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.

Hypoplasia of the corpus callosum and obsessive-compulsive symptoms.

Abnormalities in the corpus callosum, which connects the cerebral hemispheres, have been implicated in the pathogenesis of obsessive-compulsive disorder. This is a report of two cases of obsessive-compulsive disorder associated with hypoplasia of the corpus callosum. These data provide further support for corpus callosum-mediated dysfunction in obsessive-compulsive disorder.

Prefrontal cortical volume in childhood-onset major depression: preliminary findings.

BACKGROUND: Abnormalities in the prefrontal cortex have been implicated in the pathogenesis of major depressive disorder (MDD). To our knowledge, no prior study has examined prefrontal cortical anatomy in pediatric patients with MDD near the onset of illness before receiving treatment. METHODS: Volumetric magnetic resonance imaging studies were conducted in 22 psychotropic-naive patients with MDD, aged 9 to 17 years (10 males and 12 females), and 22 case-matched healthy comparison control subjects. Twelve of the 22 patients with MDD had at least 1 first-degree relative with MDD (familial MDD), whereas 10 had no clear family history of MDD (nonfamilial MDD). RESULTS: Patients with nonfamilial MDD had significantly larger left-sided but not right-sided prefrontal cortical volumes than patients with familial MDD (17% larger) and controls (11% larger). Left-sided and right-sided prefrontal cortical volumes did not differ significantly between patients with familial MDD and controls. CONCLUSIONS: These results provide new evidence of prefrontal cortical alterations in pediatric MDD that may differ in familial and nonfamilial subtypes of MDD. Our findings must be considered preliminary, however, in view of the small sample size.