BACKGROUND

The relationship of health risk behavior and disease in adulthood to the breadth of exposure to childhood emotional, physical, or sexual abuse, and household dysfunction during childhood has not previously been described.

METHODS

A questionnaire about adverse childhood experiences was mailed to 13,494 adults who had completed a standardized medical evaluation at a large HMO; 9,508 (70.5%) responded. Seven categories of adverse childhood experiences were studied: psychological, physical, or sexual abuse; violence against mother; or living with household members who were substance abusers, mentally ill or suicidal, or ever imprisoned. The number of categories of these adverse childhood experiences was then compared to measures of adult risk behavior, health status, and disease. Logistic regression was used to adjust for effects of demographic factors on the association between the cumulative number of categories of childhood exposures (range: 0-7) and risk factors for the leading causes of death in adult life.

RESULTS

More than half of respondents reported at least one, and one-fourth reported>> or = 2 categories of childhood exposures. We found a graded relationship between the number of categories of childhood exposure and each of the adult health risk behaviors and diseases that were studied (P < .001). Persons who had experienced four or more categories of childhood exposure, compared to those who had experienced none, had 4- to 12-fold increased health risks for alcoholism, drug abuse, depression, and suicide attempt; a 2- to 4-fold increase in smoking, poor self-rated health,>> or = 50 sexual intercourse partners, and sexually transmitted disease; and 1.4- to 1.6-fold increase in physical inactivity and severe obesity. The number of categories of adverse childhood exposures showed a graded relationship to the presence of adult diseases including ischemic heart disease, cancer, chronic lung disease, skeletal fractures, and liver disease. The seven categories of adverse childhood experiences were strongly interrelated and persons with multiple categories of childhood exposure were likely to have multiple health risk factors later in life.

CONCLUSIONS

We found a strong graded relationship between the breadth of exposure to abuse or household dysfunction during childhood and multiple risk factors for several of the leading causes of death in adults.

Pseudomonas aeruginosa is a ubiquitous environmental bacterium that is one of the top three causes of opportunistic human infections. A major factor in its prominence as a pathogen is its intrinsic resistance to antibiotics and disinfectants. Here we report the complete sequence of P. aeruginosa strain PAO1. At 6.3 million base pairs, this is the largest bacterial genome sequenced, and the sequence provides insights into the basis of the versatility and intrinsic drug resistance of P. aeruginosa. Consistent with its larger genome size and environmental adaptability, P. aeruginosa contains the highest proportion of regulatory genes observed for a bacterial genome and a large number of genes involved in the catabolism, transport and efflux of organic compounds as well as four potential chemotaxis systems. We propose that the size and complexity of the P. aeruginosa genome reflect an evolutionary adaptation permitting it to thrive in diverse environments and resist the effects of a variety of antimicrobial substances.

Neurogenesis in the mammalian central nervous system is believed to end in the period just after birth; in the mouse striatum no new neurons are produced after the first few days after birth. In this study, cells isolated from the striatum of the adult mouse brain were induced to proliferate in vitro by epidermal growth factor. The proliferating cells initially expressed nestin, an intermediate filament found in neuroepithelial stem cells, and subsequently developed the morphology and antigenic properties of neurons and astrocytes. Newly generated cells with neuronal morphology were immunoreactive for gamma-aminobutyric acid and substance P, two neurotransmitters of the adult striatum in vivo. Thus, cells of the adult mouse striatum have the capacity to divide and differentiate into neurons and astrocytes.

BACKGROUND

This longitudinal community study assessed the prevalence and development of psychiatric disorders from age 9 through 16 years and examined homotypic and heterotypic continuity.

METHODS

A representative population sample of 1420 children aged 9 to 13 years at intake were assessed annually for DSM-IV disorders until age 16 years.

RESULTS

Although 3-month prevalence of any disorder averaged 13.3% (95% confidence interval [CI], 11.7%-15.0%), during the study period 36.7% of participants (31% of girls and 42% of boys) had at least 1 psychiatric disorder. Some disorders (social anxiety, panic, depression, and substance abuse) increased in prevalence, whereas others, including separation anxiety disorder and attention-deficit/hyperactivity disorder (ADHD), decreased. Lagged analyses showed that children with a history of psychiatric disorder were 3 times more likely than those with no previous disorder to have a diagnosis at any subsequent wave (odds ratio, 3.7; 95% CI, 2.9-4.9; P<.001). Risk from a previous diagnosis was high among both girls and boys, but it was significantly higher among girls. Continuity of the same disorder (homotypic) was significant for all disorders except specific phobias. Continuity from one diagnosis to another (heterotypic) was significant from depression to anxiety and anxiety to depression, from ADHD to oppositional defiant disorder, and from anxiety and conduct disorder to substance abuse. Almost all the heterotypic continuity was seen in girls.

CONCLUSIONS

The risk of having at least 1 psychiatric disorder by age 16 years is much higher than point estimates would suggest. Concurrent comorbidity and homotypic and heterotypic continuity are more marked in girls than in boys.

BACKGROUND

Uncertainties exist about the prevalence and comorbidity of substance use disorders and independent mood and anxiety disorders.

OBJECTIVE

To present nationally representative data on the prevalence and comorbidity of DSM-IV alcohol and drug use disorders and independent mood and anxiety disorders (including only those that are not substance induced and that are not due to a general medical condition).

METHODS

Face-to-face survey.

METHODS

The United States.

METHODS

Household and group quarters' residents.

METHODS

Prevalence and associations of substance use disorders and independent mood and anxiety disorders.

RESULTS

The prevalences of 12-month DSM-IV independent mood and anxiety disorders in the US population were 9.21% (95% confidence interval [CI], 8.78%-9.64%) and 11.08% (95% CI, 10.43%-11.73%), respectively. The rate of substance use disorders was 9.35% (95% CI, 8.86%-9.84%). Only a few individuals with mood or anxiety disorders were classified as having only substance-induced disorders. Associations between most substance use disorders and independent mood and anxiety disorders were positive and significant (P<.05).

CONCLUSIONS

Substance use disorders and mood and anxiety disorders that develop independently of intoxication and withdrawal are among the most prevalent psychiatric disorders in the United States. Associations between most substance use disorders and independent mood and anxiety disorders were overwhelmingly positive and significant, suggesting that treatment for a comorbid mood or anxiety disorder should not be withheld from individuals with substance use disorders.

BACKGROUND

The main threats to adolescents' health are the risk behaviors they choose. How their social context shapes their behaviors is poorly understood.

OBJECTIVE

To identify risk and protective factors at the family, school, and individual levels as they relate to 4 domains of adolescent health and morbidity: emotional health, violence, substance use, and sexuality.

METHODS

Cross-sectional analysis of interview data from the National Longitudinal Study of Adolescent Health.

METHODS

A total of 12118 adolescents in grades 7 through 12 drawn from an initial national school survey of 90118 adolescents from 80 high schools plus their feeder middle schools.

METHODS

The interview was completed in the subject's home.

METHODS

Eight areas were assessed: emotional distress; suicidal thoughts and behaviors; violence; use of 3 substances (cigarettes, alcohol, marijuana); and 2 types of sexual behaviors (age of sexual debut and pregnancy history). Independent variables included measures of family context, school context, and individual characteristics.

RESULTS

Parent-family connectedness and perceived school connectedness were protective against every health risk behavior measure except history of pregnancy. Conversely, ease of access to guns at home was associated with suicidality (grades 9-12: P<.001) and violence (grades 7-8: P<.001; grades 9-12: P<.001). Access to substances in the home was associated with use of cigarettes (P<.001), alcohol (P<.001), and marijuana (P<.001) among all students. Working 20 or more hours a week was associated with emotional distress of high school students (P<.01), cigarette use (P<.001), alcohol use (P<.001), and marijuana use (P<.001). Appearing "older than most" in class was associated with emotional distress and suicidal thoughts and behaviors among high school students (P<.001); it was also associated with substance use and an earlier age of sexual debut among both junior and senior high students. Repeating a grade in school was associated with emotional distress among students in junior high (P<.001) and high school (P<.01) and with tobacco use among junior high students (P<.001). On the other hand, parental expectations regarding school achievement were associated with lower levels of health risk behaviors; parental disapproval of early sexual debut was associated with a later age of onset of intercourse (P<.001).

CONCLUSIONS

Family and school contexts as well as individual characteristics are associated with health and risky behaviors in adolescents. The results should assist health and social service providers, educators, and others in taking the first steps to diminish risk factors and enhance protective factors for our young people.

We investigated two outbreaks of an unusual gastrointestinal illness that affected at least 47 people in Oregon and Michigan in February through March and May through June 1982. The illness was characterized by severe crampy abdominal pain, initially watery diarrhea followed by grossly bloody diarrhea, and little or no fever. It was associated with eating at restaurants belonging to the same fast-food restaurant chain in Oregon (P less than 0.005) and Michigan (P = 0.0005) and with eating any of three sandwiches containing three ingredients in common (beef patty, rehydrated onions, and pickles). Stool cultures did not yield previously recognized pathogens. However, a rare Escherichia coli serotype, O157:H7, that was not invasive or toxigenic by standard tests was isolated from 9 of 12 stools collected within four days of onset of illness in both outbreaks combined, and from a beef patty from a suspected lot of meat in Michigan. The only known previous isolation of this serotype was from a sporadic case of hemorrhagic colitis in 1975. This report describes a clinically distinctive gastrointestinal illness associated with E. coli O157:H7, apparently transmitted by undercooked meat.

The striatum, which is the major component of the basal ganglia in the brain, is regulated in part by dopaminergic input from the substantia nigra. Severe movement disorders result from the loss of striatal dopamine in patients with Parkinson's disease. Rats with lesions of the nigrostriatal dopamine pathway caused by 6-hydroxydopamine (6-OHDA) serve as a model for Parkinson's disease and show alterations in gene expression in the two major output systems of the striatum to the globus pallidus and substantia nigra. Striatopallidal neurons show a 6-OHDA-induced elevation in their specific expression of messenger RNAs (mRNAs) encoding the D2 dopamine receptor and enkephalin, which is reversed by subsequent continuous treatment with the D2 agonist quinpirole. Conversely, striatonigral neurons show a 6-OHDA-induced reduction in their specific expression of mRNAs encoding the D1 dopamine receptor and substance P, which is reversed by subsequent daily injections of the D1 agonist SKF-38393. This treatment also increases dynorphin mRNA in striatonigral neurons. Thus, the differential effects of dopamine on striatonigral and striatopallidal neurons are mediated by their specific expression of D1 and D2 dopamine receptor subtypes, respectively.

OBJECTIVE

To present nationally representative data on 12-month and lifetime prevalence, correlates, and comorbidity of DSM-IV major depressive disorder (MDD) among adults in the United States. DESIGN/SETTING/ PARTICIPANTS: Face-to-face survey of more than 43 000 adults aged 18 years and older residing in households and group quarters in the United States.

METHODS

Prevalence and associations of MDD with sociodemographic correlates and Axis I and II disorders.

RESULTS

The prevalence of 12-month and lifetime DSM-IV MDD was 5.28% (95% confidence interval, 4.98-5.57) and 13.23% (95% confidence interval, 12.64-13.81), respectively. Being female; Native American; middle-aged; widowed, separated, or divorced; and low income increased risk, and being Asian, Hispanic, or black decreased risk (P<.05). Women were significantly more likely to receive treatment than men. Both current and lifetime MDD were significantly associated with other specific psychiatric disorders, notably substance dependence, panic and generalized anxiety disorder, and several personality disorders.

CONCLUSIONS

This large survey suggests a higher prevalence of MDD in the US population than large-sample estimates from the 1980s and 1990s. The shift in highest lifetime risk from young to middle-aged adults is an important transformation in the distribution of MDD in the United States and specificity in risk for an age-period cohort. Associations between MDD and Axis I and II disorders were strong and significant, with variation within broad categories by specific diagnoses signaling the need for attention to the genetic and environmental reasons for such variation, as well as the implications for treatment response.

Nitric oxide (NO), a potent vasodilator produced by endothelial cells, is thought to be the endothelium-dependent relaxing factor (EDRF) which mediates vascular relaxation in response to acetylcholine, bradykinin and substance P in many vascular beds. NO has been implicated in the regulation of blood pressure and regional blood flow, and also affects vascular smooth-muscle proliferation and inhibits platelet aggregation and leukocyte adhesion. Abnormalities in endothelial production of NO occur in atherosclerosis, diabetes and hypertension. Pharmacological blockade of NO production with arginine analogues such as L-nitroarginine (L-NA) or L-N-arginine methyl ester affects multiple isoforms of nitric oxide synthase (NOS), and so cannot distinguish their physiological roles. To study the role of endothelial NOS (eNOS) in vascular function, we disrupted the gene encoding eNOS in mice. Endothelium-derived relaxing factor activity, as assayed by acetylcholine-induced relaxation, is absent, and the eNOS mutant mice are hypertensive. Thus eNOS mediates basal vasodilation. Responses to NOS blockade in the mutant mice suggest that non-endothelial isoforms of NOS may be involved in maintaining blood pressure.

BACKGROUND

Childhood maltreatment has been linked to a variety of changes in brain structure and function and stress-responsive neurobiological systems. Epidemiological studies have documented the impact of childhood maltreatment on health and emotional well-being.

METHODS

After a brief review of the neurobiology of childhood trauma, we use the Adverse Childhood Experiences (ACE) Study as an epidemiological "case example" of the convergence between epidemiologic and neurobiological evidence of the effects of childhood trauma. The ACE Study included 17,337 adult HMO members and assessed 8 adverse childhood experiences (ACEs) including abuse, witnessing domestic violence, and serious household dysfunction. We used the number of ACEs (ACE score) as a measure of cumulative childhood stress and hypothesized a "dose-response" relationship of the ACE score to 18 selected outcomes and to the total number of these outcomes (comorbidity).

RESULTS

Based upon logistic regression analysis, the risk of every outcome in the affective, somatic, substance abuse, memory, sexual,and aggression-related domains increased in a graded fashion as the ACE score increased (P <0.001). The mean number of comorbid outcomes tripled across the range of the ACE score.

CONCLUSIONS

The graded relationship of the ACE score to 18 different outcomes in multiple domains theoretically parallels the cumulative exposure of the developing brain to the stress response with resulting impairment in multiple brain structures and functions.

Fifty-six heroin addicts and 60 age-matched controls were offered choices between monetary rewards ($11-$80) available immediately and larger rewards ($25-$85) available after delays ranging from 1 week to 6 months. Participants had a 1-in-6 chance of winning a reward that they chose on one randomly selected trial. Delay-discounting rates were estimated from the pattern of participants' choices. The discounting model of impulsiveness (Ainslie, 1975) implies that delay-discounting rates are positively correlated with impulsiveness. On average, heroin addicts' discount rates were twice those of controls (p = .004), and discount rates were positively correlated with impulsivity as measured by self-report questionnaires (p < .05). The results lend external validity to the delay-discounting rate as a measure of impulsiveness, a characteristic associated with substance abuse.

BACKGROUND

Current and comprehensive information on the epidemiology of DSM-IV 12-month and lifetime drug use disorders in the United States has not been available.

OBJECTIVE

To present detailed information on drug abuse and dependence prevalence, correlates, and comorbidity with other Axis I and II disorders.

METHODS

Face-to-face interviews using the Alcohol Use Disorder and Associated Disabilities Interview Schedule of the National Institute on Alcohol Abuse and Alcoholism in a large representative sample of US adults (N=43093).

METHODS

Twelve-month and lifetime prevalence of drug abuse and dependence and the associated correlates, treatment rates, disability, and comorbidity with other Axis I and II disorders.

RESULTS

Prevalences of 12-month and lifetime drug abuse (1.4% and 7.7%, respectively) exceeded rates of drug dependence (0.6% and 2.6%, respectively). Rates of abuse and dependence were generally greater among men, Native Americans, respondents aged 18 to 44 years, those of lower socioeconomic status, those residing in the West, and those who were never married or widowed, separated, or divorced (all P<.05). Associations of drug use disorders with other substance use disorders and antisocial personality disorder were diminished but remained strong when we controlled for psychiatric disorders. Dependence associations with most mood disorders and generalized anxiety disorder also remained significant. Lifetime treatment- or help-seeking behavior was uncommon (8.1%, abuse; 37.9%, dependence) and was not associated with sociodemographic characteristics but was associated with psychiatric comorbidity.

CONCLUSIONS

Most individuals with drug use disorders have never been treated, and treatment disparities exist among those at high risk, despite substantial disability and comorbidity. Comorbidity of drug use disorders with other substance use disorders and antisocial personality disorder, as well as dependence with mood disorders and generalized anxiety disorder, appears to be due in part to unique factors underlying each pair of these disorders studied. The persistence of low treatment rates despite the availability of effective treatments indicates the need for vigorous educational efforts for the public and professionals.

BACKGROUND

Evidence suggests that early adverse experiences play a preeminent role in development of mood and anxiety disorders and that corticotropin-releasing factor (CRF) systems may mediate this association.

OBJECTIVE

To determine whether early-life stress results in a persistent sensitization of the hypothalamic-pituitary-adrenal axis to mild stress in adulthood, thereby contributing to vulnerability to psychopathological conditions.

METHODS

Prospective controlled study conducted from May 1997 to July 1999 at the General Clinical Research Center of Emory University Hospital, Atlanta, Ga.

METHODS

Forty-nine healthy women aged 18 to 45 years with regular menses, with no history of mania or psychosis, with no active substance abuse or eating disorder within 6 months, and who were free of hormonal and psychotropic medications were recruited into 4 study groups (n = 12 with no history of childhood abuse or psychiatric disorder [controls]; n = 13 with diagnosis of current major depression who were sexually or physically abused as children; n = 14 without current major depression who were sexually or physically abused as children; and n = 10 with diagnosis of current major depression and no history of childhood abuse).

METHODS

Adrenocorticotropic hormone (ACTH) and cortisol levels and heart rate responses to a standardized psychosocial laboratory stressor compared among the 4 study groups.

RESULTS

Women with a history of childhood abuse exhibited increased pituitary-adrenal and autonomic responses to stress compared with controls. This effect was particularly robust in women with current symptoms of depression and anxiety. Women with a history of childhood abuse and a current major depression diagnosis exhibited a more than 6-fold greater ACTH response to stress than age-matched controls (net peak of 9.0 pmol/L [41.0 pg/mL]; 95% confidence interval [CI], 4.7-13.3 pmol/L [21.6-60. 4 pg/mL]; vs net peak of 1.4 pmol/L [6.19 pg/mL]; 95% CI, 0.2-2.5 pmol/L [1.0-11.4 pg/mL]; difference, 8.6 pmol/L [38.9 pg/mL]; 95% CI, 4.6-12.6 pmol/L [20.8-57.1 pg/mL]; P<.001).

CONCLUSIONS

Our findings suggest that hypothalamic-pituitary-adrenal axis and autonomic nervous system hyperreactivity, presumably due to CRF hypersecretion, is a persistent consequence of childhood abuse that may contribute to the diathesis for adulthood psychopathological conditions. Furthermore, these results imply a role for CRF receptor antagonists in the prevention and treatment of psychopathological conditions related to early-life stress. JAMA. 2000;284:592-597

BACKGROUND

Although the 1990s saw enormous change in the mental health care system in the United States, little is known about changes in the prevalence or rate of treatment of mental disorders.

METHODS

We examined trends in the prevalence and rate of treatment of mental disorders among people 18 to 54 years of age during roughly the past decade. Data from the National Comorbidity Survey (NCS) were obtained in 5388 face-to-face household interviews conducted between 1990 and 1992, and data from the NCS Replication were obtained in 4319 interviews conducted between 2001 and 2003. Anxiety disorders, mood disorders, and substance-abuse disorders that were present during the 12 months before the interview were diagnosed with the use of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). Treatment for emotional disorders was categorized according to the sector of mental health services: psychiatry services, other mental health services, general medical services, human services, and complementary-alternative medical services.

RESULTS

The prevalence of mental disorders did not change during the decade (29.4 percent between 1990 and 1992 and 30.5 percent between 2001 and 2003, P=0.52), but the rate of treatment increased. Among patients with a disorder, 20.3 percent received treatment between 1990 and 1992 and 32.9 percent received treatment between 2001 and 2003 (P<0.001). Overall, 12.2 percent of the population 18 to 54 years of age received treatment for emotional disorders between 1990 and 1992 and 20.1 percent between 2001 and 2003 (P<0.001). Only about half those who received treatment had disorders that met diagnostic criteria for a mental disorder. Significant increases in the rate of treatment (49.0 percent between 1990 and 1992 and 49.9 percent between 2001 and 2003) were limited to the sectors of general medical services (2.59 times as high in 2001 to 2003 as in 1990 to 1992), psychiatry services (2.17 times as high), and other mental health services (1.59 times as high) and were independent of the severity of the disorder and of the sociodemographic characteristics of the respondents.

CONCLUSIONS

Despite an increase in the rate of treatment, most patients with a mental disorder did not receive treatment. Continued efforts are needed to obtain data on the effectiveness of treatment in order to increase the use of effective treatments.

1. The effect of Li+ on the agonist-dependent metabolism of [3H]inositol has been studied in rat brain, rat parotid and the insect salivary gland. 2. When brain or parotid slices were incubated in the presence of [3H]inositol, Li+ was found to amplify the ability of agonists such as carbachol, phenylephrine, histamine, 5-hydroxytryptamine and Substance P to elevate the amount of label appearing in the inositol phosphates. 3. A different approach was used with the insect salivary gland, which was prelabelled with [3H]inositol. After washing out the label, the subsequent release of [3H]inositol induced by 5-hydroxytryptamine was greatly decreased by Li+. During Li+ treatment there was a large accumulation of [3H]inositol 1-phosphate. 4. This ability of Li+ to greatly amplify the agonist-dependent accumulation of myo-inositol 1-phosphate offers a novel technique for identifying those receptors that function by hydrolysing phosphatidylinositol. 5. The therapeutic action of Li+ may be explained by this inhibition of myo-inositol 1-phosphatase, which lowers the level of myo-inositol and could lead to a decrease in the concentration of phosphatidylinositol, especially in those neurons that are being stimulated excessively. This alteration in phosphatidylinositol metabolism may serve to reset the sensitivity of those multifunctional receptors that generate second messengers such as Ca2+, cyclic GMP and the prostaglandins.

Acetylcholine is believed to dilate normal blood vessels by promoting the release of a vasorelaxant substance from the endothelium (endothelium-derived relaxing factor). By contrast, if the endothelium is removed experimentally, acetylcholine constricts blood vessels. We tested the hypothesis that muscarinic cholinergic vasodilation is impaired in coronary atherosclerosis. Graded concentrations of acetylcholine and, for comparison, the nonendothelial-dependent vasodilator nitroglycerin were infused into the left anterior descending artery of eight patients with advanced coronary stenoses (greater than 50 percent narrowing), four subjects with angiographically normal coronary arteries, and six patients with mild coronary atherosclerosis (less than 20 percent narrowing). Vascular responses were evaluated by quantitative angiography. In several segments each of four normal coronary arteries, acetylcholine caused a dose-dependent dilation from a control diameter of 1.94 +/- 0.16 mm to 2.16 +/- 0.15 mm with the maximal acetylcholine dose (P less than 0.01). In contrast, all eight of the arteries with advanced stenoses showed dose-dependent constriction, from 1.05 +/- 0.05 to 0.32 +/- 0.16 mm at the highest concentration of acetylcholine (P less than 0.01), with temporary occlusion in five. Five of six vessels with minimal disease also constricted in response to acetylcholine. All vessels dilated in response to nitroglycerin, however. We conclude that paradoxical vasoconstriction induced by acetylcholine occurs early as well as late in the course of coronary atherosclerosis. Our preliminary findings suggest that the abnormal vascular response to acetylcholine may represent a defect in endothelial vasodilator function, and may be important in the pathogenesis of coronary vasospasm.

BACKGROUND

Suicide is a leading cause of death in the United States, but identifying persons at risk is difficult. Thus, the US surgeon general has made suicide prevention a national priority. An expanding body of research suggests that childhood trauma and adverse experiences can lead to a variety of negative health outcomes, including attempted suicide among adolescents and adults.

OBJECTIVE

To examine the relationship between the risk of suicide attempts and adverse childhood experiences and the number of such experiences (adverse childhood experiences [ACE] score).

METHODS

A retrospective cohort study of 17 337 adult health maintenance organization members (54% female; mean [SD] age, 57 [15.3] years) who attended a primary care clinic in San Diego, Calif, within a 3-year period (1995-1997) and completed a survey about childhood abuse and household dysfunction, suicide attempts (including age at first attempt), and multiple other health-related issues.

METHODS

Self-reported suicide attempts, compared by number of adverse childhood experiences, including emotional, physical, and sexual abuse; household substance abuse, mental illness, and incarceration; and parental domestic violence, separation, or divorce.

RESULTS

The lifetime prevalence of having at least 1 suicide attempt was 3.8%. Adverse childhood experiences in any category increased the risk of attempted suicide 2- to 5-fold. The ACE score had a strong, graded relationship to attempted suicide during childhood/adolescence and adulthood (P<.001). Compared with persons with no such experiences (prevalence of attempted suicide, 1.1%), the adjusted odds ratio of ever attempting suicide among persons with 7 or more experiences (35.2%) was 31.1 (95% confidence interval, 20.6-47.1). Adjustment for illicit drug use, depressed affect, and self-reported alcoholism reduced the strength of the relationship between the ACE score and suicide attempts, suggesting partial mediation of the adverse childhood experience-suicide attempt relationship by these factors. The population-attributable risk fractions for 1 or more experiences were 67%, 64%, and 80% for lifetime, adult, and childhood/adolescent suicide attempts, respectively.

CONCLUSIONS

A powerful graded relationship exists between adverse childhood experiences and risk of attempted suicide throughout the life span. Alcoholism, depressed affect, and illicit drug use, which are strongly associated with such experiences, appear to partially mediate this relationship. Because estimates of the attributable risk fraction caused by these experiences were large, prevention of these experiences and the treatment of persons affected by them may lead to progress in suicide prevention.

OBJECTIVE

Whether people infected with human immunodeficiency virus (HIV) are at an increased risk of acute myocardial infarction (AMI) compared with uninfected people is not clear. Without demographically and behaviorally similar uninfected comparators and without uniformly measured clinical data on risk factors and fatal and nonfatal AMI events, any potential association between HIV status and AMI may be confounded.

OBJECTIVE

To investigate whether HIV is associated with an increased risk of AMI after adjustment for all standard Framingham risk factors among a large cohort of HIV-positive and demographically and behaviorally similar (ie, similar prevalence of smoking, alcohol, and cocaine use) uninfected veterans in care.

METHODS

Participants in the Veterans Aging Cohort Study Virtual Cohort from April 1, 2003, through December 31, 2009.

METHODS

After eliminating those with baseline cardiovascular disease, we analyzed data on HIV status, age, sex, race/ethnicity, hypertension, diabetes mellitus, dyslipidemia, smoking, hepatitis C infection, body mass index, renal disease, anemia, substance use, CD4 cell count, HIV-1 RNA, antiretroviral therapy, and incidence of AMI.

METHODS

Acute myocardial infarction.

RESULTS

We analyzed data on 82 459 participants. During a median follow-up of 5.9 years, there were 871 AMI events. Across 3 decades of age, the mean (95% CI) AMI events per 1000 person-years was consistently and significantly higher for HIV-positive compared with uninfected veterans: for those aged 40 to 49 years, 2.0 (1.6-2.4) vs 1.5 (1.3-1.7); for those aged 50 to 59 years, 3.9 (3.3-4.5) vs 2.2 (1.9-2.5); and for those aged 60 to 69 years, 5.0 (3.8-6.7) vs 3.3 (2.6-4.2) (P < .05 for all). After adjusting for Framingham risk factors, comorbidities, and substance use, HIV-positive veterans had an increased risk of incident AMI compared with uninfected veterans (hazard ratio, 1.48; 95% CI, 1.27-1.72). An excess risk remained among those achieving an HIV-1 RNA level less than 500 copies/mL compared with uninfected veterans in time-updated analyses (hazard ratio, 1.39; 95% CI, 1.17-1.66).

CONCLUSIONS

Infection with HIV is associated with a 50% increased risk of AMI beyond that explained by recognized risk factors.

[Avena, N.M., Rada, P., Hoebel B.G., 2007. Evidence for sugar addiction: Behavioral and neurochemical effects of intermittent, excessive sugar intake. Neuroscience and Biobehavioral Reviews XX(X), XXX-XXX]. The experimental question is whether or not sugar can be a substance of abuse and lead to a natural form of addiction. "Food addiction" seems plausible because brain pathways that evolved to respond to natural rewards are also activated by addictive drugs. Sugar is noteworthy as a substance that releases opioids and dopamine and thus might be expected to have addictive potential. This review summarizes evidence of sugar dependence in an animal model. Four components of addiction are analyzed. "Bingeing," "withdrawal," "craving" and "cross-sensitization" are each given operational definitions and demonstrated behaviorally with sugar bingeing as the reinforcer. These behaviors are then related to neurochemical changes in the brain that also occur with addictive drugs. Neural adaptations include changes in dopamine and opioid receptor binding, enkephalin mRNA expression and dopamine and acetylcholine release in the nucleus accumbens. The evidence supports the hypothesis that under certain circumstances rats can become sugar dependent. This may translate to some human conditions as suggested by the literature on eating disorders and obesity.

OBJECTIVE

To present nationally representative data on lifetime prevalence and comorbidity of pathological gambling with other psychiatric disorders and to evaluate sex differences in the strength of the comorbid associations.

METHODS

Data were derived from a large national sample of the United States. Some 43,093 household and group quarters residents age 18 years and older participated in the 2001-2002 survey. Prevalence and associations of lifetime pathological gambling and other lifetime psychiatric disorders are presented. The diagnostic interview was the National Institute on Alcohol Abuse and Alcoholism Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version. Fifteen symptom items operationalized the 10 pathological gambling criteria.

RESULTS

The lifetime prevalence rate of pathological gambling was 0.42%. Almost three quarters (73.2%) of pathological gamblers had an alcohol use disorder, 38.1% had a drug use disorder, 60.4% had nicotine dependence, 49.6% had a mood disorder, 41.3% had an anxiety disorder, and 60.8% had a personality disorder. A large majority of the associations between pathological gambling and substance use, mood, anxiety, and personality disorders were overwhelmingly positive and significant (p < .05), even after controlling for sociodemographic and socioeconomic characteristics. Male sex, black race, divorced/separated/widowed marital status, middle age, and living in the West and Midwest were associated with increased risk for pathological gambling. Further, associations between alcohol dependence, any drug use disorder, drug abuse, nicotine dependence, major depressive episode, and generalized anxiety disorder and pathological gambling were stronger among women than men (p>> .05).

CONCLUSIONS

Pathological gambling is highly comorbid with substance use, mood, anxiety, and personality disorders, suggesting that treatment for one condition should involve assessment and possible concomitant treatment for comorbid conditions.

Substances released by platelets during blood clotting are essential participants in events that link hemostasis and angiogenesis and ensure adequate wound healing and tissue injury repair. We assessed the participation of sphingosine 1-phosphate (Sph-1-P), a biologically active phosphorylated lipid growth factor released from activated platelets, in the regulation of endothelial monolayer barrier integrity, which is key to both angiogenesis and vascular homeostasis. Sph-1-P produced rapid, sustained, and dose-dependent increases in transmonolayer electrical resistance (TER) across both human and bovine pulmonary artery and lung microvascular endothelial cells. This substance also reversed barrier dysfunction elicited by the edemagenic agent thrombin. Sph-1-P-mediated barrier enhancement was dependent upon G(ialpha)-receptor coupling to specific members of the endothelial differentiation gene (Edg) family of receptors (Edg-1 and Edg-3), Rho kinase and tyrosine kinase-dependent activation, and actin filament rearrangement. Sph-1-P-enhanced TER occurred in conjunction with Rac GTPase- and p21-associated kinase-dependent endothelial cortical actin assembly with recruitment of the actin filament regulatory protein, cofilin. Platelet-released Sph-1-P, linked to Rac- and Rho-dependent cytoskeletal rearrangement, may act late in angiogenesis to stabilize newly formed vessels, which often display abnormally increased vascular permeability.

This review gives an overview of recent findings and developments in research on brain mechanisms of reward and reinforcement from studies using the place preference conditioning paradigm, with emphasis on those studies that have been published within the last decade. Methodological issues of the paradigm (such as design of the conditioning apparatus, biased vs unbiased conditioning, state dependency effects) are discussed. Results from studies using systemic and local (intracranial) drug administration, natural reinforcers, and non-drug treatments and from studies examining the effects of lesions are presented. Papers reporting on conditioned place aversion (CPA) experiments are also included. A special emphasis is put on the issue of tolerance and sensitization to the rewarding properties of drugs. Transmitter systems that have been investigated with respect to their involvement in brain reward mechanisms include dopamine, opioids, acetylcholine, GABA, serotonin, glutamate, substance P, and cholecystokinin, the motivational significance of which has been examined either directly, by using respective agonist or antagonist drugs, or indirectly, by studying the effects of these drugs on the reward induced by other drugs. For a number of these transmitters, detailed studies have been conducted to delineate the receptor subtype(s) responsible for the mediation of the observed drug effects, particularly in the case of dopamine, the opioids, serotonin and glutamate. Brain sites that have been implicated in the mediation of drug-induced place conditioning include the 'traditional' brain reward sites, ventral tegmental area and nucleus accumbens, but the medial prefrontal cortex, ventral pallidum, amygdala and the pedunculopontine tegmental nucleus have also been shown to play important roles in the mediation of place conditioning induced by drugs or natural reinforcers. Thus, although the paradigm has also been criticized because of some inherent methodological problems, it is clear that during the past decade place preference conditioning has become a valuable and firmly established and very widely used tool in behavioural pharmacology and addiction research.

Endothelium-dependent relaxation of blood vessels is produced by a large number of agents (e.g., acetylcholine, ATP and ADP, substance P, bradykinin, histamine, thrombin, serotonin). With some agents, relaxation may be limited to certain species and/or blood vessels. Relaxation results from release of a very labile non-prostanoid endothelium-derived relaxing factor (EDRF) or factors. EDRF stimulates guanylate cyclase of the vascular smooth muscle, with the resulting increase in cyclic GMP activating relaxation. EDRF is rapidly inactivated by hemoglobin and superoxide. There is strong evidence that EDRF from many blood vessels and from cultured endothelial cells is nitric oxide (NO) and that its precursor is L-arginine. There is evidence for other relaxing factors, including an endothelium-derived hyperpolarizing factor in some vessels. Flow-induced shear stress also stimulates EDRF release. Endothelium-dependent relaxation occurs in resistance vessels as well as in larger arteries, and is generally more pronounced in arteries than veins. EDRF also inhibits platelet aggregation and adhesion to the blood vessel wall. Endothelium-derived contracting factors appear to be responsible for endothelium-dependent contractions produced by arachidonic acid and hypoxia in isolated systemic vessels and by certain agents and by rapid stretch in isolated cerebral vessels. In all such experiments, the endothelium-derived contracting factor appears to be some product or by-product of cyclooxygenase activity. Recently, endothelial cells in culture have been found to synthesize a peptide, endothelin, which is an extremely potent vasoconstrictor. The possible physiological roles and pathophysiological significance of endothelium-derived relaxing and contracting factors are briefly discussed.