These preliminary findings do not support a role for adjunctive olanzapine for underweight adolescent females with anorexia nervosa-restricting type who are receiving standard care in an eating disorder treatment program (clinical trials.gov; no. NCT00592930).

Objectives To systematically evaluate the prodrome to mania in youth. Methods New-onset/worsening symptoms/signs of ≥ moderate severity preceding first mania were systematically assessed in 52 youth (16.2 ± 2.8 years) with a research diagnosis of bipolar I disorder (BD-I). Youth and/or caregivers underwent semi-structured interviews, using the Bipolar Prodrome Symptom Scale–Retrospective. Results The mania prodrome was reported to start gradually in most youth (88.5%), with either slow (59.6%) or rapid (28.8%) deterioration, while a rapid-onset-and-deterioration prodrome was rare (11.5%). The manic prodrome, conservatively defined as requiring ≥ 3 symptoms, lasted 10.3 ± 14.4 months [95% confidence interval (CI): 6.3–14.4], being present for ≥ 4 months in 65.4% of subjects. Among prodromal symptoms reported in ≥ 50% of youth, three were subthreshold manic in nature (irritability: 61.5%, racing thoughts: 59.6%, increased energy/activity: 50.0%), two were non-specific (decreased school/work functioning: 65.4%, mood swings/lability: 57.7%), and one each was depressive (depressed mood: 53.8%) or subthreshold manic/depressive (inattention: 51.9%). A decreasing number of youth had ≥ 1 (84.6%), ≥ 2 (48.1%), or ≥ 3 (26.9%) specific subthreshold mania symptoms (i.e., elation, grandiosity, decreased need for sleep, racing thoughts, or hypersexuality), lasting 9.5 ± 14.9 months (95% CI: 5.0–14.0), 3.5 ± 3.5 months (95% CI: 2.0–4.9), and 3.0 ± 3.2 months (95% CI: 1.0–5.0) for ≥ 1, ≥ 2, or ≥ 3 specific symptoms, respectively. Conclusions In youth with BD-I, a relatively lengthy, predominantly slow-onset mania prodrome appears to be common, including subthreshold manic and depressive psychopathology symptoms. This suggests that early clinical identification and intervention may be feasible in bipolar disorder. Identifying biological markers associated with clinical symptoms of impending mania may help increase chances for early detection and prevention before full mania.

Objective-To examine white matter microstructure, as assessed via diffusion tensor imaging (DTI), in adolescents with bipolar I disorder compared with control volunteers.Method-Twenty-six (12 male and 14 female subjects) adolescents (mean age, 16.0 years) with bipolar I disorder and 26 (14 male and 12 female subjects) control volunteers (mean age, 15.3 years) completed structural and DTI examinations. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) maps were compared between groups in the brain white matter using a voxelwise analysis after intersubject registration to Talairach space. Exploratory analyses were performed to assess structure-function correlations in a subgroup of 11 patients with available neuropsychological measures.Results-Compared with the control volunteers, the patients demonstrated abnormalities in white matter regions predicted to differ a priori between groups, including lower FA in the right orbital frontal lobe and higher ADC in the right and left subgenual region (p < .005, uncorrected; cluster size ≥ 100). There were no areas of higher FA or lower ADC in patients compared with control volunteers. Lower FA across regions that differed significantly between groups correlated significantly with slower visuomotor speed among patients with bipolar disorder. Measures of the coherence of white matter fibers that can be derived from DTI include fractional anisotropy (FA), which is a measure of the tendency for water molecules to move in one direction compared with another, and the apparent diffusion coefficient (ADC), which is a measure of water mobility in brain tissue. This information thus represents a potentially powerful tool for in vivo mapping of anatomic connectivity in humans. Adolescence is a time of enormous structural changes in the brain. 9 Because adolescence is a frequent age of onset for bipolar disorder, there may be structural neurodevelopmental deficits that are associated with the expression of bipolar disorder during this period of brain development. In particular, myelination of white matter tracts occurs during this time 10 especially in the frontal lobes, 11 which are believed to be responsible for emotional regulation, response inhibition, and planning and organization, among other functions. Clinically, these are the very functions that are most disrupted during a manic episode. 12 Previous DTI studies in bipolar disorder have yielded inconsistent findings with reports of higher anisotropy, 13,14 lower anisotropy, 15,16 and no differences in anisotropy 17 between patients and controls. The majority of studies, however, used small sample sizes and a regionof-interest approach whose definitions may be unreliable. A potentially important advantage of a voxel-based approach is that abnormalities may be identified across the entire brain and with greater reliability. Moreover, examining patients early in the course of illness may limit potential confounds such as illness duration. In this study, we used DTI to investigate FA and ADC in a cohort...