Higher emotion regulation flexibility predicts more stable negative emotions and faster affective recovery in early psychosis: an experience sampling study.

BACKGROUND: While evidence shows that people with early psychosis are flexible in using different emotion regulation (ER) strategies to manage the varying contextual demands, no studies have examined the effectiveness of such regulatory flexibility in this population. We addressed this issue by investigating whether and how ER flexibility relate to different dynamic aspects (variability, instability, inertia, and recovery) of negative affect (NA) in a combined early psychosis sample, consisting of both individuals at high clinical risk for psychosis and those diagnosed with first-episode psychosis. METHODS: Participants were 148 individuals from the INTERACT project, a multi-center randomized controlled trial on the efficacy of acceptance and commitment therapy in early psychosis. We utilized data from the baseline assessment, during which all participants completed six days of experience sampling assessment of momentary NA, as well as end-of-day assessments of ER strategy use. RESULTS: Multilevel models of within-person associations showed that greater ER flexibility was associated with more stable NA, and quicker recovery of NA from stressors during the day. Linear regression analyses of between-person associations showed that people who had more variable and unstable NA reported greater ER flexibility generally. No evidence was found for associations with NA inertia. CONCLUSIONS: The current study identified unique within-person and between-person links between ER flexibility and dynamics of NA in early psychosis. These findings further provide evidence for ER flexibility in early psychosis, emphasizing the adaptive nature of regulatory flexibility in relation to reduced instability in NA and faster recovery from NA in everyday life.

The temporal association between social isolation, distress, and psychotic experiences in individuals at clinical high-risk for psychosis.

BACKGROUND: Psychotic experiences (PEs) and social isolation (SI) seem related during early stages of psychosis, but the temporal dynamics between the two are not clear. Literature so far suggests a self-perpetuating cycle wherein momentary increases in PEs lead to social withdrawal, which, subsequently, triggers PEs at a next point in time, especially when SI is associated with increased distress. The current study investigated the daily-life temporal associations between SI and PEs, as well as the role of SI-related and general affective distress in individuals at clinical high risk (CHR) for psychosis. METHODS: We used experience sampling methodology in a sample of 137 CHR participants. We analyzed the association between SI, PEs, and distress using time-lagged linear mixed-effects models. RESULTS: SI did not predict next-moment fluctuations in PEs, or vice versa. Furthermore, although SI-related distress was not predictive of subsequent PEs, general affective distress during SI was a robust predictor of next-moment PEs. CONCLUSIONS: Our results suggest that SI and PEs are not directly related on a moment-to-moment level, but a negative emotional state when alone does contribute to the risk of PEs. These findings highlight the role of affective wellbeing during early-stage psychosis development.

The association between childhood trauma and tobacco smoking in patients with psychosis, unaffected siblings, and healthy controls.

In patients with psychosis, rates of tobacco smoking and childhood trauma are significantly higher compared to the general population. Childhood trauma has been proposed as a risk factor for tobacco smoking. However, little is known about the relationship between childhood trauma and smoking in psychosis. In a subsample of the Genetic Risk and Outcome of Psychosis study (760 patients with psychosis, 991 unaffected siblings, and 491 healthy controls), tobacco smoking was assessed using the Composite International Diagnostic Interview and childhood trauma was measured with the Childhood Trauma Questionnaire. Logistic regression models were used to assess associations between trauma and smoking, while correcting for confounders. Positive associations were found between total trauma, abuse, and neglect, and an increased risk for smoking in patients, while correcting for age and gender (ORtrauma 1.77, 95% CI 1.30-2.42, p < 0.001; ORabuse 1.69, 95% CI 1.23-2.31, p = 0.001; ORneglect 1.48, 95% CI 1.08-2.02, p = 0.014). In controls, total trauma and abuse were positively associated with smoking, while correcting for age and gender (ORtrauma 2.40, 95% CI 1.49-3.88, p < 0.001; ORabuse 2.02, 96% CI 1.23-3.32, p = 0.006). All associations lost their significance after controlling for additional covariates and multiple testing. Findings suggest that the association between childhood trauma and tobacco smoking can be mainly explained by confounders (gender, cannabis use, and education) in patients with psychosis. These identified aspects should be acknowledged in tobacco cessation programs.

Obsessive-compulsive symptoms relating to psychosocial functioning for people with schizophrenia, schizoaffective disorder, or bipolar disorder.

To assess the psychosocial functioning concerning obsessive-compulsive symptoms (OCS) and/or obsessive-compulsive disorder (OCD) comorbidity in people with schizophrenia, schizoaffective disorder, or bipolar disorder diagnosed in a large case register database in Southeast London. Data were retrieved from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) register using Clinical Record Interactive Search (CRIS) system, a platform allowing research on full but de-identified electronic health records for secondary and tertiary mental healthcare services. Information of schizophrenia, schizoaffective disorder, bipolar disorder diagnosis and OCS/OCD status was ascertained from structural or free-text fields through natural language processing (NLP) algorithms based on artificial intelligence techniques during the observation window of January 2007 to December 2016. Associations between comorbid OCS/OCD and recorded Health of the Nation Outcome Scales (HoNOS) for problems with activities of daily living (ADLs), living conditions, occupational and recreational activities, and relationships were estimated by logistic regression with socio-demographic confounders controlled. Of 15,412 subjects diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder, 2,358 (15.3%) experienced OCS without OCD, and 2,586 (16.8%) had OCD recorded. The presence of OCS/OCD was associated with more problems with relationships (adj.OR = 1.34, 95% CI: 1.25-1.44), ADLs (adj.OR = 1.31, 95%CI: 1.22-1.41), and living conditions (adj.OR = 1.31, 95% CI: 1.22-1.41). Sensitivity analysis revealed similar outcomes. Comorbid OCS/OCD was associated with poorer psychosocial functioning in people with schizophrenia, schizoaffective disorder, or bipolar disorder. This finding highlights the importance of identification and treatment of comorbid OCS among this vulnerable patient group.

Attachment Style and Self-Experience: The Association Between Attachment Style and Self-Reported Altered Self-Experience in Patients With Psychotic Disorders, Unaffected Siblings, and Healthy Controls.

ABSTRACT: The present study aimed to examine the cross-sectional association between attachment style and self-reported disturbed self-awareness (disturbed sense of mineness of experiences) and depersonalization (disturbed sense of first-person perspective) in patients with psychotic disorders, unaffected siblings, and healthy controls. Data pertain to a subsample of the GROUP (Genetic Risk and Outcome of Psychosis) study. We found positive associations between anxious attachment and disturbed self-awareness and depersonalization across participants with different psychosis vulnerability. We also found a positive association between avoidant attachment and depersonalization, although on a trend level. Findings indicate that attachment style is associated with self-reported disturbed self-awareness and depersonalization over and above the influence of psychotic or depressive experiences in people across the vulnerability spectrum of psychosis. This supports the importance of attachment style, self-awareness, and depersonalization as potential targets in prevention and treatment interventions in patients with psychotic disorders or those with increased vulnerability.

Comparing psychotic experiences in low-and-middle-income-countries and high-income-countries with a focus on measurement invariance.

BACKGROUND: The prevalence of psychotic experiences (PEs) is higher in low-and-middle-income-countries (LAMIC) than in high-income countries (HIC). Here, we examine whether this effect is explicable by measurement bias. METHODS: A community sample from 13 countries (N = 7141) was used to examine the measurement invariance (MI) of a frequently used self-report measure of PEs, the Community Assessment of Psychic Experiences (CAPE), in LAMIC (n = 2472) and HIC (n = 4669). The CAPE measures positive (e.g. hallucinations), negative (e.g. avolition) and depressive symptoms. MI analyses were conducted with multiple-group confirmatory factor analyses. RESULTS: MI analyses showed similarities in the structure and understanding of the CAPE factors between LAMIC and HIC. Partial scalar invariance was found, allowing for latent score comparisons. Residual invariance was not found, indicating that sum score comparisons are biased. A comparison of latent scores before and after MI adjustment showed both overestimation (e.g. avolition, d = 0.03 into d = -0.42) and underestimation (e.g. magical thinking, d = -0.03 into d = 0.33) of PE in LAMIC relative to HIC. After adjusting the CAPE for MI, participants from LAMIC reported significantly higher levels on most CAPE factors but a significantly lower level of avolition. CONCLUSION: Previous studies using sum scores to compare differences across countries are likely to be biased. The direction of the bias involves both over- and underestimation of PEs in LAMIC compared to HIC. Nevertheless, the study confirms the basic finding that PEs are more frequent in LAMIC than in HIC.

Genetic copy number variants, cognition and psychosis: a meta-analysis and a family study.

The burden of large and rare copy number genetic variants (CNVs) as well as certain specific CNVs increase the risk of developing schizophrenia. Several cognitive measures are purported schizophrenia endophenotypes and may represent an intermediate point between genetics and the illness. This paper investigates the influence of CNVs on cognition. We conducted a systematic review and meta-analysis of the literature exploring the effect of CNV burden on general intelligence. We included ten primary studies with a total of 18,847 participants and found no evidence of association. In a new psychosis family study, we investigated the effects of CNVs on specific cognitive abilities. We examined the burden of large and rare CNVs (>200 kb, <1% MAF) as well as known schizophrenia-associated CNVs in patients with psychotic disorders, their unaffected relatives and controls (N = 3428) from the Psychosis Endophenotypes International Consortium (PEIC). The carriers of specific schizophrenia-associated CNVs showed poorer performance than non-carriers in immediate (P = 0.0036) and delayed (P = 0.0115) verbal recall. We found suggestive evidence that carriers of schizophrenia-associated CNVs had poorer block design performance (P = 0.0307). We do not find any association between CNV burden and cognition. Our findings show that the known high-risk CNVs are not only associated with schizophrenia and other neurodevelopmental disorders, but are also a contributing factor to impairment in cognitive domains such as memory and perceptual reasoning, and act as intermediate biomarkers of disease risk.

Efficacy of Acceptance and Commitment Therapy in Daily Life in Early Psychosis: Results from the Multi-Center INTERACT Randomized Controlled Trial.

INTRODUCTION/OBJECTIVE: This study aimed to investigate efficacy of Acceptance and Commitment Therapy in Daily Life (ACT-DL), combining face-to-face therapy with an Ecological Momentary Intervention (EMI), in addition to treatment as usual (TAU) for psychotic distress, in comparison to TAU. METHODS: Individuals aged 15-65 years with clinically established ultra-high risk or first episode of psychosis were randomly assigned to TAU or ACT-DL+TAU. ACT-DL+TAU consisted of 8 ACT-sessions augmented with an EMI-app. The primary outcome was psychotic distress assessed with the Comprehensive Assessment scale of At Risk Mental State (CAARMS) at post-intervention and 6- and 12-month follow-up. Secondary outcomes were functioning, symptom severity, and momentary psychotic distress. We performed multivariate mixed models according to intent-to-treat principles. RESULTS: Between June 1, 2015 and December 31, 2018, 668 participants were referred, of whom 148 were randomized to ACT-DL+TAU (n = 71) or TAU (n = 77). One hundred and fifteen (78%) provided primary outcome data at least at one follow-up assessment. There was no evidence of greater reduction in the primary outcome measure CAARMS distress in ACT-DL+TAU compared to TAU (χ2(3) = 2.36; p = 0.50). However, out of the tested secondary outcomes, global functioning (χ2(3) = 9.05; p = 0.033), and negative symptoms (χ2(3) = 19.91; p<0.001) improved in ACT-DL+TAU compared to TAU, as did momentary psychotic distress (χ2(3) = 21.56; p < 0.001). CONCLUSIONS: INTERACT did not support a significant effect of ACT-DL over TAU on the primary outcome measure of psychotic distress as assessed with the CAARMS. Although significant improvements were found for some secondary outcome measures, further replication studies are needed to confirm the strength and specificity of these effects.

[Obsessive-compulsive symptoms in psychotic disorders: pathogenesis and treatment]. / Zwangssymptome bei psychotischen Störungen: Pathogenese und Therapie.

BACKGROUND: Comorbid disorders often occur in psychoses from the schizophrenia spectrum and are an additional burden for patients' quality of life, render treatment and rehabilitation prognosis more difficult and can also contribute to suicidal ideation. Specifically, obsessive-compulsive syndrome (OCS) and OC disorder (OCD) have been reported. OBJECTIVE: What is known about the epidemiology and pathogenesis and which conclusions can be drawn regarding the diagnostics and treatment? MATERIAL AND METHODS: This review evaluated current reports on comorbid OCS during different stages of psychotic disorders, starting with the at-risk mental state (ARMS) via the first manifestation and up to chronic courses. The focus was on pharmacological and psychotherapeutic consequences. RESULTS: Patients with ARMS suffer much more often from OCS than the general population. The prevalence is even higher in patients with a first manifestation of psychosis. During the chronic courses ca. 30% of patients are affected by comorbid OCS and 12% fulfill the diagnostic criteria of a OCD. The pathogenesis can most likely be explained by a genetic disposition in the glutamatergic system, shared structural and functional abnormalities of cortical and subcortical structures, pharmacological influences and psychosocial stressors. CONCLUSION: Clozapine and other antipsychotics may induce or aggravate OCS in a dose-dependent manner. In order to alleviate symptoms clozapine should be reduced to a minimally sufficient level. This can be attempted through combination, for example with dopaminergic antipsychotics. In general, serotonergic antidepressants can be added. Cognitive behavioral therapy should be offered to every patient with comorbid OCS. For future research multimodal longitudinal studies investigating the efficacy of interventions and aimed at the subjective level will be important.

Autistic traits in psychotic disorders: prevalence, familial risk, and impact on social functioning.

BACKGROUND: Prevalence estimates of autistic traits in individuals with psychotic disorders (PD) vary greatly and it is unclear whether individuals with a familial risk (FR) for psychosis have an increased propensity to display autistic traits. Furthermore, it is unknown whether the presence of comorbid autism traits disproportionally affects the cognitive and behavioral aspects of social functioning in PD. METHODS: In total, 504 individuals with PD, 587 unaffected siblings with FR, and 337 typical comparison (TC) individuals (16-50 years) were included. Autistic and psychotic traits were measured with the Autism Spectrum Quotient (AQ) and the Community Assessment of Psychic Experiences (CAPE). Social cognition was assessed with the Picture Sequencing Task (PST) and social behavior with the Social Functioning Scale (SFS). RESULTS: For PD 6.5% scored above AQ clinical cut-off (⩾32), 1.0% for FR, and 1.2% for TC. After accounting for age, sex, and IQ, the PD group showed significantly more autistic traits and alterations in social behavior and cognition, while FR and TC only displayed marginal differences. Within the PD group autistic traits were a robust predictor of social behavior and there were no interactions with positive psychotic symptoms. CONCLUSIONS: Levels of autistic traits are substantially elevated in PD and have a profoundly negative association with social functioning. In contrast, autistic traits above the clinical cut-off are not elevated in those with FR, and only marginally on a dimensional level. These findings warrant specific clinical guidelines for psychotic patients who present themselves with autistic comorbidity to help address their social needs.

Association between cognitive phenotype in unaffected siblings and prospective 3- and 6-year clinical outcome in their proband affected by psychosis.

BACKGROUND: Cognitive alterations are a central and heterogeneous trait in psychotic disorders, driven by environmental, familial and illness-related factors. In this study, we aimed to prospectively investigate the impact of high familial risk for cognitive alterations, unconfounded by illness-related factors, on symptomatic outcomes in patients. METHODS: In total, 629 probands with non-affective psychosis and their sibling not affected by psychosis were assessed at baseline, 3- and 6-year follow-up. Familial cognitive risk was modeled by three cognitive subtypes ('normal', 'mixed' and 'impaired') in the unaffected siblings. Generalized linear mixed models assessed multi-cross-sectional associations between the sibling cognitive subtype and repeated measures of proband symptoms across all assessments. Between-group differences over time were assessed by adding an interaction effect of time and sibling cognitive subtype. RESULTS: Probands affected by psychosis with a sibling of the impaired cognitive subtype were less likely to be in symptomatic remission and showed more disorganization across all time points. When assessing differences over time, probands of siblings with the impaired cognitive subtype showed less remission and less improvement of disorganization after 3 and 6 years relative to the other subtypes. They also showed less reduction of positive, negative and excitement symptoms at 6-year follow-up compared to probands with a sibling of the normal cognitive subtype. CONCLUSIONS: Cross-sibling pathways from higher levels of familial cognitive vulnerability to worse long-term outcomes may be informative in identifying cognition-related environmental and genetic risks that impact psychotic illness heterogeneity over time.

Deep brain stimulation versus ablative surgery for treatment-refractory obsessive-compulsive disorder: A meta-analysis.

OBJECTIVE: Ablative surgery (ABL) and deep brain stimulation (DBS) are last-resort treatment options for patients suffering from treatment-refractory obsessive-compulsive disorder (OCD). The aim of this study was to conduct an updated meta-analysis comparing the clinical outcomes of the ablative procedures capsulotomy and cingulotomy and deep brain stimulation. METHODS: We conducted a PubMed search to identify all clinical trials on capsulotomy, cingulotomy, and DBS. Random effects meta-analyses were performed on 38 articles with a primary focus on efficacy in reducing OCD symptoms as measured by a reduction in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score and the responder rate (≥35% reduction in Y-BOCS score). RESULTS: With responder rates of 48% and 53% after 12-16 months and 56% and 57% at last follow-up for ABL and DBS, respectively, and large effect sizes in the reduction in Y-BOCS scores, both surgical modalities show effectiveness in treating refractory OCD. Meta-regression did not show a statistically significant difference between ABL and DBS regarding these outcomes. Regarding adverse events, a statistically significant higher rate of impulsivity is reported in studies on DBS. CONCLUSION: This meta-analysis shows equal efficacy of ABL and DBS in the treatment of refractory OCD. For now, the choice of intervention should, therefore, rely on factors such as risk of developing impulsivity, patient preferences, and experiences of psychiatrist and neurosurgeon. Future research should provide more insight regarding differences between ABL and DBS and response prediction following direct comparisons between the surgical modalities, to enable personalized and legitimate choices between ABL and DBS.

Meta-analysis of cognitive functioning in patients with psychotic disorders and obsessive-compulsive symptoms.

Obsessive-compulsive symptoms (OCS) in psychotic disorders are associated with unfavorable outcomes, whether this extends to cognitive function remains unclear. We conducted meta-analyses on several cognitive domains to investigate overall group differences between patients with a psychotic disorder and co-occurring OCS (OCS +) and those without OCS (OCS-). We used meta-regression to assess possible confounding effects. No overall associations between OCS + and OCS- in any of the 17 investigated cognitive domains were found. We predominantly found large heterogeneity in effect size and direction among studies. Post-hoc analyses of processing speed tasks not purely based on reaction-time showed worse performance in the OCS + group with a small effect size (SMD = - 0.190; p = 0.029). Meta-regression revealed advanced age was significantly correlated with worse performance of the OCS + group in processing speed (R2 = 0.7), working memory (R2 = 0.11), cognitive inhibition (R2 = 0.59), and cognitive flexibility (R2 = 0.34). Patients fulfilling the criteria for an obsessive-compulsive disorder showed less impairment in cognitive inhibition compared to the OCS + group (R2 = 0.63). Overall, comorbid OCS were not associated with cognitive impairment. However, large heterogeneity between studies highlights the complex nature of factors influencing cognition in people with psychotic disorder and comorbid OCS and warrants further research into possible moderating factors.

Obsessive-compulsive symptoms in psychotic disorders: longitudinal associations of symptom clusters on between- and within-subject levels.

Obsessive-compulsive symptoms (OCS) are frequently reported in patients with schizophrenia and have been associated with subjective distress and higher impairment. Recent studies suggest fluctuation in co-occurring OCS and associations with the course of psychotic symptoms. Current evidence is limited by few studies with long assessments intervals and a sole focus on between-subject comparisons. The aim of this study was to specifically investigate co-variation of symptom domains over time within individuals. Patients with a psychotic disorder (n = 56) and un-affected siblings (n = 49) completed monthly assessments of clinical and subclinical symptoms over 6 months. Mixed-model multilevel analyses examined the variability and relationship between OCS and positive, negative, and depressive symptoms on the between- and within-subject level. Symptom domains were associated across subjects and assessment times, in patients and siblings, with the strongest association between OCS and (subclinical) positive symptoms. Within-subjects, substantial variability and co-variation of all symptom domains was found. Particularly, between-subject differences in positive symptoms and within-subject change in depressive symptoms predicted subsequent OCS in patients 1 months later. This is the first prospective study disaggregating between and within-subject associations between co-occurring OCS and symptom cluster of psychosis. Differences on these two levels suggest different underlying mechanisms. The association between depressive symptoms and subsequent increase/decrease of OCS within patients may have important treatment implications.

Longitudinal association between motor and obsessive compulsive symptoms in patients with psychosis and their unaffected siblings.

Little is known about the co-prevalence of obsessive compulsive symptoms (OCS) and motor symptoms in patients with psychotic disorders. Cross-sectional associations between OCS and motor symptoms were assessed at baseline and at 3 years follow-up in patients (n = 726) with psychotic disorders and in their unaffected siblings (n = 761) from the Dutch Genetic Risk and Outcome of Psychosis (GROUP) study. Furthermore, longitudinal associations between changes in OCS and motor symptoms were evaluated. At baseline, OCS was not associated with any motor symptom (akathisia, dyskinesia, parkinsonism or dystonia) in patients. At follow-up, patients with OCS reported significantly more akathisia. Dividing the patients into four groups-no OCS, OCS remission with OCS only at baseline, OCS de novo with OCS only at follow-up and a persistent OCS group-revealed that the OCS de novo group already reported more akathisia at baseline compared to the no-OCS group. At follow-up, both the OCS de novo and the persistent OCS group reported more akathisia. These results remained significant after correcting for relevant confounders clozapine, GAF score, PANSS-negative score and IQ. Motor symptoms at baseline were significantly associated with OCS at follow-up, but not the other way around. In siblings, OCS at baseline was associated with akathisia, but this association was lost at follow-up. Results suggest that motor symptoms might precede co-occurring OCS in patients with psychotic disorders. However, no inference can be made about causality, and further prospective research is needed to investigate this assumption.

Reduced activity and connectivity of left amygdala in patients with schizophrenia treated with clozapine or olanzapine.

Obsessive-compulsive symptoms (OCS) in patients with schizophrenia are a common co-occurring condition, often associated with additional impairments. A subgroup of these patients develops OCS during treatment with second-generation antipsychotics (SGAs), most importantly clozapine and olanzapine. So far, little is known about possible neural mechanism of these SGAs, which seem to aggravate or induce OCS. To investigate the role of SGA treatment on neural activation and connectivity during emotional processing, patients were stratified according to their monotherapy into two groups (group I: clozapine or olanzapine, n = 20; group II: amisulpride or aripiprazole, n = 20). We used an fMRI approach, applying an implicit emotion recognition task. Group comparisons showed significantly higher frequency and severity of comorbid OCS in group I than group II. Task specific activation was attenuated in group I in the left amygdala. Furthermore, functional connectivity from left amygdala to right ventral striatum was reduced in group I. Reduced amygdala activation was associated with OCS severity. Recent literature suggests an involvement of an amygdala-cortico-striatal network in the pathogenesis of obsessive-compulsive disorder. The observed differential activation and connectivity pattern of the amygdala might thus indicate a neural mechanism for the development of SGA-associated OCS in patients with schizophrenia. Further neurobiological research and interventional studies are needed for causal inferences.

Obsessive-compulsive symptoms and overall psychopathology in psychotic disorders: longitudinal assessment of patients and siblings.

The course of obsessive-compulsive symptoms (OCS) and its association with alterations in other clinical variables in patients with psychotic disorders is insufficiently known. Patients (n = 602) and unaffected siblings (n = 652) from the Dutch Genetic Risk and Outcome of Psychosis (GROUP) study were investigated at baseline and after 3 years. Participants were assigned to four groups based on the course of OCS over time: no-OCS, persistent OCS, initial OCS and de novo OCS. In addition to cross-sectional comparisons, longitudinal associations between changes in OCS and symptoms of schizophrenia and general functioning were investigated. Patients with co-occurring OCS reported significantly higher severity of psychotic and affective symptoms as well as lower overall functioning compared to patients without OCS. These differences were stable over time for patients reporting persistent OCS. Subsequent repeated measure analysis revealed significant interaction effects for groups reporting changes in their OCS. Whereas the group with remission of initial OCS showed significant improvement in positive symptoms, emotional distress and functioning, the de novo group showed no significant change in these variables, but rather reported stable higher psychopathology. Similar results were found on a subclinical level in siblings. Patients with co-occurring OCS present a more severe clinical picture, especially if symptoms persist over time. The remission of OCS was associated with overall improvement, whereas individuals with de novo OCS already reported higher clinical impairment before OCS onset. More research is needed to elucidate causal pathways and to develop effective interventions for persistent comorbid OCS.

Increased orbitofrontal cortex activation associated with "pro-obsessive" antipsychotic treatment in patients with schizophrenia.

BACKGROUND: Patients with schizophrenia have an approximately 10-fold higher risk for obsessive-compulsive symptoms (OCS) than the general population. A large subgroup seems to experience OCS as a consequence of second-generation antipsychotic agents (SGA), such as clozapine. So far little is known about underlying neural mechanisms. METHODS: To investigate the role of SGA treatment on neural processing related to OCS in patients with schizophrenia, we stratified patients according to their monotherapy into 2 groups (group I: clozapine or olanzapine; group II: amisulpride or aripiprazole). We used an fMRI approach, applying a go/no-go task assessing inhibitory control and an n-back task measuring working memory. RESULTS: We enrolled 21 patients in group I and 19 patients in group II. Groups did not differ regarding age, sex, education or severity of psychotic symptoms. Frequency and severity of OCS were significantly higher in group I and were associated with pronounced deficits in specific cognitive abilities. Whereas brain activation patterns did not differ during working memory, group I showed significantly increased activation in the orbitofrontal cortex (OFC) during response inhibition. Alterations in OFC activation were associated with the severity of obsessions and mediated the association between SGA treatment and co-occurring OCS on a trend level. LIMITATIONS: The main limitation of this study is its cross-sectional design. CONCLUSION: To our knowledge, this is the first imaging study conducted to elucidate SGA effects on neural systems related to OCS. We propose that alterations in brain functioning reflect a pathogenic mechanism in the development of SGA-induced OCS in patients with schizophrenia. Longitudinal studies and randomized interventions are needed to prove the suggested causal interrelations.

Reduced activation in the ventral striatum during probabilistic decision-making in patients in an at-risk mental state.

BACKGROUND: Patients with schizophrenia display metacognitive impairments, such as hasty decision-making during probabilistic reasoning - the "jumping to conclusion" bias (JTC). Our recent fMRI study revealed reduced activations in the right ventral striatum (VS) and the ventral tegmental area (VTA) to be associated with decision-making in patients with schizophrenia. It is unclear whether these functional alterations occur in the at-risk mental state (ARMS). METHODS: We administered the classical beads task and fMRI among ARMS patients and healthy controls matched for age, sex, education and premorbid verbal intelligence. None of the ARMS patients was treated with antipsychotics. Both tasks request probabilistic decisions after a variable amount of stimuli. We evaluated activation during decision-making under certainty versus uncertainty and the process of final decision-making. RESULTS: We included 24 AMRS patients and 24 controls in our study. Compared with controls, ARMS patients tended to draw fewer beads and showed significantly more JTC bias in the classical beads task, mirroring findings in patients with schizophrenia. During fMRI, ARMS patients did not demonstrate JTC bias on the behavioural level, but showed a significant hypoactivation in the right VS during the decision stage. LIMITATIONS: Owing to the cross-sectional design of the study, results are constrained to a better insight into the neurobiology of risk constellations, but not prepsychotic stages. Nine of the ARMS patients were treated with antidepressants and/or lorazepam. CONCLUSION: As in patients with schizophrenia, a striatal hypoactivation was found in ARMS patients. Confounding effects of antipsychotic medication can be excluded. Our findings indicate that error prediction signalling and reward anticipation may be linked to striatal dysfunction during prodromal stages and should be examined for their utility in predicting transition risk.