponding controls participated in a second MEG measurement. Before treatment neural source estimations of magnetic fields evoked by the emotional scenes revealed a general bilateral parietal hypoactivation in depressed patients compared to controls predominately at early and mid-latency time intervals. Successful ECT treatment, as reflected by a decline in clinical scores (Hamilton Depression Scale; HAMD) led to a normalization of this distinct parietal hypoactivation. Effective treatment was also accompanied by relatively increased neural activation at right temporo-parietal regions. The present study indicates dysfunctional parietal information processing and attention processes towards emotional stimuli in MDD patients which can be returned to normal by ECT treatment. Since convergent neural hypoactivations and treatment effects have recently been shown in MDD patients before and after pharmacological therapy, this electrophysiological correlate might serve as a biomarker for objective treatment evaluation and thereby potentially advance treatment options and support the prediction of individual treatment responses. [ABSTRACT FROM AUTHOR]

It is hypothesized that the ability to discriminate between threat and safety is impaired in individuals with high dispositional negativity, resulting in maladaptive behavior. A large body of research investigated differential learning during fear conditioning and extinction protocols depending on individual differences in intolerance of uncertainty (IU) and trait anxiety (TA), two closely-related dimensions of dispositional negativity, with heterogenous results. These might be due to varying degrees of induced threat/safety uncertainty. Here, we compared two groups with high vs. low IU/TA during periods of low (instructed fear acquisition) and high levels of uncertainty (delayed non-instructed extinction training and reinstatement). Dependent variables comprised subjective (US expectancy, valence, arousal), psychophysiological (skin conductance response, SCR, and startle blink), and neural (fMRI BOLD) measures of threat responding. During fear acquisition, we found strong threat/safety discrimination for both groups. During early extinction (high uncertainty), the low IU/TA group showed an increased physiological response to the safety signal, resulting in a lack of CS discrimination. In contrast, the high IU/TA group showed strong initial threat/safety discrimination in physiology, lacking discriminative learning on startle, and reduced neural activation in regions linked to threat/safety processing throughout extinction training indicating sustained but non-adaptive and rigid responding. Similar neural patterns were found after the reinstatement test. Taken together, we provide evidence that high dispositional negativity, as indicated here by IU and TA, is associated with greater responding to threat cues during the beginning of delayed extinction, and, thus, demonstrates altered learning patterns under changing environments. • Systematic investigation of multiple measures of conditioned fear in high/low IU/TA • Fear-potentiated startle data point to poor extinction learning in high IU/TA • Reduced neural activation in threat/safety processing regions in high IU/TA • Our results suggest impaired adaptability to changing environments in high IU/TA [ABSTRACT FROM AUTHOR]

Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Chemokines and their receptors regulate inflammatory processes in major depressive disorder (MDD). Here, we characterize the expression pattern of the C-C chemokine receptor 4 (CCR4) and its ligands CCL17 and CCL22 in MDD and its clinical relevance in predicting disease severity.Methods: Expression of CCR4 on peripheral blood lymphocytes and serum CCL17/CCL22 levels were measured using multiparameter flow cytometry and multiplex assays in 33 depressed inpatients at baseline (T0) and after 6-week multimodal treatment (T1) compared with 21 healthy controls (HC). Using stratified and correlation analysis, we examined the associations of CCR4-CCL17/CCL22 expression with depression severity and symptoms according to standard clinical rating scales and questionnaires. Additionally, we assessed whether polygenic risk score (PRS) for psychiatric disorders and chronotype are associated with disease status or CCR4-CCL17/CCL22 expression. Regression analysis was performed to assess the capacity of CCR4 and PRS in predicting disease severity.Results: Compared with HC, MDD patients showed significantly decreased CCR4 expression on T cells (T0 and T1), whereas CCL17/CCL22 serum levels were increased. Stratified and correlation analysis revealed an association of CCR4 expression on CD4+ T cells with depression severity as well as Beck Depression Inventory-II items including loss of pleasure, agitation and cognitive deficits. CCR4 expression levels on CD4+ T cells together with cross-disorder and chronotype PRS significantly predicted disease severity.Limitations: This exploratory study with small sample size warrants future studies.Conclusions: This newly identified CCR4-CCL17/CCL22 signature and its predictive capacity for MDD severity suggest its potential functional involvement in the pathophysiology of MDD. [ABSTRACT FROM AUTHOR]

The present work represents the first study to investigate the relationship between adult attachment avoidance and anxiety and automatic affective responses to basic facial emotions. Subliminal affective priming methods allowed for the assessment of unconscious affective reactions. An affective priming task using masked sad and happy faces, both of which are approach-related facial expressions, was administered to 30 healthy volunteers. Participants also completed the Relationship Scales Questionnaire and measures of anxiety and depression. Attachment avoidance was negatively associated with affective priming due to sad (but not happy) facial expressions. This association occurred independently of attachment anxiety, depressivity, and trait anxiety. Attachment anxiety was not correlated with priming due to sad or happy facial expressions. The present results are consistent with the assumption that attachment avoidance moderates automatic affective reaction to sad faces. Our data indicate that avoidant attachment is related to a low automatic affective responsivity to sad facial expressions. [ABSTRACT FROM AUTHOR]

Previous studies on neuronal activation correlates of panic attacks were mostly based on challenge tests, sensory-related stimulation or fear conditioning in healthy subjects. In the present study, we report on a female patient with panic disorder experiencing a spontaneous panic attack under an auditory habituation paradigm in the last stimulation block with sine tones captured with fMRI at 3T. The panic attack was associated with a significantly increased activity in the right amygdala. This is the first report on neuronal activation correlates of a spontaneous panic attack in a patient with panic disorder as measured by fMRI, which lends further support to a pivotal role of the amygdala in the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

Abstract: Aim of this study was to examine the association of symptom dimensions of depressive symptoms and cognitive functioning in the elderly. In a population-based study with 365 participants 65–83 years of age, dimensions of depressive symptoms were assessed with the four subscales of the CES-D-score and standardized cognitive tests assessing attention, memory, cognitive speed, and motor speed were performed. Compared to men, women scored significantly higher on the subscales for depressed affect and somatic complaints. Older participants had a significantly higher score for interpersonal difficulties. Participants with lower education had higher scores on all four psychological dimensions of depressive symptoms than those with high education (only significant for depressive affect). Individuals scoring high on CES-D subscales for depressive affect and somatic complaints had statistically significant (after Bonferroni adjustment) lower scores in attention and motor function in multivariate analyses. No significant associations between the symptom dimensions of positive affect and interpersonal difficulties with any of the cognitive tests were found in univariate and multivariate analyses (after Bonferroni adjustment). Our findings suggest specific patterns in the relationships between symptom dimensions of depressive symptoms and cognitive dysfunction in the general elderly population. This novel approach might be useful in addressing the heterogeneity of cognitive impairment in depression and in predicting cognitive outcome in depression. [Copyright &y& Elsevier]

In this study automatic processing of verbal information was investigated in 22 clinically depressed inpatients and 22 healthy controls in a longitudinal design. A semantic priming task with word pronunciation was administered twice, about 7 weeks apart. Following brief presentations of prime words, subjects had to read target words aloud as quickly as possible. Prime words were directly related, indirectly related, or unrelated to the target words. Stimulus onset asynchrony (SOA) of prime and target was 250 ms. In the course of inpatient treatment, patients recovered significantly. Semantic priming occurred in both study groups for the directly and indirectly related conditions across both testing times. As expected, directly related primes resulted in stronger priming than indirectly related primes. Patients and controls did not differ in semantic priming at either time or relatedness condition. Size of priming was not associated with depression severity, anxiety level, intelligence, medication, or clinical features. We conclude that depression is not characterized by dysfunctional automatic processing of verbal information. Depression and Anxiety 23:325–330, 2006. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Alexithymia is thought to reflect a deficit in the cognitive capacity to process emotions. Prior research suggests that emotional valence has a memory enhancing effect in poor conceptual learning conditions. This study addressed the question of whether incidental learning of emotional words is a function of alexithymic tendencies. Incidental learning is unintentional learning that results from other activities. The 20-item Toronto Alexithymia Scale (TAS-20) and measures of depression and verbal intelligence were administered to 30 nonclinical subjects (15 women, 15 men) whose mean age was 355 yr. (SD = 8.6) along with a sequential word-word evaluation task. Partial correlations indicated that the TAS-20 subscale. Difficulties identifying feelings was negatively correlated with recall of positive distractor words but not with recall of neutral distractors or recall of positive or negative target words. Emotional valence appears to have less organizational power in the memory of individuals with difficulties in recognizing their feelings. [ABSTRACT FROM AUTHOR]

In the present study automatic perceptual sensitivity to facial affect information was examined in chronic schizophrenic patients. An affective priming task including subliminal and supraliminal presentations of sad and happy facial affect was administered to schizophrenia patients with a flat affect expression (n = 30), schizophrenia patients suffering from anhedonia (n = 30), schizophrenia patients not suffering from anhedonia or flat affect (n = 28), and a group of healthy controls (n = 30). Subjects had to judge valence of neutral Chinese ideographs. Anhedonic and flat affect patients but not patients without affect symptoms were found to be sensitive to negative facial affect on an automatic processing level. None of the schizophrenic patient groups but healthy controls showed a subliminal valence-congruent priming effect based on positive facial affect. Anhedonia as assessed by standardised psychiatric rating was related to a subliminal sensitivity to negative facial expression and a valence-inverted perception of positive facial expression. This pattern of results is largely consistent with predictions derived from Meehl’s model of anhedonia. The aversive automatic perception of positive facial expression primarily found in anhedonic patients but also in schizophrenic control patients could lie in structural disturbances concerning the regulation of intimacy and distance. [ABSTRACT FROM AUTHOR]

Examines the fundamental aspects of interaction-relevant emotion processing associated with depression. Association of depressive mood with a slowed spatial recognition of positive spatial facial expression and abnormal spatial processing of negative facial expression; Factors leading to a decreased perceptual sensitivity to positively valenced stimuli.

Background: The need to optimize exposure treatments for anxiety disorders may be addressed by temporally intensified exposure sessions. Effects on symptom reduction and public health benefits should be examined across different anxiety disorders with comorbid conditions.Methods: This multicenter randomized controlled trial compared two variants of prediction error-based exposure therapy (PeEx) in various anxiety disorders (both 12 sessions + 2 booster sessions, 100 min/session): temporally intensified exposure (PeEx-I) with exposure sessions condensed to 2 weeks (n = 358) and standard nonintensified exposure (PeEx-S) with weekly exposure sessions (n = 368). Primary outcomes were anxiety symptoms (pre, post, and 6-months follow-up). Secondary outcomes were global severity (across sessions), quality of life, disability days, and comorbid depression.Results: Both treatments resulted in substantial improvements at post (PeEx-I: dwithin  = 1.50, PeEx-S: dwithin  = 1.78) and follow-up (PeEx-I: dwithin  = 2.34; PeEx-S: dwithin  = 2.03). Both groups showed formally equivalent symptom reduction at post and follow-up. However, time until response during treatment was 32% shorter in PeEx-I (median = 68 days) than PeEx-S (108 days; TRPeEx-I  = 0.68). Interestingly, drop-out rates were lower during intensified exposure. PeEx-I was also superior in reducing disability days and improving quality of life at follow-up without increasing relapse.Conclusions: Both treatment variants focusing on the transdiagnostic exposure-based violation of threat beliefs were effective in reducing symptom severity and disability in severe anxiety disorders. Temporally intensified exposure resulted in faster treatment response with substantial public health benefits and lower drop-out during the exposure phase, without higher relapse. Clinicians can expect better or at least comparable outcomes when delivering exposure in a temporally intensified manner. [ABSTRACT FROM AUTHOR]

• Precision medicine needs reliable, replicable response predictions. • Studies suggest neuroimaging data as good input to predict treatment response. • We failed to replicate this in two big samples with state-of-the-art methodology. • The use of independent samples and several processing methods corroborates this. Data-based predictions of individual Cognitive Behavioral Therapy (CBT) treatment response are a fundamental step towards precision medicine. Past studies demonstrated only moderate prediction accuracy (i.e. ability to discriminate between responders and non-responders of a given treatment) when using clinical routine data such as demographic and questionnaire data, while neuroimaging data achieved superior prediction accuracy. However, these studies may be considerably biased due to very limited sample sizes and bias-prone methodology. Adequately powered and cross-validated samples are a prerequisite to evaluate predictive performance and to identify the most promising predictors. We therefore analyzed resting state functional magnet resonance imaging (rs-fMRI) data from two large clinical trials to test whether functional neuroimaging data continues to provide good prediction accuracy in much larger samples. Data came from two distinct German multicenter studies on exposure-based CBT for anxiety disorders, the Protect-AD and SpiderVR studies. We separately and independently preprocessed baseline rs-fMRI data from n = 220 patients (Protect-AD) and n = 190 patients (SpiderVR) and extracted a variety of features, including ROI-to-ROI and edge-functional connectivity, sliding-windows, and graph measures. Including these features in sophisticated machine learning pipelines, we found that predictions of individual outcomes never significantly differed from chance level, even when conducting a range of exploratory post-hoc analyses. Moreover, resting state data never provided prediction accuracy beyond the sociodemographic and clinical data. The analyses were independent of each other in terms of selecting methods to process resting state data for prediction input as well as in the used parameters of the machine learning pipelines, corroborating the external validity of the results. These similar findings in two independent studies, analyzed separately, urge caution regarding the interpretation of promising prediction results based on neuroimaging data from small samples and emphasizes that some of the prediction accuracies from previous studies may result from overestimation due to homogeneous data and weak cross-validation schemes. The promise of resting-state neuroimaging data to play an important role in the prediction of CBT treatment outcomes in patients with anxiety disorders remains yet to be delivered. [ABSTRACT FROM AUTHOR]

Theoretically, panic disorder and agoraphobia pathology can be conceptualized as a cascade of dynamically changing defensive responses to threat cues from inside the body. Guided by this trans-diagnostic model we tested the interaction between defensive activation and vagal control as a marker of prefrontal inhibition of subcortical defensive activation. We investigated ultra-short-term changes of vagally controlled high frequency heart rate variability (HRV) during a standardized threat challenge (entrapment) in n = 232 patients with panic disorder and agoraphobia, and its interaction with various indices of defensive activation. We found a strong inverse relationship between HRV and heart rate during threat, which was stronger at the beginning of exposure. Patients with a strong increase in heart rate showed a deactivation of prefrontal vagal control while patients showing less heart rate acceleration showed an increase in vagal control. Moreover, vagal control collapsed in case of imminent threat, i.e., when body symptoms increase and seem to get out of control. In these cases of defensive action patients either fled from the situation or experienced a panic attack. Active avoidance, panic attacks, and increased sympathetic arousal are associated with an inability to maintain vagal control over the heart suggesting that teaching such regulation strategies during exposure treatment might be helpful to keep prefrontal control, particularly during the transition zone from post-encounter to circa strike defense. Trial Registration Number: ISRCTN80046034. [ABSTRACT FROM AUTHOR]

There is a recurring debate on the role of the serotonin transporter gene linked polymorphic region (5-HTT LPR) in the moderation of response to cognitive behavioral therapy (CBT) in anxiety disorders. Results, however, are still inconclusive. We here aim to perform a meta-analysis on the role of 5-HTT LPR in the moderation of CBT outcome in anxiety disorders. We investigated both categorical (symptom reduction of at least 50%) and dimensional outcomes from baseline to post-treatment and follow-up. Original data were obtained from ten independent samples (including three unpublished samples) with a total of 2,195 patients with primary anxiety disorder. No significant effects of 5-HTT LPR genotype on categorical or dimensional outcomes at post and follow-up were detected. We conclude that current evidence does not support the hypothesis of 5-HTT LPR as a moderator of treatment outcome for CBT in anxiety disorders. Future research should address whether other factors such as long-term changes or epigenetic processes may explain further variance in these complex gene-environment interactions and molecular-genetic pathways that may confer behavioral change following psychotherapy. [ABSTRACT FROM AUTHOR]

Objective: Depression and coronary heart disease (CHD) are highly comorbid conditions. Brain-derived neurotrophic factor (BDNF) plays an important role in cardiovascular processes. Depressed patients typically show decreased BDNF concentrations. We analysed the relationship between BDNF and depression in a sample of patients with CHD and additionally distinguished between cognitive-affective and somatic depression symptoms. We also investigated whether BDNF was associated with somatic comorbidity burden, acute coronary syndrome (ACS) or congestive heart failure (CHF). Methods: The following variables were assessed for 225 hospitalised patients with CHD: BDNF concentrations, depression [Patient Health Questionnaire-9 (PHQ-9)], somatic comorbidity (Charlson Comorbidity Index), CHF, ACS, platelet count, smoking status and antidepressant treatment. Results: Regression models revealed that BDNF was not associated with severity of depression. Although depressed patients (PHQ-9 score >7) had significantly lower BDNF concentrations compared to non-depressed patients (p = 0.04), this was not statistically significant after controlling for confounders (p = 0.15). Cognitive-affective symptoms and somatic comorbidity burden each closely missed a statistically significant association with BDNF concentrations (p = 0.08, p = 0.06, respectively). BDNF was reduced in patients with CHF (p = 0.02). There was no covariate-adjusted, significant association between BDNF and ACS. Conclusion: Serum BDNF concentrations are associated with cardiovascular dysfunction. Somatic comorbidities should be considered when investigating the relationship between depression and BDNF. [ABSTRACT FROM AUTHOR]

Objective: To analyze the association between heart-focused anxiety, depressive symptoms, health behaviors and healthcare utilization in patients with coronary heart disease (CHD).Methods: N = 1007 patients with CHD were recruited in hospital and followed for one year in a two-site cohort study. Heart focused anxiety (Cardiac Anxiety Questionnaire [CAQ] with the three subscales fear, attention, and avoidance), depressive symptoms (depression module from the Patient Health Questionnaire [PHQ-9]), health behaviors and healthcare utilization (smoking status, alcohol consumption, physical activity, outpatient physician/psychotherapist visits) were assessed six months after the initial hospitalization. Multiple regression models were used for statistical analysis.Results: About one third of the sample exhibited clinically significant CAQ scores. Higher CAQ-avoidance scores were associated with current smoking (OR = 1.62; 95%CI: 1.33-1.98), reduced alcohol intake (OR = 0.83; 95%CI: 0.71-0.98), non-participation in a coronary exercise group (OR = 1.76; 95%CI: 1.42-2.17), less regular physical activity (OR = 2.69; 95%CI: 2.32-3.12), and more frequent contact to general practitioners (GPs; b = 0.07, SE: 0.03). CAQ-attention was associated with non-smoking (OR = 0.51; 95%CI: 0.37-0.70), exercise group participation (OR = 0.69; 95%CI: 0.51-0.94), more frequent regular physical activity (OR = 0.55; 95%CI: 0.44-0.68), and more frequent contact to specialists for internal medicine (b = 0.09, SE: 0.04). CAQ-fear was not associated with any of the health behavior or healthcare use measures. Depressive symptoms were associated with reduced regular physical activity (OR = 1.05; 95%CI: 1.02-1.08) and increased contact to mental care specialists (b = 0.03, SE: 0.01) and GPs (b = 0.02, SE: 0.01).Conclusions: Heart-focused anxiety and depressive symptoms may impede secondary prevention in patients with CHD and increase outpatient healthcare utilization. [ABSTRACT FROM AUTHOR]

Anorexia nervosa (AN) is a severe eating disorder and often associated with altered humoral immune responses. However, distinct B cell maturation stages in peripheral blood in adolescents with AN have not been characterized. Treatment effects and the relationship between clinical and B cell parameters are also not fully understood. Here we investigated the phenotype of circulating B cell subsets and the relationship with body composition in adolescents with AN before (T0, n = 24) and after 6 weeks (T1, n = 20) of treatment. Using multi-parameter flow cytometry, we found increased percentages of antigen-experienced B cells and plasmablasts in patients with AN compared to healthy controls (n = 20). In contrast, percentages of CD1d+CD5+ B cells and transitional B cells with immunoregulatory roles were reduced at T0 and T1. These B cell frequencies correlated positively with fat mass, fat mass index (FMI), free fat mass index, and body mass index standard deviation score. In addition, scavenger-like receptor CD5 expression levels were downregulated on transitional B cells and correlated with fat mass and FMI in AN. Our findings that regulatory B cell subgroups were reduced in AN and their strong relationship with body composition parameters point toward an impact of immunoregulatory B cells in the pathogenesis of AN. [ABSTRACT FROM AUTHOR]

• PBMC expression of key metabolic proteins was altered specifically in schizophrenia. • Insulin regulation was disrupted in schizophrenia. • Insulin receptor expression was associated with schizophrenia polygenic risk scores. • Peripheral metabolic markers predicted response to antipsychotics and side effects. Recent evidence suggests that comorbidities between neuropsychiatric conditions and metabolic syndrome may precede and even exacerbate long-term side-effects of psychiatric medication, such as a higher risk of type 2 diabetes and cardiovascular disease, which result in increased mortality. In the present study we compare the expression of key metabolic proteins, including the insulin receptor (CD220), glucose transporter 1 (GLUT1) and fatty acid translocase (CD36), on peripheral blood mononuclear cell subtypes from patients across the neuropsychiatric spectrum, including schizophrenia, bipolar disorder, major depression and autism spectrum conditions (n = 25/condition), relative to typical controls (n = 100). This revealed alterations in the expression of these proteins that were specific to schizophrenia. Further characterization of metabolic alterations in an extended cohort of first-onset antipsychotic drug-naïve schizophrenia patients (n = 58) and controls (n = 63) revealed that the relationship between insulin receptor expression in monocytes and physiological insulin sensitivity was disrupted in schizophrenia and that altered expression of the insulin receptor was associated with whole genome polygenic risk scores for schizophrenia. Finally, longitudinal follow-up of the schizophrenia patients over the course of antipsychotic drug treatment revealed that peripheral metabolic markers predicted changes in psychopathology and the principal side effect of weight gain at clinically relevant time points. These findings suggest that peripheral blood cells can provide an accessible surrogate model for metabolic alterations in schizophrenia and have the potential to stratify subgroups of patients with different clinical outcomes or a greater risk of developing metabolic complications following antipsychotic therapy. [ABSTRACT FROM AUTHOR]

Tardive dyskinesia caused by antipsychotic treatment is a severe problem not only in the management of schizophrenia, but also of affective disorders. Vitamin E monotherapy has been used in schizophrenic patients with tardive dyskinesia. Pharmacologists warn against high dosage of vitamin E because of its pro-oxidative effects on low-density lipoprotein with consecutive cardiac risks. Addition of vitamin C probably reduces this risk because of its interactions with vitamin E, i.e. vitamin C reduces vitamin E radicals formed when vitamin E scavenges the oxygen radicals. We have therefore tested the safety and efficacy of combining vitamin C and E in a sample of patients with affective disorders and tardive dyskinesia who had previously been treated with antipsychotics due to psychotic symptoms. In all 6 patients, a reduction of tardive symptomatology was seen. In our sample, no side effects were observed. Further studies on this combination therapy are suggested.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: 5-HTTLPR/rs25531 is suspected to be involved in the pathogenesis of both coronary heart disease (CHD)1 and depression. We aimed to investigate the role of 5-HTTLPR/rs25531 in the development of depressive symptoms among CHD patients in a longitudinal design.Methods: N = 265 participants with CHD diagnosis were included while hospitalized in a department of cardiology and genotyped for the 5-HTTLPR/rs25531. Depressive symptoms were measured using the Patient Health Questionnaire (PHQ-9)7 at baseline and after 6 and 12 months. Binary logistic regression models were used to analyze the association of 5-HTTLPR/rs25531 with the prevalence of depressive symptoms at each time point as well as with the incidence and persistence of depressive symptoms at follow-up.Results: "LALA" genotype was associated with a higher prevalence of depressive symptoms 12 months after study inclusion. "LALA" genotype was associated with a higher incidence of depressive symptoms 6 and 12 months after study inclusion. There was no association of 5-HTTLPR/rs25531 with the persistence of depressive symptoms.Limitations: Inclusion criteria did not demand a particular cardiac event at baseline, which aggravated the interpretation of the time-specific results. The majority of the participants was of male gender which could cause bias. The present study only vaguely differentiated between ethnical groups which might cause bias regarding nationality-dependent allele distributions.Conclusion: The present study suggests a time-dependent association of the "LALA" genotype with depressive symptoms in CHD patients. 5-HTTLPR/rs25531 might be an important marker to detect risk groups for later onset depressive symptoms among CHD patients. [ABSTRACT FROM AUTHOR]

Temperamental traits as ascertained by the Temperament Evaluation of Memphis, Pisa, Paris and San Diego Auto-Questionnaire (TEMPS-A) have been suggested as promising intermediate phenotypes of mental disorders. In anxiety disorders, however, TEMPS scales and their genetic underpinnings are still understudied. TEMPS-A scores in 109 patients with panic disorder (PD) were compared to a sample of 536 healthy probands. All participants were genotyped for serotonin transporter gene variation (5-HTTLPR/rs25531). PD patients displayed significantly increased scores on the dysthymic, cyclothymic, irritable and anxious subscales, and lower scores on the hyperthymic subscale, respectively (all ps < 0.001) compared to healthy probands. In the total sample, the less active 5-HTTLPR/rs25531 S/LG alleles were associated with higher scores on the dysthymic, cyclothymic, irritable and anxious temperaments (all ps < 0.01), but not the hyperthymic subscale. Mediation analyses revealed anxious temperament in particular to mediate the relationship between 5-HTT genotype and PD. Dysthymic, cyclothymic, irritable and notably anxious temperament could serve as valuable intermediate phenotypes in efforts to unravel neurobiological, particularly serotonin system related genetic pathomechanisms associated with PD and potentially contribute to a panel of vulnerability markers guiding early targeted preventive interventions. [ABSTRACT FROM AUTHOR]

Depression and coronary heart disease (CHD) are prevalent and often co-occurring disorders. Both have been associated with a dysregulated stress system. As a central element of the stress system, the FKBP5 gene has been shown to be associated with depression. In a prospective design, this study aims to investigate the association of FKBP5 with depressive symptoms in CHD patients. N = 268 hospitalized CHD patients were included. Depressive symptoms were measured using the Hospital Anxiety and Depression Scale (HADS-D) at four time points (baseline, and after 1 month, 6 months, and 12 months). The functional FKBP5 single-nucleotide polymorphism (SNP) rs1360780 was selected for genotyping. Linear regression models showed that a higher number of FKBP5 C alleles was associated with more depressive symptoms in CHD patients both at baseline (p = 0.015) and at 12-months follow-up (p = 0.025) after adjustment for confounders. Further analyses revealed that this effect was driven by an interaction of FKBP5 genotype with patients' prior CHD course. Specifically, only in patients with a prior myocardial infarction or coronary revascularization, more depressive symptoms were associated with a higher number of C alleles (baseline: p = 0.046; 1-month: p = 0.026; 6-months: p = 0.028). Moreover, a higher number of C alleles was significantly related to a greater risk for dyslipidemia (p =.016). Our results point to a relevance of FKBP5 in the association of the two stress-related diseases depression and CHD. [ABSTRACT FROM AUTHOR]

Primary schizophreniform psychoses are thought to be caused by complex gene–environment interactions. Secondary forms are based on a clearly identifiable organic cause, in terms of either an etiological or a relevant pathogenetic factor. The secondary or "symptomatic" forms of psychosis have reentered the focus stimulated by the discovery of autoantibody (Ab)-associated autoimmune encephalitides (AEs), such as anti-NMDA-R encephalitis, which can at least initially mimic variants of primary psychosis. These newly described secondary, immune-mediated schizophreniform psychoses typically present with the acute onset of polymorphic psychotic symptoms. Over the course of the disease, other neurological phenomena, such as epileptic seizures, movement disorders, or reduced levels of consciousness, usually arise. Typical clinical signs for AEs are the acute onset of paranoid hallucinatory symptoms, atypical polymorphic presentation, psychotic episodes in the context of previous AE, and additional neurological and medical symptoms such as catatonia, seizure, dyskinesia, and autonomic instability. Predominant psychotic courses of AEs have also been described casuistically. The term autoimmune psychosis (AP) was recently suggested for these patients. Paraclinical alterations that can be observed in patients with AE/AP are inflammatory cerebrospinal fluid (CSF) pathologies, focal or generalized electroencephalographic slowing or epileptic activity, and/or suspicious "encephalitic" imaging findings. The antibody analyses in these patients include the testing of the most frequently found Abs against cell surface antigens (NMDA-R, CASPR2, LGI1, AMPA-R, GABAB-R), intracellular antigens (Hu, Ri, Yo, CV2/CRMP5, Ma2 [Ta], amphiphysin, GAD65), thyroid antigens (TG, TPO), and antinuclear Abs (ANA). Less frequent antineuronal Abs (e.g., against DPPX, GABAA-R, glycine-R, IgLON5) can be investigated in the second step when first step screening is negative and/or some specific clinical factors prevail. Beyond, tissue-based assays on brain slices of rodents may detect previously unknown antineuronal Abs in some cases. The detection of clinical and/or paraclinical pathologies (e.g., pleocytosis in CSF) in combination with antineuronal Abs and the exclusion of alternative causes may lead to the diagnosis of AE/AP and enable more causal therapeutic immunomodulatory opportunities. [ABSTRACT FROM AUTHOR]

Recent genome-wide association studies have demonstrated that the genetic burden associated with depression correlates with depression severity. Therefore, conducting genetic studies of patients at the most severe end of the depressive disorder spectrum, those with treatment-resistant depression and who are prescribed electroconvulsive therapy (ECT), could lead to a better understanding of the genetic underpinnings of depression. Despite ECT being one of the most effective forms of treatment for severe depressive disorders, it is usually placed at the end of treatment algorithms of current guidelines. This is perhaps because ECT has controlled risk and logistical demands including use of general anaesthesia and muscle relaxants and side-effects such as short-term memory impairment. Better understanding of the genetics and biology of ECT response and of cognitive side-effects could lead to more personalized treatment decisions. To enhance the understanding of the genomics of severe depression and ECT response, researchers and ECT providers from around the world and from various depression or ECT networks, but not limited to, such as the Psychiatric Genomics Consortium, the Clinical Alliance and Research in ECT, and the National Network of Depression Centers have formed the Genetics of ECT International Consortium (Gen-ECT-ic). Gen-ECT-ic will organize the largest clinical and genetic collection to date to study the genomics of severe depressive disorders and response to ECT, aiming for 30,000 patients worldwide using a GWAS approach. At this stage it will be the largest genomic study on treatment response in depression. Retrospective data abstraction and prospective data collection will be facilitated by a uniform data collection approach that is flexible and will incorporate data from many clinical practices. Gen-ECT-ic invites all ECT providers and researchers to join its efforts. [ABSTRACT FROM AUTHOR]

Cigarette smoking increases the likelihood of developing anxiety disorders, among them panic disorder (PD). While brain structures altered by smoking partly overlap with morphological changes identified in PD, the modulating impact of smoking as a potential confounder on structural alterations in PD has not yet been addressed. In total, 143 PD patients (71 smokers) and 178 healthy controls (62 smokers) participated in a multicenter magnetic resonance imaging (MRI) study. T1-weighted images were used to examine brain structural alterations using voxel-based morphometry in a priori defined regions of the defensive system network. PD was associated with gray matter volume reductions in the amygdala and hippocampus. This difference was driven by non-smokers and absent in smoking subjects. Bilateral amygdala volumes were reduced with increasing health burden (neither PD nor smoking > either PD or smoking > both PD and smoking). As smoking can narrow or diminish commonly observed structural abnormalities in PD, the effect of smoking should be considered in MRI studies focusing on patients with pathological forms of fear and anxiety. Future studies are needed to determine if smoking may increase the risk for subsequent psychopathology via brain functional or structural alterations. [ABSTRACT FROM AUTHOR]

Background: Alexithymia is a risk factor for major depressive disorder (MDD) and has been associated with diminished treatment response. Neuroimaging studies have revealed structural aberrations of the anterior cingulate cortex and the fusiform gyrus in healthy controls with high levels of alexithymia. The present study tried to corroborate and extend these results to patients with MDD compared with healthy controls. Methods: We investigated the relationship between alexithymia, depression and grey matter volume in 63 patients with MDD (mean age ± standard deviation = 42.43 yr ± 11.91; 33 female) and 46 healthy controls (45.35 yr ± 8.37; 22 female). We assessed alexithymia using the Toronto Alexithymia Scale. We conducted an alexithymia x group analysis of covariance; we used a region-of-interest approach, including the fusiform gyrus and anterior cingulate cortex, and conducted whole brain analysis using voxelbased morphometry. Results: Our analysis revealed a significant alexithymia x group interaction in the fusiform gyrus (left, pFWE = 0.031; right, pFWE = 0.010). Higher alexithymia scores were associated with decreased grey matter volume in patients with MDD (pFWE = 0.009), but with increased grey matter volume of the fusiform gyrus in healthy controls (pFWE = 0.044). We found no significant main effects in the region-of-interest analysis. Limitations: Owing to the naturalistic nature of our study, patients with MDD and healthy controls differed significantly in their alexithymia scores. Conclusion: Our results showed the fusiform gyrus as a correlate of alexithymia. We also found differences related to alexithymia between patients with MDD and healthy controls in the fusiform gyrus. Our study encourages research related to the transition from risk to MDD in people with alexithymia. [ABSTRACT FROM AUTHOR]

Cognitive-behavioral therapy (CBT) has been hypothesized to act by reducing the pathologically enhanced semantic, anxiety-related associations of patients with panic disorder. This study investigated the effects of CBT on the behavioral and neural correlates of the panic-related semantic network in patients with panic disorder. An automatic semantic priming paradigm specifically tailored for panic disorder, in which panic symptoms (e.g., "dizziness") were primed by panic triggers (e.g., "elevator") compared with neutral words (e.g., "bottle"), was performed during functional MRI scanning with 118 patients with panic disorder (compared with 150 healthy control subjects) before and 42 patients (compared with 52 healthy control subjects) after an exposure-based CBT. Neural correlates were investigated by comparing 103 pairs of matched patients and control subjects at the baseline (for patients) or T1 (for control subjects) assessment and 39 pairs at the posttreatment or T2 assessment. At baseline or T1, patients rated panic-trigger/panic-symptom word pairs with higher relatedness and higher negative valence compared with healthy control subjects. Patients made faster lexical decisions to the panic-symptom words when they were preceded by panic-trigger words. This panic-priming effect in patients (compared with control subjects) was reflected in suppressed neural activation in the left and right temporal cortices and insulae and enhanced activation in the posterior and anterior cingulate cortices. After CBT, significant clinical improvements in the patient group were observed along with a reduction in relatedness and negative valence rating and attenuation of neural activation in the anterior cingulate cortex for processing of panic-trigger/panic-symptom word pairs. The findings support a biased semantic network in panic disorder, which is normalized after CBT. Attenuation of anterior cingulate cortex activation for processing of panic-related associations provides a potential mechanism for future therapeutic interventions. [ABSTRACT FROM AUTHOR]

Epigenetic alterations of the brain‐derived neurotrophic factor (BDNF) gene have been associated with psychiatric disorders in humans and with differences in amygdala BDNF mRNA levels in rodents. This human study aimed to investigate the relationship between the functional BDNF‐Val66Met polymorphism, its surrounding DNA methylation in BDNF exon IX, amygdala reactivity to emotional faces, and personality traits. Healthy controls (HC, n = 189) underwent functional MRI during an emotional face‐matching task. Harm avoidance, novelty seeking and reward dependence were measured using the Tridimensional Personality Questionnaire (TPQ). Individual BDNF methylation profiles were ascertained and associated with several BDNF single nucleotide polymorphisms surrounding the BDNF‐Val66Met, amygdala reactivity, novelty seeking and harm avoidance. Higher BDNF methylation was associated with higher amygdala reactivity (x = 34, y = 0, z = −26, t(166) = 3.00, TFCE = 42.39, p(FWE) =.045), whereby the BDNF‐Val66Met genotype per se did not show any significant association with brain function. Furthermore, novelty seeking was negatively associated with BDNF methylation (r = −.19, p =.015) and amygdala reactivity (r = −.17, p =.028), while harm avoidance showed a trend for a positive association with BDNF methylation (r =.14, p =.066). The study provides first insights into the relationship among BDNF methylation, BDNF genotype, amygdala reactivity and personality traits in humans, highlighting the multidimensional relations among genetics, epigenetics, and neuronal functions. The present study suggests a possible involvement of epigenetic BDNF modifications in psychiatric disorders and related brain functions, whereby high BDNF methylation might reduce BDNF mRNA expression and upregulate amygdala reactivity. [ABSTRACT FROM AUTHOR]

Background: Medical education in the discipline of psychiatry and psychotherapy at the University of Münster was traditionally focused on the transfer of knowledge via lectures. According to the current guidelines, the medical curriculum was modified as from the winter semester 2016/2017 to be more competency-based and the changes were evaluated. Objective: Lectures and seminars were reduced to achieve a better linkage between theoretical and practical knowledge. Moreover, learning goals were formulated based on the German National Competence-based Catalogue of Learning Objectives in Medicine (NKLM) and entrustable professional activities (EPAs). Material and methods: Almost all previous lectures are now replaced by an inverted classroom concept with e‑learning. Theoretical knowledge is deepened by immediate multiple choice (MC) examinations and a seminar, which now focusses on specific practical EPAs. At the end of the semester, the students now undergo a practical, formative examination with simulated patients (actors) in addition to the former MC test. For evaluation, a representative sample of a semester cohort which took part in the previous curriculum and a similar cohort which attended the revised curriculum were investigated. Moreover, variables which might have an impact on the results were assessed, e. g. pre-existing psychiatric knowledge and motivation. Results: Students taught by the modified curriculum showed a significantly better practical performance and no reduction of theoretical knowledge. Relevant influencing factors were not identified. Conclusion: The results show that a competency-based modification of the curriculum in the discipline of psychiatry and psychotherapy leads to more practical abilities and thus helps future physicians to be more self-determined. [ABSTRACT FROM AUTHOR]

Background: Regulation of emotional arousal is a relevant factor for mental health. The investigation of neural underpinnings of regulation styles in healthy individuals may provide important insights regarding potential risk factors. To fill the gap of structural correlates of regulation styles and to expand previous results, we focused on the association between brain structure, neural responsiveness and vigilant/avoidant regulation style.Methods: In n = 302 healthy individuals regulation style was assessed with the Mainz Coping Inventory (MCI). Participants underwent structural and functional MRI during an emotion-processing paradigm. Structural MRI (voxel-based morphometry) and functional MRI were analysed in two regions of interest (amygdala and anterior cingulate cortex [ACC]).Results: Regulation styles did not show an association with brain structure after correction for gender, age, trait anxiety, depressive symptoms. During emotion processing, a vigilant regulation style was negatively associated with ACC activation.Limitations: The cross-sectional study in a non-pathological sample is not adequate to unveil causalities or draw conclusions regarding prevention interventions.Conclusion: Regulation styles are associated with specific neural activation patterns. The association of a high-vigilant regulation style and low ACC activation during emotion processing in healthy participants might be a potential risk factor. [ABSTRACT FROM AUTHOR]

Background: Cross-sectional studies have repeatedly shown impaired white matter integrity in patients with major depressive disorder. Longitudinal analyses are missing from the current research and are crucial to elucidating the impact of disease trajectories on white matter impairment in major depressive disorder. Methods: Fifty-nine patients with major depressive disorder receiving inpatient treatment, as well as 49 healthy controls, took part in a prospective study. Participants were scanned twice (baseline and follow-up), approximately 2.25 years apart, using diffusion tensor imaging. We analyzed diffusion metrics using tract-based spatial statistics. Results: At baseline, patients had higher mean diffusivity in a large bilateral frontal cluster comprising the body and genu of the corpus callosum, the anterior and superior corona radiata, and the superior longitudinal fasciculus. A significant group × time interaction revealed a decrease of mean diffusivity in patients with major depressive disorder over time, abolishing group differences at follow-up. This effect was observed irrespective of disease course in the follow-up period. Limitations: Analyzing the course of illness is challenging because of recollection biases in patients with major depressive disorder. Conclusion: This study reports follow-up diffusion tensor imaging data in patients with major depressive disorder after an acute depressive episode. We demonstrated impaired prefrontal white matter microstructure (higher mean diffusivity) at baseline in patients with major depressive disorder, which normalized at follow-up after 2 years, irrespective of disease course. This might have been due to a general treatment effect and might have reflected recovery of white matter integrity. [ABSTRACT FROM AUTHOR]

The gene coding for glycine receptor β subunits (GLRB) has been found to be related to panic disorder and agoraphobia (PD/AG) and to be associated with altered insular BOLD activation during fear conditioning, as an intermediate phenotype of defensive system reactivity in healthy subjects. In a multicenter clinical trial on PD/AG patients we investigated in three sub-samples whether GLRB allelic variation (A/G; A-allele identified as «risk») in the single nucleotide polymorphism rs7688285 was associated with autonomic (behavioral avoidance test BAT; n = 267 patients) and neural (differential fear conditioning; n = 49 patients, n = 38 controls) measures, and furthermore with responding towards exposure-based cognitive behavioral therapy (CBT, n = 184 patients). An interaction of genotype with current PD/AG diagnosis (PD/AG vs. controls; fMRI data only) and their modification after CBT was tested as well. Exploratory fMRI results prior to CBT, revealed A-allele carriers irrespective of diagnostic status to show overall higher BOLD activation in the hippocampus, motor cortex (MC) and insula. Differential activation in the MC, anterior cingulate cortex (ACC) and insula was found in the interaction genotype X diagnosis. Differential activation in ACC and hippocampus was present in differential fear learning. ACC activation was modified after treatment, while no overall rs7688285 dependent effect on clinical outcomes was found. On the behavioral level, A-allele carriers showed pronounced fear reactivity prior to CBT which partially normalized afterwards. In sum, rs7688285 variation interacts in a complex manner with PD/AG on a functional systems level and might be involved in the development of PD/AG but not in their treatment. [ABSTRACT FROM AUTHOR]

Panic disorder (PD) is frequently comorbid with major depressive disorder (MDD), which has been associated with impaired treatment response and recovery rates. Alterations in the serotonergic system may play a crucial role in the pathogenesis of PD and MDD and might constitute a shared biological trunk of both disorders. Epigenetic patterns such as hypermethylation of the serotonin transporter gene (SLC6A4) have been associated with various mental disorders including MDD, but, to date, no association with PD has been reported. In the present study, SLC6A4 promoter methylation was investigated in two independent samples of PD patients in a case-control design (sample 1: N = 120; sample 2: N = 118), while – given the reported high comorbidity of both disorders – taking into account the effect of comorbid MDD. The functional relevance of altered SLC6A4 promoter methylation was investigated by means of luciferase-based reporter gene assays. SLC6A4 promoter hypermethylation in PD patients relative to healthy controls was driven by comorbid diagnosis of MDD (p = 9 × 10−6), whereas no altered methylation levels were observed in patients without comorbid MDD. This held true not only in comparison to healthy controls, but also in direct comparison between PD patients with and without comorbid MDD (p =.009). Functional analyses revealed increased methylation of the investigated region to confer decreased reporter gene activity. The present results suggest functionally relevant SLC6A4 promoter hypermethylation as a possibly specific epigenetic marker of MDD, but not of PD itself, and thus might constitute a selective biomarker informing differential diagnosis based on individual epigenetic profiles. [ABSTRACT FROM AUTHOR]

Although cognitive behavioral therapy (CBT) is highly effective in the treatment of anxiety disorders, many patients still do not benefit. This study investigates whether a history of traumatic event experience is negatively associated with outcomes of CBT for panic disorder. The moderating role of the monoamine oxidase A (MAOA) gene and depression symptoms as well as the association between trauma history and fear reactivity as a potential mechanism are further analyzed. We conducted a post-hoc analysis of 172 male and 60 female patients with panic disorder treated with CBT in a multi-center study. Treatment outcome was assessed at post-treatment using self-report and clinician rating scales. Fear reactivity before treatment was assessed via heart rate and self-reported anxiety during a behavioral avoidance test. Among females, we did not find any differences in treatment response between traumatized and non-traumatized individuals or any two-way interaction trauma history × MAOA genotype. There was a significant three-way interaction trauma history × MAOA genotype × depression symptoms on all treatment outcomes indicating that in traumatized female patients carrying the low-activity allele, treatment effect sizes decreased with increasing depression symptoms at baseline. No such effects were observed for males. In conclusion, we found no evidence for a differential treatment response in traumatized and non-traumatized individuals. There is preliminary evidence for poorer treatment outcomes in a subgroup of female traumatized individuals carrying the low-active variant of the MAOA gene. These patients also report more symptoms of depression symptomatology and exhibit a dampened fear response before treatment which warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: Depressive disorders are a frequent comorbidity of panic disorder with agoraphobia (PD/AG). Cognitive-behavioral therapy (CBT) for PD/AG effectively reduces anxiety and depressive symptoms, irrespective of comorbidities. However, as depressive comorbidities can confound fear circuitry activation (i.e. amygdalae, insulae, anterior cingulate cortex) in PD/AG, we investigated whether comorbid depressive disorders alter neural plasticity following CBT.Methods: Within a randomized, controlled clinical trial on exposure-based CBT, forty-two PD/AG patients including fifteen (35.7%) with a comorbid depressive disorder (PD/AG + DEP) participated in a longitudinal functional magnetic resonance imaging (fMRI) study. A differential fear conditioning task was used as probe of interest. A generalized psycho-physiological interaction analysis (gPPI) served to study functional connectivity patterns.Results: After CBT, only PD/AG patients without comorbid depressive disorders (PD/AG-DEP) showed reduced activation in the left inferior frontal gyrus (IFG) extending to the insula. While PD/AG-DEP patients showed enhanced functional connectivity (FC) between the left IFG and subcortical structures (anterior cingulate cortex, thalamus and midbrain), PD/AG + DEP patients exhibited increased FC between the left IFG and cortical structures (prefrontal, parietal regions). In both groups, FC decreased following CBT.Limitations: Primary depressed and medicated patients were excluded. Major depression and dysthymia were collapsed.Conclusions: Reduced activation in the left IFG, as previously shown in PD/AG, appears to be a specific substrate of CBT effects in PD/AG-DEP patients only. Differential patterns of FC pertaining to fear circuitry networks in patients without depression vs. cognitive networks in patients with comorbid depression may point towards different pathways recruited by CBT as a function of comorbidity. [ABSTRACT FROM AUTHOR]