Abstract
A number of neuroimaging studies have provided evidence in support of the hypothesis that faulty interactions between spatially disparate brain regions underlie the pathophysiology of schizophrenia, but it remains unclear to what degree antipsychotic medications affect these. We hypothesized that the balance between functional integration and segregation of brain networks is impaired in unmedicated patients with schizophrenia, but that it can be partially restored by antipsychotic medications. We included 32 unmedicated patients with schizophrenia (SZ) and 32 matched healthy controls (HC) in this study. We obtained resting-state scans while unmedicated, and again after 6 weeks of treatment with risperidone to assess functional integration and functional segregation of brain networks using graph theoretical measures. Compared with HC, unmedicated SZ showed reduced global efficiency and increased clustering coefficients. This pattern of aberrant functional network integration and segregation was modulated with antipsychotic medications, but only in those who responded to treatment. Our work lends support to the concept of schizophrenia as a dysconnectivity syndrome, and suggests that faulty brain network topology in schizophrenia is modulated by antipsychotic medication as a function of treatment response.
Highlights
Schizophrenia is a complex mental illness that manifests in different symptom dimensions
We found that the efficiency curves of brain networks were intermediate between the same parameters estimated in lattice and random graphs in healthy controls (HC) and schizophrenia (SZ) at both time points (Figure 1)
Baseline Brief Psychiatric Rating Scale (BPRS) total scores as well as positive and negative symptom subscales did not differ between patients who eventually responded to treatment and those who did not
Summary
Schizophrenia is a complex mental illness that manifests in different symptom dimensions. Options for pharmacological management are currently limited to dopamine D2 receptor blockers, which alleviate positive symptoms, but the success of treatment is variable.[1] This may in part be attributable to our lack of a comprehensive understanding of the pathophysiology underlying the disorder and the mechanisms of action of antipsychotic medications on a systems level. Small-world properties in the overall brain network structure, i.e., highly clustered, yet globally interconnected nodes, have been reported in functional connectivity studies in healthy humans.[7,9,10]
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