Biomedical subjects

E M Hill

Publications and source records attributed to E M Hill.

At least 19 recordsLinked to original sources

PubMed2006

Laboratory exposure to 17beta-estradiol fails to induce vitellogenin and estrogen receptor gene expression in the marine invertebrate Mytilus edulis.

To investigate the effect of estrogenic compounds on the marine mussel Mytilus edulis, an assay was developed to measure the expression of two vertebrate estrogen responsive genes-estrogen receptor (ER) and vitellogenin (VTG) genes. Expression was measured in M. edulis gonads following a 10-day exposure to 200 ng/l 17beta-estradiol (estradiol). The concentrations of esterified estradiol in mussel tissue increased 15-fold in a time-dependent manner-confirming uptake of the compound by the mussels, however there was no significant increase of free estradiol in mussel tissues during the exposure period. The ER and VTG mRNA levels in the gonads of both sexes were measured at days 1-3, 5, and 10 in control and exposed mussels. However, no significant change in the expression of either the ER or VTG genes was recorded at any of the sampled time points. The results suggest that either a regulatory mechanism exists in a mussel that is able to maintain constant levels of free estradiol by converting the excess estradiol into esterified products which may have reduced affinity for the estrogen receptor, or alternatively, that the ER and VTG genes are unresponsive to estrogens in these organisms. The significance of these findings in terms of the utility of ER and VTG as biomarkers of endocrine disruption in bivalve species is discussed.

Amino Acid Sequence↗

PubMed2005

Mixtures of estrogenic contaminants in bile of fish exposed to wastewater treatment works effluents.

Most effluents from wastewater treatment works (WwTWs) contain estrogenic chemicals that include steroidal estrogens and xenoestrogens. We investigated the nature of mixtures of estrogenic contaminants taken up by two species of fish exposed to two WwTWs effluents. Sexually immature rainbow trout, Oncorhynchus mykiss, and sexually mature roach, Rutilus rutilus, were exposed to tap water, river water, or one of two estrogenic WwTWs effluents for up to 10 days, when the fish were sacrificed and tissues removed for chemical analysis. Estrogenic contaminants in the bile and gonads were hydrolyzed, concentrated by solid-phase extraction, and fractionated by RP-HPLC. Active fractions were detected and quantified using a yeast estrogen receptor transcription screen (YES assay) and the identities of estrogenic components in the fractions determined by GC-MS. Bile from rainbow trout exposed to either tap water or river water contained low amounts of 17beta-estradiol (E2) and estrone (E1) with a total estrogenic activity (mean+/-standard error) of 10+/-5 and 31+/-9 ng of E2 equivalents/mL (ng of E2eq/mL) for male and female fish, respectively. In effluent-exposed trout the total estrogen content of bile was considerably higher with the following composition and concentrations (ng of E2eq/mL) of individual estrogens: E2 (male, 591+/-125; female, 710+/-207), E1 (male, 338+/-75; female, 469+/-164), ethinylestradiol, EE2 (male, 32+/-2; female, 40+/-6), nonylphenol (NP) and short-chain NP polyethoxylates (male, 21+/-4; female, 22+/-3). An additional estrogenic compound, 17beta-dihydroequilenin (DHQ), was identified for the first time in effluent-exposed fish, and was present in trout bile at concentrations of (male) 40+/-9 and (female) 30+/-5 ng of E2 eq/mL. DHQ, E2, E1, and EE2, but not NP or NP polyethoxylates, were also detected in bile of effluent-exposed roach, and the concentrations of all these steroidal estrogens in ng of E2eq/mL were lower in male (E2, 62+/-2; E1, 35+/-11; EE2, 10+/-2; DHQ, 1+/-1) compared with female (E2, 740+/-197; E1, 197+/-37; EE2, 40+/-6; DHQ, 8+/-2) roach. The synthetic estrogen EE2 was also detected in the testes and ovaries of effluent-exposed roach. This study shows that a mixture of estrogenic contaminants present in WwTWs effluents bioconcentrate in fish tissues, resulting in the induction of vitellogenin, and are likely to contribute to feminizing effects in wild fish living in U.K. rivers. The composition of the mixture of estrogenic contaminants in the bile is species dependent and may determine the susceptibility of fish to the effects of exposure to estrogenic effluents.

Animals↗

PubMed2005

Accounting for differences in estrogenic responses in rainbow trout (Oncorhynchus mykiss: Salmonidae) and roach (Rutilus rutilus: Cyprinidae) exposed to effluents from wastewater treatment works.

Effluents from wastewater treatment works (WwTWs) contain estrogenic substances that induce feminizing effects in fish, including vitellogenin (VTG) synthesis and gonadal intersex. Fish vary in their responsiveness to estrogenic effluents, but the physiological basis for these differences are not known. In this study, uptake of estrogen from two WwTW effluents (measured in hydrolyzed bile) and estrogenic response (VTG induction) were compared in a salmonid (rainbow trout, Onchorhynchus mykiss) and a cyprinid fish (roach, Rutilus rutilus). Immature rainbow trout were more responsive than maturing roach to the estrogenic effluents. The more potent of the two estrogenic effluents (containing between 24.3 and 104.1 ng estradiol-17beta equivalents/L [E2eq/L]) resulted in a 700-fold and 240-fold induction of plasma VTG in male and female trout, respectively, but only a 4-fold induction in roach (and in males only). The less potent effluent (varying between 4.1 and 6.8 ng E2eq/L) induced VTG in the trout only, with a 4-fold and 18-fold induction in males and females, respectively. In fish exposed to tap water, the estrogenicity of the hydrolyzed bile was 0.03+/-0.01 ng E2eq/microL (for both sexes in trout), 0.18+/-0.04 ng E2eq/microL in male roach, and 0.88+/-0.15 ng E2eq/microL in female roach. The higher bile content of estrogen in control roach reflected their more advanced sexual status (and thus higher endogenous estrogen) compared with the immature female trout. In trout maintained in effluents, the bile content of estrogen was 100-fold and 30-fold higher than controls at WwTW A and B, respectively. Bioconcentration factors (BCFs) for estrogenic activity in bile were between 16 344 and 46 134 in trout and between 3543 and 60 192 in roach (no gender differences were apparent). There were strong correlations between VTG induction and the estrogenic activity of bile extracts for both trout and roach. The results confirm that estrogenic contaminants bioconcentrate to a high degree in fish bile and that the level (and nature) of this accumulation may accountfor responsiveness to the endocrine disruptive effects of estrogenic effluents. Immature fish were the more appropriate life stage for quantifying estrogen exposure and uptake in bile, as they contain little circulating endogenous oestrogen compared with sexual maturing fish. The nature of the estrogenic contaminants is detailed in an accompanying paper.

Animals↗

PubMed2005

Analytical methodology for the identification of estrogenic contaminants in fish bile.

Effluents from wastewater treatment works (WwTWs) contain estrogenic contaminants that can cause feminised responses in fish. In order to assess the identity of estrogenic contaminants taken up by fish exposed to effluents, an analytical method was developed to detect estrogenic substances in fish bile, where many xenobiotics are excreted and concentrated. Estrogenic metabolites in bile were deconjugated using enzymatic hydrolysis and the estrogenic activity was determined using a yeast estrogen receptor transcription screen (YES). Hydrolysed samples were concentrated by solid-phase extraction (SPE) prior to fractionation by reversed-phase high-performance liquid chromatography (HPLC). Active HPLC fractions were detected by YES assay and analysed by gas chromatography-mass spectrometry (GC-MS) after trimethylsilylation. The method was validated using bile samples from immature female rainbow trout, which had been exposed to either tap water or an undiluted estrogenic effluent for 10 days. Hydrolysis of bile from effluent-exposed fish was complete within 16 h add most of the estrogenic activity in the bile was released by 3-glucuronidase rather than sulfatase or 3-glucosidase treatment. The estrogenic activity of hydrolysed bile from effluent-exposed fish ranged between 530 and 1440 ng E2eq/mL and was 17-48-fold greater than the activity of bile from reference fish exposed to tap water. The estrogenic activity of bile samples decreased with time in storage (at-70 degrees C by 7% per month). The recovery of estrogenic activity from SPE was 96 +/- 7% (mean +/- SD), from HPLC fractionation 87 +/- 7% and for the whole method 81 +/- 7% (n = 7). 17beta-Estradiol, estrone, 17alpha-ethinylestradiol, nonylphenol and short-chain nonylphenol polyethoxylates were all identified from GC-MS analysis of active HPLC fractions of bile from effluent-exposed trout, whereas only 17beta-estradiol was detected in bile from fish exposed to tap water. There were also several other minor estrogenic components, at present unidentified, in bile of effluent-exposed fish. The work shows that fractionation of fish bile is a useful approach to identifying mixtures of estrogenic contaminants taken up by fish from WwTW effluents and has the potential for application in the detection of other endocrine disrupting chemicals in fish tissues.

Animals↗

PubMed2001

Bioconcentration and distribution of 4-tert-octylphenol residues in tissues of the rainbow trout (Oncorhynchus mykiss).

Branched chain alkylphenols are weak oestrogen mimics which are present in the aquatic environment and have been implicated in the feminisation of fish. This study reports the biotransformation, bioconcentration and tissue distribution of the xenoestrogen 4-tert-octylphenol (t-OP) in juvenile rainbow trout. Fish were exposed for 10 days to a concentration of 4 micrograms/l of [14C] t-OP in a flow-through system and were sampled after 1, 4, 7 and 10 days of exposure. t-OP residues were extracted from all tissues and analysed by radio-high-performance liquid chromatography. After 1 day of exposure radioactive residues were detected in all tissues and reached steady state conditions in the whole fish after 4 days of exposure. The concentration of t-OP residues were highest in bile, followed by faeces, pyloric caeca, liver and intestine. In these tissues the majority of alkylphenol was in the form of two metabolites which were identified by gas chromatography-mass spectroscopy as the glucuronide conjugates of t-OP and t-octylcatechol. t-OP accumulated as the parent compound in fat with a bioconcentration factor (BCF) of 1190, and in brain, muscle, skin, bone, gills, and eye with BCFs of between 100 and 260. This study suggests that exposure to water-borne alkylphenols results in rapid conjugation and elimination of the chemical via the liver/bile route, but that high amounts of the parent xenoestrogen can accumulate in a variety of other fish tissues.

Animals↗

PubMed2001

Predictors of psychosocial outcomes for patients with mood disorders: the effects of self-help group participation.

This study examined the predictors of psychosocial outcomes (daily functioning and management of illness) for people with mood disorders. After controlling for demographic, severity of illness, and social support predictor variables, the study evaluated whether participation in self-help groups would predict improved psychosocial outcomes. Post-hospitalization data were examined for 144 mood disorder patients using hierarchic multiple regression. More education predicted improved daily functioning; self-help involvement and education predicted management of illness. The implications of these findings for providing recovery-oriented rehabilitation services are discussed.

Adolescent↗

PubMed2001

Drinking and parental unpredictability among adult children of alcoholics: a pilot study.

Within-family differences that mediate the relationship between family history for alcoholism and alcohol consumption were investigated. Twenty adult children of alcoholics (ACOAs) and 20 children of social drinking parents (non-ACOAs) were interviewed in 1991 (mean age 24.2 years). Participants described family functioning while growing up and indices of their alcohol consumption. Family history for alcoholism had a direct association with two aspects of drinking. ACOAs reported more lifetime drinks and tended to report drinking more frequently during high school, as compared to non-ACOAs. ACOAs also reported more parental unpredictability, which in turn was associated with the above drinking indices. Finally, family history for alcoholism had an indirect association with drinking, as unpredictability mediated this relationship. Research and prevention implications are discussed.

Adolescent↗

PubMed2000

Identification of novel metabolites of the xenoestrogen 4-tert-octylphenol in primary rat hepatocytes.

A number of environmental pollutants, including 4-tert-alkylphenols, can mimic the actions of endogenous steroids and have the potential to disrupt the endocrine function in humans and animals. The biotransformation of a 4-tert-alkylphenol in isolated rat hepatocytes was studied in order to determine the possible fate and activity of these xenoestrogens in higher vertebrates. Hepatocytes were incubated with 30 microM 4-(1',1',3', 3'-tetramethylbutyl)[U-(14)C]phenol (4-tert-octylphenol; t-OP) for up to 60 min. Radiolabelled metabolites were detected by radio-HPLC and the structures determined by gas chromatography-mass spectrometry (GC-MS) analysis of the conjugated or aglycone products. After a 15 min incubation, over 97% of t-OP was metabolised to a complex mixture of metabolites. The initial metabolites formed were identified as products of hydroxylation of the aromatic ring to form catechols and methylated catechols, as well as glucuronide conjugates of the catechol metabolites or parent phenol. These products were further metabolised by hydroxylation of the alkyl chain followed by glucuronide conjugation of the alkoxy group. The conjugated metabolites of t-OP are unlikely to retain estrogen receptor activity, however t-OP is metabolised by some pathways that are similar to that of estrogen catabolism, namely by ortho-hydroxylation to form catechols, methylation by catechol O-methyltransferases and ring conjugation by uridine diphosphoglucuronosyl transferases. Further investigations are needed to determine whether 4-tert-alkylphenols can alter circulating sex steroid profiles by acting as substrates of enzymes determining estrogen metabolism and excretion.

Animals↗

PubMed2000

Discovery of an 11 (R)- and 12(S)-lipoxygenase activity in ovaries of the mussel Mytilus edulis.

Eicosanoid biosynthesis was investigated in mussel gonads by incubation of tissue homogenates with radiolabeled arachidonic acid and analysis of the products by radio-high-performance liquid chromatography. No radiolabeled metabolites were formed in homogenates of testes, but two major metabolites were synthesized by ovarian preparations. The radiolabeled metabolites were analyzed by mass spectrometry and chiral chromatography and identified as 11 (R)-hydroxy-5,8,1 2,14-eicosatetraenoic acid and 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid. In addition, four other nonlabeled metabolites, formed from endogenous substrates, were detected in ovarian extracts. Their structures, determined by mass spectrometric analysis, were the corresponding 11- and 12-hydroxy analogs formed from eicosapentaenoic acid (11-HEPE and 12-HEPE) and 9-hydroxy-6,10,12,15-octadecatetraenoic acid (9-HOTE) and 13-hydroxy-6,9,11,15-octadecatetraenoic acid formecl from stearidonic acid. The biosynthesis of the 11 - and 12-hydroxy products was calcium dependent, localized to the 100,000 x g supernatant cell fraction, and was inhibited by nordihydroguaiaretic acid, but not inhibited by the prostaglandin synthase inhibitors aspirin and indomethacin, or the monoxygenase inhibitor proadifen. Together these data suggested that both the 11 (R)- and 12(S)-hydroxy products were formed from lipoxygenase-type enzymes. Incubation of homogenates of immature ovaries with eicosapentaenoic acid revealed the major product to be I2-HEPE, whereas in mature ovaries mainly 11-HEPE was formed. Extraction of spawned eggs with methanol revealed that predominantly 11-HEPE and 9-HOTE were formed from endogenous substrates. This study shows that female gonads of the mussel express an 11(R)- and 12(S)-lipoxygenase activity whose expression is dependent on differentiation of the ovary.

Animals↗

PubMed2000

Variation in suicidality among substance-abusing women: the role of childhood adversity.

The relationship of early adversity to suicidality in later life has been noted in diverse populations. Here we report such a relationship for a sample of African American women who smoke crack cocaine. This article is a secondary analysis of data from women (mean age = 31 years; range, 19-48) who were recruited from treatment settings (n = 152) or informal community contacts (n = 56). The present analyses focused on measures related to investment in self-preservation and development, particularly suicidal ideation and attempts. Multiple regression analyses were used to model the effect of early stress (sexual abuse, parental loss, and parental impairment) on the primary outcome measures (suicidality total, age at first consensual sexual relations, and years of education). Suicidality was associated with childhood adversity (sexual abuse, loss of mother). Of those who had experienced early sexual abuse, 42% had attempted suicide, compared to 19% of those who had not been sexually abused.

Adult↗

PubMed2000

Biotransformation of the xenoestrogen 4-tert-octylphenol in hepatocytes of rainbow trout (Oncorhynchus mykiss).

1. The biotransformation of a 4-tert-alkylphenol in rainbow trout (Oncorhynchus mykiss) liver was studied to determine the possible fate and activity of these xenoestrogens in fish. 2. Primary trout hepatocytes were incubated with 30 microM 4-(1',1',3',3'-tetramethyl-butyl)[U-14C]phenol (4-tert-octylphenol; 4-t-OP) for up to 3 h. Radiolabelled metabolites were detected by radio-HPLC and the structures were determined by GC-MS analysis of the conjugated or aglycone products. 3. During the first 15 min, 4-t-OP was metabolized at 1.06 pmol x min(-1) x 10(-6) cells. The amount of parent compound metabolized was maximum after a 1-h incubation, when 86% of 4-t-OP was transformed to five other products. 4. The major metabolite comprised 61% of the total recovered radioactivity and was identified as 4-t-OP-beta-glucuronide. 5. The remaining metabolites were formed from the hydroxylation of 4-t-OP on either the C2 (omega-3) or C4 (omega) positions of the alkyl chain, or ortho on the aromatic ring to form a catechol. These oxidized products were also metabolized to glucuronide derivatives conjugated on the phenol ring. 6. The results suggest that oestrogenic alkylphenols could be rapidly transformed in fish liver by both phase I and II metabolic pathways to a number of conjugated products which are unlikely to be active at the oestrogen receptor.

Animals↗

PubMed2000

Effects of alcohol on the geographic variation of driver fatalities in motor vehicle crashes.

OBJECTIVE: To determine whether the increased risk of dying in a rural vs nonrural motor vehicle crash (MVC) can be attributed to driver demographics, crash characteristics, or police-reported alcohol use. METHODS: A retrospective cohort study was conducted, comparing all rural (116,242) and a 20% random sample of nonrural (104,197) Michigan drivers involved in an MVC during 1994-1996. Data consisted of all police-reported traffic crashes on public roadways. A logistic regression model was created, using survival as the dependent variable and gender, age, crash characteristics, and rural or nonrural county as independent variables. Driver alcohol use, as reported by the investigating officer, was introduced into the model, and the effect was analyzed. RESULTS: Nonsurvivors represented 0.2% of the total; 99.8% were survivors. Police-reported alcohol use was reported for 3.9% of drivers. Drivers in rural MVCs were more likely to be male, to be more than 50 years of age, to have been drinking alcohol, and to have more severe vehicle deformation as a result of the MVC. The relative risk (RR) for MVC nonsurvivors was 1.69 [95% confidence interval (CI) = 1.3 to 2.1] times higher for drivers in rural than nonrural counties. After adjusting for demographic and crash characteristics, the RR was 1.56 (95% CI = 1.2 to 1.9). Controlling for alcohol and its interactions decreased the RR to 1.26 (95% CI = 0.6 to 2.4), a nonsignificant difference between rural and nonrural MVC mortalities. CONCLUSIONS: Alcohol use by drivers in Michigan was a significant contributor for nonsurvivors of rural crashes. Efforts to decrease rural MVC mortality must address alcohol use.

Accidents, Traffic↗

PubMed2000

Emergency physician attitudes concerning intervention for alcohol abuse/dependence delivered in the emergency department: a brief report.

Emergency Medicine (EM) physicians frequently see patients with alcohol abuse or dependence (AA/AD). Brief interventions delivered in the Emergency Department (ED) have been advocated for these patients, however, little is known regarding EM physician willingness to support such interventions. We conducted a study to determine EM physicians' attitudes toward the use of interventions for AA/AD in the ED. All members of the Michigan College of Emergency Physicians (n = 569) were mailed a survey to assess their attitudes toward the use of intervention for AA/AD in the ED. Of the 257 respondents (45.9%), a total of 76% agreed that AA/AD is a treatable illness and only 15% would not agree to support of ED interventions. Both supporters and non-supporters thought that the lack of sufficient time was an impediment to treating AA/AD in the ED. Our study suggests that the majority of ED physicians would support the implementation of brief intervention for AA/AD in the ED.

Adult↗

PubMed2000

Does acute alcohol ingestion and/or chronic alcohol use among motor vehicle crash victims lead to a more complicated hospital course?

Given a certain severity of crash and of injury, it is unclear whether acute and/or chronic alcohol use leads to increased morbidity, mortality or a more complicated hospital course after motor vehicle collisions. 496 patients admitted to a trauma service were retrospectively evaluated to assess the effects of acute alcohol ingestion and chronic alcohol use on outcome. Results suggest that patients with acute or chronic alcohol abuse have increased needs for nursing services in the hospital. Alcohol use did not play a role in modifying other outcome measures.

Accidents, Traffic↗

PubMed1999

Clinicopathologic study of 85 similarly treated patients with anaplastic astrocytic tumors. An analysis of DNA content (ploidy), cellular proliferation, and p53 expression.

BACKGROUND: The biologic behavior of anaplastic (World Health Organization Grade III) astrocytomas and oligoastrocytomas is highly variable, ranging from rapid progression to prolonged survival. It is difficult to predict the outcome of an individual patient based on morphology alone. METHODS: To determine the prognostic value of commonly used clinicopathologic markers, we reviewed our experience with 85 similarly treated patients enrolled in 3 North Central Cancer Treatment Group high grade glioma protocols. The pathology was comprised exclusively of primary anaplastic astrocytic tumors (66 astrocytomas and 19 oligoastrocytomas). Variables examined included patient age, morphologic type, preoperative performance score, extent of surgery, solitary versus multiple mitoses, DNA flow cytometric and image morphometric parameters, and expression of proliferating cell nuclear antigen, MIB-1, and p53 expression. RESULTS: The study was comprised of 48 men and 37 women ranging in age from 14-79 years (median age, 47 years). Overall survival ranged from <1 month to >12 years (median, 21.6 months). Statistical analyses revealed that age accounted for the majority of this extensive variability in survival. The median survival times were 65. 5 months, 22.1 months, and 4.4 months, respectively, for the groups <40 years, 40-59 years, and >/=60 years, respectively (P < 0.0001). On univariate analyses, aneuploidy by flow cytometry and a low performance score also predicted a better survival (P values of 0.04 and 0.009, respectively). Statistical trends predicting a better survival were observed for patients with a solitary mitosis and p53 immunopositivity. However, only patient age remained significant in multivariate models. CONCLUSIONS: In a small but relatively uniformly treated cohort of patients with anaplastic astrocytomas and oligoastrocytomas, patient age was associated strongly and inversely with overall survival. Once patient age was taken into account, the clinical and pathologic markers tested appeared to be of limited prognostic value.

Adolescent↗

PubMed1999

Involvement of host cell tyrosine phosphorylation in the invasion of HEp-2 cells by Bartonella bacilliformis.

We have provided evidence that exposure of human cells to protein kinase inhibitors results in decreased invasion of these cells by Bartonella bacilliformis in a dose-dependent manner. Preincubation of human laryngeal epithelial cells in the presence of genistein, a tyrosine protein kinase inhibitor, decreased the invasion of these cells by B. bacilliformis significantly. Further, exposure of normal human umbilical vein endothelial cells to staurosporine, a potent inhibitor of protein kinase C and some tyrosine protein kinases, resulted in a considerable reduction in the number of organisms internalized by these cells. Moreover, Bartonella infection of HEp-2 cells induced tyrosine phosphorylation of several Triton X-100 soluble proteins with approximate molecular masses of 243, 215 179, 172 (doublet), 160, 145 and 110 kDa that were absent or reduced in the presence of genistein in cells after 1 h of infection. Exposure of HEp-2 cell monolayers to anti-alpha 5 and anti-beta 1 chain integrin monoclonal antibodies resulted in a moderate decrease in the invasion of these cells, suggesting a possible role of alpha 5 beta 1 integrins in the uptake of Bartonella into nucleated cells.

Antibodies, Monoclonal↗

PubMed1999

Emergency medical services outcomes project I (EMSOP I): prioritizing conditions for outcomes research.

Over the past several years, out-of-hospital EMS have come under increased scrutiny regarding the value of the range of EMS as currently provided. We used frequency data and expert opinion to rank-order EMS conditions for children and adults based on their potential value for the study of effectiveness of EMS care. Relief of discomfort was the outcome parameter EMS professionals identified as having the most potential impact for the majority of children and adults in the top quartile conditions. Future work from this project will identify appropriate severity and outcome measures that can be used to study these priority conditions. The results from the first year of this project will assist those interested in EMS outcomes research to focus their efforts. Furthermore, the results suggest that nonmortality out-come measures, such as relief of discomfort, may be important parameters in determining EMS effectiveness.

Adolescent↗

PubMed1999

Potential associations among genetic markers in the serotonergic system and the antisocial alcoholism subtype.

Alcoholism is transmitted in families. The complexity and heterogeneity of this disorder has made it difficult to identify specific genetic correlates. One design with the potential to do so is the family-based association study, in which the frequencies of genetic polymorphisms are compared between affected and nonaffected members. Reduced central serotonin neurotransmission is associated with features of an antisocial subtype of alcoholism, although a primary deficit has not been traced to a particular component. Genetic markers related to the sertonergic system have been identified, located, and cloned. If associations can be discovered, the development process for pharmacotherapy could be facilitated. In this review, the evidence for the involvement of the serotonergic system in antisocial alcoholism is examined, and the potential for family-based association studies to identify specific components that may be involved is discussed.

Alcoholism↗