Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
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Neuropsychopharmacology · Dec 2004
Comparative StudyExecutive dysfunction, heart disease burden, and remission of geriatric depression.
This study investigated the relationship of executive impairment and heart disease burden to remission of major depression among elderly patients. A total of 112 elderly subjects suffering from major depression received treatment with citalopram at a target daily dose of 40 mg for 8 weeks. Diagnosis was assigned using the Research Diagnostic Criteria and the DSM-IV Criteria after an interview with the Schedule for Affective Disorders and Schizophrenia. ⋯ Impairment in other DRS cognitive domains, disability, medical burden unrelated to heart disease did not significantly influence the outcome of depression in this sample. Executive dysfunction and heart disease burden constitute independent vulnerability factors that increase the risk for chronicity of geriatric depression. The findings of this study provide the rationale for investigation of the role of specific frontostriatal-limbic pathways in predisposing to geriatric depression or worsening its course.
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Neuropsychopharmacology · Nov 2004
Comparative StudyPreconditioning with transcranial direct current stimulation sensitizes the motor cortex to rapid-rate transcranial magnetic stimulation and controls the direction of after-effects.
Rapid-rate repetitive transcranial magnetic stimulation (rTMS) can produce a lasting increase in cortical excitability in healthy subjects or induce beneficial effects in patients with neuropsychiatric disorders; however, the conditioning effects of rTMS are often subtle and variable, limiting therapeutic applications. Here we show that magnitude and direction of after-effects induced by rapid-rate rTMS depend on the state of cortical excitability before stimulation and can be tuned by preconditioning with transcranial direct current stimulation (tDCS). ⋯ Preconditioning with tDCS enhances cortical plasticity induced by rapid-rate rTMS and can shape the direction of rTMS-induced after-effects.
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Neuropsychopharmacology · Jul 2004
Randomized Controlled Trial Comparative Study Clinical TrialModafinil improves cognition and attentional set shifting in patients with chronic schizophrenia.
Modafinil, a novel cognitive enhancer, selectively improves neuropsychological task performance in healthy volunteers and adult patients with attention deficit hyperactivity disorder (ADHD). It has been argued that persistent cognitive deficits in patients with schizophrenia are responsible for the failure of many patients to rehabilitate socially even when psychotic symptoms are in remission. The present study examined the potential of modafinil as a cognitive enhancer in schizophrenia. ⋯ No effect on stop-signal performance was seen. Importantly, significant improvement in attentional set shifting was seen, despite no effect of modafinil on this task being seen in healthy volunteers or ADHD patients. Modafinil may have potential as an important therapy for cognitive impairment in patients with schizophrenia, particularly because of its beneficial effects on attentional set shifting.
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Neuropsychopharmacology · Jun 2004
Comparative StudyCorticotropin-releasing hormone antagonists, astressin B and antalarmin: differing profiles of activity in rhesus monkeys.
The present study compares the activity of two chemically distinct corticotropin-releasing hormone (CRH) antagonists at the level of the pituitary gland in rhesus monkeys, using exogenous CRH-stimulated increases in adrenocorticotropin (ACTH) and cortisol. Of chief interest was whether the CRH-R1-selective pyrrolopyrimidine, antalarmin, shown previously to have activity in the central nervous system (CNS), would differ in its antagonist profile from the CRH-R1- & 2-selective peptide, astressin B, which is unlikely to have access to the CNS following systemic administration. Nine rhesus monkeys (eight male), each with an indwelling venous catheter, were subjects in this study. ⋯ At a larger dose, antalarmin stimulated ACTH and cortisol release and produced behavioral sedation. These latter effects diminished with repeated administration of antalarmin. The differences between astressin B and antalarmin may be due either to non-CRH receptor-mediated effects of antalarmin or to a complex interaction of antalarmin's effects at both central and peripheral CRH receptors.
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Neuropsychopharmacology · Jun 2004
Comparative StudyGenetic and pharmacological evidence of a role for GABA(B) receptors in the modulation of anxiety- and antidepressant-like behavior.
Although there is much evidence for a role of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the pathophysiology of anxiety and depression, the role of GABA(B) receptors in behavioral processes related to these disorders has not yet been fully established. GABA(B) receptors are G-protein-coupled receptors, which act as functional heterodimers made up of GABA(B(1)) and GABA(B(2)) subunits. Using recently generated GABA(B(1)) -/- mice, which lack functional GABA(B) receptors, and pharmacological tools we assessed the role of GABA(B) receptors in anxiety- and antidepressant-related behaviors. ⋯ These behavioral effects are unrelated to alterations in locomotor activity. In confirmation of the genetic data, acute and chronic treatment with CGP56433A, a selective GABA(B) receptor antagonist, also decreased immobility in the FST, whereas GS39783 did not alter this behavior. Taken together, these data suggest that positive modulation of the GABA(B) receptor may serve as a novel therapeutic strategy for the development of anxiolytics, whereas GABA(B) receptor antagonism may serve as a basis for the generation of novel antidepressants.