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Brain structure, cognition, and brain age in schizophrenia, bipolar disorder, and healthy controls.

ABSTRACT: Schizophrenia and bipolar disorder (BD) may be disorders of accelerated aging. Direct comparison of healthy aging populations with schizophrenia and BD patients across the adult lifespan may help inform this theory. In total, 225 individuals (91 healthy controls, 81 schizophrenia, 53 euthymic BD) underwent 3T T1-weighted magnetic resonance imaging, diffusion tensor imaging, and cognitive testing. We analyzed associations among age, diagnosis, and cognition with cortical thickness and fractional anisotropy (FA) using general linear models. We then assessed "brain age" using a random forest algorithm, which was also assessed in an independent sample (n = 147). Participants with schizophrenia had lower cortical thickness and FA compared with the other two groups, most prominently in fronto-temporal circuitry. These brain changes were more evident in younger participants than in older ones, yet were associated with cognitive performance independent of diagnosis. Predicted age was 8 years greater than chronological age in individuals with schizophrenia in the first sample and 6 years greater in the second sample. Predicted and chronological age were not different in BD. Differences in brain circuitry are present from illness onset most prominently in schizophrenia and to a lesser extent in BD. These results support a non-progressive "early hit" hypothesis/etiology of illness in the major psychoses. Brain age differences support the hypothesized early aging mechanism in schizophrenia but not in BD.

SUBMITTER: Shahab S

PROVIDER: S-EPMC6461913 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Neuropsychological impairment is heterogeneous in psychosis. The association of intracranial volume (ICV) and total brain volume (TBV) with cognition suggests brain structure abnormalities in psychosis will covary with the severity of cognitive impairment. We tested the following hypotheses: (1) brain structure abnormalities will be more extensive in neuropsychologically impaired psychosis patients; (2) psychosis patients with premorbid cognitive limitations will show evidence of hypoplasia (ie, smaller ICV); and (3) psychosis patients with evidence of cognitive decline will demonstrate atrophy (ie, smaller TBV, but normal ICV).One hundred thirty-one individuals with psychosis and 97 healthy subjects underwent structural magnetic resonance imaging and neuropsychological testing. Patients were divided into neuropsychologically normal and impaired groups. Impaired patients were further subdivided into deteriorated and compromised groups if estimated premorbid intellect was average or below average, respectively. ICV and TBV were compared across groups. Localized brain volumes were qualitatively examined using voxel-based morphometry.Compared to healthy subjects, neuropsychologically impaired patients exhibited smaller TBV, reduced grey matter volume in frontal, temporal, and subcortical brain regions, and widespread white matter volume loss. Neuropsychologically compromised patients had smaller ICV relative to healthy subjects, and neuropsychologically normal and deteriorated patient groups, but relatively normal TBV. Deteriorated patients exhibited smaller TBV compared to healthy subjects, but relatively normal ICV. Unexpectedly, TBV, adjusted for ICV, was reduced in neuropsychologically normal patients.Patients with long-standing cognitive limitations exhibit evidence of early cerebral hypoplasia, whereas neuropsychologically normal and deteriorated patients show evidence of brain tissue loss consistent with progression or later cerebral dysmaturation.

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Brain structure, cognition, and brain age in schizophrenia, bipolar disorder, and healthy controls.

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