The spectrum of structural brain changes in schizophrenia: age of onset as a predictor of cognitive and clinical impairments and their cerebral correlates

Abstract

SYNOPSIS A range of cerebral structures was assessed in a series of 172 CT scans of groups of psychiatric patients (including 101 in-patients with chronic schizophrenia) and related to assessments of clinical state and psychological function. Ventricular indices were increased in patients with schizophrenia by comparison with patients with other psychiatric disorders: brain area, which is modestly positively correlated with ventricular indices, was significantly (P < 001) reduced in patients with schizophrenia. Among in-patients with chronic schizophrenia, measures of increased ventricular size were significantly associated with impaired social behaviour and with movement disorder. Memory for famous names in the distant past (a test of remote memory) was the only psychological test which showed significant associations with indices of ventricular size; this suggests that ventricular enlargement and its psychological sequelae occur relatively early in the disease process. Dichotomization of the sample of schizophrenic patients around the mean age of onset revealed that a range of clinical and psychological functions are significantly more abnormal in those with an early age of onset than in those in whom the onset was later. Early onset cases also perform less well academically and occupationally before illness onset. Within the early onset group some significant correlations between cognitive function and brain area were seen.The findings suggest that: (i) some at least of the structural changes in schizophrenia arise at a time when the brain is still developing; and (ii) age of onset is an important determinant of social and intellectual impairment and is relevant to the relationship between brain structure and cognitive deficits.

Dopa decarboxylase genotypes may influence age at onset of schizophrenia

“…19,20 Häfner et al 1989 21 found that, specifically for men, symptom severity decreased with later onset. In males: (a) vs (c) testing non-parametrically using Mann-Whitney Rank-sum Test (P = 0.019) and testing parametrically using Students t-test (P = 0.022, ⌬ mean age = 4.7 years, 95% CI: 0.7-8.8 years); and (c) vs (a + b) (corresponding to genotypes containing the 1-bp deletion vs those that do not), Mann-Whitney Rank-sum Test (P = 0.034), Students t-test (P = 0.043).…”

A continuum of psychosis, one human gene, and not much else — the case for homogeneity

“…(ii) Cortical mass (Zipursky et al, 1992;Ron et al, 1992) or brain size (Brown et al, 1986;Johnstone et al, 1989;Pakkenberg, 1987;Pearlson et al, 1989) is decreased.…”

Brain Changes and Negative Symptoms in Schizophrenia

“…When other factors are taken into account, those with an onset of psychosis younger than the mean are more likely to have negative symptoms and evidence of cognitive impairment [7], They are also more likely to show temporal disori entation, impairments on the Boston naming test and in the Peabody test of premorbid intellectual function. These patients are ap parently on a trajectory of dysfunction that links premorbid deficits with poor outcome.…”

“…Ovchinni kov, Snezhnevsky, Carpenter and Wing -see 6] had adopted between positive and negative symptoms could be discerned. Positive symp toms it seemed were more likely, and negative symptoms (at least when restrictively defined) less likely to respond to neuroleptic medica tion [7], Negative symptoms were more likely to be accompanied by cognitive impairments. If one accepted that there were two compo nents to the disease process a simple separa tion of the major features of the disease was possible: These syndromes were not indepen- …”