phosphocreatine and Mood-Disorders

Increasing numbers of youth are presenting for psychiatric evaluation with markedly irritable mood plus "hyperarousal" symptoms. Diagnostically homeless in current nosology, the syndrome (as well as its underlying neurobiology) is little understood. To address this problem, we conducted an exploratory proton magnetic resonance spectroscopy (MRS) study in a large sample of youth with chronic, functionally disabling irritability accompanied by hyperarousal, a clinical syndrome known as "severe mood dysregulation" (SMD), which may represent a broad phenotype of pediatric bipolar disorder. Medication-free SMD youth (N=36) and controls (N=48) underwent 1.5 Tesla MRS in four regions of interest. The following three neurometabolites, relative to creatine (Cr), were quantified with LCModel Software: (a) myo-inositol (mI), a marker of intra-cellular second messengers linked to the neurobiology of bipolar disorder; (b) glutamate/glutamine (GLX), a marker of the major excitatory neurotransmitter glutamate; and (c) N-acetyl aspartate (NAA), a marker of neuronal energetics. SMD subjects had significantly lower temporal mI/Cr versus controls. However, this difference did not survive correction for multiple comparisons. Given studies implicating mI in lithium's action in BD adults and youth, further work is necessary to determine potential therapeutic implications of our present finding and how SMD youth differ pathophysiologically from those with strictly defined BD.

Topics: Antimanic Agents; Arousal; Aspartic Acid; Attention Deficit Disorder with Hyperactivity; Bipolar Disorder; Brain Mapping; Cerebral Cortex; Chronic Disease; Creatine; Diagnosis, Differential; Dominance, Cerebral; Double-Blind Method; Glutamine; Humans; Image Processing, Computer-Assisted; Inositol; Irritable Mood; Lithium Compounds; Magnetic Resonance Spectroscopy; Mood Disorders; Phosphocreatine

Few studies have examined the neurochemical abnormalities that might be associated with pediatric bipolar disorder. The aim of this study was to use magnetic resonance spectroscopy to evaluate several brain regions implicated in bipolar disorder in children with a mood disorder and a familial risk for bipolar disorder. We hypothesized that these children would exhibit neurochemical differences compared with healthy children of parents without a psychiatric disorder. Specifically, decreased N-acetylaspartate (NAA) and creatine and phosphocreatine (Cr) of the prefrontal cortex and cerebellar vermis would reflect impairments in neuronal function and cellular metabolism, and elevated myo-inositol (mI) would reflect impaired phosphoinositide metabolism, potentially representing early markers of neurophysiologic changes that might underlie the development of bipolar disorder.. Children with a mood disorder and at least one parent with bipolar disorder (n = 9) and healthy children (n = 10) group matched for age (8-12 years), race, sex, education, and Tanner stage were evaluated using the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia. Proton magnetic resonance spectroscopy was acquired using 8-cc volumes within the frontal cortex, frontal white matter, and the cerebellar vermis. Metabolite ratios (NAA/Cr, cholines (Cho)/Cr, mI/Cr, NAA/Cho, NAA/mI, and Cho/mI) and concentrations (NAA, Cr, Cho, and mI) were calculated and compared between groups.. The trend in concentration levels of NAA and Cr was approximately 8% lower for children with a mood disorder than healthy children within the cerebellar vermis. The frontal cortex in children with a mood disorder revealed elevated mI concentration levels, approximately 16% increased, compared with healthy children.. Similar to findings in adults with bipolar disorders, neurochemical abnormalities within the frontal cortex and the cerebellar vermis were present in this preliminary comparison of children with a mood disorder and a familial risk for bipolar disorder. Larger sample sizes are needed to replicate these findings.

Topics: Aspartic Acid; Bipolar Disorder; Brain Chemistry; Cerebellum; Child; Family; Female; Frontal Lobe; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Mood Disorders; Phosphocreatine; Protons; Psychiatric Status Rating Scales; Risk; Wechsler Scales

Proton magnetic resonance spectra were recorded from a subcortical region containing the basal ganglia in 40 patients with affective disorders (18 with bipolar disorder and 22 with major depression) and in 20 normal controls. The absolute concentration of the choline-containing compounds (Cho) in the patients with bipolar disorder in the depressive state was significantly higher than that in the normal controls. The patients with bipolar disorder had significantly higher levels of the Cho/creatine + phosphocreatine (Cr) and Cho/N-acetly-1-aspartate (NAA) peak ratio compared with the normal controls in both the depressive and euthymic states, with a tendency to higher levels in the depressive state. The Cho/NAA peak ratio was also significantly higher in the patients with major depression compared with the normal controls. These results suggest that the membrane phospholipid metabolism in the basal ganglia is altered in affective disorders.

Topics: Adult; Aspartic Acid; Basal Ganglia; Bipolar Disorder; Choline; Creatine; Depressive Disorder; Female; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Mood Disorders; Phosphocreatine