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The functional connectomics of affective and psychotic pathology
Accumulating evidence suggests that psychiatric illnesses are marked by disruptions within large-scale functional brain networks. However, these observations have failed to yield clinically useful biomarkers of an individuals' current symptoms or illness risk. In healthy populations, shifts in behavior are reflected in variability across the collective set of functional brain connections (functional connectome). These data suggest that the transdiagnostic symptom profiles observed in psychiatric patients may map onto detectable patterns of network function. To examine the manner through which neurobiological variation might underlie clinical presentation, we obtained fMRI data from over 1,000 individuals, including 210 diagnosed with a primary psychotic disorder or affective psychosis, 192 presenting with an affective disorder without psychosis, and 608 healthy comparison participants. Here, we find evidence for disease connectomic “fingerprints” that are commonly disrupted across distinct forms of pathology, scaling as a function of illness severity. The presence of affective and psychotic illnesses was associated with graded disruptions in frontoparietal network connectivity. Conversely, other properties of network connectivity, including default network integrity, were preferentially disrupted in patients with psychotic illness, but not patients without psychotic symptoms. This work allows us to establish key biological and clinical features of the functional connectomes of severe mental disease.