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Introduction Decision-making and learning impairments are core characteristics of a wide range of psychiatric disorders--such as major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia--and are linked to their specific [...], Background: Decision-making alterations are present in psychiatric illnesses like major depressive disorder (MDD), obsessivecompulsive disorder (OCD), and schizophrenia, linked to symptoms of the respective disorders. We sought to analyze unique and shared decision-making alterations in these disorders, which is crucial for early diagnosis and treatment, especially given potential comorbidities. Methods: Using 2 computational modelling approaches--logistic regression and hierarchical Bayesian modelling--we analyzed alterations in model-based and model-free decision-making in a transdiagnostic cohort of patients with MDD, OCD, or schizophrenia. Our aim was to identify disorder-specific and shared alterations and their associations with symptoms. Results: We included 23 patients with MDD, 25 patients with OCD, 27 patients with schizophrenia, and 25 controls. Overall, participants of all groups relied on model-free decision-making. Patients with schizophrenia had the lowest learning rate and highest switching rate, indicating low perseverance. Furthermore, patients with OCD were more random in both task stages than controls and patients with MDD. All patient groups exhibited more randomness in responses than controls, with the schizophrenia group showing the highest levels. Increased model- free behaviour correlated with elevated depressive symptoms, and more model-based decision-making was linked to lower anhedonia levels across all patient groups. Limitations: The sample size in each group was small. Conclusion: This study highlights disorder-specific and shared decision-making alterations among people with MDD, OCD, or schizophrenia. Our findings suggest that anhedonia and depressive symptoms, which are present in all 3 disorders, share underlying behavioural mechanisms. Improving model-based behaviour may be a target for intervention and treatment. Furthermore, completely random behaviour in the 2-step task appears to distinctly differentiate patients with schizophrenia in remission.

Background and Hypothesis Abnormal thalamic nuclei volumes and their link to cognitive impairments have been observed in schizophrenia. However, whether and how this finding extends to the schizophrenia spectrum is unknown. We hypothesized a distinct pattern of aberrant thalamic nuclei volume across the spectrum and examined its potential associations with cognitive symptoms. Study Design We performed a FreeSurfer-based volumetry of T1-weighted brain MRIs from 137 healthy controls, 66 at-risk mental state (ARMS) subjects, 89 first-episode psychosis (FEP) individuals, and 126 patients with schizophrenia to estimate thalamic nuclei volumes of six nuclei groups (anterior, lateral, ventral, intralaminar, medial, and pulvinar). We used linear regression models, controlling for sex, age, and estimated total intracranial volume, both to compare thalamic nuclei volumes across groups and to investigate their associations with positive, negative, and cognitive symptoms. Study Results We observed significant volume alterations in medial and lateral thalamic nuclei. Medial nuclei displayed consistently reduced volumes across the spectrum compared to controls, while lower lateral nuclei volumes were only observed in schizophrenia. Whereas positive and negative symptoms were not associated with reduced nuclei volumes across all groups, higher cognitive scores were linked to lower volumes of medial nuclei in ARMS. In FEP, cognition was not linked to nuclei volumes. In schizophrenia, lower cognitive performance was associated with lower medial volumes. Conclusions Results demonstrate distinct thalamic nuclei volume reductions across the schizophrenia spectrum, with lower medial nuclei volumes linked to cognitive deficits in ARMS and schizophrenia. Data suggest a distinctive trajectory of thalamic nuclei abnormalities along the course of schizophrenia. [ABSTRACT FROM AUTHOR]

Negative symptoms, such as lack of motivation or social withdrawal, are highly prevalent and debilitating in patients with schizophrenia. Underlying mechanisms of negative symptoms are incompletely understood, thereby preventing the development of targeted treatments. We hypothesized that in patients with schizophrenia during psychotic remission, impaired influences of both model-based and model-free reward predictions on decision-making ('reward prediction influence', RPI) underlie negative symptoms. We focused on psychotic remission, because psychotic symptoms might confound reward-based decision-making. Moreover, we hypothesized that impaired model-based/model-free RPIs depend on alterations of both associative striatum dopamine synthesis and storage (DSS) and executive functioning. Both factors influence RPI in healthy subjects and are typically impaired in schizophrenia. Twenty-five patients with schizophrenia with pronounced negative symptoms during psychotic remission and 24 healthy controls were included in the study. Negative symptom severity was measured by the Positive and Negative Syndrome Scale negative subscale, model-based/model-free RPI by the two-stage decision task, associative striatum DSS by 18F-DOPA positron emission tomography and executive functioning by the symbol coding task. Model-free RPI was selectively reduced in patients and associated with negative symptom severity as well as with reduced associative striatum DSS (in patients only) and executive functions (both in patients and controls). In contrast, model-based RPI was not altered in patients. Results provide evidence for impaired model-free reward prediction influence as a mechanism for negative symptoms in schizophrenia as well as for reduced associative striatum dopamine and executive dysfunction as relevant factors. Data suggest potential treatment targets for patients with schizophrenia and pronounced negative symptoms. [ABSTRACT FROM AUTHOR]