PubMed Health⌕ Search

Biomedical subjects

Brent M McGrath

Publications and source records attributed to Brent M McGrath.

7 recordsLinked to original sources
PubMed2006

Lithium alters regional rat brain myo-inositol at 2 and 4 weeks: an ex-vivo magnetic resonance spectroscopy study at 18.8 T.

Lithium has been the mainstay of treatment for bipolar disorder. Early studies suggest that lithium acts via inositol depletion. This study assesses the effect of 1, 2 and 4 weeks of lithium treatment on myo-inositol concentrations across several brain regions. Thirty-six Sprague-Dawley rats were treated for 2 weeks with an intraperitoneal injection of either 1 mmol/kg/day, twice daily lithium chloride (n=18) or placebo (2 ml/kg of saline) (n=18). The rats were separated into three groups: 1 week, 2 weeks and 4 weeks. Brains were dissected into prefrontal, temporal and occipital cortical areas, as well as hippocampus, and analyzed at 18.8 T. Myo-inositol was quantified using the Chenomx Profiler software. Lithium did not alter myo-inositol concentrations at 1 week. A significant reduction exists in myo-inositol concentrations in lithium-treated rats at 2 and 4 weeks, across all four brain regions. Studies suggest brain region-specific alterations in myo-inositol concentrations among bipolar patients. Our findings suggest that lithium-induced reduction of myo-inositol is more global.

Animals↗
PubMed2005

Valproate attenuates dextroamphetamine-induced subjective changes more than lithium.

Dextroamphetamine administration in healthy controls produces a range of subjective and physiological effects, which have been likened to those occurring during mania. However, it is uncertain if these can be attenuated by lithium since conflicting results have been reported. To date there have been no previous studies examining the effects of valproate on dextroamphetamine-induced mood and physiological changes. The current study was a double-blind, placebo-controlled, study in which volunteers received either 1000 mg sodium valproate (n=12), 900 mg lithium (n=9), or placebo (n=12) pre-treatment for 14 days. Subjective and physiological measures were then obtained prior to administration of a 25 mg dose of dextroamphetamine, and at two time points after administration. Differences in the response to dextroamphetamine were assessed between the three treatment groups. The results of this study show that pre-treatment with lithium only significantly attenuated dextroamphetamine-induced change in happiness, while valproate pre-treatment significantly attenuated the effects of dextroamphetamine on happiness, energy, alertness and on the diastolic blood pressure. These results suggest that lithium and valproate do not have the same mechanism of action on dextroamphetamine-induced changes, and this finding may relate to differences in their mechanism of action in mood disorders.

Adolescent↗
PubMed2005

A review of the possible relevance of inositol and the phosphatidylinositol second messenger system (PI-cycle) to psychiatric disorders--focus on magnetic resonance spectroscopy (MRS) studies.

Myo-inositol is an important part of the phosphatidylinositol second messenger system (PI-cycle). Abnormalities in nerve cell myo-inositol levels and/or PI-cycle regulation has been suggested as being involved in the pathophysiology and/or treatment of many psychiatric disorders including bipolar disorder, major depressive disorder, panic disorder, obsessive-compulsive disorder, eating disorders and schizophrenia. This review examines the metabolism and biochemical importance of myo-inositol and the PI-cycle. It relates this to the current in vivo evidence for myo-inositol and PI-cycle involvement in these psychiatric disorders, particularly focusing upon the magnetic resonance spectroscopy (MRS) findings in patient studies to date. From this review it is concluded that while the evidence suggests probable relevance to the pathophysiology and/or treatment of bipolar disorder, there is much less support for a significant role for the PI-cycle or myo-inositol in any other psychiatric disorder. More definitive investigation is required before PI-cycle dysfunction can be considered specific to bipolar disorder.

Bipolar Disorder↗
PubMed2005

Bipolar disorder and myo-inositol: a review of the magnetic resonance spectroscopy findings.

OBJECTIVES: Myo-inositol is an important component of the phosphatidylinositol second messenger system (PI-cycle). Alterations in PI-cycle activity have been suggested to be involved in the pathophysiology and/or treatment of bipolar disorder. More specifically, lithium has been suggested to act primarily by lowering myo-inositol concentrations, the so-called inositol-depletion hypothesis. myo-Inositol concentrations can be measured in vivo with magnetic resonance spectroscopy (MRS). METHODS: The current review primarily examines animal and human MRS studies that evaluated the role of myo-inositol in bipolar illness and treatment. RESULTS: Studies have been carried out in patients who are manic, depressed, and euthymic, both on and off treatment. However, there are several limitations of these studies. CONCLUSIONS: The preclinical and clinical MRS findings were generally supportive of the involvement of myo-inositol in bipolar disorder and its treatment. Overall, in bipolar patients who are manic or depressed there are abnormalities in brain myo-inositol concentrations, with changes in frontal and temporal lobes, as well as the cingulate gyrus and basal ganglia. These abnormalities are not seen in either euthymic patients or healthy controls, possibly due to a normalizing effect of treatment with either lithium or sodium valproate. There is also increasing evidence that sodium valproate may also act upon the PI-cycle. Nonetheless, it remains uncertain if these changes in myo-inositol concentration are primary or secondary. Findings regarding the specific inositol-depletion hypothesis are also generally supportive in acutely ill patients, although it is not yet possible to definitively confirm or refute this hypothesis based on the current MRS evidence.

Animals↗
PubMed2004

Neurobiological findings in bipolar II disorder compared with findings in bipolar I disorder.

OBJECTIVE: To determine whether there are consistent neurobiological differences between patients with bipolar I disorder (BD I) and those with bipolar II disorder (BD II). METHOD: We reviewed the literature in areas where the most consistent neurobiological findings have been reported for bipolar disorder, specifically, neuroimaging and brain metabolism. The imaging studies reviewed examined structure, using magnetic resonance imaging (MRI), and function, using functional MRI, positron emission tomography, and single photon emission computed tomography. We used magnetic resonance spectroscopy to examine brain chemistry. We reviewed those metabolic studies that examined cell calcium, 3-methoxy-4-hydroxyphenylglycol, and protein kinase C. RESULTS: Some genetic studies suggest that there may be differences between BD II and BD I patients. However, our review of the imaging and metabolic studies identified few studies directly comparing these 2 groups. In those studies, there were few differences, if any, and these were not consistent. CONCLUSIONS: While genetic data suggest there may be differences between BD II patients and BD I patients, the neurobiological findings to date do not provide support. However, this may be owing to the small number of studies directly comparing the 2 groups and also to the fact that those carried out have not been adequately powered to detect possible small true differences. This is an important issue because, if there are no neurobiological differences, it would be anticipated that similar treatments would be similarly effective in both groups. Given the importance of understanding whether there are neurochemical differences between these groups, further research in this area is clearly needed.

Bipolar Disorder↗
PubMed2003

Implementing quality management in psychiatry: from theory to practice--shifting focus from process to outcome.

With the increasing emphasis on the satisfaction of patient-clients balanced by the need for cost-efficient treatment, quality management is an ever-increasing concern for mental health care providers. It is now apparent that psychiatrists must follow treatment progress and outcome to assess and improve the quality of the care they provide. Most quality measurement and management programs to date have been carried out in research settings using process measures; however, it is clear that the focus must shift from research to practice and from process to outcome measurements. We discuss the notion of quality and outcome management and propose a model for selecting outcome measures. This model suggests 5 dimensions that are commonly assessed in outcome management. We successfully implemented a computerized documentation and quality measurement system in a psychiatric outpatient setting.

Canada↗