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Background: The orbitofrontal cortex (OFC) is implicated in depression. The hypothesis investigated was whether the OFC sensitivity to reward and nonreward is related to the severity of depressive symptoms., Methods: Activations in the monetary incentive delay task were measured in the IMAGEN cohort at ages 14 years (n = 1877) and 19 years (n = 1140) with a longitudinal design. Clinically relevant subgroups were compared at ages 19 (high-severity group: n = 116; low-severity group: n = 206) and 14., Results: The medial OFC exhibited graded activation increases to reward, and the lateral OFC had graded activation increases to nonreward. In this general population, the medial and lateral OFC activations were associated with concurrent depressive symptoms at both ages 14 and 19 years. In a stratified high-severity depressive symptom group versus control group comparison, the lateral OFC showed greater sensitivity for the magnitudes of activations related to nonreward in the high-severity group at age 19 (p = .027), and the medial OFC showed decreased sensitivity to the reward magnitudes in the high-severity group at both ages 14 (p = .002) and 19 (p = .002). In a longitudinal design, there was greater sensitivity to nonreward of the lateral OFC at age 14 for those who exhibited high depressive symptom severity later at age 19 (p = .003)., Conclusions: Activations in the lateral OFC relate to sensitivity to not winning, were associated with high depressive symptom scores, and at age 14 predicted the depressive symptoms at ages 16 and 19. Activations in the medial OFC were related to sensitivity to winning, and reduced reward sensitivity was associated with concurrent high depressive symptom scores., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

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 magnetic resonance imaging data were collected from clinically stable patients with major depressive disorder (n = 53), bipolar disorder (n = 78), or schizophrenia (n = 100) and matched healthy control subjects (n = 109) using a single scanner. Group comparisons were conducted to identify transdiagnostic and illness-specific features, and 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 (Cohen's d = 0.52-0.58) networks and between subcortical-limbic (Cohen's d = 0.55-0.69) and subcortical-dorsal attention (Cohen's d = 0.56-0.61) networks. The executive control network was found to be illness-specifically disconnected from the prefrontal-limbic-pallidal circuit in major depressive disorder (Cohen's d = 0.57-0.58), prefronto-striato-parietal circuit in bipolar disorder (Cohen's d = 0.48-0.53), and default mode network in schizophrenia (Cohen's d = 0.47-0.56). Working memory deficits were associated with a linear combination of 11 transdiagnostic and 5 illness-specific dysconnectivities (r = .322, p= 9.7 × 10 -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., (Copyright © 2020 Society of Biological Psychiatry. All rights reserved.)