Elevated serum measures of lipid peroxidation and abnormal prefrontal white matter in euthymic bipolar adults: toward peripheral biomarkers of bipolar disorder.

Diffusion tensor imaging (DTI) studies consistently reported abnormalities in fractional anisotropy (FA) and radial diffusivity (RD), measures of the integrity of white matter (WM), in bipolar disorder (BD), that may reflect underlying pathophysiologic processes. There is, however, a pressing need to identify peripheral measures that are related to these WM measures, to help identify easily obtainable peripheral biomarkers of BD. Given the high lipid content of axonal membranes and myelin sheaths, and that elevated serum levels of lipid peroxidation are reported in BD, these serum measures may be promising peripheral biomarkers of underlying WM abnormalities in BD. We used DTI and probabilistic tractography to compare FA and RD in ten prefrontal-centered WM tracts, 8 of which are consistently shown to have abnormal FA (and/or RD) in BD, and also examined serum lipid peroxidation (lipid hydroperoxides, LPH and 4-hydroxy-2-nonenal, 4-HNE), in 24 currently euthymic BD adults (BDE) and 19 age- and gender-matched healthy adults (CONT). There was a significant effect of group upon FA in these a priori WM tracts (BDECONT: F[1,41]=10.3; P=0.003), and a significant between-group difference in LPH (BDE>CONT: t[40]=2.4; P=0.022), but not in 4-HNE. Multivariate multiple regression analyses revealed that LPH variance explained, respectively, 59 and 51% of the variance of FA and RD across all study participants. This is the first study to examine relationships between measures of WM integrity and peripheral measures of lipid peroxidation. Our findings suggest that serum LPH may be useful in the development of a clinically relevant, yet easily obtainable and inexpensive, peripheral biomarkers of BD.

Criterion and predictive validity of the diagnosis of adjustment disorder: a prospective study of youths with new-onset insulin-dependent diabetes mellitus.

OBJECTIVE: The authors examined the criterion and predictive validity of the diagnosis of adjustment disorder in a pediatric study group. METHOD: Ninety-two school-age children with new-onset insulin-dependent diabetes mellitus were evaluated repeatedly and were diagnosed by using DSM-III. The criteria for adjustment disorder were further operationalized by requiring four clinically significant symptoms or signs; the time frame for its onset was extended to 6 months after the diagnosis of insulin-dependent diabetes. Predictive validity was assessed in terms of new psychiatric disorders other than adjustment disorder during the next 5 years. RESULTS: Of the 92 children, 33 developed adjustment disorder and five developed other psychiatric disorders in response to the diagnosis of insulin-dependent diabetes mellitus. Mean time from diabetes diagnosis to onset of adjustment disorder was 29 days, the average episode length was 3 months, and the recovery rate was 100%. Among youths with adjustment disorder in response to the medical diagnosis, the 5-year cumulative probability of a new psychiatric disorder was 0.48, compared to 0.16 among the other youths. CONCLUSIONS: The findings generally support the criterion validity of the diagnosis of adjustment disorder. However, episode duration and the predictive validity of the diagnosis appear to be functions of the study group being examined. In nonpsychiatrically referred pediatric patients, early problems in adaptation to the stress of changed health status, as evidenced by adjustment disorder, appear to signal vulnerability to later psychopathology.