GABBR1 and SLC6A1, Two Genes Involved in Modulation of GABA Synaptic Transmission, Influence Risk for Alcoholism: Results from Three Ethnically Diverse Populations.

BACKGROUND: Animal and human studies indicate that GABBR1, encoding the GABAB1 receptor subunit, and SLC6A1, encoding the neuronal gamma-aminobutyric acid (GABA) transporter GAT1, play a role in addiction by modulating synaptic GABA. Therefore, variants in these genes might predict risk/resilience for alcoholism. METHODS: This study included 3 populations that differed by ethnicity and alcoholism phenotype: African American (AA) men: 401 treatment-seeking inpatients with single/comorbid diagnoses of alcohol and drug dependence, 193 controls; Finnish Caucasian men: 159 incarcerated alcoholics, half with comorbid antisocial personality disorder, 181 controls; and a community sample of Plains Indian (PI) men and women: 239 alcoholics, 178 controls. Seven GABBR1 tag single nucleotide polymorphisms were genotyped in the AA and Finnish samples; rs29220 was genotyped in the PI for replication. Also, a uniquely African, functional SLC6A1 insertion promoter polymorphism (IND) was genotyped in the AAs. RESULTS: We found a significant and congruent association between GABBR1 rs29220 and alcoholism in all 3 populations. The major genotype (heterozygotes in AAs, Finns) and the major allele in PIs were significantly more common in alcoholics. Moreover, SLC6A1 IND was more abundant in controls, that is, the major genotype predicted alcoholism. An analysis of combined GABBR1 rs29220 and SLC6A1 IND genotypes showed that rs29220 heterozygotes, irrespective of their IND status, had an increased risk for alcoholism, whereas carriers of the IND allele and either rs29220 homozygote were more resilient. CONCLUSIONS: Our results show that with both GABBR1 and SLC6A1, the minor genotypes/alleles were protective against risk for alcoholism. Finally, GABBR1 rs29220 might predict treatment response/adverse effects for baclofen, a GABAB receptor agonist.

Trait-aggressiveness and impulsivity: role of psychological resilience and childhood trauma in a sample of male prisoners.

BACKGROUND: One of the major challenges for research in the field of human aggression is the need to define the role of personality and trait-like dimensions, such as impulsivity and aggressiveness, in predisposing to violent behavior. AIMS: 1) To determine whether trait- aggressiveness and impulsivity may be associated with socio-demographic, clinical and crime history variables in a sample of male prisoners; 2) to detect any association of those traits with measures of early traumatic experiences and current resilience traits. METHODS: A sample of male prisoners (n = 1356) underwent the Brown-Goodwin Assessment for Lifetime History of Aggression (BGLHA) and the Barratt Impulsivity Scale (BIS). Axis I psychiatric disorders were also assessed. Early traumatic experiences and psychological resilience were detected respectively by the Childhood Trauma Questionnaire (CTQ) and the Connor-Davidson Resilience Scale (CD-RISC). Two non-linear logistic regression models were performed to test for the best predictors of trait-aggressiveness and impulsivity. RESULTS: Subjects with a history of substance use disorders and self-mutilation reported both higher BGLHA and BIS scores. Axis I disorders and suicide attempts were associated with aggressiveness, but not to impulsivity. A consistent correlation was found between BGLHA scores and early traumatic experiences. Resilience was positively correlated to impulsivity but not to aggressiveness scores. CONCLUSIONS: Our results support the view that aggressiveness and impulsivity are two different, albeit related trait-like dimensions of personality, having a different relationship with resilience, and, inferentially, a different impact over the development of psychiatric disorders.

Haplotype-based study of the association of alcohol-metabolizing genes with alcohol dependence in four independent populations.

BACKGROUND: Ethanol is metabolized by 2 rate-limiting reactions: alcohol dehydrogenases (ADH) convert ethanol to acetaldehyde that is subsequently metabolized to acetate by aldehyde dehydrogenases (ALDH). Approximately 50% of East Asians have genetic variants that significantly impair this pathway and influence alcohol dependence (AD) vulnerability. We investigated whether variation in alcohol metabolism genes might alter the AD risk in four non-East Asian populations by performing systematic haplotype association analyses to maximize the chances of capturing functional variation. METHODS: Haplotype-tagging SNPs were genotyped using the Illumina GoldenGate platform. Genotypes were available for 40 SNPs across the ADH genes cluster and 24 SNPs across the two ALDH genes in four diverse samples that included cases (lifetime AD) and controls (no Axis 1 disorders). The case control sample sizes were the following: Finnish Caucasians: 232, 194; African Americans: 267, 422; Plains American Indians: 226, 110; and Southwestern American (SW) Indians: 317, 72. RESULTS: In all four populations, as well as HapMap populations, 5 haplotype blocks were identified across the ADH gene cluster: (i) ADH5-ADH4; (ii) ADH6-ADH1A-ADH1B; (iii) ADH1C; (iv) intergenic; (v) ADH7. The ALDH1A1 gene was defined by 4 blocks and ALDH2 by 1 block. No haplotype or SNP association results were significant after correction for multiple comparisons; however, several results, particularly for ALDH1A1 and ADH4, replicated earlier findings. There was an ALDH1A1 block 1 and 2 (extending from intron 5 to the 3' UTR) yin yang haplotype (haplotypes that have opposite allelic configuration) association with AD in the Finns driven by SNPs rs3764435 and rs2303317, respectively, and an ALDH1A1 block 3 (including the promoter region) yin yang haplotype association in SW Indians driven by 5 SNPs, all in allelic identity. The ADH4 SNP rs3762894 was associated with AD in Plains Indians. CONCLUSIONS: The systematic evaluation of alcohol-metabolizing genes in four non-East Asian populations has shown only modest associations with AD, largely for ALDH1A1 and ADH4. A concentration of signals for AD with ALDH1A1 yin yang haplotypes in several populations warrants further study.

Insomnia and suicidal behaviour in prisoners.

Insomnia has been associated with suicidality. Prisoners have an increased risk of both insomnia and suicidal behaviour. Therefore, it was decided to examine for a relationship between insomnia and suicidal behaviour in a large group of 1420 prisoners. Prisoners had a semi-structured psychiatric interview, which included the Hamilton Depression Rating Scale (HDRS), and completed the Childhood Trauma Questionnaire, Eysenck Personality Questionnaire, Spielberg Anger Expression Inventory and Connor-Davidson Resilience Scale. It was found that 568 (61.2%) of the prisoners scored in the insomnia cluster of the HDRS and that 183 (12.8%) had attempted suicide. Regression analyses showed that insomnia was significantly and independently associated with a lifetime history of attempting suicide. Insomnia was also significantly related to actual suicidality. After controlling for confounders, axis 1 psychiatric disorder, childhood trauma, neuroticism, low resilience, and anger were significantly associated with insomnia in male prisoners. These data suggest the possibility of a relationship between insomnia and suicidality in prisoners. Assessing insomnia may be helpful when evaluating the risk of suicidality in prisoners.

Self-harm in prisoners.

UNLABELLED: IntroductionSelf-harm is a direct, socially unacceptable,repetitive behavior that causes minor to moderate physical injury without suicidal intent. It is also a significant and growing concern among prison inmates, although it has been rarely studied. In the present study, we aimed to investigate demographic, psychosocial, and clinical variables associated to this critical bahaviour in a high risk sample of 1,555 male prisoners. METHODS: Prisoners were interviewed about their history of self-mutilation, psychiatric history,and forensic history. The prisoners completed the Barratt Impulsivity Scale, Buss-Durkee Hostility Inventory, Eysenck Personality Questionnaire, and Childhood Trauma Questionnaire. RESULTS: Eighteen percent of prisoners had a history of self-harm. They more frequently reported childhood traumas, were more likely to be unmarried, previously imprisoned, tested positive for substance abuse, had a history of suicide attempt, and more likely showed violent tendencies.DiscussionSelf-harm among prisoners is common, being found in almost 20% of the subjects in our sample. Self-mutilation among prisoners appears to be multi-factorial with developmental, socio-demographic, psychiatric, and personality determinants. CONCLUSION: Self-harm is associated with critical behaviors such as violence, substance abuse and suicide attempts, which represent major critical problems in contention environments.

Childhood trauma and prevalence of cardiovascular disease in patients with type 1 diabetes.

OBJECTIVE: To examine the relationship between childhood trauma and prevalence of cardiovascular disease (CVD) (either coronary disease or stroke) in Type 1 diabetes (DM). METHODS: From an original cohort of 725 African Americana with Type 1 DM, 444 (61.2%) were reexamined as part of a 6-year follow-up. In both examinations, patients underwent a structured clinical interview to determine their medical history and a detailed ocular examination. At follow-up, patients completed the Childhood Trauma Questionnaire, Hostility and Direction of Hostility Questionnaire, and Beck Depression Inventory. Diabetic patients who had CVD and those had not developed CVD at the 6-year follow-up were compared for their experience of childhood trauma at the same time controlling for the presence of known risk factors for CVD. RESULTS: Of the 393 patients at risk, 60 (15.3%) had developed any CVD, 52 (12.9%) had coronary disease, and 16 (3.8%) had a stroke at the 6-year follow-up. On univariate analysis, childhood trauma was significantly associated with 6-year incidence of any CVD (p < .01), coronary disease (p < .05), and stroke (p < .01). Childhood trauma scores were also significantly associated with depression (p < .001) and hostility (p < .001) scores, age (p < .05), and renal disease (p < .05). In primary multivariate analyses, childhood trauma predicted CVD independent of age, body mass index, blood pressure, and proteinuria. Secondary analyses suggested that association between the 6-year incidence of CVD and childhood trauma was also independent of depression ratings. CONCLUSION: Childhood seems to be an independent risk factor for the incidence of CVD in Type 1 DM.

Suicide attempts and ideation in African-American type 1 diabetic patients.

In order to examine suicidality and its correlates in type 1 diabetics 412 African-American type 1 diabetics and 404 African-American controls underwent a semi-structured interview that asked if they had ever attempted suicide. Patients completed the Childhood Trauma Questionnaire (CTQ), Hostility and Direction of Hostility Questionnaire (HDHQ), and Beck Depression Inventory (BDI). Diabetics and controls were compared for their rate of suicide attempt. Diabetic patients who had or had never attempted suicide were compared on socio-demographic and clinical data. It was found that diabetics were 3 to 4 times more likely to attempt suicide than controls (13.3% vs 3.5%, respectively, P<0.001). Diabetic attempters were significantly more likely to be female, depressed and hostile, and to report a history of childhood trauma, smoking, alcohol abuse, and drug abuse than diabetic non-attempters. Multivariate analyses showed that female sex, severity of childhood abuse, history of alcohol abuse, and depression were significantly and independently associated with having attempted suicide. These results suggest that African-Americans with type 1 diabetes have a raised risk of attempting suicide. Suicide risk in diabetics appears to be multifactorial and includes gender, developmental, personality, psychiatric, and substance abuse determinants.

Association between childhood trauma and aggression in male prisoners.

Childhood trauma and aggression were examined in 540 male prisoners. The Thus 540 male prisoners had a psychiatric interview, completed the Childhood Trauma Questionnaire (CTQ), and were assessed with the Brown-Goodwin Lifetime History of Aggression (BGHA) interview. There were significant correlations between CTQ scores and BGHA scores. Also prisoners with CTQ scores above the median had significantly higher BGHA scores than prisoners with CTQ scores below the median. Significantly more of the prisoners with CTQ scores above the median had more than one conviction, and significantly more had convictions as minors, and had exhibited violent behavior in prison. However, in logistic regression analyses that included possible confounding variables, CTQ scores related only to violence in prison while BGHA scores related to violent crime, having more than one conviction, conviction as a minor, and violence in prison. The relationship between CTQ and BGHA scores suggests the possibility that childhood trauma may be one determinant of aggression in prisoners.

Risk factors for attempting suicide in prisoners.

We wished to examine determinants of suicidal behavior in prisoners. 903 male prisoners had a psychiatric interview which included various psychometric tests. Suicide attempters were compared with prisoners who had never attempted suicide. Significantly more of the attempters had a history of psychiatric disorder, substance abuse, a family history of suicidal behavior, convictions for violent crime, had exhibited aggressive behavior in jail, and had higher BGLHA aggression scores. A similar pattern of risk factors was found for prisoners with suicidal ideation. A lifetime history of attempting suicide, or of having suicidal ideation, is frequent in prisoners. Risk factors include family, developmental, aggression, personality, psychiatric, and substance abuse factors.

Association of polymorphism (Val66Met) of brain-derived neurotrophic factor with suicide attempts in depressed patients.

INTRODUCTION: Recent post-mortem studies of suicide victims have implicated brain-derived neurotrophic factor (BDNF) in suicide. Therefore, it was decided to examine the possible role of a gene in the regulation of BDNF activity in relation to suicidal behaviour among depressed patients. METHOD: A series of 170 depressed patients were evaluated for their history of suicide attempts and genotyped for the BDNF Val66Met polymorphism (SNP ID: rs6265). Depressed patients who had (n = 97) or had not (n = 73) attempted suicide were compared. RESULTS: Depressed patients who carried the BDNF Val66Met polymorphism variant (GA + AA) appeared to show a significantly increased risk of suicidal behaviour. The risk of a suicide attempt was also significantly higher among those reporting higher levels of childhood emotional, physical and sexual abuse. Secondary analyses suggested that depression severity was a significant risk factor only in the wild-type BDNF genotype, and that the risk of suicide attempts was more predictable within the wild-type group. CONCLUSION: These preliminary data suggest that BDNF may play a role in the suicidal behaviour of depressed patients.

Addictions biology: haplotype-based analysis for 130 candidate genes on a single array.

AIMS: To develop a panel of markers able to extract full haplotype information for candidate genes in alcoholism, other addictions and disorders of mood and anxiety. METHODS: A total of 130 genes were haplotype tagged and genotyped in 7 case/control populations and 51 reference populations using Illumina GoldenGate SNP genotyping technology, determining haplotype coverage. We also constructed and determined the efficacy of a panel of 186 ancestry informative markers. RESULTS: An average of 1465 loci were genotyped at an average completion rate of 91.3%, with an average call rate of 98.3% and replication rate of 99.7%. Completion and call rates were lowered by the performance of two datasets, highlighting the importance of the DNA quality in high throughput assays. A comparison of haplotypes captured by the Addictions Array tagging SNPs and commercially available whole-genome arrays from Illumina and Affymetrix shows comparable performance of the tag SNPs to the best whole-genome array in all populations for which data are available. CONCLUSIONS: Arrays of haplotype-tagged candidate genes, such as this addictions-focused array, represent a cost-effective approach to generate high-quality SNP genotyping data useful for the haplotype-based analysis of panels of genes such as these 130 genes of interest to alcohol and addictions researchers. The inclusion of the 186 ancestry informative markers allows for the detection and correction for admixture and further enhances the utility of the array.

Aggression, impulsivity, personality traits, and childhood trauma of prisoners with substance abuse and addiction.

INTRODUCTION: The aim of our study is then to analyze psychological and judicial features of a subgroup of inmates with substance abuse. METHODS: Prisoners with substance abuse (n = 312) were compared to prisoners without substance abuse (n = 591). Recruited inmates completed a semistructured interview for collection of sociodemographic and judicial data and a battery of psychometric tests for assessement of aggression, impulsivity, depression, personality traits, hostility, resilience, and childhood trauma. RESULTS: Substance abusers had on average multiple incarcerations (78.8%), more juvenile convictions (60.2%), more violent behaviors during detention (29.8%), and a history of one or more suicide attempts (20.8%). They also had higher scores on subscales for childhood trauma, higher scores for psychoticism and neuroticism, higher impulsivity levels, worse resilience, increased hostility, and prevalent suicidal ideation. CONCLUSION: Prisoners with substance abuse constitute a subgroup with increased judiciary and psychiatric issues, possibly due to early life history and psychological characteristics, such as high impulsivity and aggressiveness, poor resilience, and higher suicidal risk.

Interaction between childhood trauma and serotonin transporter gene variation in suicide.

Although the serotonin transporter promoter polymorphism (5-HTTLPR) contributes to depression and suicidality in a fashion modulated by environmental stress, 5-HTTLPR has been little examined in relation to suicidal behavior in substance dependence. Recently, a third functional allele of 5-HTTLPR was discovered enabling more of the interindividual variation in serotonin transporter expression to be predicted by genotype. We examined whether the 5-HTTLPR gene alone, or interacting with childhood trauma, was predictive of suicidal behavior in substance-dependent patients, a clinical population that is at high risk of suicide, as well as childhood trauma and other stress. We interviewed 306 abstinent male African-American substance-dependent patients about whether they had ever attempted suicide and administered the 34-item Childhood Trauma Questionnaire (CTQ). Patients and 132 male African-American controls were genotyped to determine the S, L(G), and L(A) 5-HTTLPR alleles; some analyses grouped the S and L(G) alleles on the basis of equivalent function. The distribution of 5-HTTLPR genotypes did not differ between patients and controls, nor between suicide attempters and non-attempters. However, patients with low expression 5-HTTLPR genotypes and above-median CTQ scores were more likely to have attempted suicide. Logistic regression showed increasing risk of a suicide attempt with increasing reports of childhood trauma scores; in addition, this increase was exaggerated among those with low expression forms of the 5-HTTLPR genotype. Childhood trauma interacts with low expressing 5-HTTLPR genotypes to increase the risk of suicidal behavior among patients with substance dependence.

The FEZ1 gene shows no association to schizophrenia in Caucasian or African American populations.

Schizophrenia is a complex psychiatric disorder with both genetic and environmental components and is thought to be in part neurodevelopmental in origin. The DISC1 gene has been linked to schizophrenia in two independent Caucasian populations. The DISC1 protein interacts with a variety of proteins including FEZ1, the mammalian homolog of the Caenorhabditis elegans unc-76 protein, which is involved in axonal outgrowth. Variation at the FEZ1 gene has been associated with schizophrenia in a large Japanese cohort. In this study, nine SNP markers at the FEZ1 locus were genotyped in two populations. A North American Caucasian cohort of 212 healthy controls, 178 schizophrenics, 79 bipolar disorder, and 58 with schizoaffective disorder, and an African American cohort of 133 healthy controls, 162 schizophrenics, and 28 with schizoaffective disorder. No association to schizophrenia, bipolar disorder or schizoaffective disorder was found for any of the nine markers typed in these populations at the allelic or the genotypic level. Additionally no association was found in either population between specific haplotypes and any of the psychiatric disorders. Variation at the FEZ1 locus does not play a significant role in the etiology of schizophrenia, bipolar disorder or schizoaffective disorder in North American Caucasian or African American populations.Neuropsychopharmacology (2007) 32, 190-196. doi:10.1038/sj.npp.1301177; published online 16 August 2006.

Depression is a risk factor for poor glycemic control and retinopathy in African-Americans with type 1 diabetes.

OBJECTIVE: To examine longitudinal data about depression in relationship to glycemic control and as a risk factor for diabetic retinopathy (DR). Depression is a common psychiatric disorder among diabetic persons and has been shown in cross-sectional studies to be associated with the vascular complications of diabetes. METHODS: A total of 483 African-American patients with Type 1 diabetes had a baseline examination and 6-year follow-up examination. Evaluations at both visits included administering the Beck Depression Inventory (BDI), a detailed ophthalmologic examination, retinal photographs, and measurement of glycosylated hemoglobin as an index of glycemic control. Six-year progression of DR between baseline and follow-up visits was evaluated from the change in retinopathy severity using the Early Treatment of Diabetic Retinopathy Study grading scale. RESULTS: Patients with high BDI scores at both baseline and 6-year follow-up visits had significantly higher baseline glycosylated hemoglobin values (p = .01), and were more likely to show progression of DR (odds ratio (OR) = 2.44; 95% confidence interval (CI): 1.01-5.88; p = .049) and progression to proliferative diabetic retinopathy (PDR) (OR = 3.19; 95% CI: 1.30-7.87; p = .01) than patients with low BDI scores at both visits. This was independent of baseline medical risk factors for DR. CONCLUSION: Six-year longitudinal data indicate that depression is significantly associated with both poor glycemic control and higher 6-year progression to PDR in African-Americans with Type 1 diabetes.

Risk factors for suicide attempts among alcohol dependent patients.

Suicidal behavior is a common and important problem among alcohol dependent patients. The study was designed to examine risk factors for attempting suicide in 499 alcohol dependent patients. Those who had attempted suicide (N = 198) were more likely to be female, report a family history of suicidal behavior, report more childhood trauma, report greater levels of aggressive behavior, began heavy drinking earlier, and were more likely to have received antidepressant medication. Logistic regression analysis showed that gender, family history, and childhood sexual abuse history made significant and independent contributions to the risk of a suicide attempt. Thus, developmental, personality, family history, social, and comorbidity risk factors may differentiate alcohol dependent patients who have attempted suicide from those who have not.

Low resilience in suicide attempters.

Resilience is an important personality feature that is thought to be protective against the development of psychiatric disorder. However, it appears not to have been previously examined directly in relation to suicidal behavior. Therefore, with the recent development of a resilience scale, the purpose of this preliminary study was to examine resilience in relation to attempting suicide. In order to do this 100 abstinent substance dependent patients were interviewed about whether or not they had ever attempted suicide and completed the Connor-Davidson Resilience Scale. The results showed that patients who had attempted suicide (N=41) had significantly lower resilience scale scores than patients who had never attempted suicide (N=59). This suggests the possibility that low resilience may be a risk factor for suicidal behavior. Longitudinal studies among suicide attempters, including measures of depression, may further evaluate the possible relevance of resilience to suicidal behavior.

Haplotype-based linkage of tryptophan hydroxylase 2 to suicide attempt, major depression, and cerebrospinal fluid 5-hydroxyindoleacetic acid in 4 populations.

CONTEXT: Tryptophan hydroxylase 2 (TPH2) encodes the rate-limiting enzyme for brain serotonin biosynthesis. It was recently reported that the TPH2 haplotype was linked to depression in humans. OBJECTIVE: To determine the association of TPH2 with suicide attempt, major depression, and a neurochemical intermediate phenotype, cerebrospinal fluid 5-hydroxyindoleacetic acid. DESIGN: We resequenced TPH2 coding, 5' promoter, 3'-untranslated region, and splice junction regions in 190 individuals selected for ethnic and clinical diversity, determined haplotype structure using 15 single nucleotide polymorphisms spanning 106 kilobases (kb), and performed linkage analysis in 1798 cases and controls representing 4 populations (657 African Americans, including 104 suicide attempters and 135 with major depression; 513 Finnish whites, including 150 suicide attempters; 146 US whites, including 81 with depression, anxiety disorder, or both; and 482 southwestern American Indians, including 123 suicide attempters and 191 with depression, anxiety disorder, or both) and in 94 Finnish whites for cerebrospinal fluid 5-hydroxyindoleacetic acid levels. RESULTS: Sixteen single nucleotide polymorphisms, including Pro206Ser, were detected. The 15-locus panel defined and maximized information content from 2 haplotype blocks in whites, 3 haplotype blocks in African Americans, and the single haplotype block spanning TPH2 in southwestern American Indians. Among common Block1b haplotypes were 2 in yin and yang (opposite) configuration, indicating ancient origin. The yin haplotype, 212121, was increased in frequency in suicide attempters in both populations tested (Finnish whites and African Americans). It was associated with major depression and anxiety disorders in US whites and with major depression in African Americans. The yin haplotype was moderately predictive of lower cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations in controls but not in cases. CONCLUSION: Haplotype linkage of TPH2 to suicide attempt and major depression and to a mediating phenotype, cerebrospinal fluid 5-hydroxyindoleacetic acid, provides preliminary evidence of a functional locus potentially within a haplotype block at least 52 kb in size.

Gender in suicide attempt rates and childhood sexual abuse rates: is there an interaction?

Two competing explanations for higher rates of attempted suicide in women than men were compared. Because childhood sexual abuse is more prevalent in girls than boys, one explanation of higher rates of suicide attempts in women is that it is a direct result of the higher incidence of sexual abuse in girls. Alternatively, higher rates of suicide attempts might result from gender differences in the impact of childhood sexual abuse on suicidal behavior. To compare these theories, data from 1,889 abstinent, substance-dependent patients who completed the Childhood Trauma Questionnaire (CTQ) and who were interviewed about suicide attempts was examined. Scores on each scale of the CTQ were examined as a function of gender and attempter status. Results showed higher rates of suicide attempts in women than in men, higher CTQ scores in women than men, and a higher CTQ score in attempters than nonattempters. However, logistic regression indicated that gender and abuse did not interact to determine attempter status. Thus, the data support the first hypothesis that the greater frequency of suicide attempts in women may be partly attributed to the higher prevalence of childhood sexual abuse in girls. The generalizability of these results to the general population and to other diagnostic groups requires further study.

Family history of suicide and impulsivity.

A family history of suicide indicates a raised risk for suicidal behavior; this liability might be familially transmitted as an impulsive-aggression trait. To examine the impulsivity factor, data from 258 abstinent drug dependent patients who were interviewed about their family history of suicidal behavior and who completed the Barratt Impulsivity Scale (BIS) were examined. The results showed that patients with a family history of suicidal behavior had significantly higher BIS scores for risk taking than patients without a family history of suicidal behavior. Also, patients with a family history of suicidal behavior who had themselves attempted suicide had significantly higher BIS scores for both impulsivity and risk taking than patients with a family history of suicidal behavior who had never attempted suicide.