Central cholecystokinin activity in irritable bowel syndrome, panic disorder, and healthy controls.

OBJECTIVE: Irritable bowel syndrome (IBS) and panic disorder (PD) coexist with a high frequency. However, the nature of this relationship remains obscure. We have proposed that PD and IBS may share a common dysfunction of the central cholecystokinin (CCK) system. To test this hypothesis, we assessed whether the enhanced panicogenic response to CCK-tetrapeptide (CCK-4) observed in PD is also present in IBS. METHODS: Eight psychiatrically healthy IBS patients, 8 PD patients with no history of IBS, and 12 normal controls received a bolus injection of CCK-4 and placebo on two separate days in a double-blind, randomized fashion. RESULTS: Consistent with previous findings, panicogenic sensitivity to CCK-4 was enhanced in PD patients relative to controls. In contrast, IBS patients exhibited a response that was comparable to controls. Interestingly, CCK-4-induced nausea and abdominal distress were decreased in IBS patients relative to the other groups. No diagnostic difference was noted for cardiovascular response to CCK-4. CONCLUSION: These data indicate that IBS patients with no lifetime psychiatric history do not share the CCK-2 receptor dysfunction implicated in the pathophysiology of PD and that this dysfunction may not be a common mechanism for both CNS and enteric nervous system disorders. Nevertheless, the results suggest that a dysfunction of the CCK system may be involved in the pathophysiology of some enteric symptoms associated with IBS.

Impaired decision making in suicide attempters.

OBJECTIVE: The understanding of suicidal behavior is incomplete. The stress-diathesis model suggests that a deficit in serotonergic projections to the orbitofrontal cortex is involved in susceptibility to suicidal behavior. The orbitofrontal cortex has been implicated in decision making, a cognitive function dealing with complex choices that may be under serotonergic modulation. In this preliminary study, the authors assessed decision making in suicide attempters. METHOD: The authors used the Iowa Gambling Task to investigate patients with a history of violent (N=32) or nonviolent (N=37) suicidal behavior, patients suffering from affective disorders with no history of suicidal behavior (N=25), and healthy comparison subjects (N=82). Patients were assessed when they were not suffering from a current axis I disorder. The authors also assessed the correlation of Iowa Gambling Task performance with psychometric measures of impulsivity, hostility, anger, aggression, and emotional instability. RESULTS: Both groups of suicide attempters scored significantly lower than healthy comparison subjects, and violent suicide attempters performed significantly worse than affective comparison subjects. No significant differences were observed between the groups of suicide attempters or between the two comparison groups. The differences in performance could not be accounted for by age, intellectual ability, educational level, number of suicide attempts, age at first suicide attempt, history of axis I disorder, or medication use. Iowa Gambling Task performances were correlated positively with affective lability and with anger expression but not with impulsivity. CONCLUSIONS: Impaired decision making, possibly due to emotional dysfunction, may be a neuropsychological risk factor for suicidal behavior.

A history of major depressive disorder influences intent to die in violent suicide attempters.

BACKGROUND: The inconsistency of the results obtained in biological studies of suicidal behavior may be due to the use of broad categories lacking validity. In previous genetic studies, in which we identified an association between a serotonin-related gene and violent suicide attempts, we suggested that a history of major depressive disorder (MDD) might influence this association. In this study, we aimed to clarify the relationships between the violence of suicide attempts, intent to die, and depression in a large sample of suicide attempters. METHOD: We investigated intent to die, according to history of violent suicide attempts and MDD, in 502 consecutively admitted suicide attempters. We characterized patients in terms of lifetime DSM-IV Axis I diagnoses, suicidal intent (Beck Suicide Intent Scale), and history of violent suicide attempts. RESULTS: Suicidal intent, for both the last suicide attempt before admission and the most lethal suicide attempt, was higher in those with history of MDD (p =.03 and p =.04, respectively) but was not affected by history of violent suicide attempt. In violent suicide attempters, suicidal intent was higher in patients with a history of MDD than in patients with no such history (p =.04 for last suicide attempt and p =.02 for most lethal attempt), whereas MDD had no effect on suicidal intent in nonviolent suicide attempters. CONCLUSION: Violent suicide attempters constitute a heterogeneous group in terms of suicidal intent. Our results suggest that biological and genetic studies should take into account the method used to attempt suicide, intent to die, and history of MDD.

Serotonin transporter gene may be involved in short-term risk of subsequent suicide attempts.

BACKGROUND: In the first year following a suicide attempt, patients are at high risk for reattempt and for completed suicide. We aim to determine the predictive value of two serotonin-related genes, the tryptophan hydroxylase (TPH) and serotonin transporter (5-HTTLPR) genes that have been involved in the susceptibility to suicidal behavior. METHODS: After a one-year follow-up study of 103 patients hospitalized after a suicide attempt, patients have been genotyped for both the A218C TPH and the functional S/L 5-HTTLPR polymorphisms. RESULTS: Patients who reattempted suicide during the follow-up period had significantly higher frequencies of the S allele and the SS genotype. The odds ratio for the SS genotype vs. the LL genotype was 6.5 (95% CI [1.18-35.84]). No difference was observed for TPH gene. Patients carrying the SS genotype were more impulsive. However, multivariate analysis suggested an independent effect of both the SS genotype and impulsivity on the risk of repeated suicide attempts. CONCLUSIONS: These results suggest that the 5-HTTLPR SS genotype is associated with further suicide attempts among patients who have previously attempted suicide.