The 5-HTTLPR polymorphism, impulsivity and suicide behavior in euthymic bipolar patients.

BACKGROUND: Suicide behavior is very frequent in Bipolar Disorder (BD) and they are both closely associated with impulsivity. Furthermore they are, impulsivity, BD and suicide behavior, associated with serotonergic function, at least partially, under genetic determinism and somewhat associated with the serotonin transporter gene polymorphism, the 5-HTTLPR. We aimed to assess different impulsivity components in BD sub-grouped by suicidal attempt and healthy controls. We hypothesized that the non-planning/cognitive impulsivity, could be more closely associated with suicidal behavior. We further associated 5-HTTLPR genotypes with neuropsychological results to test the hypothesis that this polymorphism is associated with cognitive impulsivity. METHOD: We assessed 95 euthymic bipolar patients sub-grouped by suicidal attempt history in comparison with 94 healthy controls. All subjects underwent a laboratory assessment of impulsivity (Continuous Performance Test and Iowa Gambling Test). Furthermore the genotyping of 5-HTTLPR was performed in all subjects. RESULTS: We found that bipolar patients are more impulsive than healthy controls in all impulsivity dimensions we studied. Furthermore bipolar patients with a suicide attempt history have a greater cognitive impulsivity when compared to both bipolar patients without such a history as well when compared to healthy controls. No association was found between 5-HTTLPR genotypes and neuropsychological measures of impulsive behavior. LIMITATIONS: The sample studied can be considered small and a potentially confounding variable - medication status - was not controlled. CONCLUSION: A lifetime suicide attempt seems associated with cognitive impulsivity independently of the socio-demographic and clinical variables studied as well with 5-HTTLPR genotype. Further studies in larger samples are necessary.

Bipolar disorders and affective temperaments: a national family study testing the "endophenotype" and "subaffective" theses using the TEMPS-A Buenos Aires.

BACKGROUND: The purpose of this study is to examine the prevalence of affective temperaments between clinically unaffected relatives of bipolar patients and secondarily to investigate the impact of these "subaffective" forms on their quality of life (QoL). METHODS: The study was performed in seven sites across Argentina. We administered the scales TEMPS-A and Quality of Life Index to a sample of 114 non-ill first degree relatives of bipolar disorder patients ("cases") and 115 comparison subjects without family history of affective illness ("controls"). We used The Mood Disorder Questionnaire to rule out clinical bipolarity. RESULTS: Mean scores on all TEMPS-A subscales were significantly higher in cases, except for hyperthymia. The prevalence of affective temperaments, according to Argentinean cut-off points, was also higher, with statistical significance for cyclothymic and anxious temperaments. Regarding QoL, we found no significant differences between both groups, except for interpersonal functioning, which was better in controls. A detailed subanalysis showed significant effects of QoL domains for all temperaments, except for the hyperthymic. LIMITATIONS: We used self-report measures. A larger sample size would have provided us greater statistical power for certain analyses. CONCLUSIONS: Our findings support the concept of a spectrum of subthreshold affective traits or temperaments - especially for the cyclothymic and anxious - in bipolar pedigrees. We further demonstrated that, except for the hyperthymic, quality of life was affected by these temperaments in "clinically well" relatives. Overall, our data are compatible with the "endophenotype" and "subaffective" theses for affective temperaments.

A comparison of recovered bipolar patients, healthy relatives of bipolar probands, and normal controls using the short TEMPS-A.

OBJECTIVE: To investigate the presence of temperament dysregulation in healthy relatives of bipolar probands (RBP), a population at high risk for developing mood disorders, by comparing them with clinically recovered bipolar patients (BP) and normal controls (NC). METHOD: 52 RBP and 23 BP were originally recruited for a multicenter genetic study in bipolar disorders. NC (n=102) were also recruited by newspaper advertisement, radio and television announcements, flyers, newsletters, or word of mouth. All volunteers were asked to complete the TEMPS-A Scale, a self-report questionnaire designed to measure temperamental variations in psychiatric patients and healthy volunteers. In scoring temperaments, we relied upon the short validated version of the TEMPS-A [J. Affect. Disord. (2004)], from which traits with loadings <0.035 had been deleted. RESULTS: To examine differences in temperament dimensions among the three groups, a MANCOVA model was constructed using diagnostic group as the fixed factor (BP vs. RBP vs. NC); effects of age and gender were adjusted as covariates. MANCOVA showed overall group effect on the dependent variables (Hotelling's F5,175=6.64, p<0.001). Four dependent variables (dysthymic, cyclothymic, irritable, and anxious temperaments) showed significant between-group differences. RBP showed lower cyclothymic temperament scores than BP, but higher scores than NC. BP and RBP showed higher anxious temperament scores than NC. Hyperthymic scores were significantly highest in the NC. LIMITATION: In view of the small cell sizes, bipolar I vs. bipolar II subanalyses could not be conducted. CONCLUSIONS: Methodologic strengths of the present analyses is that the BP group had clinically recovered, and we used the validated short version of the TEMPS-A for the present analyses. Our findings suggest that some clinically healthy relatives of bipolar probands exhibit a subclinical cyclothymic instability in mood, interest, self-confidence, sleep, and/or energy as well as anxiety proneness that is not observed among normal controls. These traits may represent vulnerability markers and could presumably be used to identify individuals at high risk for developing bipolar spectrum disorders, or specific clinical subtypes (e.g., bipolar I, bipolar II) within this spectrum. This is a conceptual perspective with many unanswered questions. Resolution of these questions will require innovative definitions of phenotypes to be included in the analyses of the temperament subscales in different populations. The temperament subscales themselves need to be calibrated properly, to find out which traits or specific combinations of trains are most promising. More extensive and complex quantitative trait analyses of these temperaments in a much expanded sample are reported elsewhere in this issue [J. Affect. Disord. (2004)].