Bipolar Disorder and Suicide -- Neurotransmitter.net

(Updated 1/12/04)

Muller-Oerlinghausen B, Berghofer A, Bauer M.
Bipolar disorder.
Lancet 2002 Jan 19;359(9302):241-7
"Bipolar, or manic-depressive, disorder is a frequent, severe, mostly recurrent mood disorder associated with great morbidity. The lifetime prevalence of bipolar disorder is 1.3 to 1.6%. The mortality rate of the disease is two to three times higher than that of the general population. About 10-20% of individuals with bipolar disorder take their own life, and nearly one third of patients admit to at least one suicide attempt. The clinical manifestations of the disease are exceptionally diverse. They range from mild hypomania or mild depression to severe forms of mania or depression accompanied by profound psychosis. Bipolar disorder is equally prevalent across sexes, with the exception of rapid cycling, a severe and difficult to treat variant of the disorder, which arises mostly in women. Because of the high risk of recurrence and suicide, long-term prophylactic pharmacological treatment is indicated." [Abstract]

Rihmer Z, Kiss K.
Bipolar disorders and suicidal behaviour.
Bipolar Disord. 2002;4 Suppl 1:21-5.
"Major depressive disorder is the leading cause of suicide, particularly in the absence of adequate treatment. The aim of this paper is to analyse the relationship between different forms of major mood disorders and suicidal behaviour. Population-based epidemiological surveys as well as clinical studies on the clinically explorable suicide risk factors in bipolar and unipolar depressive disorders are reviewed. The present literature shows that patients with bipolar disorders are at higher risk of attempted and completed suicide than that of patients with unipolar major depression. Contrasting only bipolar I and bipolar II patients, current findings indicate that the rate of prior suicide attempt is higher in bipolar II patients, and bipolar II disorder is overrepresented in depressed suicide victims. Among patients with different clinical manifestations of major mood disorders (unipolar major depression. bipolar I and bipolar II disorder), bipolar patients in general, and bipolar II subjects in particular carry the highest risk of suicide." [Abstract]

Rihmer Z, Pestality P.
Bipolar II disorder and suicidal behavior.
Psychiatr Clin North Am 1999 Sep;22(3):667-73, ix-x
"Despite the fact that the nosologic position of bipolar II disorder continues to be debated, several lines of research indicate that it is a distinct nosologic category that should be separated from both bipolar I and unipolar major depression. This review of the authors' and others' work demonstrates that the lifetime risk of suicide attempts is highest in bipolar II and lowest in unipolar patients, whereas risk is intermediate in bipolar I patients. Moreover, two reports show that bipolar II patients are over represented among suicide victims. Clinicians must take great care in not missing this diagnosis, which, when untreated, has ominous prognostic implications." [Abstract]

Oquendo MA, Mann JJ.
Identifying and managing suicide risk in bipolar patients.
J Clin Psychiatry 2001;62 Suppl 25:31-4
"Bipolar patients have been shown to be at high risk for suicidal behavior. Therefore, identifying potentially suicidal patients is necessary in the treatment of bipolar patients. A stress-diathesis model for suicidal behavior has been proposed to assist clinicians in determining which patients are at risk. In the model, suicidal behavior is the result of the interaction between an individual's threshold for suicidal acts and the stressors that can lead to suicidal behavior. Suicide risk factors can then be categorized as either diathesis-related or stress-related. In a study applying the model of suicidal behavior to bipolar disorder, bipolar patients who attempted suicide had higher levels of suicidal ideation, lifetime aggression, and substance abuse than the comparison group of nonattempters. Attempters had twice the number of major depressive episodes. Once high-risk patients are identified, their suicide risk can be managed through treatments such as prophylactic lithium treatment and other pharmacologic approaches." [Abstract]

Dalton EJ, Cate-Carter TD, Mundo E, Parikh SV, Kennedy JL.
Suicide risk in bipolar patients: the role of co-morbid substance use disorders.
Bipolar Disord. 2003 Feb;5(1):58-61.
"OBJECTIVE: Bipolar disorder is associated with a high frequency of both completed suicides and suicide attempts. The primary aim of this study was to identify clinical predictors of suicide attempts in subjects with bipolar disorder. METHODS: We studied 336 subjects with a diagnosis of bipolar I, bipolar II, or schizoaffective disorder (bipolar type). The Structured Clinical Interview for DSM-IV (SCID-I) was administered and subsequently two expert psychiatrists established a diagnosis. Predictors of suicide attempts were examined in attempters and non-attempters. RESULTS: The lifetime rate of suicide attempts for the entire sample was 25.6%. A lifetime co-morbid substance use disorder was a significant predictor of suicide attempts: bipolar subjects with co-morbid substance use disorders (SUD) had a 39.5% lifetime rate of attempted suicide, while those without had a 23.8% rate (odds ratio = 2.09, 95% CI = 1.03-4.21, chi2 = 4.33, df = 1, p = 0.037). CONCLUSIONS: Lifetime co-morbid SUD were associated with a higher rate of suicide attempts in patients with bipolar disorder. This relationship may have a genetic origin and/or be explained by severity of illness and trait impulsivity." [Abstract]

Daskalopoulou EG, Dikeos DG, Papadimitriou GN, Souery D, Blairy S, Massat I, Mendlewicz J, Stefanis CN.
Self-esteem, social adjustment and suicidality in affective disorders.
Eur Psychiatry. 2002 Sep;17(5):265-71.
"Self-esteem (SE) and social adjustment (SA) are often impaired during the course of affective disorders; this impairment is associated with suicidal behaviour. The aim of the present study was to investigate SE and SA in unipolar or bipolar patients in relation to demographic and clinical characteristics, especially the presence of suicidality (ideation and/or attempt). Forty-four patients, 28 bipolar and 16 unipolar, in remission for at least 3 months, and 50 healthy individuals were examined through a structured clinical interview. SE and SA were assessed by the Rosenberg self-esteem scale and the social adjustment scale, respectively. The results have shown that bipolar patients did not differ from controls in terms of SE, while unipolar patients had lower SE than bipolars and controls. No significant differences in the mean SA scores were found between the three groups. Suicidality during depression was associated only in bipolar patients with lower SE at remission; similar but not as pronounced was the association of suicidality with SA. It is concluded that low SE lasting into remission seems to be related to the expression of suicidality during depressive episodes of bipolar patients, while no similar pattern is evident in unipolar patients." [Abstract]

Simpson SG, Jamison KR.
The risk of suicide in patients with bipolar disorders.
J Clin Psychiatry 1999;60 Suppl 2:53-6; discussion 75-6, 113-6
"Patients with bipolar disorder have a high risk of committing suicide, but determining the exact risk is complicated. For many years, the lifetime suicide risk in bipolar disorder was accepted as 15%, but recent researchers have suggested that the lifetime suicide risk may be lower. The group of bipolar patients at highest risk of suicide are young men who are in an early phase of the illness, especially those who have made a previous suicide attempt, those abusing alcohol, and those recently discharged from the hospital. The risk is also increased in patients who are in the depressed phase of bipolar illness, who have mixed states, or who have psychotic mania." [Abstract]

Vieta E, Colom F, Gasto C, Nieto E, Benabarre A, Otero A.
[Bipolar II disorder: course and suicidal behavior]
Actas Luso Esp Neurol Psiquiatr Cienc Afines 1997 May-Jun;25(3):147-51
"INTRODUCTION: Bipolar II disorder seems to be more than a mild form of classic manic-depressive illness. Differences with bipolar I concern genetic, biological, clinical and pharmacological aspects. Nevertheless, studies on suicidal behavior in both groups have resulted in inconsistent results PATIENTS AND METHOD: Twenty-two patients fulfilling Research Diagnostic Criteria for the diagnosis of bipolar II disorder and 38 bipolar I were evaluated with the Schedule for Affective Disorders and Schizophrenia by two independent interviewers, and compared. RESULTS: Bipolar II patients had significantly more previous episodes (p = 0.001), including both depressive (p = 0.003) and hypomanic switches (p = 0.006), but had been hospitalized (p = 0.001) and presented psychotic symptoms (p < 0.001) less frequently. CONCLUSIONS: There were no significant differences between both groups regarding suicidal behavior variables. These results suggest that bipolar II disorder is less severe than bipolar I regarding symptoms intensity, but more severe with respect to episodes frequency, and that suicide attempts rates are not useful to discriminate between both groups." [Abstract]

Leverich GS, Altshuler LL, Frye MA, Suppes T, Keck PE Jr, McElroy SL, Denicoff KD, Obrocea G, Nolen WA, Kupka R, Walden J, Grunze H, Perez S, Luckenbaugh DA, Post RM.
Factors associated with suicide attempts in 648 patients with bipolar disorder in the Stanley Foundation Bipolar Network.
J Clin Psychiatry. 2003 May;64(5):506-15.
"BACKGROUND: Clinical factors related to suicide and suicide attempts have been studied much more extensively in unipolar depression compared with bipolar disorder. We investigated demographic and course-of-illness variables to better understand the incidence and potential clinical correlates of serious suicide attempts in 648 outpatients with bipolar disorder. METHOD: Patients with bipolar I or II disorder (DSM-IV criteria) diagnosed with structured interviews were evaluated using self-rated and clinician-rated questionnaires to assess incidence and correlates of serious suicide attempts prior to study entry. Clinician prospective ratings of illness severity were compared for patients with and without a history of suicide attempt. RESULTS: The 34% of patients with a history of suicide attempts, compared with those without such a history, had a greater positive family history of drug abuse and suicide (or attempts); a greater personal history of early traumatic stressors and more stressors both at illness onset and for the most recent episode; more hospitalizations for depression; a course of increasing severity of mania; more Axis I, II, and III comorbidities; and more time ill on prospective follow-up. In a hierarchical logistic regression, a history of sexual abuse, lack of confidant prior to illness onset, more prior hospitalizations for depression, suicidal thoughts when depressed, and cluster B personality disorder remained significantly associated with a serious suicide attempt. CONCLUSION: Our retrospective findings, supplemented by prospective follow-up, indicate that a history of suicide attempts is associated with a more difficult course of bipolar disorder and the occurrence of more psychosocial stressors at many different time domains. Greater attention to recognizing those at highest risk for suicide attempts and therapeutic efforts aimed at some of the correlates identified here could have an impact on bipolar illness-related morbidity and mortality." [Abstract]

Oquendo MA, Waternaux C, Brodsky B, Parsons B, Haas GL, Malone KM, Mann JJ.
Suicidal behavior in bipolar mood disorder: clinical characteristics of attempters and nonattempters.
J Affect Disord 2000 Aug;59(2):107-17
"OBJECTIVE: Bipolar Disorder is associated with a higher frequency of attempted suicide than most other psychiatric disorders. The reasons are unknown. This study compared bipolar subjects with a history of a suicide attempt to those without such a history, assessing suicidal behavior qualitatively and quantitatively, and examining possible demographic, psychopathologic and familial risk factors. METHODS: Patients (ages 18 to 75) with a DSM III-R Bipolar Disorder (n = 44) diagnosis determined by a structured interview for Axis I disorders were enrolled. Acute psychopathology, hopelessness, protective factors, and traits of aggression and impulsivity were measured. The number, method and degree of medical damage was assessed for suicide attempts, life-time. RESULTS: Bipolar suicide attempters had more life-time episodes of major depression, and twice as many were in a current depressive or mixed episode, compared to bipolar nonattempters. Attempters reported more suicidal ideation immediately prior to admission, and fewer reasons for living even when the most recent suicide attempt preceded the index hospitalization by more than six months. Attempters had more lifetime aggression and were more likely to be male. However, attempters did not differ from nonattempters on lifetime impulsivity. LIMITATIONS: The generalizability of the results is limited because this is a study of inpatients with a history of suicide attempts. Patients with Bipolar I and NOS Disorders were pooled and a larger sample is needed to look at differences. We could not assess psychopathology immediately prior to the suicide attempt because, only half of the suicide attempters had made attempts in the six months prior to admission. Patients with current comorbid substance abuse were excluded. No suicide completers were studied. CONCLUSIONS: Bipolar subjects with a history of suicide attempt experience more episodes of depression, and react to them by having severe suicidal ideation. Their diathesis for acting on feelings of anger or suicidal ideation is suggested by a higher level of lifetime aggression and a pattern of repeated suicide attempts." [Abstract]
Michaelis BH, Goldberg JF, Singer TM, Garno JL, Ernst CL, Davis GP.
Characteristics of first suicide attempts in single versus multiple suicide attempters with bipolar disorder.
Compr Psychiatry. 2003 Jan-Feb;44(1):15-20.
"Although suicidality remains highly prevalent among patients with bipolar disorder, little research exists examining the characteristics of successive attempts among individuals who make and survive a first suicide attempt. We compared bipolar subjects with a history of one suicide attempt to those with multiple attempts and assessed demographic characteristics, family histories, psychopathology, and clinical dimensions of suicidal behavior. Fifty-two DSM-IV bipolar patients (age 21 to 74 years) with a history of at least one suicide attempt were consecutively evaluated in the Bipolar Disorders Research Clinic of the New York Presbyterian Hospital. Circumstances surrounding each lifetime suicide attempt were assessed by direct interviews, questionnaires, and chart reviews along with family psychiatric histories, substance abuse histories, current psychopathology, and features of impulsivity and aggression. Multiple suicide attempts occurred in approximately two thirds of the study group. Single attempters were significantly more likely than multiple attempters to show high seriousness of intent at their first attempt (OR = 0.65, 95% CI = 0.43 to 0.99), and tended to be less likely than multiple attempters to exhibit mixed states at their first attempt (OR = 0.54, 95% CI = 0.28 to 1.01). Seriousness of intent was consistent across the first and second attempts (r =.48, P <.01) and second and third attempts (r =.74, P <.05). Single and multiple attempters differed in no other clinical or demographic characteristics studied. We conclude that multiple suicide attempts are common among bipolar patients. Those who survive an initial suicide attempt involving high seriousness of intent appear less likely than those with low intent to make subsequent attempts. Consequently, single attempters may represent a group more closely resembling those who complete suicide on a first attempt, in terms of the risk for death associated with their first attempt. However, multiple suicide attempts among bipolar patients are not necessarily associated with a higher risk for lethality in first suicide attempt survivors." [Abstract]

Shyovitz M.
A family member's legal experience with an insurer's refusal to recertify inpatient mental health treatment.
J Clin Psychiatry 2001;62 Suppl 25:44-50
"My son Nathaniel has bipolar disorder and was hospitalized for 6 months, during which time our insurance company was prepared to refuse certification more than once despite a policy that included 365 days of inpatient mental health treatment. A break in coverage by the insurance company would have meant that Nathaniel, still suicidal, would not receive the life-saving care he needed. Fortunately, I am a lawyer, which enabled me to act as a legal advocate for my son when our insurer threatened not to recertify. Because my son's experience with the insurance company is not unusual--many patients with mental illness struggle with insurance companies who refuse to certify treatment--I believe that the family or support people of seriously ill psychiatric patients should be prepared to act in circumstances similar to mine. Psychiatric inpatient units should, as a matter of course, provide information on legal remedies that can be obtained before irreparable harm occurs." [Abstract]
Gray SM, Otto MW.
Psychosocial approaches to suicide prevention: applications to patients with bipolar disorder.
J Clin Psychiatry 2001;62 Suppl 25:56-64
"Hopelessness, dysfunctional attitudes, and poor problem-solving abilities are psychosocial risk factors that have been identified as predictors of suicide. These psychosocial risk factors may help clinicians apply specific therapies and treatments to patients with bipolar disorder at risk for suicide. A search of the literature on suicide prevention revealed 17 randomized, controlled studies, which the authors reviewed to determine the efficacy of strategies aimed at eliminating psychosocial risk factors for suicide. Three strategies emerged as efficacious: (1) applying interventions to elicit emergency care by patients at times of distress; (2) training in problem-solving strategies; and (3) combining comprehensive interventions that include problem solving with intensive rehearsal of cognitive, social, emotional-labeling, and distress-tolerance skills. On the basis of their review of the literature, the authors make recommendations for suicide prevention for patients with bipolar disorder." [Abstract]
Potash JB, Kane HS, Chiu YF, Simpson SG, MacKinnon DF, McInnis MG, McMahon FJ, DePaulo JR Jr.
Attempted suicide and alcoholism in bipolar disorder: clinical and familial relationships.
Am J Psychiatry 2000 Dec;157(12):2048-50
"OBJECTIVE: This study examined the clinical and familial relationships between comorbid alcoholism and attempted suicide in affectively ill relatives of probands with bipolar I disorder. METHOD: In 71 families ascertained for a genetic linkage study, 337 subjects with major affective disorder were assessed by using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version. RESULTS: Subjects with bipolar disorder and alcoholism had a 38.4% lifetime rate of attempted suicide, whereas those without alcoholism had a 21.7% rate. Attempted suicide among subjects with bipolar disorder and alcoholism clustered in a subset of seven families. Families with alcoholic and suicidal probands had a 40.7% rate of attempted suicide in first-degree relatives with bipolar disorder, whereas other families had a 19.0% rate. CONCLUSIONS: Comorbid alcoholism was associated with a higher rate of attempted suicide among family members with bipolar disorder. Attempted suicide and alcoholism clustered in a subset of families. These relationships may have a genetic origin and may be mediated by intoxication, mixed states, and/or temperamental instability." [Abstract]

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Recent Bipolar Disorder & Suicide Research
1) Azorin JM, Kaladjian A, Adida M, Hantouche E, Hameg A, Lancrenon S, Akiskal HS
Toward the delineation of mania subtypes in the French National EPIMAN-II Mille Cohort : Comparisons with prior cluster analytic investigations.
Eur Arch Psychiatry Clin Neurosci. 2008 Jun 20;
BACKGROUND: Knowledge about psychopathologic presentations of mania in current clinical practice has to be refined in order to improve diagnosis and treatment. METHODS: One thousand ninety manic patients included in the French National Study EPIMAN-II Mille were submitted to a cluster analysis on the basis of multiple variables related to the history of bipolar illness and symptoms of the current episode. RESULTS: Four clusters were identified: "classic mania" (29.3% of patients) with less severe mania; "psychotic mania" (22.7%) with psychotic symptoms, more severe mania, younger age and social impairment; "depressive mania" (30.4%) characterized by female gender, suicide attempts, high number of previous episodes and residual symptoms; and "dual mania" (17.6%) characterized by male gender, substance use, earlier onset and poor compliance. Patients groups also differed in manic symptoms, marital status, stressors preceding illness onset, prior diagnoses, first episode polarity and temperamental characteristics. LIMITATIONS: Cross-sectional assessment of patients. CONCLUSIONS: In comparing our findings with those of four prior cluster analytic studies, we integrate clinical characteristics of mania subtypes found in this very large representative French sample in contemporary practice, we suggest how such convergence of data may help improve earlier recognition, differential response to different treatments, and prevention of these subtypes. We finally suggest that such subtyping might provide clues to phenotype delineation suitable for pharmacogenetic investigations. [PubMed Citation] [Order full text from Infotrieve]

2) Gos T, Krell D, Bielau H, Brisch R, Tr�bner K, Steiner J, Bernstein HG, Jankowski Z, Bogerts B
Tyrosine hydroxylase immunoreactivity in the locus coeruleus is elevated in violent suicidal depressive patients.
Eur Arch Psychiatry Clin Neurosci. 2008 Jun 20;
Our postmortem study aimed to determine the impact of suicide on the number of noradrenergic neurons of the locus coeruleus (LC) in suicidal depressive patients. Noradrenergic neurons were shown by immunostaining tyrosine hydroxylase in the LC of 22 non-elderly patients with mood disorders compared to 21 age- and sex-matched normal controls. Eleven patients were suicide victims and the other eleven died of natural causes. Seven violent suicide victims revealed an increased number of tyrosine hydroxylase immunoreactive (TH-ir) neurons compared with non-violent suicide victims and controls. No difference was found between the number of TH-ir neurons in all suicidal patients and controls and between non-suicidal patients and controls. The differences of TH-immunoreactivity could neither be attributed to medication nor to the polarity of depressive disorder (unipolar/bipolar). The numbers of TH-ir neurons in suicidal patients correlated negatively with the mean doses of antidepressants. The study suggested a presynaptic noradrenergic dysregulation in the LC related to the level of self-aggression. Traditional antidepressants may, therefore, regulate noradrenergic activity of the LC in suicide patients, however, without demonstrating the suicide-preventing effect. [PubMed Citation] [Order full text from Infotrieve]

3) Feldcamp LA, Souza RP, Romano-Silva M, Kennedy JL, Wong AH
Reduced prefrontal cortex DARPP-32 mRNA in completed suicide victims with schizophrenia.
Schizophr Res. 2008 Jun 21;
Dopamine-and-cAMP-regulated neuronal phosphoprotein (32 kDa) (DARPP-32), encoded by PPP1R1B, is expressed in brain regions receiving dopaminergic projections, including the prefrontal cortex (PFC), and is implicated in the pathophysiology of schizophrenia. The broad functional capacity of DARPP-32 has potential relevance to both psychotic and negative symptoms of schizophrenia. We wished to determine if DARPP-32 gene expression and variation at selected SNPs correlated significantly with patient phenotypes. We performed RT-PCR to quantify DARPP-32 mRNA from brain samples (Brodmann Area 46) donated by the Stanley Medical Research Institute (SMRI, Array Collection): 35 from unaffected controls (UC), 35 from patients with schizophrenia (SCZ), and 35 with bipolar disorder (BP). Relative mRNA expression was calculated in relation to the housekeeping gene Cyclophilin. SNP genotyping was conducted by PCR on DNA obtained from Brodmann Area 46. We found a significant difference in gene expression levels between SCZ patients who died by suicide (SCZ-S) (n=6) vs. other causes of death (SCZ-NS) (P<0.004), as well as between SCZ-S and UC (P<0.04). We genotyped the intron SNP rs907094 and found that the SCZ-S group was more similar to UC than to the SCZ-NS population. DARPP-32 expression differences between SCZ-S, SCZ-NS, and UC populations are consistent with previous literature suggesting that serotonin system components are also altered in suicide. Work in a larger sample is needed to confirm these findings. [PubMed Citation] [Order full text from Infotrieve]

4) Pompili M, Innamorati M, Mann JJ, Oquendo MA, Lester D, Del Casale A, Serafini G, Rigucci S, Romano A, Tamburello A, Manfredi G, De Pisa E, Ehrlich S, Giupponi G, Amore M, Tatarelli R, Girardi P
Periventricular white matter hyperintensities as predictors of suicide attempts in bipolar disorders and unipolar depression.
Prog Neuropsychopharmacol Biol Psychiatry. 2008 May 20;
The aim of this study was to evaluate whether deep white matter hyperintensities (DWMH) and periventricular white matter hyperintensities (PVH) are associated with suicidal behavior in patients with major affective disorders. Subjects were 99 consecutively admitted inpatients (42 men; 57 women; mean age: 46.5 years [SD=15.2; Min./Max.=19/79]) with a diagnosis of major affective disorder (bipolar disorder type I, bipolar disorder type-II and unipolar major depressive disorder). 44.4% of the participants had made at least one previous suicide attempt. T2-weighted brain magnetic resonance images were rated for the presence and extension of WMH using the modified Fazekas scale. Patients were interviewed for clinical data on average 5 days after admission. Bivariate analyses, corrected for multiple-testing, and logistic regression analysis were used to test the association between suicide attempts and clinical variables. Attempters and nonattempters differed only in the presence of PVH-the former were more likely to have PVH. The logistic regression indicated that the presence of PVH was robustly associated with suicidal behaviors after controlling for age (OR: 8.08). In conclusion, neuroimaging measures may be markers of risk for suicidal attempts in patients with major affective disorders. [PubMed Citation] [Order full text from Infotrieve]

5) Yen CF, Cheng CP, Ko CH, Yen JY, Huang CF, Chen CS
Suicidality and its association with insight and neurocognition in taiwanese patients with bipolar I disorder in remission.
J Nerv Ment Dis. 2008 Jun;196(6):462-7.
The aims of this study were to examine the relationships between suicidality, insight, and neurocognition in patients with bipolar I disorder who were in a remitted state. Using the Violence and Suicide Assessment Scale, we evaluated 96 patients with bipolar I disorder in remission to determine their suicidal ideations and attempts over the previous year. We also evaluated their level of insight by using the Schedule of Assessment of Insight (SAI) and its expanded version (SAI-E), as well as their neurocognitive function by a series of neurocognitive function tests. Insight and neurocognitive functions of bipolar subjects who had and who had no suicidal ideations or attempts over the previous year were compared. The results indicated that the remitted bipolar subjects who had suicidal ideations or attempts over the previous year had higher insight scores on all 3 SAI dimensions and on the SAI-E compared with those who had no suicidal ideations or attempts. However, no difference in any neurocognitive function was found between the 2 groups of remitted bipolar subjects. The results of this study suggest clinicians need to be particularly alert to the potential for suicide in bipolar patients with a high level of insight. [PubMed Citation] [Order full text from Infotrieve]

6) Casiano H, Belik SL, Cox BJ, Waldman JC, Sareen J
Mental disorder and threats made by noninstitutionalized people with weapons in the national comorbidity survey replication.
J Nerv Ment Dis. 2008 Jun;196(6):437-45.
Controversy exists as to whether mental disorders are associated with a higher risk of violent behavior. Data from the nationally-representative National Comorbidity Survey Replication was examined. Multiple logistic regression was used to determine whether mood, anxiety, impulse control, and substance use disorders were associated with a higher rate of potentially violent behavior as assessed by threatening others with a gun or other weapon. After adjusting for sociodemographic factors, an association was found between mood, anxiety, impulse control, and substance use disorders and the rate of threatening others. A significant association was found between threats made against others with a gun and both substance use disorders (adjusted odds ratio [AOR] 2.27; 95% confidence interval [CI] 1.62-3.20) and impulse control disorders (AOR 2.67; 95% CI 1.95-3.66). Threats made against others with any other type of weapon were significantly associated with any anxiety (AOR 1.76; 95% CI 1.34-2.31), substance (AOR 2.63; 95% CI 1.87-3.71), or impulse control disorder (AOR 2.49; 95% CI 1.96-3.18). Of the disorders studied, social phobia, specific phobia, and impulse control disorders seemed to have their onset before the act of threatening others with weapons. This finding was also true for those who had attempted suicide. Further research is needed to determine whether treatment of mental disorders decreases the risk of violence in this population. [PubMed Citation] [Order full text from Infotrieve]

7) Raja M, Azzoni A, Koukopoulos AE
Psychopharmacological treatment before suicide attempt among patients admitted to a Psychiatric Intensive Care Unit.
J Affect Disord. 2008 Jun 7;
BACKGROUND: It is difficult to assess the effectiveness of treatments in lowering suicide incidence. METHODS: To ascertain the impact of antidepressants (AD) on suicidal behavior, we compared the psychopharmacological treatment taken in the previous 3 months by cases who had made or not a suicide attempt (SA) just before their admission to a hospital. RESULTS: In comparison with not SA cases, SA cases were more likely to have received AD and benzodiazepines (BZD) before hospitalization. On the contrary, they were less likely to have received antipsychotics, antiepileptic mood stabilizers, and lithium. Similar results were observed when the analysis was restricted to cases with a diagnosis of Major Depression, Bipolar Depression or Bipolar Mixed state, Schizoaffective Disorder, Depressive or Mixed type. Previous AD treatment seemed to be not related to the severity of psychopathology in general or to the severity of depressive and anxiety symptoms. CONCLUSIONS: The results suggest that the use of AD in patients with mood disorders is not associated with a reduction of SA rate. Rather, it is not possible to exclude that AD or BZD can induce, worsen, or precipitate suicidal behavior in some patients, especially in those affected by mood disorders with Depressive or Mixed features. The results must be considered preliminary since this is an open, non-randomized, non-controlled study that was carried out at a single facility. [PubMed Citation] [Order full text from Infotrieve]

8) Gos T, G�nther K, Bielau H, Dobrowolny H, Mawrin C, Tr�bner K, Brisch R, Steiner J, Bernstein HG, Jankowski Z, Bogerts B
Suicide and depression in the quantitative analysis of glutamic acid decarboxylase-immunorective neuropil.
J Affect Disord. 2008 Jun 5;
BACKGROUND: Alterations of GABAergic neurotransmission are assumed to play a crucial role in the pathophysiology of mood disorders. Glutamic acid decarboxylase (GAD) is the key enzyme of GABA synthesis. METHODS: Immunohistochemical staining of GAD 65/67 was performed in the orbitofrontal, anterior cingulate and dorsolateral prefrontal cortex (DLC), the entorhinal cortex (EC), the hippocampal formation, and the medial dorsal and lateral dorsal thalamic nuclei, with consecutive determination of GAD-immunoreactive (-ir) neuropil relative density. The study was performed on paraffin-embedded brains from 21 depressed patients (14 of whom had committed suicide) and 18 matched controls. The data were tested using Kruskal-Wallis, Mann-Whitney (U) and Spearman statistical procedures. RESULTS: As shown by post-hoc U-tests, an increase in the relative density of GAD-ir neuropil was present in the hippocampal formation, specific for suicidal patients. The EC was the only area where non-suicidal patients also revealed an increase compared with controls. On the contrary, the DLC was the only area where a significant decrease existed, specific for non-suicidal patients. Numerous negative correlations were found between the investigated parameter and psychotropic medication. LIMITATIONS: A major limitation of this study is the relatively small case number. A further limitation is given by the lack of data on drug exposure across the whole life span. The possible impact of unipolar-bipolar dichotomy of mood disorders on the obtained results should also be considered. CONCLUSION: The study, revealing predominantly an increased relative density of GAD-ir neuropil, suggests the diathesis of GABAergic system specific for depressed suicidal patients. [PubMed Citation] [Order full text from Infotrieve]

9) De Luca V, Tharmaligam S, Strauss J, Kennedy JL
5-ht2c receptor and mao-a interaction analysis: no association with suicidal behaviour in bipolar patients.
Eur Arch Psychiatry Clin Neurosci. 2008 May 26;
The serotonin 2C (HTR2C) receptor has been implicated in suicide-related behaviours, however there are not many studies to date about HTR2C and suicidality. We studied HTR2C haplotypes in suicide attempters, where our sample composed of 306 families with at least one member affected by bipolar disorder. HTR2C (Cys23Ser and a common STR in the promoter) variants were analyzed with respect to attempter status and the severity of suicidal behaviour. The X-linked haplotype analysis in relation to suicide attempt did not reveal any significant association. Furthermore, we performed a particular gene-gene interaction for the X-linked serotonergic genes (HTR2C and MAOA), and found no association among this intergenic haplotype combination and suicidal behaviour in bipolar disorder. [PubMed Citation] [Order full text from Infotrieve]

10) Richardson-Vejlgaard R, Sher L, Oquendo MA, Lizardi D, Stanley B
Moral objections to suicide and suicidal ideation among mood disordered Whites, Blacks, and Hispanics.
J Psychiatr Res. 2008 May 20;
Understanding the beliefs that protect individuals against suicide can help to enhance suicide prevention strategies. One measure of suicide non-acceptability is the moral objections to suicide (MOS) sub-scale of the reasons for living inventory (RFLI). This study examined the MOS and suicidal ideation of White, Black, and Hispanic individuals with mood disorders. We expected minority individuals to have stronger objections to suicide. METHOD: Eight hundred and four, White (588), Black (122) and Hispanic (94) participants with DSM-IV diagnoses of MDD or bipolar disorder were administered the scale for suicide ideation, the reasons for living inventory and several measures of clinical distress. RESULTS: Higher suicidal ideation was modestly correlated with lower MOS scores overall (r=0.15, p=0.001). Among Blacks however the relationship was inverted: despite having higher suicidal ideation than Whites or Hispanics, Blacks reported the least accepting attitudes toward suicide. CONCLUSION: These results suggest that attitudes regarding the acceptability of suicide may be independent of suicidal ideation. [PubMed Citation] [Order full text from Infotrieve]

11) Malloy-Diniz LF, Neves FS, Abrantes SS, Fuentes D, Corr�a H
Suicide behavior and neuropsychological assessment of type I bipolar patients.
J Affect Disord. 2008 May 15;
BACKGROUND: Neuropsychological deficits are often described in patients with bipolar disorder (BD). Some symptoms and/or associated characteristics of BD can be more closely associated to those cognitive impairments. We aimed to explore cognitive neuropsychological characteristics of type I bipolar patients (BPI) in terms of lifetime suicide attempt history. METHOD: We studied 39 BPI outpatients compared with 53 healthy controls (HC) matched by age, educational and intellectual level. All subjects were submitted to a neuropsychological assessment of executive functions, decision-making and declarative episodic memory. RESULTS: When comparing BDI patients, regardless of suicide attempt history or HC, we observed that bipolar patients performed worse than controls on measures of memory, attention, executive functions and decision-making. Patients with a history of suicide attempt performed worse than non-attempters on measures of decision-making and there were a significant negative correlation between the number of suicide attempts and decision-making results (block 3 and net score). We also found significant positive correlation between the number of suicide attempts and amount of errors in Stroop Color Word Test (part 3). LIMITATIONS: The sample studied can be considered small and a potentially confounding variable - medication status - were not controlled. CONCLUSION: Our results show the presence of neuropsychological deficits in memory, executive functions, attention and decision-making in BPI patients. Suicide attempts BPI scored worse than non-suicide attempt BPI on measures of decision-making. More suicide attempts were associated with a worse decision-making process. Future research should explore the relationship between the association between this specific cognitive deficits in BPIs, serotonergic function and suicide behavior in bipolar patients as well other diagnostic groups. [PubMed Citation] [Order full text from Infotrieve]

12) Talamo A, Baldessarini RJ, Centorrino F
Comparison of mania patients suitable for treatment trials versus clinical treatment.
Hum Psychopharmacol. 2008 May 19;
It remains uncertain whether bipolar disorder (BPD) patients in randomized-controlled trials (RCTs) are sufficiently representative of clinically encountered patients as to guide clinical-therapeutic practice. We complied inclusion/exclusion criteria by frequency from reports of 21 RCTs for mania, and applied them in a pilot study of patients hospitalized for DSM-IV BPD manic/mixed states to compare characteristics and clinical responses of patients who did versus did not meet exclusion criteria. From 27 initially identified inclusion/exclusion criteria ranked by citation frequency, we derived six inclusion, and 10 non-redundant-exclusion factors. Of 67 consecutive patients meeting inclusion criteria, 15 (22.4%) potential "research subjects" met all 10 exclusion criteria. The remaining 52 "clinical patients" differed markedly on exclusion criteria, including more psychiatric co-morbidity, substance abuse, involuntary hospitalization, and suicide attempts or violence, but were otherwise similar. In both groups responses to clinically determined inpatient treatments were similar, including improvement in mania ratings. Based on applying reported inclusion/exclusion criteria for RCTs to a pilot sample of hospitalized-manic patients, those likely to be included in modern RCTs were similar to patients who would be excluded, most notably in short-term antimanic-treatment responses. The findings encourage further comparisons of subjects included/excluded from RCTs to test potential clinical generalizability of research findings. The pilot study is limited in numbers and exposure times with which to test for the minor differences between "research subjects" and "clinical patients." Copyright (c) 2008 John Wiley & Sons, Ltd. [PubMed Citation] [Order full text from Infotrieve]

13) Ndetei DM, Khasakhala L, Maru H, Pizzo M, Mutiso V, Ongecha-Owuor FA, Kokonya DA
Clinical epidemiology in patients admitted at Mathari Psychiatric Hospital, Nairobi, Kenya.
Soc Psychiatry Psychiatr Epidemiol. 2008 May 8;
BACKGROUND: Knowledge of types and co-morbidities of disorders seen in any facility is useful for clinical practice and planning for services. AIM: To study the pattern of co-morbidities of and correlations between psychiatric disorders in in-patients of Mathari Hospital, the premier psychiatric hospital in Kenya. STUDY DESIGN: Cross-sectional. METHODS: All the patients who were admitted at Mathari Hospital in June 2004 and were well enough to participate in the study were approached for informed consent. Trained psychiatric charge nurses interviewed them using the Structured Clinical Interview for DSM-IV Axis I disorders Clinical Version (SCID-I). Information on their socio-demographic profiles and hospital diagnoses was extracted from their clinical notes using a structured format. RESULTS: Six hundred and ninety-one patients participated in the study. Sixty-three percent were male. More than three quarters (78%) of the patients were aged between 21 and 45 years. More than half (59.5%) of the males and slightly less than half (49.4%) of the females were single. All the patients were predominantly of the Christian faith. Over 85% were dependants of another family member and the remainder were heads of households who supported their own families. Schizophrenia, bipolar I disorder, psychosis, substance use disorder and schizo-affective disorder were the most common hospital and differential diagnoses. Of the anxiety disorders, only three patients were under treatment for post-traumatic stress disorder (PTSD). Nearly a quarter (24.6%) of the patients were currently admitted for a similar previous diagnosis. Schizophrenia was the most frequent DSM-IV (Diagnostic and Statistical Manual of Mental Disorders-fourth edition) diagnosis (51%), followed by bipolar I disorder (42.3%), substance use disorder (34.4%) and major depressive illness (24.6%). Suicidal features were common in the depressive group, with 14.7% of this group reporting a suicidal attempt. All DSM-IV anxiety disorders, including obsessive-compulsive disorders, were highly prevalent although, with the exception of three cases of PTSD, none of these anxiety disorders were diagnosed clinically. Traumatic events were reported in 33.3% of the patients. These were multiple and mainly violent events. Despite the multiplicity of these events, only 7.4% of the patients had a PTSD diagnosis in a previous admission while 4% were currently diagnosed with PTSD. The number of DSM-IV diagnoses was more than the total number of patients, suggesting co-morbidity, which was confirmed by significant 2-tailed correlation tests. CONCLUSION: DSM-IV substance use disorders, major psychiatric disorders and anxiety disorders were prevalent and co-morbid. However, anxiety disorders were hardly diagnosed and therefore not managed. Suicidal symptoms were common. These results call for more inclusive clinical diagnostic practice. Standardized clinical practice using a diagnostic tool on routine basis will go a long way in ensuring that no DSM-IV diagnosis is missed. This will improve clinical management of patients and documentation. [PubMed Citation] [Order full text from Infotrieve]

14) Peh AL, Tay LK
Demographical profile and clinical features of patients with bipolar disorder in an outpatient setting in Singapore.
Singapore Med J. 2008 May;49(5):380-3.
INTRODUCTION: Bipolar disorder, or manic depressive psychosis, is a psychiatric disorder characterised by extreme changes in mood, thinking, energy and behaviour. Western studies on this condition show a delay in diagnosis and treatment. The aim of this study is to examine the demographical profile and clinical features of this group of patients in Singapore to see if there is a similar delay. METHODS: Data of patients diagnosed with this condition and treated in two separate outpatient practices in the private sector from January 1999 to October 2003 were retrieved from case files and analysed. RESULTS: Of the 121 patients with bipolar disorder treated, there were 45 percent male and 55 percent female patients, and most of them were in the 20-39 year age group. Chinese formed the largest ethnic group while Malays were underrepresented. 58 percent were employed, and 48 percent were married. While the age of onset of illness ranged mainly from age 10 to 29 years, the age when they first sought treatment was from 20 to 39 years. A duration of illness of more than two years was found in 79 percent of these patients. In terms of diagnostic categories, 17 percent were bipolar I, 76 percent were bipolar II and 7 percent of the bipolar disorders, not otherwise specified. The first episode presented was depression in 75 percent and bipolar disorder was the initial diagnosis in only 34 percent of the cases. A delay in the correct diagnosis for more than two years accounted for 34 percent of the cases. Only 17 percent had a family history of bipolar disorder. 28 percent had a history of antidepressant-induced manic episodes and 17 percent had a previous episode of mixed state. Psychotic symptoms were absent in 75 percent, and 65 percent had never been hospitalised for their condition. Nine percent had made a past suicide attempt and 39 percent had a comorbid diagnosis. 46 percent were treated with a combination of mood stabilizers, neuroleptics and antidepressants and 16 percent had electroconvulsive therapy. Only 34 percent were in full remission of their illness. CONCLUSION: There was a preponderance towards the younger age groups for the age of onset, and the type of first episode was typically depression. There was a significant delay in diagnosis and treatment of patients with bipolar disorder. These features were strikingly similar to Western studies. Bipolar II was the diagnostic category seen more than bipolar I in the outpatient setting. Polypharmacy was the norm and a large group of patients did not achieve full remission. [Free Full Text] [PubMed Citation] [Order full text from Infotrieve]

15) Langevin R, Langevin M, Curnoe S, Bain J
The prevalence of diabetes among sexual and violent offenders and its co-occurrence with cognitive impairment, mania, psychotic symptoms and aggressive behavior.
Int J Prison Health. 2008 Jun;4(2):83-95.
The prevalence of diabetes among 915 sexual, violent, and non-violent non-sex offenders was found to be more than twice the prevalence in the general population. Diabetes was most common among violent offenders and among sex offenders who victimized children. The older diabetics presented significantly more often with cognitive impairment and younger diabetics more often with manic and psychotic symptoms. Younger diabetics were significantly more likely to use force and a weapon in their offenses and were most likely to injure their victims when compared to older diabetics and younger and older non-diabetic offenders. In more than one in four cases, the diabetes was undiagnosed at the time of their offenses prior to clinical assessment, suggesting that undiagnosed diabetes may be a possible mitigating factor in some sexual and violent offenses. Results indicate that a routine endocrine evaluation with blood tests would be a valuable addition to the assessment of violent and sexual offenders. [PubMed Citation] [Order full text from Infotrieve]

16) Melhem NM, Walker M, Moritz G, Brent DA
Antecedents and sequelae of sudden parental death in offspring and surviving caregivers.
Arch Pediatr Adolesc Med. 2008 May;162(5):403-10.
OBJECTIVES: To examine the psychiatric antecedents that put parents at risk for early death, and the psychological sequelae of bereavement in offspring and caregivers. DESIGN: A population-based study. SETTING: Bereaved families were recruited through the coroner's records and by advertisement. Control families were recruited by random-digit dialing and advertisement. PARTICIPANTS: Families with biological offspring from 7 to 25 years of age in which 1 parent died of suicide, accident, or sudden natural death were included (n = 140). Controls (n = 99) had 2 living parents and their biological offspring and had no death of a first-degree relative within the past 2 years. MAIN OUTCOME MEASURES: Lifetime psychiatric history for deceased parents (probands) and new-onset psychiatric disorders, self-reported symptoms, and functional status in offspring and surviving caregivers. RESULTS: Bipolar disorder, substance abuse, and personality disorders are more common in probands who died of suicide or accident than in control parents. Bereaved offspring and their caregivers were at increased risk for depression and posttraumatic stress disorder. Bereaved offspring had a 3-fold (95% confidence interval, 1.3-7.0) increased risk of depression, even after controlling for antecedent and concomitant risk factors. Offspring bereaved by suicide showed similar outcomes compared with those bereaved by other types of death. CONCLUSIONS: Bereavement conveys an increased risk of depression and posttraumatic stress disorder above and beyond other vulnerability factors. Better integration of medical and psychiatric care may prevent premature parental death, but once it occurs, physicians should be alert to the increased risk for depression and posttraumatic stress disorder in bereaved offspring and their caregivers. [Free Full Text] [PubMed Citation] [Order full text from Infotrieve]

17) Nakagawa A, Grunebaum MF, Sullivan GM, Currier D, Ellis SP, Burke AK, Brent DA, Mann JJ, Oquendo MA
Comorbid anxiety in bipolar disorder: does it have an independent effect on suicidality?
Bipolar Disord. 2008 Jun;10(4):530-8.
OBJECTIVE: Comorbid anxiety disorder is reported to increase suicidality in bipolar disorder. However, studies of the impact of anxiety disorders on suicidal behavior in mood disorders have shown mixed results. The presence of personality disorders, often comorbid with anxiety and bipolar disorders, may explain these inconsistencies. This study examined the impact of comorbid Cluster B personality disorder and anxiety disorder on suicidality in bipolar disorder. METHODS: A total of 116 depressed bipolar patients with and without lifetime anxiety disorder were compared. Multiple regression analysis tested the association of comorbid anxiety disorder with past suicide attempts and severity of suicidal ideation, adjusting for the effect of Cluster B personality disorder. The specific effect of panic disorder was also explored. RESULTS: Bipolar patients with and without anxiety disorders did not differ in the rate of past suicide attempt. Suicidal ideation was less severe in those with anxiety disorders. In multiple regression analysis, anxiety disorder was not associated with past suicide attempts or with the severity of suicidal ideation, whereas Cluster B personality disorder was associated with both. The results were comparable when comorbid panic disorder was examined. CONCLUSIONS: Comorbid Cluster B personality disorder appears to exert a stronger influence on suicidality than comorbid anxiety disorder in persons with bipolar disorder. Assessment of suicide risk in patients with bipolar disorder should include evaluation and treatment of Cluster B psychopathology. [PubMed Citation] [Order full text from Infotrieve]

18) Hajek T, Hahn M, Slaney C, Garnham J, Green J, Růzickov� M, Zvolsk� P, Alda M
Rapid cycling bipolar disorders in primary and tertiary care treated patients.
Bipolar Disord. 2008 Jun;10(4):495-502.
OBJECTIVE: Rapid cycling (RC) affects 13-30% of bipolar patients. Most of the data regarding RC have been obtained in tertiary care research centers. Generalizability of these findings to primary care populations is thus questionable. We examined clinical and demographic factors associated with RC in both primary and tertiary care treated populations. METHOD: Clinical data were obtained by interview from 240 bipolar I disorder (BDI) or bipolar II disorder (BDII) community-treated patients and by chart reviews from 119 bipolar patients treated at an outpatient clinic of a teaching hospital. RESULTS: Lifetime history of rapid cycling was present in 33.3% and 26.9% of patients from the primary and tertiary care samples, respectively. Among community-treated patients, lifetime history of RC was significantly associated with history of suicidal behavior and higher body mass index. There was a trend for association between RC and BDII, psychiatric comorbidity, diabetes mellitus, as well as lower age of onset of mania/hypomania. In the tertiary care treated sample there was a trend for association between lifetime history of RC and suicidal behavior. Tertiary versus primary care treated subjects with lifetime history of RC demonstrated markedly lower response to mood stabilizers. CONCLUSIONS: Lifetime history of RC is highly prevalent in both primary and tertiary settings. Even primary care treated subjects with lifetime history of RC seem to suffer from a more complicated and less treatment-responsive variant of bipolar disorder. Our findings further suggest relatively good generalizability of data from tertiary to primary care settings. [PubMed Citation] [Order full text from Infotrieve]

19) Goldstein BI, Strober MA, Birmaher B, Axelson DA, Esposito-Smythers C, Goldstein TR, Leonard H, Hunt J, Gill MK, Iyengar S, Grimm C, Yang M, Ryan ND, Keller MB
Substance use disorders among adolescents with bipolar spectrum disorders.
Bipolar Disord. 2008 Jun;10(4):469-78.
OBJECTIVE: We set out to examine the prevalence and correlates of substance use disorders (SUD) in a large sample of adolescents with bipolar disorder (BP). METHODS: Subjects were 249 adolescents ages 12 to 17 years old who fulfilled DSM-IV criteria for bipolar I disorder [(BPI), n = 154], or bipolar II disorder [(BPII), n = 25], or operationalized criteria for BP not otherwise specified [(BP NOS), n = 70], via the Schedule for Affective Disorders and Schizophrenia for School-Aged Children (K-SADS). As part of the multi-site Course and Outcome of Bipolar Youth study, demographic, clinical, and family history variables were measured via intake clinical interview with the subject and a parent/guardian. RESULTS: The lifetime prevalence of SUD among adolescents with BP was 16% (40/249). Results from univariate analyses indicated that subjects with, as compared to without, SUD were significantly less likely to be living with both biological parents, and that there was significantly greater lifetime prevalence of physical abuse, sexual abuse, suicide attempts, conduct disorder, and posttraumatic stress disorder among subjects with SUD. Subjects with SUD reported significantly greater 12-month prevalence of trouble with police, and females with SUD reported significantly greater 12-month prevalence of pregnancy and abortion. Significant predictors of SUD in a logistic regression model included living with both biological parents (lower prevalence), conduct disorder and suicide attempts (increased prevalence). In logistic regression analyses controlling for demographic differences and conduct disorder, SUD remained significantly associated with trouble with police, whereas the association of SUD with pregnancy and abortion was reduced to a statistical trend. The prevalence of SUD was not significantly different among child- versus adolescent-onset BP subjects. CONCLUSIONS: SUD among adolescents with BP is associated with profound hazards including suicide attempts, trouble with police, and teenage pregnancy and abortion. [PubMed Citation] [Order full text from Infotrieve]

20) Shi J, Badner JA, Hattori E, Potash JB, Willour VL, McMahon FJ, Gershon ES, Liu C
Neurotransmission and bipolar disorder: A systematic family-based association study.
Am J Med Genet B Neuropsychiatr Genet. 2008 Apr 28;
Neurotransmission pathways/systems have been proposed to be involved in the pathophysiology and treatment of bipolar disorder for over 40 years. In order to test the hypothesis that common variants of genes in one or more of five neurotransmission systems confer risk for bipolar disorder, we analyzed 1,005 tag single nucleotide polymorphisms in 90 genes from dopaminergic, serotonergic, noradrenergic, GABAergic, and glutamatergic neurotransmitter systems in 101 trios and 203 quads from Caucasian bipolar families. Our sample has 80% power to detect ORs >/= 1.82 and >/=1.57 for minor allele frequencies of 0.1 and 0.5, respectively. Nominally significant allelic and haplotypic associations were found for genes from each neurotransmission system, with several reaching gene-wide significance (allelic: GRIA1, GRIN2D, and QDPR; haplotypic: GRIN2C, QDPR, and SLC6A3). However, none of these associations survived correction for multiple testing in an individual system, or in all systems considered together. Significant single nucleotide polymorphism associations were not found with sub-phenotypes (alcoholism, psychosis, substance abuse, and suicide attempts) or significant gene-gene interactions. These results suggest that, within the detectable odds ratios of this study, common variants of the selected genes in the five neurotransmission systems do not play major roles in influencing the risk for bipolar disorder or comorbid sub-phenotypes. (c) 2008 Wiley-Liss, Inc. [PubMed Citation] [Order full text from Infotrieve]