Jean-Michel Aubry

OBJECTIVE: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen) study. MATERIALS AND METHODS: Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (κ)] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling. RESULTS: Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (κ = 0.66 and κ = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (ICC1 = 0.71 and ICC2 = 0.75, respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders). CONCLUSIONS: We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study.

; OR = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.

BACKGROUND: Suicide rates generally peak in the second half of life and are particularly high in older men; however, little is known about the contribution of dispositional factors to late-life suicide. Maladaptive personality traits have been strongly implicated in suicide among younger adults, but the extent to which they continue to play a role in late-life suicidal behavior is unclear. We also do not know whether specific personality profiles interact with the stressors of aging to cause suicidal behavior. METHODS: a systematic review using the PubMed, Google Scholar, PsycInfo, Scopus, Ovid, Web of Science, Embase, and Cochrane search engines. The included key words related to three descriptors: "personality," "suicide," and "elderly." Included articles evaluated personality based on the Five-Factor Model (FFM) or ICD/DSM diagnostic criteria in older samples with minimum age cutoffs of 50 years or older. Our original search identified 1,183 articles, of which 31 were retained. RESULTS: Included studies were heterogeneous in their design and personality measurements. Studies of categorical personality disorders were particularly scarce and suggested a stronger association with late-life suicidal ideation than with death by suicide. Only obsessive-compulsive and avoidant personality traits were associated with death by suicide in old age, but only in studies that did not control for depression. All personality constructs were positively linked to suicidal ideation, except for histrionic personality, which emerged as a negative predictor. Studies employing the FFM also indicated that older adults who died by suicide were less likely to display a maladaptive personality profile than elderly suicide attempters and younger suicide victims, having both lower levels of neuroticism and higher levels of conscientiousness than these comparison groups. Nevertheless, older suicide victims displayed lower levels of openness to experience than younger victims in two samples. CONCLUSION: Maladaptive personality manifests in milder, subthreshold, and more heterogeneous forms in late-life vs. early-life suicide. An inability to adapt to the changes occurring in late life may help explain the association between suicide in old age and higher conscientiousness as well as obsessive-compulsive and avoidant personality disorders.