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Regional cerebral blood flow (rCBF) data from two PET-15O water schizophrenia studies were analyzed using individually placed, magnetic resonance (MR)-guided hippocampal volumes of interest (VOI). In one study, normal (N = 10) and schizophrenic (N = 18) volunteers performed an overlearned auditory discrimination task in rest, control, and decision conditions. In the other study, schizophrenic and normal volunteers received the noncompetitive NMDA receptor antagonist ketamine and placebo and had sequential rCBF evaluations. Moreover, the schizophrenic volunteers were off drug in one study and on antipsychotic drug in the second study, allowing an additional comparison of medication status. VOIs were placed on anterior, middle, and posterior hippocampal areas in each PET image from both studies, redirected from an MR scan, and individually adjusted. While no hippocampal activation was apparent in either the normal or schizophrenic group in the task vs. condition comparison, rCBF was higher in the schizophrenic than in the normal hippocampus in both task and control conditions, independently. In addition, at rest rCBF was significantly higher in the unmedicated group of schizophrenics than in the group of medicated patient volunteers and higher than in the normal comparison group. This suggests that schizophrenia is associated with elevated rCBF in the hippocampus, which "normalizes" with antipsychotic drug treatment. Ketamine, the noncompetitive NMDA receptor antagonist, was more potent in reducing rCBF in the schizophrenic group compared to the normal volunteer group. These data are consistent with a previous report from our laboratory of reduced NMDA receptor NR1 subunit expression and possible abnormal NMDA receptor composition in schizophrenia. These data show an abnormality of hippocampal function in schizophrenia and suggest that this abnormality may be associated with the pathophysiology of the illness.

Intra-individual variability on a computer-based working memory task was examined among 25 children/adolescents with ADHD and 24 typically developing peers. Participants completed the Visual Serial Addition Task (VSAT) and reaction time data were fit to an ex-Gaussian distribution. ADHD participants demonstrated significantly more variable performance than controls, and effects of working memory load were observed. Event rate, however, had no influence on group differences in performance. Follow-up correlations revealed associations between VSAT performance and ADHD symptomatology. This study supports intra-individual variability as a hallmark feature of ADHD beyond the domain of response inhibition and reinforces the need to consider variability in ADHD more broadly.

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The aim of this study was to examine the potential of serial rCBF studies to directly characterize the regional effects and dynamic time course of the centrally active drug ketamine. The value of a broader application of this technique to other neurally active drugs to characterize the pharmacodynamics of CNS compounds is suggested by these data. Thirteen normal subjects received a 0.3 mg/kg intravenous dose of ketamine over 60 seconds; ten other individuals received placebo in the same manner. For each subject, three baseline PET rCBF scans and seven sequential post-ketamine scans at 10-minute intervals were obtained using H(2)(15)O water. SPM techniques were employed to identify the maxima of any cluster significant by spatial extent analysis at any post-ketamine time point between 0 and 36 min. These extremes from the ketamine group, were identified in placebo scans similarly and grown to a 6x6x12 mm voxel set. The average rCBF values of the ketamine-defined clusters were determined in the drug and placebo conditions at all time points. rCBF across time was plotted for each cluster and compared between drug and placebo. Area under the curve (AUC) was calculated between baseline and 36 minutes. The kinetic characteristics of the ketamine-induced rCBF curves were compared to induced behaviors in each maxima. Ketamine produced distinct patterns of rCBF change over time in different brain regions; maxima within an anatomically defined region responded similarly. Ketamine induced rCBF activations in anterior cingulate, medial frontal and inferior frontal cortices. All maxima with a relative flow reduction with ketamine were in the cerebellum. The pattern of all activations and suppressions was monophasic with the peak changes at 6-16 minutes. In preliminary analysis, individual C(max) and AUC of maxima in the anterior cingulate/medial frontal region tended to correlate with the mild psychotomimetic action of ketamine; whereas, there was no tendency toward correlation with this psychological change in cerebellar maxima. The direct action of a centrally active drug can be assessed regionally and dynamically in brain using rCBF and a scan sequence optimally timed to complement the drug's time course. Ketamine pharmacodynamic response can be related to concurrent behavioral changes, tending to link the behavior with a brain region. This experimental design provides direct characterization of drug action in the CNS in ways heretofore unavailable.

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Objectives Veterans with serious mental illness are at increased risk of obesity, sedentary lifestyle, and a host of related chronic diseases. Although evidence suggests that lifestyle interventions can help mental health consumers achieve modest weight loss, several studies have failed to show a benefit and most have concluded that significant challenges remain in delivering effective interventions. In 2006, the Veterans Health Administration introduced MOVE!, a weight management program that includes behaviorally based dietary and physical activity self-management support. This article describes modifications used to manualize MOVE! for veterans with serious mental illness and reports findings from a randomized controlled trial of the new intervention. Methods Between January 2007 and June 2009, overweight or obese veterans with serious mental illness were randomly assigned to a six-month trial of MOVE! (N=53), which includes both individual and group sessions, or to a control condition that offered basic information about diet and exercise every month (N=56). Weight and metabolic, attitudinal, behavioral, and functional variables were measured at baseline and six months, and weight was also measured monthly. Results Thirty participants in MOVE! and 41 participants in the control group completed the six-month assessment, and only seven lost 5% of their baseline weight; there was no effect of group assignment on weight loss. There were no significant group × time differences in any metabolic, dietary, physical activity, attitudinal, or functional measure. Conclusions Despite the negative findings of this study, research is crucial to identify lifestyle interventions and related supports and services to help veterans with mental illness reduce overweight and obesity.