Biological psychiatry
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Biological psychiatry · Jul 2011
ReviewUsing brain imaging measures in studies of procognitive pharmacologic agents in schizophrenia: psychometric and quality assurance considerations.
The first phase of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICs) initiative focused on the identification of cognitive constructs from human and animal neuroscience that were relevant to understanding cognitive deficits in schizophrenia, as well as promising task paradigms that could be used to assess these constructs behaviorally. The current phase of CNTRICs has the goal of expanding this initial work by including measures of brain function that can augment these behavioral tasks as biomarkers to be used in drug development processing. ⋯ In addition, we review quality assurance concerns, issues associated with multicenter trials, concerns associated with potential pharmacologic confounds on imaging measures, as well as power and analysis considerations. Although review is couched in the context of the use of biomarkers for treatment studies in schizophrenia, we believe the issues and suggestions included are relevant to the entire range of neuropsychiatric disorders as well as to a wide range of imaging modalities (i.e., functional magnetic resonance imaging, positron emission tomography, event-related potentials, electroencephalography, transcranial magnetic stimulation, near infrared spectroscopy, etc.) and are relevant to both pharmacologic and psychological intervention approaches.
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Biological psychiatry · Jul 2011
General and specific functional connectivity disturbances in first-episode schizophrenia during cognitive control performance.
Cognitive control impairments in schizophrenia are thought to arise from dysfunction of interconnected networks of brain regions, but interrogating the functional dynamics of large-scale brain networks during cognitive task performance has proved difficult. We used functional magnetic resonance imaging to generate event-related whole-brain functional connectivity networks in participants with first-episode schizophrenia and healthy control subjects performing a cognitive control task. ⋯ The first episode of schizophrenia is associated with a generalized connectivity impairment affecting most brain regions but that is particularly pronounced for frontal cortex. Superimposed on this generalized deficit, patients show more specific cognitive-control-related functional connectivity reductions in frontoparietal regions. These connectivity deficits occur in the context of relatively preserved global network organization.
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Biological psychiatry · Jun 2011
Meta AnalysisTranslational approaches to frontostriatal dysfunction in attention-deficit/hyperactivity disorder using a computerized neuropsychological battery.
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent condition associated with cognitive dysfunction. The Cambridge Neuropsychological Test Automated Battery is a computerized set of tests that has been widely used in ADHD and in translation/back-translation. Following a survey of translational research relevant to ADHD in experimental animals, a comprehensive literature review was conducted of studies that had used core Cambridge Neuropsychological Test Automated Battery tests 1) to evaluate cognitive dysfunction in ADHD and 2) to evaluate effects of salient drugs in patients and in volunteers. ⋯ Results were paralleled by findings in experimental animals on comparable tests, enabling further analysis of drug mechanisms. Substantial cognitive deficits are present in ADHD, which can be remediated somewhat with current medications and which can readily be modeled in experimental animals using back-translational methodology. The findings suggest overlapping but also distinct early cognitive effects of ADHD medications and have important implications for understanding the pathophysiology of ADHD and for future trials.
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Biological psychiatry · May 2011
Effect of chronic antipsychotic treatment on brain structure: a serial magnetic resonance imaging study with ex vivo and postmortem confirmation.
There is increasing evidence that antipsychotic (APD) may affect brain structure directly. To examine this, we developed a rodent model that uses clinically relevant doses and serial magnetic resonance imaging (MRI), followed by postmortem histopathological analysis to study the effects of APD on brain structures. ⋯ This is the first systematic whole-brain MRI study of the effects of APD, which highlights significant effects on the cortex. Although caution needs to be exerted when extrapolating results from animals to patients, the approach provides a tractable method for linking in vivo MRI findings to their histopathological origins.
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Biological psychiatry · Apr 2011
Individuals family history positive for alcoholism show functional magnetic resonance imaging differences in reward sensitivity that are related to impulsivity factors.
Substance-abusing individuals tend to display abnormal reward processing and a vulnerability to being impulsive. Detoxified alcoholics show differences in regional brain activation during a monetary incentive delay task. However, there is limited information on whether this uncharacteristic behavior represents a biological predisposition toward alcohol abuse, a consequence of chronic alcohol use, or both. ⋯ Overall, results demonstrate that sensitivity of the reward circuit, including NAcc, is functionally different in alcoholism family history positive individuals in multiple regards.