Transdiagnostic and Illness-specific Functional Dysconnectivity Across Schizophrenia, Bipolar Disorder and Major Depression

Abstract Background Mental disorders are typically defined as distinct diagnostic entities, but similar patterns of clinical and cognitive impairments are frequently found across diagnostic groups. We investigated whether these transdiagnostic deficits result from common neural substrates across disorders, or various illness-specific mechanisms, or a combination of both. Methods Functional MRI data were collected from clinically stable patients with major depressive disorder (MDD; n=53), bipolar disorder (BIP; n=78), or schizophrenia (SCZ; n=100), and matched healthy controls (n=109) using a single scanner. Group comparisons were conducted to identify transdiagnostic and illness-specific features, possible confounding effects of medication were considered. A multivariate approach with cross-validation was used to associate dysconnectivity features with shared cognitive deficits. Results Transdiagnostic dysconnectivities were identified within somatomotor (Cohen’s d:0.50-0.58) and salience (d:0.52-0.58) networks and between subcortical-limbic (d:0.55-0.69) and subcortical-dorsal attention (d:0.56-0.61) networks. The executive control network was found to be illness-specifically disconnected from prefrontal-limbic-pallidal circuit in MDD (d:0.57-0.58), prefronto-striato-parietal circuit in BIP (d: 0.48-0.53), and default-mode network in SCZ (d:0.47-0.56). Working memory deficits were associated with linear combination of 11 transdiagnostic and 5 illness-specific dysconnectivity (r=0.322, p=9.7e-4, n=340). The associations of the identified dysconnectivities with medication dosage were nonsignificant. Conclusions Disconnectivity in the somatomotor network was a common transdiagnostic profile, while there were illness-specific patterns in different parts of the prefrontal cortex for different disorders. These findings suggest that prominent psychiatric disorders share common impairments, possibly linked to perception and motor output, as well as unique dysconnectivity profiles that hypothetically mediate the more distinctive features of the disorder-specific psychopathology.