Structural brain and neuropsychometric changes associated with pediatric bipolar disorder with psychosis.

OBJECTIVES: To identify neuropsychological and structural brain changes using a combination of high-resolution structural and diffusion tensor imaging in pediatric bipolar disorder (PBD) with psychosis (presence of delusions and or hallucinations). METHODS: We recruited 15 patients and 20 euthymic age- and gender-matched healthy controls. All subjects underwent high-resolution structural and diffusion tensor imaging. Voxel-based morphometry (VBM), tract-based spatial statistics (TBSS), and probabilistic tractography were used to analyse magnetic resonance imaging data. RESULTS: The PBD subjects had normal overall intelligence with specific impairments in working memory, executive function, language function, and verbal memory. Reduced gray matter (GM) density was found in the left orbitofrontal cortex, left pars triangularis, right premotor cortex, occipital cortex, right occipital fusiform gyrus, and right crus of the cerebellum. TBSS analysis showed reduced fractional anisotropy (FA) in the anterior corpus callosum. Probabilistic tractography from this cluster showed that this region of the corpus callosum is connected with the prefrontal cortices, including those regions whose density is decreased in PBD. In addition, FA change was correlated with verbal memory and working memory, while more widespread reductions in GM density correlated with working memory, executive function, language function, and verbal memory. CONCLUSIONS: The findings suggest widespread cortical changes as well as specific involvement of interhemispheric prefrontal tracts in PBD, which may reflect delayed myelination in these tracts.

A Preliminary Study of an Extension of a Community Dialectic Behaviour Therapy (DBT) Programme to Adolescents in the Looked After Care System.

BACKGROUND: Adolescents in the Looked After Care (LAC) system demonstrate high rates of psychiatric disorder and self-harm; however, there is little evidence for therapies reducing self-harm in this population. METHOD: An open evaluation of DBT for adolescents with repeated serious self-harm in the LAC system was undertaken. RESULTS: An intention-to-treat (ITT) analysis showed that DBT was successful at reducing the core elements of depression, hopelessness and self-harm; however, 35% (7/20) failed to engage. CONCLUSION: DBT is a useful treatment option; the failure, however, of some adolescents to engage in therapy may be due to their higher initial rates of depression and hopelessness.

Evidence for abnormalities of cortical development in adolescent-onset schizophrenia.

Voxel-Based Morphometry (VBM) identifies differences in grey matter brain structure in patients with schizophrenia relative to healthy controls, with particularly prominent differences found in patients with the more severe, adolescent-onset form of the disease. However, as VBM is sensitive to a combination of changes in grey matter thickness, intensity and folding, specific neuropathological interpretations are not possible. Here, we attempt to more precisely define cortical changes in 25 adolescent-onset schizophrenic patients and 25 age- and sex-matched healthy volunteers using Surface-Based Morphometry (SBM) to disambiguate the relative contributions of cortical thickness and surface area differences to changes in regional grey matter (GM) density measured with VBM. Cortical changes in schizophrenia were widespread, including particularly the prefrontal cortex and superior temporal gyrus. Nine regions of apparent reduction in GM density in patients relative to healthy matched controls were found using VBM that were not found with SBM-derived cortical thickness measures. In Regions of Interest (ROIs) derived from the VBM group results, we confirmed that local surface area differences accounted for these VBM changes. Our results emphasize widespread, but focally distinct cortical pathology in adolescent-onset schizophrenia. Evidence for changes in local surface area (as opposed to simply cortical thinning) is consistent with a neurodevelopmental contribution to the underlying neuropathology of the disease.

A Preliminary Community Study of Dialectical Behaviour Therapy (DBT) with Adolescent Females Demonstrating Persistent, Deliberate Self-Harm (DSH).

A study of dialectical behaviour therapy (DBT) for 16 older female adolescents with persistent and severe deliberate self-harm was undertaken. Independent assessments were carried out pre- and post-treatment, and at eight months follow-up. On average subjects completed more than 78% of sessions. There was a marked reduction in self reported depression (F = 12.8, df = 2, p < .001); hopelessness (F = 15.9, df = 2, p < .001); episodes of deliberate self-harm (F = 23.9, df = 2, p < .001); alongside an increase in general functioning (F = 22.9, df = 2, p < .001).

Changes in gray matter volume and white matter microstructure in adolescents with obsessive-compulsive disorder.

BACKGROUND: There is a paucity of neuroimaging data in pediatric-onset obsessive-compulsive disorder (OCD). This multimodal neuroimaging study aimed to identify structural gray (GM) and white matter (WM) microstructure changes in pediatric OCD. METHODS: We obtained structural and diffusion tensor magnetic resonance images from 26 OCD patients and 26 matched healthy adolescents. We carried out a series of image analyses including, volumetric and shape analysis of subcortical gray structures, as well as voxel-based morphometry on GM volume and fractional anisotropy of the WM. RESULTS: Patients had increased GM volume in the caudate bilaterally and right putamen. Shape analyses revealed specific hypertrophy of the dorsal caudate in pediatric OCD. The striatum was larger in healthy boys compared with healthy girls, whereas such a gender effect was not seen in the OCD group. OCD subjects showed higher fractional anisotropy values in left inferior longitudinal fasciculus, bilateral superior longitudinal fasciculus, right inferior fronto-occipital fasciculus, bilateral corticospinal tract, corpus callosum splenium and genu, bilateral forceps major, bilateral forceps minor, left cingulum, and right uncinate fasciculus. OCD symptom severity was positively correlated with GM volume in right insula, posterior orbitofrontal cortex, brainstem, and cerebellum and inversely correlated with widespread reduction in cortical GM volume. Furthermore, symptom severity positively correlated with increased WM fractional anisotropy in various WM tracts, including the anterior limb of the internal capsule. CONCLUSIONS: Adolescents with OCD had a wide range of GM and WM changes compared to healthy control subjects that are broadly consistent with those identified in the adult OCD literature but are more extensive.