We investigated the relationship between basal ganglia volume and treatment response to the atypical antipsychotic medication risperidone in unmedicated patients with schizophrenia. and age but not gender time off antipsychotic medication or exposure to previous antipsychotic medication. The caudate GW788388 volume was the basal ganglia region that GW788388 demonstrated the strongest correlation with treatment response and was significantly negatively correlated with patient age. Caudate volume was not significantly correlated with any other measure. We demonstrated a novel finding that the caudate volume explains a significant amount of the variance in treatment response over the course of six-weeks of risperidone pharmacotherapy even GW788388 when controlling for baseline symptom severity and duration of illness. ask patients to discontinue antipsychotic drugs to enroll in our study. Diagnoses were established using participants’ medical records and the Diagnostic Interview for Genetic Studies (DIGS) (Nurnberger et al. 1994 The diagnosis was made as a consensus reached by a board-certified psychiatrist and a trained Master’s level program manager. The program manager also administered the Brief Psychiatric Rating Scale (BPRS) (Overall and Gorham 1962 which was used to characterize symptom severity and response to antipsychotic treatment. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) (Randolph 2010 was used to characterize general cognitive function. Table 1 Demographic and clinical data of patients with schizophrenia. The exclusion criteria were other major medical conditions substance abuse within the past 6 months GW788388 previous serious head injury neurological disorders loss of consciousness and pregnancy. The University of Alabama at Birmingham Institutional Review Board approved the study and all participants gave written informed consent. See Fig. 1 for a flowchart of the subject-exclusion process. Six subjects were excluded because they did not complete the 6-week treatment period and one subject was excluded because the magnetic resonance imaging (MRI) data contained too much noise because of motion and could not be analyzed with the Freesurfer pipeline. This left a final group of 23 subjects with schizophrenia. Fig. 1 Flowchart showing criteria used to exclude subjects from study and reach final sample size. 2.2 Treatment response Treatment response over the course of the 6-week period was measured with the BRPS total score. The total scale which was administered by a trained rater comprises 20 items scored on a 1-7 Likert scale. Treatment response was defined as the absolute change in BPRS total score from baseline (off medication) to week 6 of treatment. To correct for the patients’ differences in initial symptom severity baseline BPRS total scores were entered in the first step of the hierarchical regression analysis. 2.3 Image analysis Volumetric segmentation of structural MRI data was performed using the Freesurfer image analysis suite which is documented and freely available online (version 4.5.0 http://surfer.nmr.mgh.harvard.edu). The main Freesurfer pipeline involves removal of non-brain tissue registration to Talairach space segmentation of subcortical white and gray matter intensity normalization identification of gray matter and white matter boundaries topology correction and registration to a spherical atlas. Each of the resulting cortical maps was visually inspected to detect errors. Errors in the segmentation protocol were fixed using an automated algorithm gcut which adjusted the threshold boundary between brain and non-brain tissue such as dura mater and scalp. One subject who still had GW788388 substantial mistakes after this step was excluded. The Freesurfer pipeline generated a total of 50 regional subcortical volumes. Only the three volumes of the basal ganglia (caudate putamen and pallidum) were analyzed for MMP15 this study. Subcortical volumetric measures from the left and right hemisphere were averaged to reduce the number of comparisons. In total three MRI quantities (caudate putamen and pallidum) through the Freesurfer output had been used for additional evaluation. All subcortical quantities had been normalized by each subject’s intracranial quantity (Westman et al. 2012 which is dependant on an affine transform in Freesurfer. This segmentation strategy has been utilized previously for biomarker finding (Thambisetty et al. 2010 2.4 Demographic variables analyzed To check our second hypothesis that the quantity of regions inside the basal ganglia would clarify variance in treatment response even after controlling.