Sex differences in the absence of massa intermedia in patients with schizophrenia versus healthy controls.

OBJECTIVE: To evaluate sexual dimorphism and incidence of absent massa intermedia (MI), a midline thalamic structure, in patients with schizophrenia and healthy controls. METHODS: Thin slice magnetic resonance images of the brain were obtained. The presence of MI was determined by viewing sagittal, coronal, and axial planes. RESULTS: In healthy controls, females had a significantly lower incidence of absent MI (13.56%) compared with males (32.08%). In patients with schizophrenia, there was a sex by diagnosis interaction. Female patients had significantly higher incidence of absent MI (32.76%) compared with their healthy controls (13.56%), whereas the male patients showed no difference in incidence of absent MI compared with their controls. CONCLUSION: The MI, a sexually dimorphic midline structure, is more commonly absent in female patients with schizophrenia. These results support the growing literature reporting structural aberration of the thalamus, as well as other midline structures in the brains of patients with schizophrenia.

An MRI study of midbrain morphology in patients with schizophrenia: relationship to psychosis, neuroleptics, and cerebellar neural circuitry.

BACKGROUND: The midbrain contains the perikarya of all the dopamine neurons in the human brain. Although other neurochemicals may well be involved, dopamine dysregulation is central in the pathophysiology of psychosis. Despite this, few imaging studies have evaluated the morphology of the midbrain. METHODS: Using high-resolution magnetic resonance imaging, morphology of three posterior fossa and brain stem structures were measured: midbrain, pons, and medulla. The patient sample consisted of 50 men with schizophrenia, matched by gender and age to 50 healthy control subjects. RESULTS: Patients had significantly smaller midbrain measures compared with control subjects. There were no differences between groups in measures of pons or medulla. Furthermore, midbrain size was significantly and inversely correlated with positive symptoms and cumulative neuroleptic exposure, but not with negative or disorganized symptoms. After controlling for the effect of cumulative neuroleptic exposure, the relationship between midbrain morphology and positive symptoms remained significant. CONCLUSIONS: Midbrain morphology of patients with schizophrenia is abnormal, being smaller in patients compared with control subjects. Although this appears to be specifically related to psychotic symptoms, there is also a robust medication effect, with greater exposure to neuroleptics being associated with greater morphologic abnormality. We discuss the role of dopaminergic dysregulation and possible neural circuit involvement.

An MRI study of cerebellar vermis morphology in patients with schizophrenia: evidence in support of the cognitive dysmetria concept.

BACKGROUND: Cumulative evidence suggests the cerebellum is involved in cognition and may be important in the pathoetiology of schizophrenia. Functional imaging studies have identified a possible neural circuit that includes the cerebellum and may be abnormal in patients with schizophrenia, manifesting as a fundamental cognitive deficit conceptualized as cognitive dysmetria. To explore the role of the cerebellum in cognitive dysfunction and schizophrenia, this study was designed to evaluate the morphology of the cerebellar vermis, its relationship to other cortical areas, and to cognitive function in patients with schizophrenia. METHODS: Male patients with schizophrenia (n = 65) were matched by age and gender to 65 healthy male controls. Volume measures of the 4 cerebral lobes and total cerebellum were obtained using automated methods. The area of the cerebellar vermis (divided into three lobes) was traced on a midsaggital MRI slice. RESULTS: Patients had smaller frontal and temporal lobes. There were no group differences in total cerebellar volume. Patients had a smaller vermis area, accounted for by a smaller anterior lobe. The anterior vermis area was positively correlated with total cerebellar volume, temporal lobe volume, and FSIQ in patients, but not controls. CONCLUSIONS: These findings support the theory that regions of the cerebellum may be involved in a neural circuit that is structurally and functionally abnormal in patients with schizophrenia, leading to cognitive dysmetria.

Frequency and severity of enlarged cavum septi pellucidi in childhood-onset schizophrenia.

OBJECTIVE: Patients with schizophrenia have been reported to have a higher frequency of enlarged cavum septi pellucidi (CSP) in comparison with normal subjects. Neurodevelopmental models of schizophrenia suggest that the more severe the brain dysgenesis, the earlier the onset of psychotic symptoms. Study of patients with childhood-onset schizophrenia allows the opportunity to test this hypothesis. METHOD: Two groups of subjects were evaluated: healthy volunteers (N=95, mean age=11.7 years) and patients with childhood-onset schizophrenia (N=24, mean age=14.6 years). Magnetic resonance images of 1-mm resampled contiguous brain slices were rated blind to diagnosis. The size of the CSP was recorded as the number of consecutive slices in which the CSP was present. Abnormal enlargement was defined as a CSP greater than 6 mm in length. RESULTS: The frequency of an enlarged CSP was significantly higher in the patient group: 12.5% (three of 24 subjects) versus 1.1% (one of 95 subjects). Also, two of the three patients with an enlarged CSP had complete nonfusion of the septal leaflets, a more severe anomaly than was found in the one comparison subject with an enlarged CSP and typically more severe than anomalies seen in groups with adult-onset schizophrenia. CONCLUSIONS: These findings suggest that patients with extremely early-onset (childhood) forms of schizophrenia may have more severe developmental brain anomalies than those with adult onset.

Gray matter heterotopias in schizophrenia.

Gray matter heterotopias (GMHs) are a type of neuronal migration anomaly in which collections of normal neurons are abnormally located secondary to an arrest of radial migration. They are often manifested clinically by seizures and cognitive, motor, and language deficits. Through magnetic resonance imaging, we have observed two cases in patients presenting with symptoms of schizophrenia, but no neurological abnormalities, and otherwise normal scans. While the incidence of GMH among normal individuals is unknown, it is possible that this particular anomaly may occur in schizophrenic patients at a higher rate than in the normal population. Furthermore, neuronal migration abnormalities may be involved in the pathogenesis of the disorder among a small subset of patients with schizophrenia.