Lack of evidence for predictive utility from resting state fMRI data for individual exposure-based cognitive behavioral therapy outcomes: A machine learning study in two large multi-site samples in anxiety disorders.

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.

Depressive symptom complexes of community-dwelling older adults: a latent network model.

Late-life depression has multiple, heterogeneous clinical presentations. The aim of the study was to identify higher-order homogeneous clinical features (symptom complexes), while accounting for their potential causal interactions within the network approach to psychopathology. We analyzed cross-sectional data from community-dwelling adults aged 65-85 years recruited by the European MentDis_ICF65+ study (n = 2623, mean age 74, 49% females). The severity of 33 depressive symptoms was derived from the age-adapted Composite International Diagnostic Interview. Symptom complexes were identified using multiple detection algorithms for symptom networks, and their fit to data was assessed with latent network models (LNMs) in exploratory and confirmatory analyses. Sensitivity analyses included the Partial Correlation Likelihood Test (PCLT) to investigate the data-generating structure. Depressive symptoms were organized by the Walktrap algorithm into eight symptom complexes, namely sadness/hopelessness, anhedonia/lack of energy, anxiety/irritability, self-reproach, disturbed sleep, agitation/increased appetite, concentration/decision making, and thoughts of death. An LNM adequately fit the distribution of individual symptoms' data in the population. The model suggested the presence of reciprocal interactions between the symptom complexes of sadness and anxiety, concentration and self-reproach and between self-reproach and thoughts of death. Results of the PCLT confirmed that symptom complex data were more likely generated by a network, rather than a latent-variable structure. In conclusion, late-life depressive symptoms are organized into eight interacting symptom complexes. Identification of the symptom complexes of late-life depression may streamline clinical assessment, provide targets for personalization of treatment, and aid the search for biomarkers and for predictors of outcomes of late-life depression.

Mapping Research Domain Criteria using a transdiagnostic mini-RDoC assessment in mental disorders: a confirmatory factor analysis.

This study aimed to build on the relationship of well-established self-report and behavioral assessments to the latent constructs positive (PVS) and negative valence systems (NVS), cognitive systems (CS), and social processes (SP) of the Research Domain Criteria (RDoC) framework in a large transnosological population which cuts across DSM/ICD-10 disorder criteria categories. One thousand four hundred and thirty one participants (42.1% suffering from anxiety/fear-related, 18.2% from depressive, 7.9% from schizophrenia spectrum, 7.5% from bipolar, 3.4% from autism spectrum, 2.2% from other disorders, 18.4% healthy controls, and 0.2% with no diagnosis specified) recruited in studies within the German research network for mental disorders for the Phenotypic, Diagnostic and Clinical Domain Assessment Network Germany (PD-CAN) were examined with a Mini-RDoC-Assessment including behavioral and self-report measures. The respective data was analyzed with confirmatory factor analysis (CFA) to delineate the underlying latent RDoC-structure. A revised four-factor model reflecting the core domains positive and negative valence systems as well as cognitive systems and social processes showed a good fit across this sample and showed significantly better fit compared to a one factor solution. The connections between the domains PVS, NVS and SP could be substantiated, indicating a universal latent structure spanning across known nosological entities. This study is the first to give an impression on the latent structure and intercorrelations between four core Research Domain Criteria in a transnosological sample. We emphasize the possibility of using already existing and well validated self-report and behavioral measurements to capture aspects of the latent structure informed by the RDoC matrix.

Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression.

Panic disorder (PD) has a lifetime prevalence of 2-4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0-34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p < 1 × 10-4 were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10 × 10-7). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of <0.0001 in the combined follow up cohort (p = 0.048). The present integrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD.

Incidence and risk factors of mental disorders in the elderly: The European MentDis_ICF65+ study.

OBJECTIVE: While incidence rates of depression and anxiety disorders in the elderly have been comprehensively investigated, the incidence rates of other mental disorders have rarely been researched. The incidence rate and predictors of various mental disorders in the elderly were evaluated in different European and associated countries. METHODS: A cross-sectional and longitudinal multi-centre survey of Diagnostic and Statistical Manual of Mental Disorders (4th ed.) diagnoses was conducted in different European and associated countries (Germany, Italy, Spain, Switzerland, the United Kingdom and Israel) to collect data on the prevalence and incidence of mental disorders in the elderly. The sample size of the longitudinal wave was N = 2592 elderly. RESULTS: The overall 1-year incidence rate for any mental disorder in the elderly is 8.65%. At 5.18%, any anxiety disorder had the highest incidence rate across all diagnostic groups. The incidence rate for any affective disorder was 2.97%. The lowest incidence rates were found for agoraphobia (1.37%) and panic disorder (1.30%). Risk factors for the development of any mental disorder were never having been married, no religious affiliation, a higher number of physical illnesses and a lower quality of life. CONCLUSION: In comparison to other studies, lower incidence rates for any affective disorder and middle-range incidence for any anxiety disorder were found. To the authors' knowledge, no prior studies have reported 1-year incidence rates for somatoform disorder, bipolar disorder and substance misuse in community-dwelling elderly. These findings indicate the need to raise awareness of psychosocial problems in the elderly and to ensure adequate availability of mental health services.

Neural adaptation of cingulate and insular activity during delayed fear extinction: A replicable pattern across assessment sites and repeated measurements.

Adapting threat-related memories towards changing environments is a fundamental ability of organisms. One central process of fear reduction is suggested to be extinction learning, experimentally modeled by extinction training that is repeated exposure to a previously conditioned stimulus (CS) without providing the expected negative consequence (unconditioned stimulus, US). Although extinction training is well investigated, evidence regarding process-related changes in neural activation over time is still missing. Using optimized delayed extinction training in a multicentric trial we tested whether: 1) extinction training elicited decreasing CS-specific neural activation and subjective ratings, 2) extinguished conditioned fear would return after presentation of the US (reinstatement), and 3) results are comparable across different assessment sites and repeated measures. We included 100 healthy subjects (measured twice, 13-week-interval) from six sites. 24 h after fear acquisition training, extinction training, including a reinstatement test, was applied during fMRI. Alongside, participants had to rate subjective US-expectancy, arousal and valence. In the course of the extinction training, we found decreasing neural activation in the insula and cingulate cortex as well as decreasing US-expectancy, arousal and negative valence towards CS+. Re-exposure to the US after extinction training was associated with a temporary increase in neural activation in the anterior cingulate cortex (exploratory analysis) and changes in US-expectancy and arousal ratings. While ICCs-values were low, findings from small groups suggest highly consistent effects across time-points and sites. Therefore, this delayed extinction fMRI-paradigm provides a solid basis for the investigation of differences in neural fear-related mechanisms as a function of anxiety-pathology and exposure-based treatment.

Efficacy of temporally intensified exposure for anxiety disorders: A multicenter randomized clinical trial.

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.

Help-Seeking Behavior and Treatment Barriers in Anxiety Disorders: Results from a Representative German Community Survey.

Although effective therapies exist, treatment rates of anxiety disorders (AD) are low, raising the question why affected individuals do not receive treatment. We provide data from the nationally representative German Health Interview and Examination Survey-2011 (DEGS1) on the help-seeking behavior and perceived treatment barriers of 650 subjects with Diagnostic and Statistical Manual of Mental Disorders' (DSM-IV AD). Only 26% of all cases with AD in the community reported having had contact with mental health services because of their anxiety problems in their lifetime. 16% were currently receiving professional help, most frequently by psychotherapists (8%), psychiatrists (5%) and general practitioners (5%). 40% of all cases never even considered seeking help and 31% reported barriers to treatment, such as self-reliance (18%) or beliefs that treatments were ineffective (9%), unavailable (8%) or too stigmatizing (7%). Measures to increase treatment rates should thus target individual as well as public attitudes and health literacy to increase awareness of and access to evidence-based interventions.

An investigation of genetic variability of DNA methyltransferases DNMT3A and 3B does not provide evidence for a major role in the pathogenesis of panic disorder and dimensional anxiety phenotypes.

While DNA methylation patterns have been studied for a role in the pathogenesis of anxiety disorders, the role of the enzymes establishing DNA methylation-DNA methyltransferases (DNMTs)-has yet to be investigated. In an effort to investigate DNMT genotype-specific effects on dimensional anxiety traits in addition to the categorical phenotype of panic disorder, 506 panic disorder patients and 3112 healthy participants were assessed for anxiety related cognition [Agoraphobic Cognitions Questionnaire (ACQ)], anxiety sensitivity [Anxiety Sensitivity Index (ASI)] as well as pathological worry [Penn State Worry Questionnaire (PSWQ)] and genotyped for five single nucleotide polymorphisms (SNPs) in the DNMT3A (rs11683424, rs1465764, rs1465825) and DNMT3B (rs2424932, rs4911259) genes, which have previously been found associated with clinical and trait-related phenotypes. There was no association with the categorical phenotype panic disorder. However, a significant association was discerned between DNMT3A rs1465764 and PSWQ scores in healthy participants, with the minor allele conveying a protective effect. In addition, a marginally significant association between questionnaire scores (PSWQ, ASI) in healthy participants and DNMT3B rs2424932 was detected, again with the minor allele conveying a protective effect. The present results suggest a possible minor role of DNMT3A and DNMT3B gene variation in conveying resilience towards anxiety disorders. As the observed associations indicated a protective effect of two SNPs particularly with pathological worry, future studies are proposed to explore these variants in generalized anxiety disorder rather than panic disorder.

Quality of life, level of functioning, and its relationship with mental and physical disorders in the elderly: results from the MentDis_ICF65+ study.

BACKGROUND: An ageing population worldwide needs to investigate quality of life (QoL) and level of functioning (LoF) in the elderly and its associated variables. We aimed to study the relationship between Quality of Life (QoL) and Level of Functioning (LoF) in an elderly population in Europe. METHOD: As part of the Ment_Dis65+ European Project, 3142 community-dwelling adults aged 65-84 years in six countries were assessed by using the adaptation for the elderly of the Composite International Diagnostic Interview (CIDI65+) to provide psychiatric diagnosis according to the International Classification of Diseases (10th edition) (ICD-10 Classification of Mental and Behavioural Disorders). Socio-demographic and clinical interviews, and two self-report tools, the World Health Organization QoL assessment (WHO QoL BREF), to assess QoL, and the WHO Disability Assessment Schedule -II (WHODAS-II), to assess LoF, were also administered. RESULTS: Most subjects reported good levels of QoL (56.6%) and self-rated health (62%), with no or mild disability (58.8%). There was a linear decrease of the QoL and the LoF by increase of age. Elderly with ICD-10 mental disorder (e.g. somatoform, affective and anxiety disorders) had poorer QoL and lower LoF. There were a number of predictors of lower levels of QoL and disability, including both socio-demographic variables (e.g. male gender, increase in age, poor financial situation, retirement, reduced number of close significant others), ICD-10 psychiatric diagnosis (mainly anxiety, somatoform disorders) and presence of medical disorders (mainly heart and respiratory diseases). CONCLUSIONS: The study indicates that QoL and LoF were quite acceptable in European elderly people. A series of variables, including psychiatric and somatic disorders, as well as socio-demographic factor influenced in a negative way both QoL and LoF. More specific links between mental health, social and health services dedicated to this segment of the population, should be implemented in order to provide better care for elderly people with conditions impacting their QoL and functioning.

Correction to: Test-retest reliability of the computer-assisted DIA-X-5 interview for mental disorders.

An amendment to this paper has been published and can be accessed via the original article.

Test-retest reliability of the computer-assisted DIA-X-5 interview for mental disorders.

BACKGROUND: There is a need of comprehensive standardized diagnostic assessment tools of psychopathology that match recent changes in diagnostic classification systems, such as the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Therefore, the computer-assisted DIA-X-5 was developed and its test-retest reliability was explored. The DIA-X-5 is based on the DIA-X/M-CIDI (Diagnostisches Expertensystem für psychische Störungen/Munich-Composite International Diagnostic Interview) which referred to the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). METHODS: A convenience sample (N = 60, age: 15-67) was interviewed twice with the computer-assisted DIA-X-5 interview, on average nine days apart, by trained and blinded interviewers. The DIA-X-5 is a standardized instrument for research purposes covering symptoms, syndromes and diagnoses from eleven classes of mental disorders according to the DSM-5 with matching F codes of the 10th edition of the International Classification of Diseases (ICD-10). RESULTS: Kappa values ranged from 0.90 for post-traumatic stress disorder to 0.30 for social anxiety disorder. For age of onset and age of recency, test-retest reliability as measured by intra-class correlation was satisfying with values above 0.90 for most disorders. CONCLUSIONS: Test-retest reliability of the DIA-X-5 syndromes and diagnoses were comparable to those of previous DSM-IV/DIA-X diagnoses for most disorders. Due to low case numbers for some diagnoses, further research in larger samples is required.

Specific traumatic events elevate the risk of a suicide attempt in a 10-year longitudinal community study on adolescents and young adults.

Traumatic events (TEs) have been associated with suicide attempts (SAs). However, the empirical status of some TEs is inconclusive. This also concerns community adolescents and young adults, known to be a high-risk group for SAs. We examined associations between (a) a range of prior TEs (physical attack, rape/sexual abuse, serious accident, and witnessing somebody else experiencing a TE) and a subsequent SA, and (b) the number of prior TEs and an SA, and (c) we estimated attributable proportions of SAs, in relation to each TE. Over a 10-year period, the Early Developmental Stages of Psychopathology (EDSP) study prospectively assessed community members, aged 14-24 years at baseline. Starting with 3021 subjects, each individual was assessed up to four times. Assessment was based on the Munich-Composite International Diagnostic Interview. Temporal associations were estimated using the Cox model with time-dependent covariates. Attributable proportions were based on the results of the Cox models. All four TEs elevated the risk for a subsequent SA, adjusting for confounders. Highest risk was found for the combined TE rape/sexual abuse. Results showed that 56-90% of SAs could be attributed to TEs in the exposed group; on the population level, attributable proportions ranged between 6.9% and 23.5%. Different TEs have been shown to elevate the risk of an SA in a young community sample. Our results suggest that both health professionals and health policy decision-makers consider specific TEs and the number of prior TEs as risk factors for SAs.

Cognitive decline in Parkinson's disease: the impact of the motor phenotype on cognition.

OBJECTIVES: Parkinson's disease (PD) is the second most common neurodegenerative disorder and is further associated with progressive cognitive decline. In respect to motor phenotype, there is some evidence that akinetic-rigid PD is associated with a faster rate of cognitive decline in general and a greater risk of developing dementia.The objective of this study was to examine cognitive profiles among patients with PD by motor phenotypes and its relation to cognitive function. METHODS: Demographic, clinical and neuropsychological cross-sectional baseline data of the DEMPARK/LANDSCAPE study, a multicentre longitudinal cohort study of 538 patients with PD were analysed, stratified by motor phenotype and cognitive syndrome. Analyses were performed for all patients and for each diagnostic group separately, controlling for age, gender, education and disease duration. RESULTS: Compared with the tremor-dominant phenotype, akinetic-rigid patients performed worse in executive functions such as working memory (Wechsler Memory Scale-Revised backward; p=0.012), formal-lexical word fluency (p=0.043), card sorting (p=0.006), attention (Trail Making Test version A; p=0.024) and visuospatial abilities (Leistungsprüfungssystem test 9; p=0.006). Akinetic-rigid neuropsychological test scores for the executive and attentive domain correlated negatively with non-tremor motor scores. Covariate-adjusted binary logistic regression analyses showed significant odds for PD-mild cognitive impairment for not-determined as compared with tremor-dominant (OR=3.198) and akinetic-rigid PD (OR=2.059). The odds for PD-dementia were significant for akinetic-rigid as compared with tremor-dominant phenotype (OR=8.314). CONCLUSION: The three motor phenotypes of PD differ in cognitive performance, showing that cognitive deficits seem to be less severe in tremor-dominant PD. While these data are cross-sectional, longitudinal data are needed to shed more light on these differential findings.

Differences between unipolar mania and bipolar-I disorder: Evidence from nine epidemiological studies.

OBJECTIVES: Although clinical evidence suggests important differences between unipolar mania and bipolar-I disorder (BP-I), epidemiological data are limited. Combining data from nine population-based studies, we compared subjects with mania (M) or mania with mild depression (Md) to those with BP-I with both manic and depressive episodes with respect to demographic and clinical characteristics in order to highlight differences. METHODS: Participants were compared for gender, age, age at onset of mania, psychiatric comorbidity, temperament, and family history of mental disorders. Generalized linear mixed models with adjustment for sex and age as well as for each study source were applied. Analyses were performed for the pooled adult and adolescent samples, separately. RESULTS: Within the included cohorts, 109 adults and 195 adolescents were diagnosed with M/Md and 323 adults and 182 adolescents with BP-I. In both adult and adolescent samples, there was a male preponderance in M/Md, whereas lifetime generalized anxiety and/panic disorders and suicide attempts were less common in M/Md than in BP-I. Furthermore, adults with mania revealed bulimia/binge eating and drug use disorders less frequently than those with BP-I. CONCLUSIONS: The significant differences found in gender and comorbidity between mania and BP-I suggest that unipolar mania, despite its low prevalence, should be established as a separate diagnosis both for clinical and research purposes. In clinical settings, the rarer occurrence of suicide attempts, anxiety, and drug use disorders among individuals with unipolar mania may facilitate successful treatment of the disorder and lead to a more favorable course than that of BP-I disorder.

A comparison of DSM-5 and DSM-IV agoraphobia in the World Mental Health Surveys.

BACKGROUND: The Diagnostic and Statistical Manual of Mental Disorders, version 5 (DSM-5) definition of agoraphobia (AG) as an independent diagnostic entity makes it timely to re-examine the epidemiology of AG. Study objective was to present representative data on the characteristics of individuals who meet DSM-IV criteria for AG (AG without a history of panic disorder [PD] and PD with AG) but not DSM-5 criteria, DSM-5 but not DSM-IV criteria, or both sets of criteria. METHODS: Population-based surveys from the World Mental Health Survey Initiative including adult respondents (n = 136,357) from 27 countries across the world. The Composite International Diagnostic Interview was used to assess AG and other disorders. RESULTS: Lifetime and 12-month prevalence estimates of DSM-5 AG (1.5% and 1.0%) were comparable to DSM-IV (1.4% and 0.9%). Of respondents meeting criteria in either system, 57.1% met criteria in both, while 24.2% met criteria for DSM-5 only and 18.8% for DSM-IV only. Severe role impairment due to AG was reported by a lower proportion of respondents who met criteria only for DSM-IV AG (30.4%) than those with both DSM-5 and DSM-IV AG (44.0%; χ 21 = 4.7; P = 0.031). The proportion of cases with any comorbidity was lower among respondents who met criteria only for DSM-IV AG (78.7%) than those who met both sets (92.9%; χ 21 = 14.5; P < 0.001). CONCLUSIONS: This first large survey shows that, compared to the DSM-IV, the DSM-5 identifies a substantial group of new cases with AG, while the prevalence rate remains stable at 1.5%. Severity and comorbidity are higher in individuals meeting DSM-5 AG criteria compared with individuals meeting DSM-IV AG criteria only.

Does prior traumatization affect the treatment outcome of CBT for panic disorder? The potential role of the MAOA gene and depression symptoms.

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.

Neural correlates of instrumental responding in the context of alcohol-related cues index disorder severity and relapse risk.

The influence of Pavlovian conditioned stimuli on ongoing behavior may contribute to explaining how alcohol cues stimulate drug seeking and intake. Using a Pavlovian-instrumental transfer task, we investigated the effects of alcohol-related cues on approach behavior (i.e., instrumental response behavior) and its neural correlates, and related both to the relapse after detoxification in alcohol-dependent patients. Thirty-one recently detoxified alcohol-dependent patients and 24 healthy controls underwent instrumental training, where approach or non-approach towards initially neutral stimuli was reinforced by monetary incentives. Approach behavior was tested during extinction with either alcohol-related or neutral stimuli (as Pavlovian cues) presented in the background during functional magnetic resonance imaging (fMRI). Patients were subsequently followed up for 6 months. We observed that alcohol-related background stimuli inhibited the approach behavior in detoxified alcohol-dependent patients (t = - 3.86, p < .001), but not in healthy controls (t = - 0.92, p = .36). This behavioral inhibition was associated with neural activation in the nucleus accumbens (NAcc) (t(30) = 2.06, p < .05). Interestingly, both the effects were only present in subsequent abstainers, but not relapsers and in those with mild but not severe dependence. Our data show that alcohol-related cues can acquire inhibitory behavioral features typical of aversive stimuli despite being accompanied by a stronger NAcc activation, suggesting salience attribution. The fact that these findings are restricted to abstinence and milder illness suggests that they may be potential resilience factors.Clinical trial: LeAD study, http://www.lead-studie.de , NCT01679145.

Effects of alcohol intoxication on self-reported drinking patterns, expectancies, motives and personality: a randomized controlled experimental study.

Alcohol intoxication may affect self-reports of alcohol use and related constructs, such as impulsivity and dependence symptoms. Improved knowledge about potential systematic reporting biases induced by alcohol, e.g. through disinhibition, may be relevant for the assessment of intoxicated individuals both in clinical routine and research. We therefore randomly assigned 54 socially drinking males aged 18 to 19 without lifetime diagnosis of DSM-IV alcohol dependence to one of two experimental arms: either placebo infusion at day 1 and alcohol infusion at day 2, or vice versa. The lab-based intravenous alcohol infusion produced a constant blood alcohol level of 0.08 percent. On each day, participants completed the Alcohol Use Disorders Identification Test, as well as other questionnaires on alcohol expectancies, drinking motives and substance use-related temperament traits. We found that alcohol significantly increased self-reported expectancies (tension reduction) and motives (conformity; η2  = .16-.23), but we observed no effect of sequence, i.e. alcohol first versus placebo first (Pcorr  ≥ .118). High baseline alcohol expectancies did not moderate alcohol effects (Pcorr  ≥ .462). We conclude that moderate alcohol intoxication might not generally affect the reliability of self-reported alcohol use, alcohol use problems and psychological concepts related to drinking behavior in young males without alcohol dependence. Future studies could examine larger, less selective and clinical samples for possible alcohol effects on self-report measures related to alcohol consumption.

The role of meaning in life in community-dwelling older adults with depression and relationship to other risk factors.

OBJECTIVES: The aims of this study were to examine the association of Meaning in Life (MiL) with sociodemographic and physical factors, and its association with depression in older people. METHOD: A cross-sectional survey with a sample of N = 2104 older adults from communities of four European countries was conducted, using an age-appropriate interview for the diagnosis of depression and the Schedule for Meaning in Life Evaluation (SMiLE) questionnaire to assess MiL. RESULTS: Overall, MiL was particularly low in old male participants, in older people from Ferrara (Italy), those with a lower religious affiliation, fewer social contacts, and poorer physical health. Furthermore, younger old age (65-69 compared to 80-84 year olds), female gender, being married, living in Geneva and poorer physical health were significantly associated with a higher risk for depression. In addition, lower MiL significantly increased the likelihood to suffer from depression in older people. An interaction effect of study center and MiL also emerged: with decreasing MiL the risk for depression significantly increases in Hamburg compared to the other study centers. CONCLUSION: This study underlines the association of MiL and depression in old age. Integration of meaning-specific aspects in treatment for older adults with depression may be promising.