Effect of antipsychotics on pituitary gland volume in treatment-naïve first-episode schizophrenia: a pilot study

The objective of this study was to examine the effect of antipsychotics on pituitary volume in schizophrenic subjects. Pituitary volumes were measured in 16 patients with schizophrenia at baseline and 12 months after treatment with an antipsychotic medication using magnetic resonance imaging (MRI). A group of 12 healthy controls was evaluated at baseline and after 12 months. Pituitary volume significantly increased in the schizophrenic subjects after treatment (12% increase). This appeared to be specific to the prolactin-elevating drugs. In controls, pituitary volume did not change significantly (3% decrease). Pituitary volume may be a useful biomarker for treatments that affect neuroendocrine function.     

Evidence of gray matter reduction and dysfunction in chromosome 22q11.2 deletion syndrome

Chromosome 22q11.2 deletion syndrome (22q11DS) is associated with cognitive deficits and morphometric brain abnormalities in childhood and a markedly elevated risk of schizophrenia in adolescence/early adulthood. Determining the relationship between neurocognition and neuroimaging findings would yield crucial information about childhood neurodevelopment and provide a basis for the study of the trajectory that occurs on the pathway to psychosis. We compared morphometric brain findings between non-psychotic children with 22q11DS (n = 22) and healthy controls (n = 16), and examined the association between neurocognitive functioning and morphometric brain findings. Volumetric regional gray matter differences between the 22q11DS and control subjects were measured, and correlations of the regional gray matter volumes and neurocognition were performed. Children with 22q11DS demonstrated reductions in gray matter in several brain regions, chiefly the frontal cortices, the cingulate gyrus and the cerebellum. The volumetric reductions in these salient areas were associated with poor performance in sustained attention, executive function and verbal memory; however, the relation of brain volume with cognitive performance did not differ between the patient and control groups. Thus, children with 22q11DS demonstrate gray matter reductions in multiple brain regions that are thought to be relevant to schizophrenia. The correlation of these volumetric reductions with poor neurocognition indicates that these brain regions may mediate higher neurocognitive functions implicated in schizophrenia.     

Neuroanatomical correlates of neurological soft signs in antipsychotic-naive schizophrenia

Recent imaging studies suggest that the so-called “soft” neurological signs in schizophrenia might have neuroanatomical validity. We examined gray matter volume correlates of neurological soft signs (NSS) in antipsychotic-naive schizophrenia patients using an automated image analysis technique. NSS were assessed using a modified neurological evaluation scale with good inter-rater reliability. Magnetic resonance images of 30 schizophrenia patients and 27 age-, sex-, education- and handedness-matched healthy controls were processed using optimized voxel-based morphometry (VBM). Logistic regression analysis showed that only the Motor Sequencing Signs (MSS) sub-score was a significant predictor of subject's status among the NSS sub-scores. Optimized VBM analysis showed that the MSS sub-score had a significant negative correlation with total and regional gray matter volumes (prefrontal, posterior cingulate, temporal cortices, putamen, and cerebellum) in schizophrenia patients but not in controls. Prefrontal and temporal cortices, putamen and cerebellum had significant volume deficits in patients. Cortical and cerebellar correlates of the sub-score MSS support the concept of “cognitive dysmetria” in schizophrenia.     

Maturation of widely distributed brain function subserves cognitive development

Cognitive and brain maturational changes continue throughout late childhood and adolescence. During this time, increasing cognitive control over behavior enhances the voluntary suppression of reflexive/impulsive response tendencies. Recently, with the advent of functional MRI, it has become possible to characterize changes in brain activity during cognitive development. In order to investigate the cognitive and brain maturation subserving the ability to voluntarily suppress context-inappropriate behavior, we tested 8-30 year olds in an oculomotor response-suppression task. Behavioral results indicated that adult-like ability to inhibit prepotent responses matured gradually through childhood and adolescence. Functional MRI results indicated that brain activation in frontal, parietal, striatal, and thalamic regions increased progressively from childhood to adulthood. Prefrontal cortex was more active in adolescents than in children or adults; adults demonstrated greater activation in the lateral cerebellum than younger subjects. These results suggest that efficient top-down modulation of reflexive acts may not be fully developed until adulthood and provide evidence that maturation of function across widely distributed brain regions lays the groundwork for enhanced voluntary control of behavior during cognitive development.     

Volumetric alterations of the orbitofrontal cortex in autism

Recent evidence has implicated the orbitofrontal cortex (OFC) in the pathophysiology of social deficits in autism. An MRI-based morphometric study of the OFC was conducted involving 11 children with autism (age range 8.1-12.7 years) and 18 healthy, age-matched controls (age range 8.9-12.8 years). Decreased grey matter volume in the right lateral OFC in the patient group was found, and correlations were observed between social deficits and white, but not grey, matter structures of the OFC. These findings support the role of OFC in autism and warrant further investigations of this structure using structural and functional methodologies.     

No difference in the prevalence of cavum septum pellucidum (CSP) between first-episode schizophrenia patients, offspring of schizophrenia patients and healthy controls

The reported prevalence of cavum septum pellucidum (CSP), is extremely variable (from 0.1% to 85%) depending upon the measurement method or imaging resolution. Higher prevalence of CSP has been found in schizophrenia. In this study, we examined the prevalence of CSP in a large number of first-episode schizophrenia patients, young relatives of schizophrenia patients and healthy controls. We manually measured CSP using 1.5 mm T1 MRI scans from ongoing studies at University of Pittsburgh in 89 first-episode patients with schizophrenia (age=23.8+/-7.4, M/F=61/28), 64 genetically at-risk individuals (offspring and siblings of schizophrenia patients, age 15.2+/-3.7, M/F=29/32) and 120 comparison subjects (n=120, age=22.1+/-7.9, M/F62/50). CSP was present in 64% of the first-episode patients (mean length 1.87+/-2.3 mm), 64.6% of the at-risk individuals (1.64+/-1.96 mm) and 64.2% of the normal controls (1.88+/-2.0 mm). There was no difference in the prevalence of CSP exceeding 4 mm. We also did not find any influence of the sex or age in the presence or size of CSP. Our data cast doubt on the significance of CSP as markers of neurodevelopmental pathology in schizophrenia.