Neurochemical alteration in the caudate: Implications for the pathophysiology of bipolar disorder
ABSTRACT Several lines of evidence suggest that the neuropathophysiology of bipolar disorder is marked by structural and functional abnormalities in the caudate. We used magnetic resonance spectroscopy imaging (MRSI) to examine potential neurochemical changes in the caudate of adult bipolar patients (BP). 2D-MRSI scans including the caudate were obtained from 25 BP and 9 healthy subjects (HS). BP patients were further divided into medicated (n=14) and unmedicated (n=11) groups; the majority of medicated patients received atypical antipsychotics (AAP). Ratios of Cr/Cho, Cho/NAA and Cr/NAA in the caudate were compared between groups, controlling for age, gender and gray/white ratio. BP and HS did not significantly differ on any ratios. The Cr/Cho ratio, however, was significantly greater in medicated BP compared to HS. Conversely, the Cho/NAA ratio was non-significantly lower in medicated BP vs. HS. Medicated BP also showed significantly greater Cr/Cho and significantly smaller Cho/NAA ratios than unmedicated BP. Although we did not observe significant overall differences between BP and HS, our findings suggest the presence of reduced choline levels in the caudate of medicated BP receiving AAP. While speculative, these results suggest that AAP do not cause oxidative injury to neuronal membranes.
SourceAvailable from: Michele Poletti[Show abstract] [Hide abstract]
ABSTRACT: This study proposes a transdiagnostic framework for delusion development, analysing psychiatric (schizophrenia, bipolar disorder, major depressive disorder) and neurological disorders (stroke, and neurodegenerative diseases) in which delusions are predominant. Our aim is to identify a transdiagnostic core of neural and cognitive alterations associated with delusions across distinct clinical disorders. Reviewed empirical evidence suggests delusions are associated: on the neural level with changes in the ventromedial prefrontal cortex (vmPFC) networks, and on the neuropsychological level with dysfunction in the processes (generation of affective value, the construction of internal models of the world, and the reflection about Self and/or Other's mental states) that these network mediate. The concurrent aberration of all these processes could be critical for the clinical transition to a psychotic delusional state. In particular, delusions could become clinically manifest when (1) stimuli are attributed an aberrant affective salience, that (2) is explained by the patient within distorted explanatory internal models that (3) are poorly inhibited by cognitive control systems. This framework extends the two-factor account of delusion model and suggests that common neural mechanisms for the delusions in psychiatric and in neurological disorders.08/2013; 210(3). DOI:10.1016/j.psychres.2013.07.032
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ABSTRACT: Bipolar disorder (BD) is a severe neuropsychiatric disorder, affecting approximately 1–2% of the world population. The present study designed to investigate whether omega-3 fatty acids could impinge the effect of methylphenidate (MPD) induced mania in mice after treatment with aripiprazole and lithium. Mice were subjected to mania paradigm daily for a period of 14 days to induce mania-like behavior by administration of MPD. The effect of supplementation of omega-3 fatty acids on MPD induced mania mice was examined by behavioral analysis such as open field test, forced swim test and actophotometer test. Supplementation of omega-3 fatty acids with aripiprazole and lithium reduced methylphenidate-induced hyperlocomotion. As a result MPD causes mania-like behavior in mice, as indicated by significant decrease in duration of immobility in forced swim test. Supplementation of omega-3 fatty acids (1.5 ml/kg), aripiprazole (1.5 mg/kg), lithium (50 mg/kg), significantly reduced the acute administration of MPD (5 mg/kg) induced mania-like behavior in open field test. Based on the behavioral analysis mice shows decreased total locomotion, duration of immobility time and the locomotor counts. In conclusion, the results of the present study suggested that omega-3 fatty acids supplementation alleviated the MPD-induced manic behavior in mice.11/2013; DOI:10.1016/j.phanu.2013.11.128
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ABSTRACT: Although brain lactate levels are typically low and difficult to measure, a few previous investigators have reported that brain lactate levels are elevated in patients with bipolar disorder. The present study investigated the distribution of lactate in bipolar and healthy brains using 2D proton magnetic resonance spectroscopic imaging on a 4-Tesla magnetic resonance imaging system. Ratios of the concentration of lactate to N-acetylaspartate, and of lactate to total creatine, were significantly higher in bipolar than in healthy subjects. Lactate signals were primarily localized to the bipolar subjects' caudate and anterior cingulate cortices, components of the frontal-subcortical circuit, suggesting that affective dysregulation may be related to metabolic abnormalities in this network.06/2013; 213(3). DOI:10.1016/j.pscychresns.2013.03.004