Obsessive-compulsive disorder (OCD) is rarely associated with schizophrenia, whereas 20 to 30% of schizophrenic patients, suffer from comorbid obsessive-compulsive symptoms (OCS). So far no single ...pathogenetic theory convincingly explained this fact suggesting heterogeneous subgroups. Based on long-term case observations, one hypothesis assumes that second-onset OCS in the course of schizophrenia might be a side effect of second generation antipsychotics (SGA), most importantly clozapine (CLZ). This review summarizes the supporting epidemiological and pharmacological evidence: Estimations on prevalence of OCS increase in more recent cross-sectional studies and in later disease stages. Longitudinal observations report the de novo-onset of OCS under clozapine treatment. This association has not been reported with first generation antipsychotics (FGA) or SGAs with mainly dopaminergic mode of action. Finally, significant correlations of OCS-severity with duration of treatment, dose and serum levels suggest clozapine-induced OCS. However, supposed causal interactions need further verifications. It is also unclear, which neurobiological mechanisms might underlie the pathogenetic process. Detailed genotypic and phenotypic characterizations of schizophrenics with comorbid OCS regarding neurocognitive functioning and activation in sensitive tasks of functional magnetic imaging are needed. Multimodal large-scaled prospective studies are necessary to define patients at risk for second-onset OCS and to improve early detection and therapeutic interventions.
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 (
R
2
= 0.7), working memory (
R
2
= 0.11), cognitive inhibition (
R
2
= 0.59), and cognitive flexibility (
R
2
= 0.34). Patients fulfilling the criteria for an obsessive–compulsive disorder showed less impairment in cognitive inhibition compared to the OCS + group (
R
2
= 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.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A large subgroup of around 25% of schizophrenia patients suffers from obsessive-compulsive symptoms (OCS) and about 12% fulfill the diagnostic criteria of an obsessive-compulsive disorder (OCD). The ...additional occurrence of OCS is associated with high subjective burden of disease, additional neurocognitive impairment, poorer social and vocational functioning, greater service utilization and high levels of anxiety and depression. Comorbid patients can be assigned to heterogeneous subgroups. One hypothesis assumes that second generation antipsychotics (SGAs), most importantly clozapine, might aggravate or even induce second-onset OCS. Several arguments support this assumption, most importantly the observed chronological order of first psychotic manifestation, start of treatment with clozapine and onset of OCS. In addition, correlations between OCS-severity and dose and serum levels and duration of clozapine treatment hint toward a dose-dependent side effect. It has been hypothesized that genetic risk-factors dispose patients with schizophrenia to develop OCS. One study in a South Korean sample reported associations with polymorphisms in the gene SLC1A1 (solute carrier family 1A1) and SGA-induced OCS. However, this finding could not be replicated in European patients. Preliminary results also suggest an involvement of polymorphisms in the BDNF gene (brain-derived neurotrophic factor) and an interaction between markers of SLC1A1 and the gene DLGAP3 (disc large associated protein 3) as well as GRIN2B (N-methyl-D-aspartate receptor subunit 2B). Further research of well-defined samples, in particular studies investigating possible interactions of genetic risk-constellations and pharmacodynamic properties, are needed to clarify the assumed development of SGA-induced OCS. Results might improve pathogenic concepts and facilitate the definition of at risk populations, early detection and monitoring of OCS as well as multimodal therapeutic interventions.
In patients with a psychotic disorder, rates of substance use (tobacco, cannabis, and alcohol) are higher compared to the general population. However, little is known about associations between ...substance use and self-reported aspects of social functioning in patients with a psychotic disorder.
In this cross-sectional study of 281 community-dwelling patients with a psychotic disorder, linear regression models were used to assess associations between substance use (tobacco, cannabis, or alcohol) and self-reported aspects of social functioning (perceived social support, stigmatization, social participation, or loneliness) adjusting for confounders (age, gender, and severity of psychopathology).
Compared to nonsmokers, both intermediate and heavy smokers reported lower scores on loneliness (E = -0.580, SE = 0.258, p = 0.025 and E = -0.547, SE = 0,272, p = 0.046, respectively). Daily cannabis users reported less social participation deficits than non-cannabis users (E = -0.348, SE = 0.145, p = 0.017). Problematic alcohol use was associated with more perceived social support compared to non-alcohol use (E = 3.152, SE = 1.102, p = 0.005). Polysubstance users reported less loneliness compared to no users (E = -0.569, SE = 0.287, p = 0.049).
Substance use in patients with psychosis is associated with more favorable scores on various self-reported aspects of social functioning.
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.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Obsessive and Compulsive Symptoms (OCS) or Obsessive Compulsive Disorder (OCD) in the context of schizophrenia or related disorders are of clinical importance as these are associated with a range of ...adverse outcomes. Natural Language Processing (NLP) applied to Electronic Health Records (EHRs) presents an opportunity to create large datasets to facilitate research in this area. This is a challenging endeavour however, because of the wide range of ways in which these symptoms are recorded, and the overlap of terms used to describe OCS with those used to describe other conditions. We developed an NLP algorithm to extract OCS information from a large mental healthcare EHR data resource at the South London and Maudsley NHS Foundation Trust using its Clinical Record Interactive Search (CRIS) facility. We extracted documents from individuals who had received a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder. These text documents, annotated by human coders, were used for developing and refining the NLP algorithm (600 documents) with an additional set reserved for final validation (300 documents). The developed NLP algorithm utilized a rules-based approach to identify each of symptoms associated with OCS, and then combined them to determine the overall number of instances of OCS. After its implementation, the algorithm was shown to identify OCS with a precision and recall (with 95% confidence intervals) of 0.77 (0.65-0.86) and 0.67 (0.55-0.77) respectively. The development of this application demonstrated the potential to extract complex symptomatic data from mental healthcare EHRs using NLP to facilitate further analyses of these clinical symptoms and their relevance for prognosis and intervention response.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Oxford Mental Illness and Violence (OxMIV) addresses the need in mental health services for a scalable, transparent and valid tool to predict violent behaviour in patients with severe mental illness. ...However, external validations are lacking. Therefore, we have used a Dutch sample of general psychiatric patients with schizophrenia spectrum disorders (N = 637) to evaluate the performance of OxMIV in predicting interpersonal violence over 3 years. The predictors and outcome were measured with standardized instruments and multiple sources of information. Patients were mostly male (n = 493, 77%) and, on average, 27 (SD = 7) years old. The outcome rate was 9% (n = 59). Discrimination, as measured by the area under the curve, was moderate at 0.67 (95% confidence interval 0.61-0.73). Calibration-in-the-large was adequate, with a ratio between predicted and observed events of 1.2 and a Brier score of 0.09. At the individual level, risks were systematically underestimated in the original model, which was remedied by recalibrating the intercept and slope of the model. Probability scores generated by the recalibrated model can be used as an adjunct to clinical decision-making in Dutch mental health services.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract Patients with schizophrenia suffer from deficits in monitoring and controlling their own thoughts. Within these so-called metacognitive impairments, alterations in probabilistic reasoning ...might be one cognitive phenomenon disposing to delusions. However, so far little is known about alterations in associated brain functionality. A previously established task for functional magnetic resonance imaging (fMRI), which requires a probabilistic decision after a variable amount of stimuli, was applied to 23 schizophrenia patients and 28 healthy controls matched for age, gender and educational levels. We compared activation patterns during decision-making under conditions of certainty versus uncertainty and evaluated the process of final decision-making in ventral striatum (VS) and ventral tegmental area (VTA). We replicated a pre-described extended cortical activation pattern during probabilistic reasoning. During final decision-making, activations in several fronto- and parietocortical areas, as well as in VS and VTA became apparent. In both of these regions schizophrenia patients showed a significantly reduced activation. These results further define the network underlying probabilistic decision-making. The observed hypo-activation in regions commonly associated with dopaminergic neurotransmission fits into current concepts of disrupted prediction error signaling in schizophrenia and suggests functional links to reward anticipation. Forthcoming studies with patients at risk for psychosis and drug-naive first episode patients are necessary to elucidate the development of these findings over time and the interplay with associated clinical symptoms.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background:
Body image (BI) disturbances have been identified in both clinical and non-clinical populations. Virtual reality (VR) has recently been used as a tool for modulating BI disturbances ...through the use of eliciting a full body illusion (FBI). This meta-analysis is the first to collate evidence on the effectiveness of an FBI to reduce BI disturbances in both clinical and non-clinical populations.
Methods:
We performed a literature search in MEDLINE (PubMed), EMBASE, PsychINFO, and Web of Science with the keywords and synonyms for “virtual reality” and “body image” to identify published studies until September 2020. We included studies that (1) created an FBI with a modified body shape or size and (2) reported BI disturbance outcomes both before and directly after the FBI. FBI was defined as a head-mounted display (HMD)-based simulation of embodying a virtual body from an egocentric perspective in an immersive 3D computer-generated environment.
Results:
Of the 398 identified unique studies, 13 were included after reading full-texts. Four of these studies were eligible for a meta-analysis on BI distortion inducing a small virtual body FBI in healthy females. Significant post-intervention results were found for estimations of shoulder width, hip width, and abdomen width, with the largest reductions in size being the estimation of shoulder circumference (SMD = −1.3; 95% CI: −2.2 to −0.4;
p
= 0.004) and hip circumference (SMD = −1.0; 95% CI: −1.6 to −0.4;
p
= 0.004). Mixed results were found in non-aggregated studies from large virtual body FBIs in terms of both estimated body size and BI dissatisfaction and in small virtual body FBI in terms of BI dissatisfaction.
Conclusions:
The findings presented in this paper suggest that the participants' BIs were able to conform to both an increased as well as a reduced virtual body size. However, because of the paucity of research in this field, the extent of the clinical utility of FBIs still remains unclear. In light of these limitations, we provide implications for future research about the clinical utility of FBIs for modulating BI-related outcomes.
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 pre-psychotic 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.
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