RESUMEN
Bipolar disorder (BD) and alcohol dependence (AD) frequently co-occur, and co-occurring BD and AD are associated with devastating public health costs. Minimal neurobiological research exists to guide the development of effective treatments for this treatment-resistant population. We believe the present study represents the first investigation of prefrontal gamma-aminobutyric acid (GABA) and glutamate levels in co-occurring BD and current AD. The participants were 78 individuals who met DSM-IV criteria for BD I/II and current AD (n=20), BD I/II alone (n=19), current AD alone (n=20) or no diagnosis (n=19). The participants completed a baseline diagnostic visit, then returned approximately 4 days later for a two-dimensional J-resolved proton magnetic resonance spectroscopy (1H-MRS) acquisition in dorsal anterior cingulate cortex (dACC). All participants were required to demonstrate ⩾1 week of abstinence from alcohol/drugs via serial biomarker testing before 1H-MRS. A 2 × 2 factorial analysis of variance of cerebrospinal fluid (CSF)-corrected GABA/water concentrations demonstrated a significant BD × AD interaction (F=2.91, P<0.05), signifying uniquely low levels of GABA in BD+AD; this effect doubled when the sample was restricted to individuals who consumed alcohol within 2 weeks of 1H-MRS. There were no overall effects of BD/AD on CSF-corrected glutamate/water levels. However, the BD × AD interaction, signifying uniquely low levels of glutamate in BD+AD, approached statistical significance (F=3.83, P=0.06) in individuals who consumed alcohol within 2 weeks of 1H-MRS. The dACC GABA levels were significantly, negatively associated with Barratt Impulsiveness Scale (r=-0.28, P=0.02) and Obsessive Compulsive Drinking Scale (r=-0.35, P<0.01) scores. If replicated, these results may suggest that future treatment studies should preferentially evaluate therapeutics in BD+AD known to increase prefrontal GABA and glutamate levels.
Asunto(s)
Alcoholismo/metabolismo , Trastorno Bipolar/metabolismo , Ácido Glutámico/metabolismo , Giro del Cíngulo/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Adulto , Alcoholismo/complicaciones , Alcoholismo/psicología , Trastorno Bipolar/complicaciones , Trastorno Bipolar/psicología , Ansia , Femenino , Humanos , Conducta Impulsiva , Masculino , Persona de Mediana Edad , Corteza Prefrontal/metabolismo , Espectroscopía de Protones por Resonancia MagnéticaRESUMEN
Despite the prevalence of migraine, the pathophysiology of the disease remains unclear. Current understanding of migraine has alluded to the possibility of a hyperexcitable brain. The aim of the current study is to investigate human brain metabolite differences in the anterior cingulate cortex (ACC) during the interictal phase in migraine patients. We hypothesized that there may be differences in levels of excitatory neurotransmitters and/or their derivatives in the migraine cohort in support of the theory of hyperexcitability in migraine. 2D J-resolved proton magnetic resonance spectroscopy ((1)H-MRS) data were acquired on a 3 Tesla (3 T) MRI from a voxel placed over the ACC of 32 migraine patients (MP; 23 females, 9 males, age 33 ± 9.6 years) and 33 healthy controls (HC; 25 females, 8 males, age 32 ± 9.6 years). Amplitude correlation matrices were constructed for each subject to evaluate metabolite discriminability. ProFit-estimated metabolite peak areas were normalized to a water reference signal to assess subject differences. The initial analysis of variance (ANOVA) was performed to test for group differences for all metabolites/creatine (Cre) ratios between healthy controls and migraineurs but showed no statistically significant differences. In addition, we used a multivariate approach to distinguish migraineurs from healthy subjects based on the metabolite/Cre ratio. A quadratic discriminant analysis (QDA) model was used to identify 3 metabolite ratios sufficient to minimize minimum classification error (MCE). The 3 selected metabolite ratios were aspartate (Asp)/Cre, N-acetyl aspartate (NAA)/Cre, and glutamine (Gln)/Cre. These findings are in support of a 'complex' of metabolite alterations, which may underlie changes in neuronal chemistry in the migraine brain. Furthermore, the parallel changes in the three-metabolite 'complex' may confer more subtle but biological processes that are ongoing. The data also support the current theory that the migraine brain is hyperexcitable even in the interictal state.
Asunto(s)
Ácido Aspártico/análogos & derivados , Ácido Glutámico/metabolismo , Glutamina/metabolismo , Giro del Cíngulo/metabolismo , Trastornos Migrañosos/patología , Adolescente , Adulto , Análisis de Varianza , Ácido Aspártico/metabolismo , Estudios de Cohortes , Femenino , Giro del Cíngulo/diagnóstico por imagen , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Trastornos Migrañosos/diagnóstico por imagen , Espectroscopía de Protones por Resonancia Magnética , Adulto JovenRESUMEN
Pediatric bipolar disorder is a severe mental illness whose pathophysiology is poorly understood and for which there is an urgent need for improved diagnosis and treatment. MR spectroscopy is a neuroimaging method capable of in vivo measurement of neurochemicals relevant to bipolar disorder neurobiology. MR spectroscopy studies of adult bipolar disorder provide consistent evidence for alterations in the glutamate system and mitochondrial function. In bipolar disorder, these 2 phenomena may be linked because 85% of glucose in the brain is consumed by glutamatergic neurotransmission and the conversion of glutamate to glutamine. The purpose of this article is to review the MR spectroscopic imaging literature in pediatric bipolar disorder, at-risk samples, and severe mood dysregulation, with a focus on the published findings that are relevant to glutamatergic and mitochondrial functioning. Potential directions for future MR spectroscopy studies of the glutamate system and mitochondrial dysfunction in pediatric bipolar disorder are discussed.
Asunto(s)
Trastorno Bipolar/diagnóstico , Trastorno Bipolar/metabolismo , Encéfalo/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Pediatría , Niño , HumanosRESUMEN
The sampling of gall bladder bile for analytical studies remains an invasive procedure. We demonstrate the application of the non-invasive methodology of (1)H-MR spectroscopy to the qualitative and quantitative assessment of human gall bladder bile in vivo. Spectral profiles in vivo are shown in relation to model and porcine gall bladder bile and the quantitation in man of the trimethylamine (choline) and lecithin concentrations were estimated to range from 25.9 mM to 48.4 mM (mean: 35.8 mM, standard deviation: 9.8). The composition of human gall bladder bile together with the quantitation of various constituents can be studied non-invasively in vivo.