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Steven J Garlow

Publications and source records attributed to Steven J Garlow.

14 recordsLinked to original sources

Genetic analysis of the hypothalamic neurotensin system.

This study used B x D recombinant inbred mice to detect and localize genes that control the hypothalamic neurotensin (NT) system. Abundance of transcripts that encode NT and NT receptors 1, 2, and 3 (NTR1, NTR2, and NTR3) in total hypothalamic RNA was the quantitative trait measured. Analysis of transcript abundance data revealed associations with quantitative trait loci (QTL) for NT transcript abundance (NTta) on chromosome 1, 3, 6, 7, 8, and 9; for NTR1ta on chromosome 3, 8, 12, and X; for NTR2ta on chromosome 2, 4, 9, 10, 12, 13, and 17; for NTR3ta on chromosome 1, 7, 11, and 12. NTta QTL on chromosomes 3, 7, and 8 coincide with QTL previously identified that impact NT peptide content and NTR2ta QTL on chromosome 2 and 12 coincide with genes previously associated with NTR2 receptor abundance. The NTta, NTR1ta, and NTR3ta QTL were not linked to their respective structural genes, but there is a highly significant (p<0.001) association for NTR2ta on chromosome 12 that includes the Ntsr2 structural gene. There are areas of potential shared genetic regulation between NTta and NTR3ta on chromosome 1 and 7 and for all three receptors on proximal chromosome 12. The NTta QTL on chromosome 9 includes the dopamine D2 receptor (Drd2) gene and QTL involved in responses to dopaminergic agents (Hts), antipsychotics (Hpic1) and cocaine (Cocrb8), and ethanol (Etohc3). These results further strengthen the hypothesis that the NT system is involved in mediating the actions of antipsychotic agents and drugs of abuse.

Adaptor Proteins, Vesicular Transport↗

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

The goal of this investigation was to determine whether cocaine and ethanol use was a differentiating factor between African American and white teenage suicide victims. This is a retrospective analysis of medical examiner's records of all completed suicides in Fulton County, GA from 01/1989 to 12/2003, and included 1296 cases. There were 79 suicide victims aged 19 and younger during the study interval, and of this group, 49 (62%) were African American, 26 (33%) were white, and 4 (5%) other race, compared to adults (20 years) where 28.5% were African American, 68.6% white and 2.9% other race (chi(2)=42.678, d.f.=2, p<0.0001). Of the black teenaged victims, 82.2% had no cocaine or alcohol detected at autopsy, while 41.7% of the white victims were positive for one or both substance (chi(2)=4.633, d.f.=1, p=0.04). Only 8.9% of the black teenage suicide victims had used cocaine prior to death compared to 28% of the whites (chi(2)=4.432; d.f.=1; p<0.04). The suicide rate (suicide/100,000/year) for black teens was 5.48 compared to 4.16 for whites, but the rate of cocaine positive teen suicides was 1.12 for whites and 0.45 for blacks. The pattern of cocaine use changes dramatically in the adult group, with 27% of African American suicide victims compared to 7.7% of whites being positive (chi(2)=73.272; d.f.=1; p<0.001). Use of intoxicating substances does differentiate teenage suicide victims, as only a small proportion of black teenagers had used cocaine or alcohol prior to death compared to almost half of all whites.

Adolescent↗

Genetic analysis of the hypothalamic corticotropin-releasing factor system.

The goal of this study was to use BxD recombinant inbred mice to search for genes that control the hypothalamic corticotrophin-releasing factor (CRF) system. The specific phenotype that was measured was abundance of transcripts that encode CRF, CRF receptor (Crf-R1), CRF binding protein, and arginine vasopressin (AVP) in total hypothalamic RNA. The strain distribution patterns for the transcript abundances for each target were continuously distributed, consistent with these being quantitative traits. Marker regression and interval mapping revealed associations with quantitative trait loci (QTL) for CRF transcript abundance on chromosome 1 (at 89.2 cM), chromosome 12 (between 54-58 cM), and chromosome 13 (between 26-30 cM); for Crf-R1 transcript abundance on chromosome 7 (at 1.5 cM), chromosome 12 (at 37 cM), and chromosome X (at 30 cM); for CRF binding protein transcript abundance on chromosome 7 (at 48.5 cM), chromosome 8 (at 65 cM), and chromosome 12 (at 19 cM); and for AVP transcript abundance on chromosome 7 (at 1 cM), chromosome 12 (at 13 cM), and chromosome 13 (at 45 cM). The transcript abundance QTL were not linked to their respective structural genes. Interval mapping on chromosome 7 reveals substantial overlap between QTL that control AVP and Crf-R1 transcript abundance and on chromosome 12 for QTL that control CRF and Crf-R1, which may indicate loci that coordinate regulation of the CRF system. There are QTL for all four targets on chromosome 12. There are a number of neurodevelopmental genes in very close proximity to the transcript abundance QTL that are potential candidate genes.

Animals↗

Ethnic differences in patterns of suicide across the life cycle.

OBJECTIVE: The authors analyzed suicide across the life cycle of different ethnic groups in an urban population equally divided between blacks (44.6%) and whites (48.1%). METHOD: Two data sets were used: 1) all suicides in Fulton County, Ga., from January 1994 through December 2002 and 2) all U.S. suicides reported by the National Center for Injury Prevention in 1999 and 2000. RESULTS: The population rates for suicide in Fulton County were 1.22 per 100,000 black females, 10.74 per 100,000 black males, 9.89 per 100,000 white females, and 21.04 per 100,000 white males. In Fulton County, age at completed suicide was more than a decade lower in blacks than in whites. The median age of black victims was 32 years, with an interquartile range (IQR) of 23-45, and the median for whites was 44 years (IQR=31-58); the difference was significant. The mean ages of victims who were black (mean=36.1 years, SD=17.0) and of "other" race (mean=35.7, SD=14.3) were significantly lower than the mean for whites (mean=46.2, SD=18.5). The national data were similar, but minorities accounted for an even smaller percentage of suicides. Median age at completed suicide for African Americans nationally was 34 years (IQR=24-45) compared to 44 years (IQR=32-58) for Caucasians. CONCLUSIONS: African Americans commit suicide at rates much lower than those for whites, but they do so when much younger and they have a narrow, age-defined window of vulnerability. Age-specific psychopathological processes and protective factors may define suicide risk for each demographic group.

Adult↗

The Collaborative Cross, a community resource for the genetic analysis of complex traits.

The goal of the Complex Trait Consortium is to promote the development of resources that can be used to understand, treat and ultimately prevent pervasive human diseases. Existing and proposed mouse resources that are optimized to study the actions of isolated genetic loci on a fixed background are less effective for studying intact polygenic networks and interactions among genes, environments, pathogens and other factors. The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way we approach human health and disease.

Animals↗

Reduction of episodes of seclusion and restraint in a psychiatric emergency service.

The authors developed a comprehensive plan focusing on the early identification and management of problematic behaviors in an effort to reduce seclusion and restraint in a psychiatric emergency service and to increase adherence to hospital standards for its use. Hospital data for nine months before and nine months after the implementation of the plan were retrospectively reviewed. Two key factors that were believed to increase the likelihood of episodes of seclusion and restraint were ineffectual management of problematic behavior and inadequate monitoring. The plan, when instituted, was associated with a 39 percent reduction of instances of seclusion and restraint. Compliance with hospital standards increased to 100 percent.

Behavior Therapy↗

Suicide prevention: a vital national public health issue.

Suicide continues to be a major public health problem in the United States, with 30,000 deaths per year. The suicide rate, which hovers around 10-12/100,000, has remained virtually unchanged over the past three decades. In 1999 the Surgeon General proposed a national plan to serve as a roadmap toward developing a comprehensive national suicide prevention strategy. The key features of this plan were encapsulated in the acronym AIM, Awareness, Intervention and Methodology, to define the relevant components of a national strategy. This refers to increasing public awareness of the problem of mental illness and suicide, providing increased access to treatment and prevention resources and developing improved research methodologies. Despite the overall numbers, suicide is a low base-rate event, which makes studying intervention and prevention strategies very difficult, as very large subject samples are required for meaningful outcome assessments. Suicide prevention and prevention research have received substantially fewer public resources than many other medical conditions, and apparent public health risks such as bioterrorism. It is for this reason that a comprehensive, national public health based suicide prevention program is required.

Awareness↗

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.

Adult↗

And now, transcriptomics.

In this issue of Neuron, report different patterns of 5-HT2C pre-mRNA editing in suicide victims, as compared to controls. Treatment of mice with fluoxetine alters the pattern of 5-HT2C transcript editing in the direction opposite that observed for suicide victims. The authors speculate on a possible serotonergic mechanism controlling 5-HT2C pre-mRNA editing.

Animals↗

Age, gender, and ethnicity differences in patterns of cocaine and ethanol use preceding suicide.

OBJECTIVE: The goal of this study was to examine the relationship between suicide and substance use among completed suicides in Fulton County, Ga., from 1994 through 1998. METHOD: Extensive data on completed suicides were obtained from records of the Office of the Medical Examiner. Specific characteristics of the victims who had used cocaine, ethanol, or both before committing suicide were compared across demographic groups. RESULTS: There were important race, sex, and age differences among the victims who had used cocaine and ethanol before committing suicide. Almost all (94.6%) of the suicide victims in whom cocaine was detected were male, 51.4% of the cocaine-positive victims were African American men, and 43.2% were white men. Substance use by teenage victims differed dramatically across ethnic lines. The vast majority (86.7%) of African American teenagers did not use either substance before committing suicide, whereas 50.0% of the white teenage victims had used one or both substances, with 41.7% of the white teenagers having used ethanol. Overall, ethanol use was much more common among white victims of all age groups. CONCLUSIONS: Intoxicant use preceding suicide occurred in specific age-, ethnic-, and gender-based patterns.

Adolescent↗

The relationship of restrictions on state hospitalization and suicides among emergency psychiatric patients.

OBJECTIVE: This study explored the relationship between mandated decreases in transfers to a state hospital from a large urban psychiatric emergency facility and the occurrence of suicide in the catchment area served. METHODS: During 1996, new admission criteria that emphasized psychiatric diagnosis and potential benefit from hospitalization and that restricted the admission of recidivistic patients and of those with a primary diagnosis of a substance use disorder were phased in. Data on the number of patients seen in a psychiatric emergency service and the number transferred to the state hospital were obtained for the period 1994-1998. Data on all completed suicides in the county served by the hospital were also obtained. RESULTS: During 1994 and 1995, a total of 9,308 patients were transferred to the state hospital. In 1997 and 1998, a total of 4,072 patients were transferred. The number of patients seen in the emergency service remained constant throughout the study period. No change was noted in the absolute number or the rate of suicide in the county after the new admission criteria were implemented. A total of 164 suicides were recorded in 1994-1995 (12 per 100,000 population per year), compared with 152 in 1997-1998 (ten per 100,000 population per year). CONCLUSIONS: Transfers to the state hospital were reduced by 56 percent, with no change in the suicide rate. This finding suggests that the availability of inpatient psychiatric hospitalization may not have a direct effect on the suicide rate.

Emergency Service, Hospital↗

Pain medication use among patients with posttraumatic stress disorder.

The relationship of analgesic medication use with posttraumatic stress disorder (PTSD) diagnosis was investigated among a sample of 173 African Americans presenting for routine outpatient visits at an urban mental health center. Seventy-eight (43.5%) of the sample met DSM-IV PTSD criteria. Those with PTSD had significantly higher use of analgesic medication (both opiate and non-opiate), as compared with non-PTSD patients. PTSD symptoms, as measured by the Posttraumatic Symptom Scale, were significantly higher in subjects who were prescribed analgesics. The authors conclude that there may be a relationship between PTSD and use of pain medications warranting further examination of the endogenous opiate system in the pathophysiology of PTSD.

Adult↗