Sarah Eifler

Stable Cognitive Deficits in Schizophrenia Patients With Comorbid Obsessive-Compulsive Symptoms: A 12-Month Longitudinal Study

BACKGROUND Amongst schizophrenia patients, a large subgroup of up to 25% also suffers from comorbid obsessive-compulsive symptoms (OCSs). The association between comorbid OCSs in these patients and neuropsychological impairment remains unclear and somewhat contradictory. Longitudinal approaches investigating the stability of OCS-associated cognitive deficits are missing. METHODS Thirty-seven patients with schizophrenia and comorbid OCSs and 43 schizophrenia patients without OCS were assessed with a comprehensive cognitive test battery and compared at baseline and, again, 12 months later. RESULTS Schizophrenia patients with comorbid OCSs showed significant pronounced deficits, with increasing effect sizes over the 12-month assessment period in specific cognitive areas such as visuospatial perception and visual memory (WAIS-R block design, Rey-Osterrieth Complex Figure Test), executive functioning (perseveration in the Wisconsin Card Sorting test), and cognitive flexibility (Trail Making test B). These cognitive domains are correlated with OCS severity and are known to be candidate cognitive domains in obsessive-compulsive disorder (OCD). CONCLUSIONS OCSs in schizophrenia is associated with specific and longitudinally stable cognitive deficits, strongly arguing for at least partially overlapping neurobiological mechanisms with OCD. Prospective studies involving patients with at-risk mental states for psychosis are necessary to decipher the interaction of cognitive impairment and the clinical manifestations of schizophrenia and OCSs. This might facilitate the definition of patients at high risk for OCSs, an early detection of subclinical levels, therapeutic interventions, and clinical monitoring.

Reduced activation in ventral striatum and ventral tegmental area during probabilistic decision-making in schizophrenia

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.

Differential effects of antipsychotic agents on obsessive–compulsive symptoms in schizophrenia: a longitudinal study

Indirect evidence supports the assumption that antiserotonergic second-generation antipsychotics (SGA) induce and aggravate obsessive–compulsive symptoms (OCS) in schizophrenia. However, multimodal studies assessing the long-term interaction of pharmacotherapy and psychopathology are missing. Over 12 months, we followed-up 75 schizophrenia patients who were classified into two groups according to antipsychotic treatment: clozapine or olanzapine (group I) versus aripiprazole or amisulpride (group II). We applied the Yale Brown Obsessive Compulsive Scale (YBOCS) and investigated between-group changes over time as the primary endpoint. Group I showed markedly higher YBOCS scores at both time points. Repeated measure analyses of variance (ANOVAs) revealed significant interaction effects of group and time (per protocol sample (PP): p=0.006). This was due to persistently high OCS severity within group I, and decreasing YBOCS scores within group II. OCS severity correlated significantly with the negative and general psychopathology subscales of the Positive and Negative Syndrome Scale (PANSS), as well as with depressive symptoms. The progressive differences in OCS severity between our groups support the assumption of differential pharmacodynamic effects on comorbid OCS in schizophrenia. Further studies should address the pathogenetic mechanism, define patients at risk and facilitate early detection as well as therapeutic interventions.

Functional Social Support within a Medical Supervised Outpatient Treatment Program

Background: This study examined functional social support (FSS) and its impact on treatment outcome in alcohol-dependent outpatients treated with supervised disulfiram. Method: FSS was assessed cross-sectionally in 46 severe alcohol-dependent patients participating in a close-meshed biopsychosocial treatment program. The FSS was measured with the Medical Outcome Study Social Support Survey. Results: We found significantly higher FSS levels in patients with a current partnership. No significant influence was found of the FSS on days until relapse and retention time. However, FSS was positively correlated with cumulative abstinence. In comparison with another patient sample, it can be shown that the patients of the close-meshed biopsychosocial treatment program seemed to perceive more FSS, presumably through the higher frequency of the outpatient treatment contacts. Conclusion: High FSS is associated with a current partnership and with a higher cumulative time of abstinence through close professional supervision. A better understanding of the underlying mechanisms of social relationships in alcohol-dependent patients would probably help to improve treatment outcome in the future.

Overconfidence in incorrect perceptual judgments in patients with schizophrenia

Background Patients with schizophrenia show overconfidence in memory and social cognition errors. The present investigation examined whether this cognitive distortion also manifests in perceptual tasks. Methods A total of 55 individuals with schizophrenia, 58 with obsessive–compulsive disorder (OCD) as well as 45 non-clinical controls were presented 24 blurry black and white pictures, half of which contained a hidden object; the other half contained (“snowy”) visual noise. Participants had to judge whether the pictures depicted an object or not and how confident they were in this judgment. Results Participants with schizophrenia showed overconfidence in errors and an enhanced knowledge corruption index (i.e. rate of high-confident errors on all high-confident responses) relative to both control groups. In contrast, accuracy scores did not differ between clinical groups. Metacognitive parameters were correlated with self-rated levels of current paranoia. Discussion To the best of our knowledge, this is the first study to demonstrate overconfidence in errors among individuals with psychosis using a visual perception task. Speaking to the specificity of this abnormality for schizophrenia and its pathogenetic relevance, overconfidence in errors and knowledge corruption were elevated in patients with schizophrenia relative to both control groups and were correlated with paranoia.

Neurocognitive capabilities modulate the integration of evidence in schizophrenia

Previous studies have demonstrated a cognitive bias in the integration of disconfirmatory evidence (BADE) in patients with schizophrenia. This bias has been associated with delusions. So far, it is unclear how the integration of evidence is associated with neurocognitive capabilities. In the current study, 31 patients with schizophrenia and 29 healthy controls, matched on age, gender, education and premorbid verbal intelligence, underwent a BADE task. Written scenarios of three consecutive sentences each were presented, which progressively reduced the ambiguity of situations. Participants were asked to rate the plausibility of four possible interpretations and adjust their ratings in response to the provided sentences. Psychometric rating scales and a neuropsychological test battery were applied. Patients displayed a bias in the integration of confirmatory, but not disconfirmatory evidence and a liberal acceptance of belief formation. Correlation analyses revealed no associations of evidence integration with the severity of positive symptoms, but with neurocognitive domains, especially with processing speed, executive functioning, vigilance and working memory. In conclusion, patients with schizophrenia show a bias in evidence integration. Neurocognitive functioning emerged as a modulatory factor that should be considered in further research. Studies investigating BADE in earlier stages of psychosis will be necessary to reveal causal relationships.

Metamemory in schizophrenia: Retrospective confidence ratings interact with neurocognitive deficits

Prior studies with schizophrenia patients described a reduced ability to discriminate between correct and false memories in terms of confidence compared to control groups. This metamemory bias has been associated with the emergence and maintenance of delusions. The relation to neuropsychological performance and other clinical dimensions is incompletely understood. In a cross-sectional study, metamemory functioning was explored in 32 schizophrenia patients and 25 healthy controls. Metamemory was assessed using a verbal recognition task combined with retrospective confidence level ratings. Associations of metamemory performance with six neuropsychological domains (executive functioning/problem solving, speed of processing, working memory, verbal and visual learning, and attention/vigilance) and psychopathological measures were analyzed. Results revealed a significantly smaller discrepancy between confidence ratings for correct and incorrect recognitions in the patient group. Furthermore, patients showed significantly lower recognition accuracy in the metamemory task and marked deficits in all neuropsychological domains. Across all participants, metamemory performance significantly correlated with executive functioning and working memory. No associations with delusions were found. This data confirms prior findings of metamemory biases in schizophrenia. Selective neuropsychological abilities seem to be modulating factors of metamemory functioning. Longitudinal studies in at risk mental state and first-episode patients are needed to reveal causal interrelations.

855 – Cognitive deficits in patients with schizophrenia and comorbid obsessivecompulsive symptoms: a 12 month longitudinal study

Background Epidemiological studies estimated that amongst patients with schizophrenia a large subgroup of up to 25% also suffers from comorbid obsessive compulsive symptoms (OCS). The association between these comorbid OCS and neuropsychological impairment remains unclear and somewhat contradictory. Longitudinal approaches which investigate the stability of OCS related cognitive deficits are missing. Methods 37 patients with schizophrenia and comorbid OCS and 43 schizophrenia patients without OCS were assessed with a comprehensive cognitive test-battery and compared at baseline and again 12 months later. Results Schizophrenia patients with comorbid OCS showed significant pronounced deficits with increasing effect sizes over the 12 month assessment period in specific cognitive areas such as visuo-spatial perception and visual memory (WAIS-R block design, Rey-Osterrieth Complex Figure Test), executive functioning (perseveration in the Wisconsin card sorting test) and cognitive flexibility (Trail making test B). These cognitive domains correlated with OCS severity and are known to be candidate domains in obsessive compulsive disorder (OCD). Conclusions OCS in schizophrenia is associated longitudinally stable specific cognitive deficits. Prospective studies involving patients with at risk mental states for psychosis are necessary to decipher the interaction of cognitive impairment and the clinical manifestation of schizophrenia and OCS. This might facilitate the definition of patients at high risk for OCS, an early detection of subclinical levels, therapeutic interventions and clinical monitoring.