Structural cerebellar abnormalities in antipsychotic-naive schizophrenia: Evidence for cognitive dysmetria

Abstract

Byline: Rashmi. Arasappa, Naren. Rao, G. Venkatasubramanian, P. Jayakumar, B. Gangadhar Background: Cognitive has been proposed as a unifying model to explain the pathogenesis of schizophrenia. Most of the previous studies examining structural cerebellar abnormalities in schizophrenia were confounded by various factors like antipsychotic treatment, comorbid alcohol dependence, and low-resolution imaging procedure with manual morphometric analysis. In this study, we describe the first report of structural cerebellar abnormalities in antipsychotic-naive schizophrenia patients using high-resolution imaging (3.0 Tesla MRI). Aim: This study was aimed at examining the structural cerebellar abnormalities in antipsychotic-naive schizophrenia patients and its correlation with psychopathology. Methods: Brain imaging of 20 antipsychotic-naive schizophrenia patients and their age, gender, and years of education matched 20 healthy controls was done using 3.0 Tesla MRI machine. Image analysis was done using the optimized Voxel Based Morphometry (VBM), an automated unbiased technique. Results: Antipsychotic-naive schizophrenia patients had significant cerebellar gray matter volume deficits compared to healthy controls. The Scale for the Assessment of Negative Symptoms (SANS) score in patients had negative correlation with cerebellar gray matter volume. Conclusion: Structural cerebellar abnormalities and their negative correlation with negative syndrome in antipsychotic-naive schizophrenia patients support the cognitive dysmetria. Introduction Cerebellum, well known for its motor coordination, has been suggested in recent times to have an important role in cognition.[sup] [1] The motor coordination is brought about by the feedback between sensory motor cortex and the cerebellum, mediated through thalamus. Similar circuit (where the feedback is between cerebellum and prefrontal cortex, mediated through thalamus - the corticocerebellar thalamic cortical circuit (CCTCC)) has been implicated in the function of monitoring and coordinating the smooth execution of mental activity, that is, synchrony. Disruption in this circuit has been proposed as to cause cognitive dysmetria leading on to disordered cognition and symptoms of schizophrenia.[sup] [2] Some of the earlier studies in patients with schizophrenia, using structural and functional imaging methods, have shown abnormalities in the cerebellum. CT scan study[sup] [3] showed degeneration of cerebellar vermis and enlargement of third ventricle and on magnetic resonance imaging (MRI) small cerebellar volume, smaller vermian and its subregions volume, and reversed cerebellar asymmetry in males were seen.[sup] [4],[5],[6] In addition, a proton magnetic resonance spectroscopy (MRS) study[sup] [7] showed lower N-acetylaspartate in cerebellar cortex and vermis in schizophrenia patients. Similar abnormalities have been noted in functional MRI (fMRI) study.[sup] [8] On positron emission tomography (PET) scan, decreased blood flow was seen in right anterior cingulate, right thalamus, and bilateral cerebellum during novel memory task.[sup] [9] Another study[sup] [10] showed absence of normal activation of prefrontal thalamic circuit in schizophrenia patients. However, there are few studies with conflicting results - In one study, there was no difference between patients and controls in cerebellar vermis and height of fourth ventricle.[sup] [11] In another study, no abnormality in posterior fossa structures size was found in patients with schizophrenia.[sup] [12] These discrepancies in findings could potentially be due to some of the methodological factors like selection of patients and image acquisition. *One of the important confounding factors is effect of drugs on brain volume, and only a few studies have been conducted on drug-naive patients.[sup] [13],[5] *Effect of comorbid conditions like alcohol dependence syndrome (ADS) can confound the results due to the effect of alcohol on cerebellum. …