Malvin N. Janal

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, LG, and LA 5-HTTLPR alleles; some analyses grouped the S and LG 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.

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.

Retinal Venular Diameter as an Early Indicator of Progression to Proliferative Diabetic Retinopathy With and Without High-Risk Characteristics in African Americans With Type 1 Diabetes Mellitus

OBJECTIVEnTo examine the relationship between retinal arteriolar and venular diameter and the 6-year progression of diabetic retinopathy (DR) in African Americans with type 1 insulin-dependent diabetes mellitus.nnnMETHODSnIncluded were 468 African Americans with type 1 diabetes mellitus who participated in the New Jersey 725 and who had undergone a 6-year follow-up examination. Seven standard field retinal photographs were obtained at both examinations. Computer-assisted grading, from digitized images of field 1 of baseline retinal photographs, was accomplished to determine the average diameter of retinal arterioles (central retinal arteriolar equivalent [CRAE]) and venules (central retinal venular equivalent [CRVE]). Retinal vessel diameter was examined in relation to the 6-year incidence and/or progression of DR.nnnRESULTSnFor right and left eyes, mean (SD) CRAE was 168.8 (16.0) μm and mean CRVE was 254.2 (25.2) μm. Both CRAE and CRVE were correlated between eyes (P < .001). Multivariate analysis with generalized estimating equations showed that larger CRVE in either the right or left eye was significantly associated with 6-year progression to either proliferative DR (PDR) or PDR with high-risk characteristics after adjusting for baseline clinical risk factors. Notably, a significant association between baseline CRVE and progression to PDR was present for eyes with no to moderate nonproliferative DR and also between baseline CRVE and progression to PDR with high-risk characteristics for eyes with no or nonproliferative DR.nnnCONCLUSIONnLarger retinal venular diameter is an independent and early indicator of progression to either PDR or PDR with high-risk characteristics in African Americans with type 1 diabetes mellitus.

Family history of suicide, female sex, and childhood trauma: separate or interacting risk factors for attempts at suicide?

Objective:u2002 Female sex, childhood trauma, and a family history of suicidal behavior are three well established risk factors for attempting suicide. However, interactions between these three factors in attempting suicide have been little studied.

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.

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 1diabetes (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. CTQ = Childhood Trauma Questionnaire; CVD = cardiovascular disease; DM = diabetes mellitus; BDI = Beck Depression Inventory; IHD = ischemic heart disease; HDHQ = Hostility and Direction of Hostility Questionnaire.

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.

Relationship of Retinal Vessel Caliber to Cardiovascular Disease and Mortality in African Americans With Type 1 Diabetes Mellitus

OBJECTIVEnTo examine the relationship between retinal arteriolar and venular diameter and the 6-year incidence of cardiovascular disease and mortality among African Americans with type 1 diabetes mellitus.nnnMETHODSnIncluded were 468 African Americans with type 1 diabetes mellitus who participated in the New Jersey 725 and who had undergone a 6-year follow-up examination. At both baseline and 6-year follow-up, hypertension and presence of heart disease, stroke, or lower extremity arterial disease (LEAD) were documented and confirmed by review of hospital admission and medical records. Computer-assisted grading from digitized images of retinal photographs was accomplished to determine the average diameter of retinal arterioles (central retinal arteriolar equivalent) and venules (central retinal venular equivalent). Retinal vessel diameter size was examined in relation to the 6-year incidence of hypertension, any cardiovascular disease (heart disease, stroke, or LEAD), heart disease or stroke, LEAD, and mortality.nnnRESULTSnNarrower central retinal arteriolar equivalent at baseline significantly and independently predicted 6-year incidence of any cardiovascular disease and LEAD, whereas larger retinal venular diameter at baseline significantly and independently predicted 6-year incidence of hypertension. Proteinuria and retinopathy severity at baseline were stronger predictors of mortality than retinal vascular diameter.nnnCONCLUSIONnIn African Americans with type 1 diabetes mellitus, baseline retinal vessel caliber is an independent predictor of incident hypertension and LEAD.

Medical and Psychological Risk Factors for Incident Hypertension in Type 1 Diabetic African-Americans

Objective. To determine risk factors for the development of hypertension among African-Americans living with type 1 diabetes. Methods. African-Americans with type 1 diabetes (n = 483) participated in a 6-year followup. At both baseline and followup blood pressure was measured twice in both sitting and standing positions using a standard protocol. Patients had a structured clinical interview, ocular examination, retinal photographs, and blood and urine assays and completed the Hostility and Direction of Hostility Questionnaire (HDHQ) and the Beck Depression Inventory (BDI). Results. Of the 280 diabetic patients with no hypertension at baseline, 82 (29.3%) subsequently developed hypertension over the 6-year followup. Baseline older age, longer duration of diabetes, family history of hypertension, greater mean arterial blood pressure, overt proteinuria, increasing retinopathy severity, peripheral neuropathy, smoking, and higher hostility scores were significantly associated with the development of hypertension. Multivariate analyses showed that higher hostility scores and overt proteinuria were significantly and independently associated with the development of hypertension in this population. Conclusions. The development of hypertension in African-Americans living with type 1 diabetes appears to be multifactorial and includes both medical (overt proteinuria) as well as psychological (high hostility) risk factors.