Neurochemical alteration in the caudate: Implications for the pathophysiology of bipolar disorder
Division of Bipolar Disorders Research, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH 45267, United States. Psychiatry Research
(Impact Factor: 2.47).
06/2011; 193(2):107-12. DOI: 10.1016/j.pscychresns.2011.01.014
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.
Available from: Jing-Huei Lee
- "An oblique axial scout image was acquired along a line at 25 mm above the AC-PC line for the reference of 2D 1 H MRSI data acquisition (Fig. 1a) (Shahana et al., 2011). The 2D 1 H MRSI data were acquired, using a modified LASER (Localized by Adiabatic SElective Refocusing) sequence in a 10-mm-thick slab with 192 mm Â 192 mm field of view (FOV) (Garwood and DelaBarre, 2001; Shahana et al., 2011). Two dimensions of a 24 Â 24 phase-encoding scheme were applied for spectral localization. "
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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
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ABSTRACT: Proton magnetic resonance spectroscopy (1H MRS) enables the observation of brain function in vivo. Several brain metabolites can be measured by the means of 1H MRS: N-acetylaspartate (NAA), choline containing compounds (Cho), myo-inositol (mI) and glutamate (Glu), glutamine (Gln) and GABA (together as Glx complex or separately). 1H MRS measures have been found to be abnormal in psychotic disorders such as schizophrenia. Here we specifically review the influence exerted by antipsychotic drugs on brain metabolism, as detected by1H MRS. We systematically reviewed the available literature and uncovered 27 studies, 16 before-after treatment and 11 cross-sectional. Most of them addressed the effects of antipsychotics in schizophrenia and mainly focusing on NAA alterations. Follow up studies indicated antipsychotic drugs may act by increasing NAA levels in selected brain areas (the frontal lobe and thalamus), especially during the short-time observation. This phenomenon seems to vanish after longer observation. Other studies indicated that glutamate measures are decreasing along with the duration of the disease, suggesting both a neurodegenerative process present in schizophrenic brain as well as an influence of antipsychotics. The above results were reviewed according to the most recent theories in the field accounting for the impact of antipsychotics 1HMRS measures.
Current Medicinal Chemistry 11/2012; 20(3). DOI:10.2174/0929867311320030013 · 3.85 Impact Factor
Available from: Michele Poletti
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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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