phosphocreatine and Obsessive-Compulsive-Disorder

Previous neuroimaging studies implied that the dysfunction of cortico-striato-thalamo-cortical (CSTC) circuit served as the neural basis for the pathophysiology of obsessive-compulsive disorder (OCD). The imbalances in neuronal metabolite and neurotransmitter within CSTC circuit have been shown as the leading reasons of the OCD onset. The aim of this study is to investigate the metabolic alterations, especially the glutamatergic signal dysfunction within CSTC circuit, and the relationships between neural metabolites and the symptom severity of OCD patients.. Single voxel magnetic resonance spectroscopy (MRS) was conducted in medial prefrontal cortex (mPFC) and bilateral thalamus areas for thirteen unmedicated adult OCD patients with age-, gender-, and education-matched healthy controls. Quantification and multivariate analysis were performed to identify vital metabolic biomarkers for patients and healthy controls group differentiation. Moreover, we performed Spearman׳s rank correlation analysis for OCD patients to examine the relationship between the metabolite concentration level and OCD symptomatology.. Patients with OCD showed significantly decreased glutamate level in mPFC (p=0.021) and right thalamus (p=0.039), and significantly increased choline compounds in left thalamus (p=0.044).The glutamate in right thalamus was shown as the most important metabolite for group separation from multivariate analysis (Q(2)=0.134) and was significantly correlated with the patients׳ compulsion scores (Spearman r=-0.674, p=0.016).. Limited sample size, the use of creatine and phosphocreatine (Cr) ratios rather than absolute concentrations and unresolved glutamine (Gln) are limitations of the present study.. Our study results consolidated the hypothesis about glutamatergic signaling dysfunction in OCD. To our knowledge, it is the first finding about a reduced thalamic glutamate level in adult unmedicated OCD patients. The dysregulation of glutamate serves as a potential target for the OCD pharmacotherapy and the detailed mechanisms underlying the glutamate alterations within CSTC circuits merit further investigations.

Topics: Adult; Case-Control Studies; Confounding Factors, Epidemiologic; Creatine; Female; Glutamic Acid; Humans; Male; Middle Aged; Multivariate Analysis; Obsessive-Compulsive Disorder; Phosphocreatine; Proton Magnetic Resonance Spectroscopy; Sample Size; Severity of Illness Index; Signal Transduction; Thalamus

Altered brain creatine-phosphocreatine levels might reflect changes in brain energy use and have been implicated in the pathogenesis of obsessive-compulsive disorder and major depressive disorder. We used proton magnetic resonance spectroscopy to measure absolute concentrations of creatine-phosphocreatine in the right and left medial thalami in 18 pediatric patients with major depressive disorder 9 to 17 years of age, 18 case-matched healthy controls, and 27 patients with obsessive-compulsive disorder 7 to 16 years old. The two patient groups were psychotropic drug naive and were not comorbid for the diagnosis of the comparison group. We found significantly increased left and right medial thalamic creatine-phosphocreatine concentrations in patients with obsessive-compulsive disorder compared with both healthy controls and patients with major depression. Creatine-phosphocreatine concentrations did not differ significantly between patients with major depression and healthy controls. Our data suggest that increased medial thalamic creatine-phosphocreatine concentrations in patients with untreated obsessive-compulsive disorder reflect altered energy use in the medial thalamus and might differentiate patients with obsessive-compulsive disorder from healthy controls and patients with major depression. Although these results must be considered preliminary, further study of the diagnostic specificity of creatine-phosphocreatine in obsessive-compulsive disorder is indicated.

Topics: Adolescent; Brain Mapping; Child; Creatine; Depressive Disorder, Major; Dominance, Cerebral; Energy Metabolism; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Obsessive-Compulsive Disorder; Phosphocreatine; Predictive Value of Tests; Reference Values; Thalamus

To examine in vivo glutamatergic neurochemical alterations in the anterior cingulate cortex of pediatric patients with obsessive-compulsive disorder (OCD) without major depressive disorder (MDD) versus pediatric patients with MDD without OCD and healthy controls.. Single-voxel proton magnetic resonance spectroscopic examinations of the anterior cingulate cortex were conducted in 14 psychotropic-naïve children and adolescents with MDD without OCD, 10 to 19 years of age, 14 case-matched healthy controls, and 20 nondepressed, psychotropic-naïve pediatric patients with OCD 7 to 19 years of age.. Anterior cingulate glutamatergic concentrations were significantly reduced in both patients with OCD (15.1% decrease) and patients with MDD (18.7% decrease) compared with controls. Anterior cingulate glutamatergic concentrations did not differ significantly between patients with OCD and those with MDD.. Altered anterior cingulate glutamatergic neurotransmission may be involved in the pathogenesis of OCD and MDD. These preliminary findings further suggest that reduced anterior cingulate glutamate does not differentiate pediatric patients with OCD from pediatric patients with MDD.

Topics: Adolescent; Aspartic Acid; Child; Choline; Creatine; Depressive Disorder, Major; Female; Glutamic Acid; Glutamine; Gyrus Cinguli; Humans; Inositol; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Obsessive-Compulsive Disorder; Personality Assessment; Phosphocreatine; Reference Values; Synaptic Transmission

Neurobiological abnormalities in the thalamus, particularly the dorsomedial nucleus of the thalamus, are believed to be involved in the pathophysiology of obsessive-compulsive disorder. Although obsessive-compulsive disorder commonly arises in childhood and adolescence, no prior study has examined the thalamus in pediatric obsessive-compulsive disorder patients.. In this study, N-acetyl-aspartate, a putative marker of neuronal viability, creatine/phosphocreatine, and choline levels were measured in the lateral and medical subregions of the left and right thalami using a multislice proton magnetic resonance spectroscopic imaging sequence in 11 treatment-naive, nondepressed obsessive-compulsive disorder outpatients, 8-15 years old, and 11 case-matched control subjects.. A significant reduction in N-acetyl-aspartate/choline and N-acetyl-aspartate/(creatine/phosphocreatine + choline) was observed in both the right and left medial thalami in obsessive-compulsive disorder patients compared with control subjects. The N-acetyl-aspartate/choline and N-acetyl-aspartate/(creatine/phosphocreatine + choline) levels did not differ significantly between case-control pairs in either the left or the right lateral thalamus. Reduction in N-acetyl-aspartate levels in the left medial thalamus was inversely correlated with increased obsessive-compulsive disorder symptom severity.. These findings provide new evidence of localized functional neurochemical marker abnormalities in the thalamus in pediatric obsessive-compulsive disorder. Our results must be considered preliminary, however, given the small sample size.

Topics: Adolescent; Aspartic Acid; Brain Mapping; Case-Control Studies; Cerebral Cortex; Child; Choline; Corpus Striatum; Creatine; Dominance, Cerebral; Female; Humans; Magnetic Resonance Spectroscopy; Male; Nerve Net; Neural Pathways; Obsessive-Compulsive Disorder; Phosphocreatine; Reference Values; Thalamus