Hippocampus and amygdala volumes in schizophrenia and other psychoses in the Northern Finland 1966 birth cohort

Abstract

Structural brain differences have been reported in many studies with schizophrenia, but few have involved a general population birth cohort. We investigated differences in volume, shape and laterality of hippocampus and amygdala in patients with schizophrenia, all psychoses and comparison subjects within a large general birth cohort sample, and explored effects of family history of psychosis, perinatal risk and age-at-onset of illness. All subjects with psychosis from the Northern Finland 1966 birth cohort were invited to a survey including MRI scan of the brain, conducted in 1999–2001. Comparison subjects not known to have psychosis were randomly selected from the same cohort. Volumes of hippocampus and amygdala were measured in 56 subjects with DSM-III-R schizophrenia, 26 patients with other psychoses and 104 comparison subjects. Small hippocampal volume reductions in schizophrenia (2%) and all psychoses (3%) were not significant when adjusted for total brain volume. The shape of hippocampus in schizophrenia did not differ significantly from comparison subjects. Right hippocampus and amygdala were significantly larger than the left in all groups. Mean amygdala volume in schizophrenia or all psychoses did not differ from comparison subjects. Patients with family history of psychosis had larger hippocampus than patients without. Neither perinatal risk nor age-at-onset of illness had any effect on hippocampal or amygdala volumes. Small hippocampal volume reduction in schizophrenia and all psychoses was not disproportionate to reduced whole brain volume in this population-based sample. Perinatal events that have been suggested as of etiological importance in structural pathology of psychosis had no effect.

Introduction

Reviews of structural brain differences in schizophrenia have reported volume reductions of hippocampus and amygdala or the amygdala–hippocampal complex (Nelson et al., 1998, Shenton et al., 2001, Wright et al., 2000). Shenton et al. (2001) found that 74% of studies evaluating medial temporal lobe structures reported positive and 26% reported negative findings. Nelson et al. (1998) found bilateral hippocampal volume reduction of 4% in their meta-analysis. Most of the imaging studies have addressed solely schizophrenia with few including subjects with schizophreniform, schizoaffective or bipolar disorders (Brambilla et al., 2002, Lieberman et al., 2001).

Hippocampal shape has been proposed to be more sensitive to pathological change in schizophrenia than volume difference (Csernansky et al., 1998, Csernansky et al., 2002). Some studies have reported selectively reduced anterior (Pegues et al., 2003) or posterior hippocampal volumes (Narr et al., 2001). It has also been proposed that disturbances in the normal right–left asymmetry may be characteristic in schizophrenia (Fukuzako et al., 1997).

In terms of the cause of these effects in hippocampus and amygdala, it has been suggested that genetic or perinatal factors or long duration of illness may be important etiologically (Cannon et al., 2002b, Lawrie et al., 1999, Stefanis et al., 1999, Velakoulis et al., 2002). There is some evidence of genetic mediation of structural brain abnormalities in schizophrenia (Lawrie et al., 1999). Complications of pregnancy or delivery have been found to be associated with schizophrenia (Cannon et al., 2002a, Jones et al., 1998), and some studies suggest structural brain abnormalities in schizophrenia patients with history of fetal hypoxia (Cannon et al., 2002b). Increased illness duration has been suggested to be associated with smaller right medial temporal volume (Velakoulis et al., 2002).

Most imaging studies concerning schizophrenia or other psychoses have drawn non-random samples from the population of patients and from the general population, which can constrain generalizability of their findings (Jones et al., 1994). Only a few extant imaging studies, such as that of Cannon et al. (2002b), have used epidemiologically principled population-based strategies.

We studied hippocampal and amygdala volumes, and hippocampal shape and right/left asymmetry, in a general population birth cohort, comparing subjects with schizophrenia or any psychosis with non-psychotic comparison subjects sampled from the same cohort. We wanted to test the hypothesis that structural change in these regions was most salient in psychotic patients with a family history of psychosis, a history of perinatal risk or early age-at-onset of illness. Furthermore, we wished to investigate whether any such changes were limited to patients with schizophrenia or were also evident in the broader class of patients with psychosis.