Positron emission tomography quantification of serotonin transporter binding in medication-free bipolar disorder.

OBJECTIVES: Bipolar disorder (BD) is associated with abnormalities in the serotonin transporter (5-HTT), but specific in vivo findings have been discrepant. Using positron emission tomography (PET) and [(11)C]DASB, we compared 5-HTT binding between unmedicated depressed BD subjects and healthy volunteers (HVs). EXPERIMENTAL DESIGN: 5-HTT binding in six brain regions was compared between 17 depressed, unmedicated BD subjects and 31 HVs, using the outcome measure of VT/fP (proportional to the total number of available transporters). Alternative outcome measures were examined as well. 47% of BD were BP I; and 65% reported a prior suicide attempt. PRINCIPAL OBSERVATIONS: 5-HTT binding (VT/fP ) did not differ between BD and HV groups considering six brain regions of interest simultaneously (P = 0.24). In contrast, alternative outcome measures (BPF*, BPP*, and BPND*) indicated lower binding in BD compared with HV across these six regions of interest (BPF*: P = 0.047; BPP*: P = 0.032; BPND*: P = 0.031). 5-HTT binding was unrelated to suicide attempt history, depression severity, bipolar subtype, or history of past substance use disorder. CONCLUSIONS: Choice of outcome measure strongly affects comparisons of serotonin transporter binding using PET with [(11)C]DASB. We do not find evidence of abnormal 5-HTT binding in bipolar depression using our primary outcome measure, VT /fP . However, we did observe lower 5-HTT binding in BD with alternative outcome measures that are frequently used with [(11)C]DASB. Relative merits and assumptions of different outcome measures are discussed. Evaluation in larger samples and during different mood states, including remission, is warranted.

Does first episode polarity predict risk for suicide attempt in bipolar disorder?

BACKGROUND: Defining bipolar disorder (BD) subtypes with increased risk of suicidal behavior may help clinical management. We tested the hypothesis that the polarity of a patient's first mood episode would be a marker for BD subtypes with differential risk for suicidality. METHODS: One hundred thirteen subjects with DSM-IV defined BD were classified based on whether their first reported episode was manic/hypomanic (FM) or depressed (FD). They were compared on demographic and clinical variables. Logistic regression adjusting for potential confounds tested the association between first episode polarity and history of suicide attempt. RESULTS: Multiple logistic regression analysis showed that FD group membership was associated with eightfold odds of a past suicide attempt, adjusting for years ill and total number of lifetime major depressive episodes. LIMITATIONS: Sample size, retrospective design, recall bias, assessment during a mood episode, and imprecise recall of hypomania. CONCLUSIONS: Polarity of patients' first reported mood episode suggested a depression-prone subtype with a greater probability of past suicide attempt. The FM group had more alcoholism and psychosis, but less likelihood of past suicide attempt. Validation of these putative subtypes requires prospective study.

Effect of exposure to suicidal behavior on suicide attempt in a high-risk sample of offspring of depressed parents.

OBJECTIVE: Exposure to suicidal behavior in peers and relatives is thought to increase risk for suicidal behavior in vulnerable individuals, possibly as a result of imitation or modeling. This study examines exposure to suicidal behavior and likelihood of suicide attempt in a high-risk cohort of offspring of a depressed parent. METHOD: A total of 449 offspring of 255 probands with a mood disorder were enrolled in a family study. Probands and offspring were assessed for psychopathology and suicide attempt history, and offspring for suicide exposure. Generalized estimating equations (GEE) and generalized least squares models were used to compare suicide attempt history in exposed and nonexposed offspring as well as characteristics of exposure in exposed offspring suicide attempters and exposed nonattempters. GEE was used to compare exposure occurring before first attempt in attempter offspring and exposure occurring before the same age in matched nonattempter offspring. RESULTS: Offspring reporting exposure to suicidal behavior were four times more likely to report a lifetime suicide attempt compared with unexposed offspring, controlling for age. Suicide attempt status was not associated with age at first exposure, total number or degree (attempt or threat) of exposures, or relationship. Analysis of exposure occurring before age at first suicide attempt found no association between exposure and suicide attempt. CONCLUSIONS: Offspring exposed to suicidal behavior are more likely to report a lifetime suicide attempt than nonexposed offspring. However, when examining the temporal sequence of exposure and attempt, the association is no longer significant, suggesting that imitation is not sufficient explanation.