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Low physical activity (PA) and sedentary behavior (SB) are major contributors to mental health burden and increased somatic comorbidity and mortality in people with schizophrenia and related psychoses. Movement disorders are highly prevalent in schizophrenia populations and are related to impaired functioning and poor clinical outcome. However, the relationship between movement disorders and PA and SB has remained largely unexplored. Therefore, we aimed to examine the relationship between movement disorders (akathisia, dyskinesia, dystonia, and parkinsonism) and PA and SB in 216 patients with schizophrenia and related psychoses. Actigraphy, the St. Hans Rating Scale for extrapyramidal syndromes, and psychopathological ratings (PANSS-r) were applied. Data were analyzed using multiple linear regression, adjusting for sex, age, negative symptoms, and defined daily dose of prescribed antipsychotics. Parkinsonism was significantly associated with decreased PA (β = −0.21, P < .01) and increased SB (β = 0.26, P < .001). For dystonia, only the relationship with SB was significant (β = 0.15, P < .05). Akathisia was associated with more PA (β = 0.14, P < .05) and less SB (β = −0.15, P < .05). For dyskinesia, the relationships were non-significant. In a prediction model, akathisia, dystonia, parkinsonism and age significantly predicted PA (F(5,209) = 16.6, P < .001, R2Adjusted = 0.27) and SB (F(4,210) = 13.4, P < .001, R2Adjusted = 0.19). These findings suggest that movement disorders, in particular parkinsonism, are associated with reduced PA and increased SB in patients with psychotic disorders. Future studies should take movement disorders into account when examining PA and SB, to establish the clinical value of movement disorders in activating people with psychotic disorders to improve their mental and somatic health.

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Transdiagnostic approaches to psychiatry have significant potential in overcoming the limitations of conventional diagnostic paradigms. However, while frameworks such as the Research Domain Criteria have garnered significant enthusiasm among researchers and clinicians from a theoretical angle, examples of how such an approach might translate in practice to understand the biological mechanisms underlying complex patterns of behaviors in realistic and heterogeneous populations have been sparse. In a richly phenotyped clinical sample (n = 186) specifically designed to capture the complex nature of heterogeneity and comorbidity within- and between stress- and neurodevelopmental disorders, we use exploratory factor analysis on a wide range of clinical questionnaires to identify four stable functional domains that transcend diagnosis and relate to negative valence, cognition, social functioning and inhibition/arousal before replicating them in an independent dataset (n = 188). We then use connectopic mapping to map inter-individual variation in fine-grained topographical organization of functional connectivity in the striatum—a central hub in motor, cognitive, affective and reward-related brain circuits—and use multivariate machine learning (canonical correlation analysis) to show that these individualized topographic representations predict transdiagnostic functional domains out of sample (r = 0.20, p = 0.026). We propose that investigating psychiatric symptoms across disorders is a promising path to linking them to underlying biology, and can help bridge the gap between neuroscience and clinical psychiatry.

Objective: To uncover transdiagnostic domains of functioning across stress- and neurodevelopmental disorders, and to map these on to the topographic functional organization of cortico-striatal circuitry. Methods: In a clinical sample (n=186) of subjects with high rates of comorbidity of major depressive disorder, anxiety disorder, attention-deficit/hyperactivity disorder and/or autism spectrum disorder, we use exploratory factor analysis on a wide range of clinical questionnaires to identify consistent functional domains of symptomatology across disorders, then replicate these functional domains in an independent dataset (n=188). Then, we use canonical correlation analysis link these functional domains to the topographic organization of the striatum as represented by connectopic maps. Results: We reveal four functional domains that transcend current diagnostic categories relating to negative valence, cognition, social functioning and inhibition/arousal. These functional domains are replicated in an independent sample and are associated with the fine-grained topographical organization of functional connectivity in the striatum (out of sample r=0.20, p=0.026), a central hub in motor, cognitive, affective and reward-related brain circuits. Conclusions and relevance: Functional domains across stress- and neurodevelopmental disorders are associated with the functional organization of the striatum. We propose that investigating psychiatric symptoms across disorders is a promising path to linking them to underlying biology, and can help bridge the gap between neuroscience and clinical psychiatry.

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