The Effects of Antipsychotic Drugs on Brain Metabolism in Healthy Individuals

Change in brain nicotinamide adenine dinucleotide NAD+/NADH metabolite ratio as measured by in vivo 31P magnetic resonance spectroscopy

Change in Phosphocreatine (PCr) metabolite concentration as measured by in vivo 31P magnetic resonance spectroscopy

Change in forward reaction rate constant (kf) of the creatine kinase (CK) as measured by in vivo 31P magnetic resonance spectroscopy magnetization transfer

Change in brain parenchymal pH as measured by in vivo 31P magnetic resonance spectroscopy

Change in the gray matter volumes (cubic millimeters) of the frontal, parietal and temporal lobes as defined by Freesurfer's Desikan-Killiany Brain Atlas. Data was acquired using structural magnetic resonance imaging (MRI) at 3T.

Change in the cortical surface area (millimeters squared) of the frontal, parietal and temporal lobes as defined by Freesurfer's Desikan-Killiany Brain Atlas. Data was acquired using structural magnetic resonance imaging (MRI) at 3T.

Change in resting state functional connectivity to the medial prefrontal cortex and superior parietal lobules following olanzapine administration period. Whole-brain, seed-to-voxel analyses were conducted utilizing anatomically-defined seed regions and age-corrected within-subjects f-tests were run to determine the presence and size (in voxels) of clusters where connectivity changed significantly following olanzapine administration. Results are reported in units of voxels for each cluster meeting a threshold of voxel-level uncorrected p<.001 and cluster-level p-FDR<.05. A result of zero indicates that no clusters were identified within subjects as changed in connectivity relative to the seed regions.

Change in GABA concentration measured by proton magnetic resonance spectroscopy.

Change in fractional anisotropy (FA), a scalar measure of diffusivity, of water in the brain assessed by DTI at 3T. FA values range from 0 (isotropic, meaning diffusion is equally restricted in 3D space) to 1 (anisotrophic, meaning that diffusion is completely restricted to a single direction).

Change in glutamate metabolite concentration measured by proton magnetic resonance spectroscopy.

Change in the MATRICS Cognitive Consensus Battery (MCCB), that includes 10 tasks that measure processing speed (Brief Assessment of Cognition in Schizophrenia - Symbol Coding, Animal Fluency, Trails A), attention (Continuous Performance Test), working memory (WMS-III Spatial Span, Letter-Number Span), verbal learning (Hopkins Verbal Learning Test - Revised), visual learning (Brief Visuospatial Memory Test - Revised), problem solving (Neuropsychological Assessment Battery Mazes) and social cognition (Mayer-Salovey-Caruso Emotional Intelligence Test). Scores from each subtest are normed and their T-scores are summed to yield a MCCB composite score, then the total composite T-score is standardized to normative data among a healthy population. The composite T-score has a mean of 50 and a standard deviation of 10. Higher total composite scores indicate better cognitive outcomes.

Change in Montgomery-Asberg Depression Rating Scale (MADRS) score, a 0-60 point scale rating depressive symptoms. Higher scores indicate more severe clinical symptoms.

Change in Beck Depression Inventory (BDI) score, a self-report questionnaire measuring depressive symptoms on a scale of 0-63. Scores ranging 0-9 generally indicate minimal depressive symptoms, while scores 10-18 indicate mild, 19-29 indicates moderate, and 30-63 indicates severe depressive symptoms, respectively.

Change in Young Mania Rating Scale (YMRS) score, an interview-based, 11-item scale that measures the severity of core features of clinical mania. 7 items are scored on a 0-4 point scale, while the remaining 4 are scored on a 0-8 point scale, for a total possible range of 0-64. Higher scores indicate more severe manic symptoms.

Change in Beck Anxiety Inventory (BAI) score, a self-report measure of anxiety symptoms. Scores range from 0-63, with higher scores indicating more severe anxiety.

Change in The Columbia Suicide Severity Rating Scale score, a self-report scale measuring suicidality. Only the total score, not subscale of suicidal ideation intensity, will be measured. Total scores can range from 0-10, with higher scores indicating increased suicidality.

Change in Pittsburgh Sleep Quality Index score, a measurement of sleep quality. The index measures 7 sleep components on a 0-3 scale; each of the 7 raw scores is summed to get a global score. The global score ranges from 0-21, with higher scores indicating poor sleep quality. Scores >5 are typically considered poor sleep quality.

Change in LUNSERS (Liverpool University Neuroleptic Side Effect Rating Scale) score, a self-report measure of antipsychotic side effects. The scale has 51 questions, 41 of which are about side-effects and 10 "red herrings" for validation purposes. The total neuroleptic side effect score is derived from the sum of the 41 side-effect questions, with a potential range of 0-164. Higher scores indicate more severe neuroleptic side effects.

Change in participant body weight in kg, as measured using a standing scale.

Change in the hip circumference measurement, taken as an average of 3 measures by tape measure

Change in waist circumference measurements, taken as an average of 3 measures by tape measure.

Change in fasting serum glucose levels.

Change in fasting total cholesterol level

Change in fasting, Hemoglobin A1c level

Change in insulin fasting serum levels

Change prolactin serum levels

Change in total caloric intake as assessed by the ASA24 Dietary Recall and Food Frequency Questionnaire - Revised. The ASA24 is a self-administered 24-hour dietary recall assessment.

Change in Wisconsin Schizotypy Scales (WSS) Short Form score, a self-report questionnaire assessing schizotypy in clinical and non-clinical samples. The measure has four scales, each with 15 True/False questions. There are 13 red-herring questions, that, if answered "True" invalidate the test. Each "false" response is scored 0, and each "true" response is scored 1. Scores for each scale range from 0 - 15, with higher scores indicating greater schizotypy. The WSS positive schizotypy score consists of the summed score of the perceptual aberration and magical ideation scales and scores range from 0-30, with higher scores indicating greater positive schizotypy. The WSS negative schizotypy score sums scores from the physical anhedonia and social anhedonia scales and ranges from 0-30, with higher scores indicating greater negative schizotypy.

Change in the Early Psychosis Social Scale score item of missed absences from school or work. Scores range from 1-5, with higher scores indicating more absences from school or work.

Change in the Prodromal Questionnaire, Brief Version score, a 21 item self-report questionnaire designed to help identify those at ultra-high risk for developing psychotic symptoms. The total score is derived as the sum of all 21 items, with a possible range of 0-21. Higher scores indicate greater psychopathology.

Changes in the Symptoms Checklist - 90 - Revised scale, which measures 9 domains of psychological dysfunction, summing to create an overall psychological distress (Global Severity Score). The scores of each of the 9 domains - somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation and psychoticism - combine for a total of 90 items, each measured on a 5-point scale. The sums of all 90 item scores, ranging 0-360, creates the Global Severity score. Higher scores indicate greater psychopathology.

Change in the State-Trait Anxiety Inventory for Adults, which measures both state and trait anxiety using 2 subscales for a total of 40 items. Each subscale has a range of 20-80, with higher scores indicating greater state or trait anxiety, respectively.

Change in the World Health Organization Quality of Life questionnaire score, a 26-item assessment of overall quality of life. The questionnaire encompasses 4 domains: physical health, psychological health, social relationships, and environment. There are two additional questions, which assess the participant's perceptions of their own quality of life and physical health. Higher scores indicate better quality of life. Scores are summed within each domain. Total score is obtained by transforming for a total range of 0-100 within each domain.