Michelle Rose

AMYGDALA AND HIPPOCAMPAL VOLUMES IN FAMILIAL EARLY ONSET MAJOR DEPRESSIVE DISORDER

BACKGROUND Abnormalities in the amygdala and hippocampus have been implicated in the pathogenesis of major depressive disorder (MDD). To our knowledge, no prior study has examined amygdala-hippocampus anatomy in pediatric patients with familial MDD (at least one first degree relative with MDD). METHODS Thirty-two psychotropic-naive patients with familial MDD, aged 8-21 years (12 males and 20 females), and 35 group-matched healthy participants (13 males and 22 females) underwent volumetric magnetic resonance imaging in order to evaluate hippocampal and amygdala volumes. RESULTS Patients with familial MDD had significantly smaller left hippocampal (p = .007, effect size [d] = .44) and right hippocampal volumes (p = .025, d = .33) than controls. No differences were noted in amygdala volumes between groups (right: p > .05, left: p > .05). No correlations between hippocampal or amygdala volumes and demographic or clinical variables were noted. CONCLUSIONS Reduced hippocampal volume may be suggestive of a risk factor for developing MDD.

Reduced Anterior Cingulate Glutamate in Pediatric Major Depression: A Magnetic Resonance Spectroscopy Study

BACKGROUND Anterior cingulate cortex has been implicated in the pathogenesis of major depressive disorder (MDD). With single voxel proton magnetic resonance spectroscopy, we reported reductions in anterior cingulate glutamatergic concentrations (grouped value of glutamate and glutamine) in 14 pediatric MDD patients versus 14 case-matched healthy control subjects. These changes might reflect a change in glutamate, glutamine, or their combination. METHODS Fitting to individually quantify anterior cingulate glutamate and glutamine was performed in these subjects with a new basis set created from data acquired on a 1.5 Tesla General Electric Signa (GE Healthcare, Waukesha, Wisconsin) magnetic resonance imaging scanner with LCModel (Version 6.1-0; Max-Planck-Institute, Gottingen, Germany). RESULTS Reduced anterior cingulate glutamate was observed in MDD patients versus control subjects (8.79 +/- 1.68 vs. 11.46 +/- 1.55, respectively, p = .0002; 23% decrease). Anterior cingulate glutamine did not differ significantly between patients with MDD and control subjects. CONCLUSIONS These findings provide confirmatory evidence of anterior cingulate glutamate alterations in pediatric MDD.

Reduced anterior cingulate cortex glutamatergic concentrations in childhood major depression

OBJECTIVE To examine in vivo glutamatergic neurochemical alterations in the anterior cingulate cortex of children with major depressive disorder (MDD). METHOD Single-voxel proton magnetic resonance spectroscopic (H-MRS) examinations of the anterior cingulate cortex were conducted in 13 psychotropic-naïve children and adolescents with MDD and 13 age- and sex-matched healthy children and adolescents. Ten of the 13 MDD patient-control pairs also had a H-MRS examination of occipital cortex. RESULTS Anterior cingulate glutamatergic (Glx) concentrations were significantly lower (19% decrease) in MDD patients versus controls (9.27 +/- 0.43 versus 11.47 +/- 0.26, respectively, p = 0.000). Reduced anterior cingulate Glx in MDD patients was associated with increased severity of functional impairment. These results remained comparably significant after controlling for age and anterior cingulate volume. Occipital cortex Glx did not differ between MDD patients and controls. CONCLUSIONS These preliminary findings provide new evidence of localized functional neurochemical marker alterations in Glx in anterior cingulate cortex in pediatric MDD. Altered anterior cingulate Glx neurotransmission may be involved in the pathogenesis of MDD.

Increased medial thalamic choline found in pediatric patients with obsessive-compulsive disorder versus major depression or healthy control subjects: A magnetic resonance spectroscopy study

BACKGROUND Neurobiologic abnormalities in medial thalamus have been implicated in the pathogenesis of obsessive-compulsive disorder (OCD). We previously used multislice proton magnetic resonance spectroscopic imaging (1-H MRSI) to identify localized functional neurochemical marker alterations in choline (Cho) in medial but not lateral thalamus in treatment-naïve pediatric patients with OCD compared with matched control subjects. Altered brain Cho levels have also been implicated in the pathogenesis of mood disorders. METHODS We used 1-H MRSI to study absolute Cho concentrations in 18 psychotropic-naïve pediatric patients with major depressive disorder (MDD) not suffering from OCD, 9-17 years of age, 18 case-matched healthy control subjects, and 27 nondepressed, psychotropic-naïve pediatric patients with OCD, 7-16 years of age. RESULTS Significantly increased left and right medial thalamic Cho concentrations were observed in OCD patients compared with both healthy control subjects and patients with MDD. Medial thalamic Cho concentrations did not differ significantly between patients with MDD and control subjects. CONCLUSIONS These results suggest that localized functional neurochemical marker alterations in medial thalamic Cho differentiate patients with OCD from healthy control subjects and patients with MDD. Although these results must be considered preliminary, further study of the diagnostic specificity of Cho as a relevant biomarker in OCD is clearly warranted.

Glutamate receptor gene (GRIN2B) associated with reduced anterior cingulate glutamatergic concentration in pediatric obsessive-compulsive disorder

In this preliminary study, 16 psychotropic-naïve pediatric patients with obsessive-compulsive disorder (OCD) were studied using magnetic resonance spectroscopy (MRS) and genotyped for six candidate polymorphisms in two glutamate system genes. A significant association was identified between the rs1019385 polymorphism of the glutamate receptor, ionotropic, N-methyl-d-aspartate 2B (GRIN2B) and decreased anterior cingulate cortex (ACC) glutamatergic concentration (Glx) but not with occipital Glx. These results suggest that GRIN2B may be associated with Glx in the ACC, a region consistently implicated in OCD.

Pituitary Volume in Treatment-Naïve Pediatric Major Depressive Disorder

BACKGROUND Prior pilot investigation identified a larger pituitary gland volume (PGV) in pediatric patients with major depressive disorder (MDD) compared with healthy pediatric control subjects that was most prominent in boys with MDD. In this independent sample, we focus on gender differences in pituitary volume in a larger sample of pediatric patients with MDD. METHODS Volumetric magnetic resonance imaging studies were conducted in 35 psychotropic drug-naïve children (15 boys, 20 girls), ages 8-17 years, and 35 case-matched healthy control subjects. RESULTS The MDD boys had larger PGV (19%) compared with male control subjects. No significant diagnostic group differences in pituitary volume were observed in girls. Healthy boys had significantly smaller PGV (27%) than healthy girls, whereas MDD boys did not differ from girls with MDD. Nonfamilial (without a family history of mood disorder) boys with MDD had significantly larger PGV (35%) than male healthy control subjects and tended to have a larger PGV (27%) than familial (at least one first-degree relative with MDD) boys with MDD. Boys with familial MDD did not differ from control subjects. CONCLUSIONS These findings provide new evidence of increased pituitary volume in psychotropic-naïve pediatric patients with MDD that seems to be more prominent in male patients with nonfamilial MDD.

Increased medial thalamic creatine- phosphocreatine found by proton magnetic resonance spectroscopy in children with obsessive-compulsive disorder versus major depression and healthy controls

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. (J Child Neurol 2006;21:106—111; DOI 10.2310/7010.2006.00016).

Pituitary Volume in Pediatric Obsessive-Compulsive Disorder

BACKGROUND Abnormalities in the limbic-hypothalamic-pituitary-adrenal (LHPA) axis have been implicated in the pathogenesis of obsessive-compulsive disorder (OCD). To our knowledge, however, no prior study has measured pituitary gland volume in OCD. METHODS Volumetric magnetic resonance imaging studies were conducted in 31 psychotropic drug-naïve children (10 boys, 21 girls) aged 8-17 years and 31 case-matched healthy comparison subjects. RESULTS Pituitary volume was significantly smaller in patients with OCD as compared with healthy control subjects (11% smaller). Smaller pituitary volume in patients with OCD was associated with increased compulsive but not obsessive symptom severity. Boys with OCD had smaller pituitary gland volumes compared with control boys (20% smaller). No significant differences in pituitary volume were observed between girls with OCD and control girls. Boys with OCD had significantly smaller pituitary volumes than girls with OCD (31% smaller), whereas control boys also had smaller pituitary gland volumes compared with control girls (21% smaller). CONCLUSIONS These findings provide new evidence of reduced pituitary volume in pediatric OCD that seems to be more prominent in male patients. The observed alterations in pituitary volume are consistent with neuroendocrine studies that have reported abnormalities in the LHPA axis in OCD.

Glutamate System Genes Associated with Ventral Prefrontal and Thalamic Volume in Pediatric Obsessive-Compulsive Disorder

This pilot study was undertaken to determine if there was a significant association between specific glutamate system genes and regional volumes of interest implicated in the pathogenesis of obsessive-compulsive disorder (OCD). Volumetric magnetic resonance imaging (MRI) and genotyping of seven polymorphisms in two genes, glutamate receptor, ionotropic, N-methyl-d-aspartate 2B (GRIN2B) and solute linked carrier, family 1, member 1 (SLC1A1) were conducted in 31 psychotropic-naïve pediatric OCD patients. The rs1805476 variant of GRIN2B was associated with left but not right orbital frontal cortex (OFC) (p = 0.04) and right but not left anterior cingulate cortex (ACC) volume (p = 0.02). The SLC1A1 rs3056 variant was associated with increased total (p = 0.01), left (p = 0.02) and right (p = 0.02) thalamic volume. These results suggest that GRIN2B and SLC1A1 may be associated with regional volumetric alterations in OFC, ACC, and thalamus in children with OCD.