David Purselle

The dexamethasone/corticotropin-releasing factor test in men with major depression: role of childhood trauma

BACKGROUND The dexamethasone/corticotropin-releasing factor (CRF) test is considered to be the most sensitive measure of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity and has been demonstrated to be altered in patients with major depression (MDD). Although childhood trauma is a demonstrated risk factor for MDD and patients with a history of childhood abuse and MDD demonstrate HPA axis hyperactivity, the dexamethasone/CRF test remains unstudied in this population. We determined the impact of childhood trauma on dexamethasone/CRF test results in patients with MDD. METHODS Forty-nine healthy men, ages 18-60 years, without mania or psychosis, active substance abuse, or eating disorder and medication-free were recruited into four study groups, including: 1) normal subjects with no childhood abuse history or psychiatric disorder (n = 14); 2) men with childhood abuse histories without current MDD (n = 14); 3) men with childhood abuse histories with current MDD (n = 15); and 4) men with current MDD and no childhood abuse history (n = 6). Plasma adrenocorticotropin (ACTH) and cortisol concentrations were measured in response to dexamethasone/CRF administration. RESULTS Men with childhood trauma histories exhibited increases in ACTH and cortisol responses to dexamethasone/CRF compared with non-abused men. In particular, abused men with current MDD showed increased responsiveness compared with control subjects and depressed men without childhood abuse experience. Increased response was associated with the severity, duration, and earlier onset of the abuse. The effects were not explained by concurrent posttraumatic stress disorder. CONCLUSIONS Childhood trauma increases HPA axis activity as measured with the dexamethasone/CRF test in adult men with MDD, potentially reflecting environmental risk for developing depression.

Serotonin Transporter: A Potential Substrate in the Biology of Suicide

Suicide is a serious public health problem in the US, yet its neurobiological underpinnings are poorly understood. Suicide is highly correlated with depressive symptoms, and considerable evidence suggests that depression is associated with a relative deficiency in serotonergic neurotransmission. Serotonergic circuits also mediate impulsivity, a trait obviously relevant to suicide. These findings, taken together, suggest that alterations in the serotonergic system might contribute to suicidal behavior, serving as an impetus for researchers to scrutinize the serotonin transporter (SERT) as a potential substrate for the pathophysiology of suicide. Using post-mortem brain tissue, platelets, and DNA from suicide completers and attempters have not provided unequivocal evidence for a pre-eminent role for the SERT in the pathophysiology of suicide. This paper provides a review of several studies that have evaluated the role of the SERT in the pathophysiology of suicide.

Cocaine use disorders and suicidal ideation

The goal of this study was to determine the contribution of substance abuse to the expression of suicidal ideation in a sample of patients referred for evaluation of chemical dependency in a large urban Psychiatric Emergency Service (PES). Records from 777 consecutive patients referred to the chemical dependency service of the PES were analyzed. Of this sample, 43.7% of the patients with only a cocaine use disorder expressed suicidal ideation compared to 38% of those with both cocaine and alcohol use disorders, 24.3% with only an alcohol use disorder and 17% with other drug use disorders (chi(2)=24.768; df=3; P<0.0001). More than half of the patients (55.26%) with a substance-induced mood or psychotic disorder expressed suicidal ideation (chi(2)=23.174, df=1, P<0.0001), and the majority (85%) of these patients had a cocaine use disorder (chi(2)=12.309, df=1, P<0.0005). In this sample of patients served by an urban PES, cocaine use is associated with suicidal ideation, more so than other substances of abuse.

Differential association of socioeconomic status in ethnic and age-defined suicides.

Suicide rates vary among racel- and age-defined groups, yet little is known about how suicide risk factors differentially impact individual groups. This study assessed differential associations of socioeconomic status among age- and race-defined groups of suicide victims. A database containing demographic information on declared suicides in Fulton County, GA, from 1 January 1988 through 31 December 2003 was combined with annual per capita income by zip code in Atlanta, GA. Analyses were performed to evaluate differential associations of socioeconomic status among age- and race-defined groups of suicide victims. Compared with the respective ethnic populations of Fulton County, white suicide victims lived in areas with lower per capita income (

DECREASED BRAINSTEM AND PUTAMEN SERT BINDING POTENTIAL IN DEPRESSED SUICIDE ATTEMPTERS USING [11C]-ZIENT PET IMAGING

51,232 vs.

Compartmental Modeling of 11C-HOMADAM Binding to the Serotonin Transporter in the Healthy Human Brain

35,893); African American suicide victims did not (

Ethnic Differences in Patterns of Suicide Across the Life Cycle

17,384 vs.

Reduction of Episodes of Seclusion and Restraint in a Psychiatric Emergency Service

18,179). Elderly suicide victims (>or= 65 years) were more likely to live in the lowest per capita income areas compared with other age groups (OR 1.80, 95% C.I. 1.14, 2.84). Cox proportional hazards models showed increasing income increased the instantaneous risk of suicide among adolescents (HR 2.76; 95% C.I. 2.15, 3.53), particularly African American adolescents (HR 4.22; 95% C.I. 2.19, 8.11), and decreased risk among the elderly (HR 0.58; 95% C.I. 0.50, 0.68). Socioeconomic status had differential associations among age- and race-defined groups of suicide victims.

Cocaine and alcohol use preceding suicide in African American and white adolescents.

Deficits in serotonergic neurotransmission have been implicated in the pathogenesis of depression and suicidality. The present study utilized a novel positron‐emission tomography (PET) ligand to quantitate and compare brain regional serotonin transporter (SERT) binding potential in depressed patients with a past history of suicide attempts to that of healthy comparison subjects.

Carbon-11 HOMADAM: A novel PET radiotracer for imaging serotonin transporters

The novel PET radioligand 11C-N,N-dimethyl-2-(2′-amino-4′-hydroxymethylphenylthio)benzylamine (11C-HOMADAM) binds with high affinity and selectively to the serotonin transporter (SERT). The purpose of this study was to develop a reliable kinetic model to describe the uptake of 11C-HOMADAM in the healthy human brain. Methods: Eight volunteers participated in the study; 5 of them were fitted with arterial catheters for blood sampling and all were scanned on a high-resolution research tomograph after the injection of 11C-HOMADAM. Regional distribution volumes and binding potentials were calculated with 2- and 4-parameter arterial-input compartment models, a 3-parameter reference tissue compartment model, and the Logan graphic approach. Results: The 2-parameter arterial-input compartment model was statistically superior to the 4-parameter model and described all brain regions. Calculated binding potentials agreed well between the arterial-input model and the reference tissue model when the cerebellum was used as the reference tissue. The Logan graphic approach was not able to estimate the higher concentration of SERT in the dorsal raphe than in the midbrain. Conclusion: 11C-HOMADAM is a highly promising radioligand with high ratios of specific binding to nonspecific binding in known SERT-rich structures, such as the raphe nuclei. The 3-parameter reference tissue model approach permits a simplified quantitatively accurate method for estimating SERT binding potentials.