Development and heritability of subcortical brain volumes at ages 9 and 12.

Subcortical brain structures are involved in a variety of cognitive and emotional functions and follow different trajectories of increase and decrease in volume from childhood to adulthood. The heritability of development of subcortical brain volumes during adolescence has not been studied comprehensively. In a longitudinal twin study, we estimated to what extent subcortical brain volumes are influenced by genetic factors at ages 9 and 12. In addition, we assessed whether new genes are expressed at age 12 and whether there is evidence for genotype by sex interaction. Brain scans were acquired for 112 and 89 twin pairs at 9 and 12 years of age. In both boys and girls, there was an increase in volumes of the thalamus, hippocampus, amygdala and pallidum, and a decrease in volumes of the caudate and nucleus accumbens. The putamen showed a decrease in boys bilaterally and an increase in girls in the left hemisphere. Heritability was high (>50%) for all structures - except for the left nucleus accumbens - with heritabilities ranging from 0.50 to 0.91 at age 9, and from 0.59 to 0.88 at age 12. There were no significant new genetic effects coming into play at age 12, and there was no evidence for genotype by sex interactions. These findings suggest that despite their sensitivity to environmental effects, the heritability of subcortical brain structures is high from childhood on, resembling estimates found in adult samples.

Brain morphology in antipsychotic-naïve schizophrenia: a study of multiple brain structures.

BACKGROUND: Although brain volume changes are found in schizophrenia, only a limited number of structural magnetic resonance imaging studies have exclusively examined antipsychotic-naïve patients. AIMS: To comprehensively investigate multiple brain structures in a single sample of patients who were antipsychotic-naïve. METHOD: Twenty antipsychotic-naïve patients with first-episode schizophrenia and 20 healthy comparison subjects were included. Intracranial, total brain, frontal lobe, grey and white matter, cerebellar, hippocampal, parahippocampal, thalamic, caudate nucleus and lateral and third ventricular volumes were measured. Repeated-measures analyses of (co)variance were conducted with intracranial volume as covariate. RESULTS: Third ventricle volume enlargement was found in patients compared with the healthy subjects. No differences were found in other brain regions. CONCLUSIONS: These findings suggest that some brain abnormalities are present in the early stages of schizophrenia. Moreover, it suggests that brain abnormalities reported in patients with chronic schizophrenia develop in a later stage of the disease and/or are medication induced.

Structural brain abnormalities in chronic schizophrenia at the extremes of the outcome spectrum.

OBJECTIVE: This study investigated the relationship between outcome and structural brain abnormalities in schizophrenia. METHOD: Intracranial volume and volumes of the cerebrum, gray and white matter, lateral and third ventricles, frontal lobes, thalamus, and cerebellum were measured in 20 patients with a poor outcome, 25 with a favorable outcome, and 23 healthy comparison subjects with magnetic resonance imaging. RESULTS: Thalamic volume was significantly smaller both in poor-outcome patients and good-outcome patients. In contrast, only poor-outcome patients displayed significantly smaller cerebral gray matter, particularly prefrontal, and enlargement of the lateral and third ventricles. No significant differences were found for intracranial, cerebellar, or cortical CSF volumes. CONCLUSIONS: Smaller thalamic volumes in schizophrenia may reflect a greater susceptibility for the disorder and seem unrelated to outcome. In contrast, gray matter volume loss of the cerebrum, particularly in the frontal lobes, and lateral and third ventricular enlargement appear related to outcome in schizophrenia.

Frontal lobe damage and thalamic volume changes.

The aim of this study was to investigate whether frontal lobe damage affects thalamic volume in humans. Ipsilateral and contralateral thalamic areas were measured in 0.5T T1-weighted sagittal magnetic resonance images in 12 patients, first at the time of their surgery for relief of a unilateral frontal lobe brain tumor and at follow-up approximately 2 years later. A 5% decrease in ipsilateral and 4.5% increase in contralateral thalamic area was found over time (F(1,11) = 6.15, p < 0.05). We conclude that unilateral frontal lobe damage results in a decrease in the ipsilateral thalamus and an increase in the contralateral thalamus in humans in vivo. The findings may have implications for the interpretation of the reported changes in thalamic volume in neuropsychiatric diseases.

Partial volume decrease of the thalamus in relatives of patients with schizophrenia.

OBJECTIVE: The authors' goal was to compare the thalamic, total brain, and intracranial volumes of patients with schizophrenia, their healthy siblings, and normal comparison subjects. METHOD: Magnetic resonance imaging (MRI) brain scans were obtained for 32 same-sex siblings who were discordant for schizophrenia and 32 matched normal comparison subjects. RESULTS: Mean total thalamic volume, corrected for total brain volume, was significantly different among affected siblings, unaffected siblings, and comparison subjects. Thalamic volume was smallest in the patients; thalamic volume in their siblings was smaller than that of comparison subjects but larger than that of the patients with schizophrenia. CONCLUSIONS: These results suggest that healthy siblings of patients with schizophrenia partially share the thalamic abnormalities of their affected relatives.