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.

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.

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.

Use of low-dose selective serotonin reuptake inhibitors for severe, refractory choking phobia in childhood.

Difficulty swallowing solids and/or liquids accompanied by intense anxiety that results in restricted eating patterns or complete avoidance of eating may not have an easily identified underlying medical cause. This type of "eating disorder," which has also been described as "choking phobia," may occur in the absence of body image distortion, fear of becoming fat, or the desire to be thinner. The primary complaint in these children may be physical discomfort accompanied by high anxiety. Negative consequences can be severe and include social withdrawal, family distress, and deleterious effects on the child's physical health. Prompt recognition in the pediatric setting is, therefore, critical to avoid escalation of symptoms and treatment delays. Three pediatric cases of severe choking phobia refractory to prior intervention are presented in which rapid and sustained improvement followed low-dose therapy with a selective serotonin reuptake inhibitor (SSRI). Possible predictors of response to low-dose SSRI treatment in children with choking phobia and future avenues for investigation are explored.

Reduced anterior cingulate glutamatergic concentrations in childhood OCD and major depression versus healthy controls.

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

Brain structural abnormalities in psychotropic drug-naive pediatric patients with obsessive-compulsive disorder.

OBJECTIVE: The authors investigated structural abnormalities in brain regions comprising cortical-striatal-thalamic-cortical loops in pediatric patients with obsessive-compulsive disorder (OCD). METHOD: Volumes of the caudate nucleus, putamen, and globus pallidus and gray and white matter volumes of the anterior cingulate gyrus and superior frontal gyrus were computed from contiguous 1.5-mm magnetic resonance images from 23 psychotropic drug-naive pediatric patients with OCD (seven male patients and 16 female patients) and 27 healthy volunteers (12 male subjects and 15 female subjects). RESULTS: Patients had smaller globus pallidus volumes than healthy volunteers, but the two groups did not differ in volumes of the caudate nucleus, putamen, or frontal white matter regions. Compared to healthy volunteers, patients had more total gray matter in the anterior cingulate gyrus but not the superior frontal gyrus. Total anterior cingulate gyrus volume correlated significantly and positively with globus pallidus volume in the healthy volunteers but not in patients. CONCLUSIONS: These findings provide evidence of smaller globus pallidus volume in patients with OCD without the potentially confounding effects of prior psychotropic drug exposure. Volumetric abnormalities in the anterior cingulate gyrus appear specific to the gray matter in OCD, at least at the gross anatomic level, and are consistent with findings of functional neuroimaging studies that have reported anterior cingulate hypermetabolism in the disorder.

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.

Amygdala volume reductions in pediatric patients with obsessive-compulsive disorder treated with paroxetine: preliminary findings.

The amygdala is believed to be highly relevant to the pathophysiology of obsessive-compulsive disorder (OCD) given its prominent role in fear conditioning and because it is an important target of the serotonin reuptake inhibitors (SRIs), the pharmacotherapy of choice for OCD. In the present study, we measured in vivo volumetric changes in the amygdala in pediatric patients with OCD following 16 weeks of monotherapy with the selective SRI, paroxetine hydrochloride. Amygdala volumes were computed from contiguous 1.5 mm magnetic resonance (MR) images in 11 psychotropic drug-naive patients with OCD prior to and then following treatment. Eleven healthy pediatric comparison subjects also had baseline and follow-up scans, but none of these subjects received medication. Patients demonstrated significant asymmetry of the amygdala (L>R) prior to pharmacologic intervention in contrast to healthy comparison subjects who showed no asymmetry at the time of their baseline scan. Mixed model analyses using age and total brain volume as time varying covariates indicated that left amygdala volume decreased significantly in patients following treatment. The reduction in left amygdala volume in patients correlated significantly with higher paroxetine dosage at the time of the follow-up scan and total cumulative paroxetine exposure between the scans. No significant changes in either right or left amygdala volume were evident among healthy comparison subjects from the baseline to the follow-up scan. These preliminary findings suggest that abnormal asymmetry of the amygdala may play a role in the pathogenesis of OCD and that paroxetine treatment may be associated with a reduction in amygdala volume.

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.

Childhood anxiety disorders and developmental issues in anxiety.

Anxiety disorders are common disorders in childhood, and developmental differences must be considered when diagnosing and treating patients in this age group. Recent research has illuminated the course of childhood anxiety disorders, including how they can be precursors to continued anxiety and mood problems in adulthood. Recent studies of cognitive-behavioral therapy, the first-line psychosocial treatment for childhood anxiety, have focused on the following issues: the relative efficacy of group versus individual cognitive-behavioral therapy; the role of parent involvement; and the application of specific techniques to certain diagnostic groups (eg, social skills techniques in social phobia). Selective serotonin reuptake inhibitors have been associated with high acute response rates in controlled studies of children with anxiety disorders, and more recent evidence suggests they are efficacious and well tolerated when taken for longer periods. This article will review significant diagnostic and developmental issues, and highlight recent studies in psychosocial and pharmacologic therapies of pediatric anxiety disorders.

Localized functional neurochemical marker abnormalities in dorsolateral prefrontal cortex in pediatric obsessive-compulsive disorder.

BACKGROUND: Neurobiological abnormalities in the prefrontal cortex have been implicated in the pathogenesis of obsessive-compulsive disorder (OCD). Although OCD commonly arises during childhood and adolescence, to our knowledge, no prior study has examined prefrontal cortex neurochemistry in pediatric patients with OCD. METHODS: A multislice spectroscopic imaging sequence with validated phantom replacement methodology was used to measure N-acetyl-aspartate (NAA), a putative neuronal marker; choline compounds (Cho); and creatine/phosphocreatine (Cr) in right and left dorsolateral prefrontal cortex (DLPFC) of 15 treatment-naïve OCD patients, 8-15 years of age, and 15 case-matched healthy comparison subjects. RESULTS: A significant increase (21% higher) in NAA was observed in left but not right DLPFC in OCD patients versus control subjects. No significant differences in Cho or Cr were observed between groups in left or right DLPFC. CONCLUSIONS: These results provide new evidence of localized functional neurochemical marker alterations in left DLPFC in pediatric OCD. Increased left DLPFC NAA may represent neuronal hypertrophy or hyperplasia, glial hypoplasia, and/or abnormal pruning of neural brain elements in DLPFC.

Increased amygdala: hippocampal volume ratios associated with severity of anxiety in pediatric major depression.

BACKGROUND: Neurobiologic abnormalities in the temporal lobe, particularly medial temporolimbic circuits, have been implicated in the pathogenesis of major depressive disorder (MDD). Although MDD commonly emerges during childhood and adolescence, to our knowledge, no prior study has examined temporal lobe anatomy in pediatric patients with MDD near the onset of illness before treatment. METHODS: Volumetric magnetic resonance imaging scans were conducted in 23 psychotropic drug-naïve pediatric patients with MDD, aged 8-17 years, and 23 case-matched healthy comparison subjects. RESULTS: Pediatric patients with MDD had significantly larger left (14%) and right (11%) amygdala:hippocampal volume ratios than controls. Increased left and right amygdala:hippocampal volume ratios were associated with increased severity of anxiety but not increased severity of depression or duration of illness. CONCLUSION: These results suggest that alterations in amygdala:hippocampal volume ratios in pediatric MDD may more reflect severity of associated anxiety than depression. These results underscore the importance of assessment for comorbidity in the study of MDD.