Study protocol TransTAM: Transdiagnostic research into emotional disorders and cognitive-behavioral therapy of the adaptive mind.

BACKGROUND: Emotional disorders such as depression and anxiety disorders share substantial similarities in their etiology and treatment. In recent decades, these commonalities have been increasingly recognized in classification systems and treatment programs crossing diagnostic boundaries. METHODS: To examine the prospective effects of different transdiagnostic markers on relevant treatment outcomes, we plan to track a minimum of N = 200 patients with emotional disorders during their routine course of cognitive behavioral therapy at two German outpatient clinics. We will collect a wide range of transdiagnostic markers, ranging from basic perceptual processes and self-report measures to complex behavioral and neurobiological indicators, before entering therapy. Symptoms and psychopathological processes will be recorded before entering therapy, between the 20th and 24th therapy session, and at the end of therapy. DISCUSSION: Our results could help to identify transdiagnostic markers with high predictive power, but also provide deeper insights into which patient groups with which symptom clusters are less likely to benefit from therapy, and for what reasons. TRIAL REGISTRATION: The trial was preregistered at the German Clinical Trial Register (DRKS-ID: DRKS00031206; 2023-05-09).

Toward Centrality Evaluation of Yearning Symptoms for Prolonged Grief Disorder: A Cross-Cultural Approach.

BACKGROUND: The new ICD-11 diagnosis of prolonged grief disorder (PGD) is characterized by the prominent role of yearning as hallmark symptom. A secondary analysis of eight international datasets on PGD was conducted to evaluate this assumption. Additionally, cross-cultural comparison explored whether the centrality of yearning differs across world regions. METHODS: Primary studies originated from German-speaking countries (n = 4 samples), other European countries and Israel (n = 3 samples), as well as China (n = 1 samples). Different PGD measures were used, including yearning and longing as symptoms. For the centrality assessment of yearning, PGD symptoms were ranked by their factor loadings from confirmatory factor analyses, followed by statistical testing to determine significant differences between yearning and other symptoms of PGD in their factor loading estimates. Subsequently, ranking positions of yearning in three world regions (German-speaking, other Europe-Israel, and China) were compared. Finally, proxy thresholds for individuals at high-risk states for PGD were defined for the different datasets, and sensitivity-specificity analyses of yearning were performed. RESULTS: Yearning was ranked high in five out of 12 models tested. In the German-speaking region, it was predominantly ranked among the most central symptoms; in the other Europe-Israel region as well as China, it tended to fall into the middle or lower rankings of symptom centrality. Sensitivity values were consistently high, while specificity values indicated moderate levels. DISCUSSION: In line with previous research on the general outcomes of grief, the present study showed that yearning may be subject to a culture-specific distribution. Other central symptoms such as feeling as if a part of oneself died have also been shown to potentially play a central role in PGD across world regions. On the other hand, the sensitivity-specificity analyses revealed that yearning can be considered a significant (diagnostically highly sensitive) symptom for individuals in high-risk states for PGD, although it has only moderate specificity (i.e., its absence does not necessarily indicate individuals experiencing normative grief). Nonetheless, a culture-sensitive approach to psychopathology should consider the cultural differences in the centrality of this symptom group. More research is needed to better understand the role of yearning and its determinants across world regions.

Revisiting deficits in threat and safety appraisal in obsessive-compulsive disorder.

Current behavioural treatment of obsessive-compulsive disorder (OCD) is informed by fear conditioning and involves iteratively re-evaluating previously threatening stimuli as safe. However, there is limited research investigating the neurobiological response to conditioning and reversal of threatening stimuli in individuals with OCD. A clinical sample of individuals with OCD (N = 45) and matched healthy controls (N = 45) underwent functional magnetic resonance imaging. While in the scanner, participants completed a well-validated fear reversal task and a resting-state scan. We found no evidence for group differences in task-evoked brain activation or functional connectivity in OCD. Multivariate analyses encompassing all participants in the clinical and control groups suggested that subjective appraisal of threatening and safe stimuli were associated with a larger difference in brain activity than the contribution of OCD symptoms. In particular, we observed a brain-behaviour continuum whereby heightened affective appraisal was related to increased bilateral insula activation during the task (r = 0.39, pFWE = .001). These findings suggest that changes in conditioned threat-related processes may not be a core neurobiological feature of OCD and encourage further research on the role of subjective experience in fear conditioning.

Symptom dimensions of major depression in a large community-based cohort.

BACKGROUND: Our understanding of major depression is complicated by substantial heterogeneity in disease presentation, which can be disentangled by data-driven analyses of depressive symptom dimensions. We aimed to determine the clinical portrait of such symptom dimensions among individuals in the community. METHODS: This cross-sectional study consisted of 25 261 self-reported White UK Biobank participants with major depression. Nine questions from the UK Biobank Mental Health Questionnaire encompassing depressive symptoms were decomposed into underlying factors or 'symptom dimensions' via factor analysis, which were then tested for association with psychiatric diagnoses and polygenic risk scores for major depressive disorder (MDD), bipolar disorder and schizophrenia. Replication was performed among 655 self-reported non-White participants, across sexes, and among 7190 individuals with an ICD-10 code for MDD from linked inpatient or primary care records. RESULTS: Four broad symptom dimensions were identified, encompassing negative cognition, functional impairment, insomnia and atypical symptoms. These dimensions replicated across ancestries, sexes and individuals with inpatient or primary care MDD diagnoses, and were also consistent among 43 090 self-reported White participants with undiagnosed self-reported depression. Every dimension was associated with increased risk of nearly every psychiatric diagnosis and polygenic risk score. However, while certain psychiatric diagnoses were disproportionately associated with specific symptom dimensions, the three polygenic risk scores did not show the same specificity of associations. CONCLUSIONS: An analysis of questionnaire data from a large community-based cohort reveals four replicable symptom dimensions of depression with distinct clinical, but not genetic, correlates.

Reward-Based Decision-Making Engages Distinct Modes of Cross-Frequency Coupling.

Prefrontal cortex exerts control over sensory and motor systems via cross-frequency coupling. However, it is unknown whether these signals play a role in reward-based decision-making and whether such dynamic network configuration is altered in a major depressive episode. We recruited men and women with and without depression to perform a streamlined version of the Expenditure of Effort for Reward Task during recording of electroencephalography. Goal-directed behavior was quantified as willingness to exert physical effort to obtain reward, and reward-evaluation was the degree to which the decision to exert effort was modulated by incentive level. We found that the amplitude of frontal-midline theta oscillations was greatest in participants with the greatest reward-evaluation. Furthermore, coupling between frontal theta phase and parieto-occipital gamma amplitude was positively correlated with reward-evaluation. In addition, goal-directed behavior was positively correlated with coupling between frontal delta phase to motor beta amplitude. Finally, we performed a factor analysis to derive 2 symptom dimensions and found that mood symptoms positively tracked with reward-evaluation and motivation symptoms negatively tracked with goal-directed behavior. Altogether, these results provide evidence that 2 aspects of reward-based decision-making are instantiated by different modes of prefrontal top-down control and are modulated in different symptom dimensions of depression.

Symptom Dimension Breakpoints for the Obsessive-Compulsive Inventory-Child Version (OCI-CV).

Pediatric obsessive-compulsive disorder (OCD) clusters around three major symptom dimensions: contamination/cleaning, symmetry/ordering, and disturbing thoughts/checking. The Obsessive-Compulsive Inventory-Child Version (OCI-CV) is a self-report questionnaire that provides scores along six theory-based OCD dimensions, but no study has evaluated how well OCI-CV identifies clinically significant symptoms within each of the three major symptom dimensions of OCD. We examined this question using data from 197 Swedish and Spanish youth with OCD. All youth completed the OCI-CV and clinically significant symptom severity within each major OCD dimension was established with a validated interview-based measure. Results showed that a score ≥ 3 on the OCI-CV washing scale excellently captured those with clinically significant contamination/cleaning symptoms (AUC = 0.85 [0.80-0.90], 79% accuracy). A score ≥ 4 on the obsessing scale adequately captured those with disturbing thoughts/checking symptoms (AUC = 0.71 [0.64-0.78], 67% accuracy) and a score ≥ 3 on the ordering scale adequately captured those with symmetry/ordering symptoms (AUC = 0.72 [0.65-0.79], 70% accuracy). Similar accuracy of the breakpoints was found in the Swedish and Spanish samples. OCI-CV works well to identify youth with pediatric OCD that have clinically significant contamination/cleaning symptoms. The measure can also with adequate precision identify those with clinically significant disturbing thoughts/checking and symmetry/ordering symptoms. The breakpoints provided in this study can be used to examine differences in clinical presentation and treatment outcome for youth with different types of OCD.

Obsessive-Compulsive Symptom Dimensions and Their Relationships with Obsessive Beliefs: A Structural Equation Modeling Analysis.

Dysfunctional beliefs are central in the development and maintenance of obsessive-compulsive disorder (OCD) as well as its treatment. Yet, research suggests that not all dysfunctional beliefs are equally important for each of the symptom dimensions of OCD. However, results are inconsistent in that studies contradict each other regarding the associations between specific symptom dimensions and belief domains. The aim of the present study was to clarify which belief domain is specifically associated with which OCD symptom dimension. Results could help to tailor treatments more specifically to the patient's OCD symptom dimension. In- and outpatients with OCD (N = 328; 43.6% male and 56.4% female) filled out questionnaires on symptom dimensions of OCD (Obsessive-Compulsive Inventory Revised) and dysfunctional beliefs (Obsessive Beliefs Questionnaire). A structural equation model analysis was conducted to identify the associations between dysfunctional beliefs and symptom dimensions. Our results showed that perfectionism/intolerance of uncertainty was associated with hoarding and symmetry/ordering, (2) overestimation of threat/inflated responsibility was associated with checking compulsions, and (3) importance of thoughts/control of thoughts was associated with obsessing. These results were largely supported by a backward selection. Our results demonstrated associations of specific dysfunctional beliefs and specific OCD symptom dimensions. However, future studies are necessary to replicate these findings with other measures (e.g., clinician ratings).

The role of depressive symptoms and symptom dimensions in actigraphy-assessed sleep, circadian rhythm, and physical activity.

BACKGROUND: Considering the heterogeneity of depression, distinct depressive symptom dimensions may be differentially associated with more objective actigraphy-based estimates of physical activity (PA), sleep and circadian rhythm (CR). We examined the association between PA, sleep, and CR assessed with actigraphy and symptom dimensions (i.e. mood/cognition, somatic/vegetative, sleep). METHODS: Fourteen-day actigraphy data of 359 participants were obtained from the Netherlands Study of Depression and Anxiety. PA, sleep, and CR estimates included gross motor activity (GMA), sleep duration (SD), sleep efficiency (SE), relative amplitude between daytime and night-time activity (RA) and sleep midpoint. The 30-item Inventory of Depressive Symptomatology was used to assess depressive symptoms, which were categorised in three depression dimensions: mood/cognition, somatic/vegetative, and sleep. RESULTS: GMA and RA were negatively associated with higher score on all three symptom dimensions: mood/cognition (GMA: ß = -0.155, p < 0.001; RA: ß = -0.116, p = 0.002), somatic/vegetative (GMA: ß = -0.165, p < 0.001; RA: ß = -0.133, p < 0.001), sleep (GMA: ß = -0.169, p < 0.001; RA: ß = -0.190, p < 0.001). The association with sleep was more pronounced for two depression dimensions: longer SD was linked to somatic/vegetative (ß = 0.115, p = 0.015) dimension and lower SE was linked to sleep (ß = -0.101, p = 0.011) dimension. CONCLUSION: As three symptom dimensions were associated with actigraphy-based low PA and dampened CR, these seem to be general indicators of depression. Sleep disturbances appeared more linked to the somatic/vegetative and sleep dimensions; the effectiveness of sleep interventions in patients reporting somatic/vegetative symptoms may be explored, as well as the potential of actigraphy to monitor treatment response to such interventions.

Towards a definitive symptom structure of obsessive-compulsive disorder: a factor and network analysis of 87 distinct symptoms in 1366 individuals.

BACKGROUND: The symptoms of obsessive-compulsive disorder (OCD) are highly heterogeneous and it is unclear what is the optimal way to conceptualize this heterogeneity. This study aimed to establish a comprehensive symptom structure model of OCD across the lifespan using factor and network analytic techniques. METHODS: A large multinational cohort of well-characterized children, adolescents, and adults diagnosed with OCD (N = 1366) participated in the study. All completed the Dimensional Yale-Brown Obsessive-Compulsive Scale, which contains an expanded checklist of 87 distinct OCD symptoms. Exploratory and confirmatory factor analysis were used to outline empirically supported symptom dimensions, and interconnections among the resulting dimensions were established using network analysis. Associations between dimensions and sociodemographic and clinical variables were explored using structural equation modeling (SEM). RESULTS: Thirteen first-order symptom dimensions emerged that could be parsimoniously reduced to eight broad dimensions, which were valid across the lifespan: Disturbing Thoughts, Incompleteness, Contamination, Hoarding, Transformation, Body Focus, Superstition, and Loss/Separation. A general OCD factor could be included in the final factor model without a significant decline in model fit according to most fit indices. Network analysis showed that Incompleteness and Disturbing Thoughts were most central (i.e. had most unique interconnections with other dimensions). SEM showed that the eight broad dimensions were differentially related to sociodemographic and clinical variables. CONCLUSIONS: Future research will need to establish if this expanded hierarchical and multidimensional model can help improve our understanding of the etiology, neurobiology and treatment of OCD.

Impact of brain-derived neurotrophic factor Val66Met polymorphism and response to escitalopram or paroxetine in obsessive-compulsive disorder.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a severe psychiatric disorder characterized by its heterogeneous nature and by different dimensions of obsessive-compulsive (OC) symptoms. Serotonin reuptake inhibitors (SRIs) are used to treat OCD, but up to 40% to 60% of patients do not show a significant improvement with these medications. In this study, we aimed to test the impact of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism on the efficacy of antidepressants in OCD overall, and in relation to the different OC dimensions. METHODS: In a 6-month prospective treatment study, 69 Caucasian OCD patients were treated with escitalopram for 24 weeks or with escitalopram for 12 weeks followed by paroxetine for an additional 12-week period. Patients were genotyped and assessed for treatment response. The main clinical outcomes were improvement of the Yale-Brown Obsessive-Compulsive Scale score and in different OC symptom dimension scores. RESULTS: The Val/Val group comprised 43 (62%) patients, the Val/Met and Met/Met group comprised 26 (38%) patients. Forty-two patients were classified as responders at 12 weeks and 38 at 24 weeks; no significant association was found between BDNF Val66Met and SRIs response at 12 and 24 weeks. In analyses of the different OC symptom dimensions, the Met allele was associated with a slightly reduced score in the aggressive/checking dimension at 6 months (P = .048). CONCLUSIONS: Our findings do not support the usefulness of BDNF Val66Met genotyping to predict overall response to treatment with SRIs in OCD; they did however suggest a better outcome at 6 months for the aggressive/checking symptom dimension for patients carrying the Met allele.

Jumping to conclusions, general intelligence, and psychosis liability: findings from the multi-centre EU-GEI case-control study.

BACKGROUND: The 'jumping to conclusions' (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ. METHODS: A total of 817 first episode psychosis patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC, and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia. RESULTS: The estimated proportion of the total effect of case/control differences on JTC mediated by IQ was 79%. Schizophrenia polygenic risk score was non-significantly associated with a higher number of beads drawn (B = 0.47, 95% CI -0.21 to 1.16, p = 0.17); whereas IQ PRS (B = 0.51, 95% CI 0.25-0.76, p < 0.001) significantly predicted the number of beads drawn, and was thus associated with reduced JTC bias. The JTC was more strongly associated with the higher level of psychotic-like experiences (PLEs) in controls, including after controlling for IQ (B = -1.7, 95% CI -2.8 to -0.5, p = 0.006), but did not relate to delusions in patients. CONCLUSIONS: Our findings suggest that the JTC reasoning bias in psychosis might not be a specific cognitive deficit but rather a manifestation or consequence, of general cognitive impairment. Whereas, in the general population, the JTC bias is related to PLEs, independent of IQ. The work has the potential to inform interventions targeting cognitive biases in early psychosis.

Daily use of high-potency cannabis is associated with more positive symptoms in first-episode psychosis patients: the EU-GEI case-control study.

BACKGROUND: Daily use of high-potency cannabis has been reported to carry a high risk for developing a psychotic disorder. However, the evidence is mixed on whether any pattern of cannabis use is associated with a particular symptomatology in first-episode psychosis (FEP) patients. METHOD: We analysed data from 901 FEP patients and 1235 controls recruited across six countries, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We used item response modelling to estimate two bifactor models, which included general and specific dimensions of psychotic symptoms in patients and psychotic experiences in controls. The associations between these dimensions and cannabis use were evaluated using linear mixed-effects models analyses. RESULTS: In patients, there was a linear relationship between the positive symptom dimension and the extent of lifetime exposure to cannabis, with daily users of high-potency cannabis having the highest score (B = 0.35; 95% CI 0.14-0.56). Moreover, negative symptoms were more common among patients who never used cannabis compared with those with any pattern of use (B = -0.22; 95% CI -0.37 to -0.07). In controls, psychotic experiences were associated with current use of cannabis but not with the extent of lifetime use. Neither patients nor controls presented differences in depressive dimension related to cannabis use. CONCLUSIONS: Our findings provide the first large-scale evidence that FEP patients with a history of daily use of high-potency cannabis present with more positive and less negative symptoms, compared with those who never used cannabis or used low-potency types.

The associations of obsessive-compulsive symptom dimensions and general severity with suicidal ideation in patients with obsessive-compulsive disorder: The role of specific stress responses to COVID-19.

Suicidal ideation is prevalent in patients with obsessive-compulsive disorder (OCD); but, during COVID-19, it may be increased. The present study aimed to examine the effects of obsessive-compulsive (OC) symptom dimensions and OCD severity on suicidal ideation by considering the role of stress responses in reaction to COVID-19 in a clinical sample of patients with OCD. In a cross-sectional study, 304 patients with OCD completed measures of OC symptom dimensions, OCD severity, general mental health (depression and anxiety), and COVID-19-related stress. Results showed that after controlling for depression, anxiety, comorbidity, and lifetime suicide attempts, the OC symptom dimensions of responsibility for harm and unacceptable obsessional thoughts as well as general severity had indirect effects on suicidal ideation through the specific stress responses to COVID-19, including traumatic stress and compulsive checking. The study shows that OCD patients with specific OC symptom dimensions and severe OCD are more likely to have suicidal ideation during the pandemic. Further, the specific stress responses to COVID-19 may be an underlying mechanism. Clinicians should carefully assess suicidal ideation in patients with OCD who experience responsibility for harm and unacceptable thoughts, particularly during the pandemic.

Correlates of Obsessive-Compulsive Symptoms Among Black Caribbean Americans.

Despite the rapid growth of the Black Caribbean population in the United States, we know little about the presentation and prevalence of obsessive-compulsive disorder (OCD) among these groups. This study examines the demographic correlates and the effect of racial discrimination on OCD symptoms among a nationally-representative sample of Black Caribbean and African American adults (n = 5,191). Drawing on the Composite International Diagnostic Interview Short Form (CIDI-SF) for OCD, we examine two types of obsessions (harm and contamination) and four types of compulsions (repeating, washing, ordering, and counting). There we no significant differences between Black Caribbeans and African Americans in obsessions and compulsions. Analysis among Black Caribbeans found that compared with Jamaican and Trinidadian Americans, Haitian American individuals reported the fewest number of obsessions and compulsions. We show that Black Caribbean Americans with lower income, lower self-rated physical and mental health, and more experiences with racial discrimination report higher levels of OCD. More specifically, racial discrimination was associated with contamination and harm obsessions, as well as washing and repeating compulsions. Our findings highlight the need to consider specific domains of OCD relative to Black Caribbeans, and the relationship between social and demographic variables on symptomology.

Neuroimaging auditory verbal hallucinations in schizophrenia patient and healthy populations.

BACKGROUND: Auditory verbal hallucinations (AVH) are a cardinal feature of schizophrenia, but they can also appear in otherwise healthy individuals. Imaging studies implicate language networks in the generation of AVH; however, it remains unclear if alterations reflect biologic substrates of AVH, irrespective of diagnostic status, age, or illness-related factors. We applied multimodal imaging to identify AVH-specific pathology, evidenced by overlapping gray or white matter deficits between schizophrenia patients and healthy voice-hearers. METHODS: Diffusion-weighted and T1-weighted magnetic resonance images were acquired in 35 schizophrenia patients with AVH (SCZ-AVH), 32 healthy voice-hearers (H-AVH), and 40 age- and sex-matched controls without AVH. White matter fractional anisotropy (FA) and gray matter thickness (GMT) were computed for each region comprising ICBM-DTI and Desikan-Killiany atlases, respectively. Regions were tested for significant alterations affecting both SCZ-AVH and H-AVH groups, relative to controls. RESULTS: Compared with controls, the SCZ-AVH showed widespread FA and GMT reductions; but no significant differences emerged between H-AVH and control groups. While no overlapping pathology appeared in the overall study groups, younger (<40 years) H-AVH and SCZ-AVH subjects displayed overlapping FA deficits across four regions (p < 0.05): the genu and splenium of the corpus callosum, as well as the anterior limbs of the internal capsule. Analyzing these regions with free-water imaging ascribed overlapping FA abnormalities to tissue-specific anisotropy changes. CONCLUSIONS: We identified white matter pathology associated with the presence of AVH, independent of diagnostic status. However, commonalities were constrained to younger and more homogenous groups, after reducing pathologic variance associated with advancing age and chronicity effects.

Not just thinking, but believing: Obsessive beliefs and domains of cognitive fusion in the prediction of OCD symptom dimensions.

Cognitive fusion (CF) involves the tendency to "buy in" to thoughts and feelings and consists of three empirically established domains: somatic concerns, emotion regulation, and negative evaluation. CF is hypothesized to play a role in obsessive-compulsive disorder (OCD). The present study examined how well the CF domains, relative to traditional cognitive-behavioural constructs (i.e., obsessive beliefs such as inflated responsibility), predict OCD symptoms. Fifty-two treatment-seeking adults with OCD completed self-report measures of CF, obsessive beliefs, OCD symptoms, and general distress. Domains of CF were differentially associated with the responsibility for harm, symmetry, and unacceptable thoughts of OCD dimensions; yet after accounting for obsessive beliefs, only the negative evaluation domain of CF significantly predicted symmetry OCD symptoms. Obsessive beliefs significantly predicted all OCD dimensions except for contamination. These findings provide additional support for existing cognitive-behavioural models of OCD across symptom dimensions, with the exception of contamination symptoms, and suggest that the believability of thoughts and feelings about negative evaluation adds to the explanation of symmetry symptoms. Conceptual and treatment implications, study limitations, and future directions are discussed.

[The clinical assessment of obsessive-compulsive symptoms in children and adolescents - A study with the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS-D)]. / Die klinische Beurteilung von Zwangssymptomen bei Kindern und Jugendlichen.

The clinical assessment of obsessive-compulsive symptoms in children and adolescents - A study with the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS-D) Abstract. Objective: The CY-BOCS is internationally the most widely used instrument for the assessment of juvenile obsessive-compulsive disorder (OCD). In this study, for the first time, the psychometric properties of a German version of the CY-BOCS (CY-BOCS-D) are examined in a pediatric OCD sample (n = 169; age 11-18 years). Method: The factor structure, internal consistencies, convergent and divergent validity are analyzed. Results: The exploratory factor analyses confirm a two-factor structure of the CY-BOCS-D Rating Scale and reveal a four-factor structure of the CY-BOCS-D Checklist. The internal consistencies are satisfactory to very good, convergent and divergent validity are confirmed. Conclusions: The results support the CY-BOCS as a "gold standard" also for OCD-diagnostics in German-speaking countries.

Transdiagnostic dimensions of psychopathology at first episode psychosis: findings from the multinational EU-GEI study.

BACKGROUND: The value of the nosological distinction between non-affective and affective psychosis has frequently been challenged. We aimed to investigate the transdiagnostic dimensional structure and associated characteristics of psychopathology at First Episode Psychosis (FEP). Regardless of diagnostic categories, we expected that positive symptoms occurred more frequently in ethnic minority groups and in more densely populated environments, and that negative symptoms were associated with indices of neurodevelopmental impairment. METHOD: This study included 2182 FEP individuals recruited across six countries, as part of the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study. Symptom ratings were analysed using multidimensional item response modelling in Mplus to estimate five theory-based models of psychosis. We used multiple regression models to examine demographic and context factors associated with symptom dimensions. RESULTS: A bifactor model, composed of one general factor and five specific dimensions of positive, negative, disorganization, manic and depressive symptoms, best-represented associations among ratings of psychotic symptoms. Positive symptoms were more common in ethnic minority groups. Urbanicity was associated with a higher score on the general factor. Men presented with more negative and less depressive symptoms than women. Early age-at-first-contact with psychiatric services was associated with higher scores on negative, disorganized, and manic symptom dimensions. CONCLUSIONS: Our results suggest that the bifactor model of psychopathology holds across diagnostic categories of non-affective and affective psychosis at FEP, and demographic and context determinants map onto general and specific symptom dimensions. These findings have implications for tailoring symptom-specific treatments and inform research into the mood-psychosis spectrum.

Serotonin system genes and obsessive-compulsive trait dimensions in a population-based, pediatric sample: a genetic association study.

BACKGROUND: Serotonin system genes are commonly studied in obsessive-compulsive disorder (OCD), but genetic studies to date have produced inconsistent results, possibly because phenotypic heterogeneity has not been adequately accounted for. In this paper, we studied candidate serotonergic genes and homogenous phenotypic subgroups as presented through obsessive-compulsive (OC) trait dimensions in a general population of children and adolescents. We hypothesized that different serotonergic gene variants are associated with different OC trait dimensions and, furthermore, that they vary by sex. METHODS: Obsessive-compulsive trait dimensions (Cleaning/Contamination, Counting/Checking, Symmetry/Ordering, Superstition, Rumination, and Hoarding) were examined in a total of 5,213 pediatric participants in the community using the Toronto Obsessive-Compulsive Scale (TOCS). We genotyped candidate serotonin genes (directly genotyping the 5-HTTLPR polymorphism in SLC6A4 for 2018 individuals and using single nucleotide polymorphism (SNP) array data for genes SLC6A4, HTR2A, and HTR1B for 4711 individuals). We assessed the association between variants across these genes and each of the OC trait dimensions, within males and females separately. We analyzed OC traits as both (a) dichotomized based on a threshold value and (b) quantitative scores. RESULTS: The [LG + S] variant in 5-HTTLPR was significantly associated with hoarding in males (p-value of 0.003 and 0.004 for categorical and continuous analyses, respectively). There were no significant findings for 5-HTTLPR in females. Using SNP array data, there were significant findings for rumination in males for HTR2A SNPs (p-value of 1.04e-6 to 5.20e-6). CONCLUSIONS: This represents the first genetic association study of OC trait dimensions in a community-based pediatric sample. Our strongest results indicate that hoarding and rumination may be distinct in their association with serotonin gene variants and that serotonin gene variation may be specific to sex. Future genetic association studies in OCD should properly account for heterogeneity, using homogenous subgroups stratified by symptom dimension, sex, and age group.

Negative Affect Mediates Impulsivity in Generalized Anxiety Disorder.

INTRODUCTION: Although anxiety and impulsivity are intuitively thought to be inversely correlated, increased impulsivity has been associated both with generalized anxiety disorder (GAD) diagnosis and GAD symptoms in non-clinical samples. The emotional dysregulation model of GAD posits that patients experience more frequent and intense negative emotions while having poor regulatory control over emotional states and greater negative reactivity to their emotions. We hypothesized that poor regulatory control in the presence of negative emotions might explain the increased impulsivity found in GAD patients. In this study, we examined if negative affect mediates the relationship between GAD and impulsivity. METHODS: Thirty-four GAD patients and 35 healthy controls were included, and evaluated with measurements of impulsivity, negative and positive emotions, the severity of worrying and GAD symptoms, depression, and 5-factor personality traits. RESULTS: Global impulsivity scores and the attentional facet of impulsivity were higher in the patient group when compared to the controls. Negative affect was correlated with global impulsivity in the patient group only and explained impulsivity in our regression model while worrying and depressive symptoms did not. An indirect relationship was found between diagnosis and impulsivity through negative affect. CONCLUSION: Our study showed that the cardinal symptom of GAD - worrying - was not independently related to impulsivity in our sample. Increased impulsivity in GAD seems to be mediated by the increased presence of negative emotions, as it is common in mood and impulse-control disorders, indicating an unspecific shared vulnerability factor to psychopathology.