A transdiagnostic neuroanatomical signature of psychiatric illness

Abstract

Despite an increasing focus on transdiagnostic approaches to mental health, it remains unclear whether different diagnostic categories share a common neuronatomical basis. The current investigation sought to investigate whether a transdiagnostic set of structural alterations characterized schizophrenia, depression, post-traumatic stress disorder, and obsessive-compulsive disorder, and determine whether any such alterations reflected markers of psychiatric illness or pre-existing familial vulnerability. A total of 404 patients with a psychiatric diagnosis were recruited (psychosis, n = 129; unipolar depression, n = 92; post-traumatic stress disorder, n = 91; obsessive-compulsive disorder, n = 92) alongside n = 201 healthy controls and n = 20 unaffected first-degree relatives. We collected structural magnetic resonance imaging scans from each participant, and tested for transdiagnostic alterations using Voxel-based morphometry. Inferences were made at p < 0.05 after family-wise error correction for multiple comparisons. The four psychiatric groups relative to healthy controls were all characterized by significantly greater gray matter volume in the putamen (right: z-score: 5.97, p-value < 0.001; left: z-score: 4.97, p-value = 0.001); the volume of this region was positively correlated with severity of symptoms across groups (r = 0.313; p < 0.001). Putamen enlargement was also evident in unaffected relatives compared to healthy controls (right: z-score: 8.13, p-value < 0.001; left: z-score: 9.38, p-value < 0.001). Taken collectively, these findings indicate that increased putamen volume may reflect a transdiagnostic marker of familial vulnerability to psychopathology. This is consistent with emerging conceptualizations of psychiatric illness, in which each disorder is understood as a combination of diagnosis-specific features and a transdiagnostic factor reflecting general psychopathology.

Fig. 1

Transdiagnostic gray matter increases in patients relative to healthy controls. Left: mean gray matter volume in the five groups; the values on the y-axis refer to cubic millimeters per voxel with error bars representing SD. Right: regions of the left and right putamen where transdiagnostic increases were detected. FEP first-episode psychosis, OCD obsessive-compulsive disorder, PTSD post-traumatic stress disorder, MDD major depressive disorder, HC healthy controls, GMV gray matter volume measured as mm³ of gray matter per voxel

Fig. 2

Partial correlation between gray matter volume in the right (a) and left (b) putamen and the disease severity, controlling for age and gender. To ensure disease severity scores were comparable across different disorders, these scores were normalized accordingly within each diagnostic group with the following formula: normalized individual value = (individual value − minimum score)/(maximum score − minimum score). Following the application of this formula, the disease severity score of each patient ranged between 0 and 1. GMV gray matter volume measured as mm³ of gray matter per voxel

Fig. 3

Transdiagnostic gray matter increases in unaffected relatives relative to healthy controls. Left: mean gray matter volume in the two groups; the values on the y-axis refer to cubic millimeters per voxel with error bars representing SD. Right: regions of the left and right putamen where transdiagnostic increases were detected. GMV gray matter volume measured as mm³ of gray matter per voxel