Rare, low frequency and common coding variants in CHRNA5 and their contribution to nicotine dependence in European and African Americans.

The common nonsynonymous variant rs16969968 in the α5 nicotinic receptor subunit gene (CHRNA5) is the strongest genetic risk factor for nicotine dependence in European Americans and contributes to risk in African Americans. To comprehensively examine whether other CHRNA5 coding variation influences nicotine dependence risk, we performed targeted sequencing on 1582 nicotine-dependent cases (Fagerström Test for Nicotine Dependence score⩾4) and 1238 non-dependent controls, with independent replication of common and low frequency variants using 12 studies with exome chip data. Nicotine dependence was examined using logistic regression with individual common variants (minor allele frequency (MAF)⩾0.05), aggregate low frequency variants (0.05>MAF⩾0.005) and aggregate rare variants (MAF<0.005). Meta-analysis of primary results was performed with replication studies containing 12 174 heavy and 11 290 light smokers. Next-generation sequencing with 180 × coverage identified 24 nonsynonymous variants and 2 frameshift deletions in CHRNA5, including 9 novel variants in the 2820 subjects. Meta-analysis confirmed the risk effect of the only common variant (rs16969968, European ancestry: odds ratio (OR)=1.3, P=3.5 × 10(-11); African ancestry: OR=1.3, P=0.01) and demonstrated that three low frequency variants contributed an independent risk (aggregate term, European ancestry: OR=1.3, P=0.005; African ancestry: OR=1.4, P=0.0006). The remaining 22 rare coding variants were associated with increased risk of nicotine dependence in the European American primary sample (OR=12.9, P=0.01) and in the same risk direction in African Americans (OR=1.5, P=0.37). Our results indicate that common, low frequency and rare CHRNA5 coding variants are independently associated with nicotine dependence risk. These newly identified variants likely influence the risk for smoking-related diseases such as lung cancer.

Latent classes of childhood trauma exposure predict the development of behavioral health outcomes in adolescence and young adulthood.

BACKGROUND: To develop latent classes of exposure to traumatic experiences before the age of 13 years in an urban community sample and to use these latent classes to predict the development of negative behavioral outcomes in adolescence and young adulthood. METHOD: A total of 1815 participants in an epidemiologically based, randomized field trial as children completed comprehensive psychiatric assessments as young adults. Reported experiences of nine traumatic experiences before age 13 years were used in a latent class analysis to create latent profiles of traumatic experiences. Latent classes were used to predict psychiatric outcomes at age ⩾13 years, criminal convictions, physical health problems and traumatic experiences reported in young adulthood. RESULTS: Three latent classes of childhood traumatic experiences were supported by the data. One class (8% of sample), primarily female, was characterized by experiences of sexual assault and reported significantly higher rates of a range of psychiatric outcomes by young adulthood. Another class (8%), primarily male, was characterized by experiences of violence exposure and reported higher levels of antisocial personality disorder and post-traumatic stress. The final class (84%) reported low levels of childhood traumatic experiences. Parental psychopathology was related to membership in the sexual assault group. CONCLUSIONS: Classes of childhood traumatic experiences predict specific psychiatric and behavioral outcomes in adolescence and young adulthood. The long-term adverse effects of childhood traumas are primarily concentrated in victims of sexual and non-sexual violence. Gender emerged as a key covariate in the classes of trauma exposure and outcomes.

Smoking cessation is associated with lower rates of mood/anxiety and alcohol use disorders.

BACKGROUND: The psychological outcomes that accompany smoking cessation are not yet conclusive but positive outcomes could help to persuade quitting. METHOD: We used data from the longitudinal National Epidemiological Study of Alcohol and Related Conditions. Logistic regression was used to examine associations between cigarette smoking reduction and Wave 2 status of addiction/mental health disorder among daily smokers at Wave 1, stratified by status of the diagnosis of interest at Wave 1. We adjusted for differences in baseline covariates between smokers with different levels of smoking reduction between Wave 1 and Wave 2 using propensity score regression adjustment. RESULTS: After adjusting for propensity scores and other mental health/addiction co-morbidities at Wave 2, among daily smokers who had current or lifetime history diagnosis of the outcome of interest at Wave 1, quitting by Wave 2 predicted a decreased risk of mood/anxiety disorder [adjusted odds ratio (aOR) 0.6, 95% confidence interval (CI) 0.4-0.9] and alcohol disorder (aOR 0.7, 95% CI 0.5-0.99) at Wave 2. Among daily smokers with no lifetime history diagnosis of the outcome of interest at Wave 1, quitting smoking by Wave 2 predicted a decreased risk of drug use disorder at Wave 2 (aOR 0.3, 95% CI 0.1-0.9). CONCLUSIONS: There is no support in our data for the concern that smoking cessation would result in smokers' increased risk of some mental disorders. To the contrary, our data suggest that smoking cessation is associated with risk reduction for mood/anxiety or alcohol use disorder, even among smokers who have had a pre-existing disorder.

Childhood maltreatment, juvenile disorders and adult post-traumatic stress disorder: a prospective investigation.

BACKGROUND: We examine prospectively the influence of two separate but potentially inter-related factors in the etiology of post-traumatic stress disorder (PTSD): childhood maltreatment as conferring a susceptibility to the PTSD response to adult trauma and juvenile disorders as precursors of adult PTSD. METHOD: The Dunedin Multidisciplinary Health and Development Study (DMHDS) is a birth cohort (n = 1037) from the general population of New Zealand's South Island, with multiple assessments up to age 38 years. DSM-IV PTSD was assessed among participants exposed to trauma at ages 26-38. Complete data were available on 928 participants. RESULTS: Severe maltreatment in the first decade of life, experienced by 8.5% of the sample, was associated significantly with the risk of PTSD among those exposed to adult trauma [odds ratio (OR) 2.64, 95% confidence interval (CI) 1.16-6.01], compared to no maltreatment. Moderate maltreatment, experienced by 27.2%, was not associated significantly with that risk (OR 1.55, 95% CI 0.85-2.85). However, the two estimates did not differ significantly from one another. Juvenile disorders (ages 11-15), experienced by 35% of the sample, independent of childhood maltreatment, were associated significantly with the risk of PTSD response to adult trauma (OR 2.35, 95% CI 1.32-4.18). CONCLUSIONS: Severe maltreatment is associated with risk of PTSD response to adult trauma, compared to no maltreatment, and juvenile disorders, independent of earlier maltreatment, are associated with that risk. The role of moderate maltreatment remains unresolved. Larger longitudinal studies are needed to assess the impact of moderate maltreatment, experienced by the majority of adult trauma victims with a history of maltreatment.

Influence of predispositions on post-traumatic stress disorder: does it vary by trauma severity?

BACKGROUND: Only a minority of trauma victims (<10%) develops post-traumatic stress disorder (PTSD), suggesting that victims vary in predispositions to the PTSD response to traumas. It is assumed that the influence of predispositions is inversely related to trauma severity: when trauma is extreme predispositions are assumed to play a secondary role. This assumption has not been tested. We estimate the influence of key predispositions on PTSD induced by an extreme trauma - associated with a high percentage of PTSD - (sexual assault), relative to events of lower magnitude (accidents, disaster, and unexpected death of someone close). METHOD: The National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) is representative of the adult population of the USA. A total of 34 653 respondents completed the second wave in which lifetime PTSD was assessed. We conducted three series of multinomial logistic regressions, comparing the influence of six predispositions on the PTSD effect of sexual assault with each comparison event. Three pre-existing disorders and three parental history variables were examined. RESULTS: Predispositions predicted elevated PTSD risk among victims of sexual assault as they did among victims of comparison events. We detected no evidence that the influence of predispositions on PTSD risk was significantly lower when the event was sexual assault, relative to accidents, disasters and unexpected death of someone close. CONCLUSIONS: Important predispositions increase the risk of PTSD following sexual assault as much as they do following accidents, disaster, and unexpected death of someone close. Research on other predispositions and alternative classifications of event severity would be illuminating.

Neuroticism and post-traumatic stress disorder: a prospective investigation.

BACKGROUND: Neuroticism has been consistently correlated with the post-traumatic stress disorder (PTSD) response to traumatic events. Interpretation of these findings is limited by the retrospective nature of these findings: neuroticism was measured after the trauma had occurred. The prospective association of neuroticism with PTSD has not been examined (the relationship of neuroticism with PTSD symptoms was examined in a few prospective studies). We evaluate prospectively the relationship of neuroticism, measured at baseline, with the cumulative occurrence of PTSD during the subsequent 10 years, using data from a longitudinal epidemiological study of young adults. METHOD: A sample of 1007 young adults randomly selected from the membership of a large health maintenance organization in southeast Michigan was assessed at baseline and followed up at 3, 5 and 10 years later. We conducted a series of multinomial logistic regressions to estimate the relative risk (RR) of exposure to trauma and PTSD by neuroticism at baseline, adjusting for history of major depression (n = 990). RESULTS: During the 10-year follow-up, 50.2% of the sample experienced traumatic events and 5.2% developed PTSD. Neuroticism score at baseline increased significantly the RR of PTSD response to trauma. Additional analysis revealed that, among persons with history of major depression at baseline, RR for PTSD associated with neuroticism was equal to the null value of 1, but was increased significantly among those with no history of major depression. CONCLUSIONS: The results confirm the role of neuroticism as diathesis in the PTSD response to traumatic experiences.

ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry.

A coding variant in alcohol dehydrogenase 1B (ADH1B) (rs1229984) that leads to the replacement of Arg48 with His48 is common in Asian populations and reduces their risk for alcoholism, but because of very low allele frequencies the effects in European or African populations have been difficult to detect. We genotyped and analyzed this variant in three large European and African-American case-control studies in which alcohol dependence was defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, and demonstrated a strong protective effect of the His48 variant (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.24, 0.48) on alcohol dependence, with genome-wide significance (6.6 × 10(-10)). The hypothesized mechanism of action involves an increased aversive reaction to alcohol; in keeping with this hypothesis, the same allele is strongly associated with a lower maximum number of drinks in a 24-hour period (lifetime), with P=3 × 10(-13). We also tested the effects of this allele on the development of alcoholism in adolescents and young adults, and demonstrated a significantly protective effect. This variant has the strongest effect on risk for alcohol dependence compared with any other tested variant in European populations.

Race/ethnic differences in exposure to traumatic events, development of post-traumatic stress disorder, and treatment-seeking for post-traumatic stress disorder in the United States.

BACKGROUND: To identify sources of race/ethnic differences related to post-traumatic stress disorder (PTSD), we compared trauma exposure, risk for PTSD among those exposed to trauma, and treatment-seeking among Whites, Blacks, Hispanics and Asians in the US general population. METHOD: Data from structured diagnostic interviews with 34 653 adult respondents to the 2004-2005 wave of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) were analysed. RESULTS: The lifetime prevalence of PTSD was highest among Blacks (8.7%), intermediate among Hispanics and Whites (7.0% and 7.4%) and lowest among Asians (4.0%). Differences in risk for trauma varied by type of event. Whites were more likely than the other groups to have any trauma, to learn of a trauma to someone close, and to learn of an unexpected death, but Blacks and Hispanics had higher risk of child maltreatment, chiefly witnessing domestic violence, and Asians, Black men, and Hispanic women had higher risk of war-related events than Whites. Among those exposed to trauma, PTSD risk was slightly higher among Blacks [adjusted odds ratio (aOR) 1.22] and lower among Asians (aOR 0.67) compared with Whites, after adjustment for characteristics of trauma exposure. All minority groups were less likely to seek treatment for PTSD than Whites (aOR range: 0.39-0.61), and fewer than half of minorities with PTSD sought treatment (range: 32.7-42.0%). CONCLUSIONS: When PTSD affects US race/ethnic minorities, it is usually untreated. Large disparities in treatment indicate a need for investment in accessible and culturally sensitive treatment options.

Multiple cholinergic nicotinic receptor genes affect nicotine dependence risk in African and European Americans.

Several independent studies show that the chromosome 15q25.1 region, which contains the CHRNA5-CHRNA3-CHRNB4 gene cluster, harbors variants strongly associated with nicotine dependence, other smoking behaviors, lung cancer and chronic obstructive pulmonary disease. We investigated whether variants in other cholinergic nicotinic receptor subunit (CHRN) genes affect the risk of nicotine dependence in a new sample of African Americans (AAs) (N = 710). We also analyzed this AA sample together with a European American (EA) sample (N = 2062, 1608 of which have been previously studied), allowing for differing effects in the two populations. Cases are current nicotine-dependent smokers and controls are non-dependent smokers. Variants in or near CHRND-CHRNG, CHRNA7 and CHRNA10 show modest association with nicotine dependence risk in the AA sample. In addition, CHRNA4, CHRNB3-CHRNA6 and CHRNB1 show association in at least one population. CHRNG and CHRNA4 harbor single nucleotide polymorphisms (SNPs) that have opposite directions of effect in the two populations. In each of the population samples, these loci substantially increase the trait variation explained, although no loci meet Bonferroni-corrected significance in the AA sample alone. The trait variation explained by three key associated SNPs in CHRNA5-CHRNA3-CHRNB4 is 1.9% in EAs and also 1.9% in AAs; this increases to 4.5% in EAs and 7.3% in AAs when we add six variants representing associations at other CHRN genes. Multiple nicotinic receptor subunit genes outside chromosome 15q25 are likely to be important in the biological processes and development of nicotine dependence, and some of these risks may be shared across diverse populations.

Change in teachers' ratings of attention problems and subsequent change in academic achievement: a prospective analysis.

BACKGROUND: Recent research has documented a link between attention problems at school entry and later academic achievement. Little is known about the association of change in attention problems during the early school years with subsequent change in academic achievement. METHOD: A community-based cohort was followed up and assessed for attention problems at ages 6 and 11 (Teacher Report Form; TRF) and for academic achievement in math and reading at ages 11 and 17 (Woodcock-Johnson Psycho-Educational Battery). Complete data were available on 590 children (72% of the initial sample). Ordinary least squares regressions were used to estimate change in academic achievement from age 11 to age 17 in relation to change in TRF-attention problems from age 6 to age 11. Children's IQ and family factors were statistically controlled. RESULTS: Change in teachers' ratings of attention problems from age 6 to age 11 was negatively associated with change in math and reading from age 11 to age 17, controlling for children's IQ and family factors. Externalizing problems had no significant association with change in math or reading, when added to the multivariable model. CONCLUSIONS: Increases in teacher-rated attention problems from age 6 to age 11 were followed by declines in academic achievement from age 11 to age 17; decreases were followed by gains. The results underscore the need for research on the course of attention problems, the testing of interventions to address children's early attention problems and the evaluation of their effects on subsequent academic achievement.

The latent structure of post-traumatic stress disorder: tests of invariance by gender and trauma type.

BACKGROUND: Measurement invariance of Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) post-traumatic stress disorder (PTSD) criterion symptoms was tested by gender and trauma type, assaultive and non-assaultive. METHOD: Analysis was conducted using latent class analysis (LCA), based on findings that the three-class LCA model from Breslau et al. (Archives of General Psychiatry 2005, 62, 1343-1351) fits the data across the four groups best. The classes represent three levels of PTSD-related disturbance: no disturbance, intermediate disturbance and pervasive disturbance, with the last one approximating the DSM-IV PTSD diagnosis. RESULTS: Analysis of measurement invariance showed that, with respect to gender, there was no evidence of differential symptom reporting within the same disturbance class. DSM-IV symptom indicators represent the latent structure of PTSD equally in males and females. We found that more female than male victims of assaultive violence experienced pervasive disturbance. In the absence of measurement variability associated with gender, the finding is likely to reflect a gender difference in susceptibility. The analysis of measurement invariance detected evidence of variability associated with trauma type. Victims of assaultive violence in the pervasive disturbance class report more severe distress (especially emotional numbing) than do victims of non-assaultive violence in the same class. CONCLUSIONS: The finding of measurement bias associated with type of trauma raises questions about the applicability of a single definition for PTSD associated with assaultive violence and PTSD associated with traumatic events of lesser magnitude.

Estimating post-traumatic stress disorder in the community: lifetime perspective and the impact of typical traumatic events.

BACKGROUND: Community surveys have assessed post-traumatic stress disorder (PTSD) in relation to traumatic events designated by respondents as the worst they have ever experienced. An assessment of PTSD in relation to all reported traumas would impose too great a burden on respondents, a considerable proportion of whom report multiple traumas. The 'worst event' method is efficient for identifying persons with PTSD, but may overestimate the conditional probability of PTSD associated with the entire range of PTSD-level traumas. In this report, we evaluate this potential bias. METHOD: The Detroit Area Survey of Trauma (n = 2181) estimated the PTSD risk from two samples of traumas: (1) a representative sample of traumas formed by selecting a random trauma from each respondent's list of traumas; and (2) traumas designated by respondents as the worst (the standard method). RESULTS: Both estimation methods converged on key findings, including identifying trauma types with the highest probability of PTSD and sex differences in the risk of PTSD. Compared to the random events, the 'worst event' method yielded a moderately higher conditional probability for PTSD (0.136 v. 0.092). The bias was due almost entirely to the deviation of the distribution of the worst events from expected values, if all event types had equal prior selection probabilities. Direct adjustment, setting the distribution equal to expected values and applying the observed probabilities of PTSD associated with individual event types brought the estimate close to the unbiased estimate, based on the randomly selected traumas. CONCLUSIONS: Only the 'worst event' method can be used as a short-cut to assessing all traumas. The bias in the estimated risk of PTSD is modest and is attenuated by direct adjustment.

Daily smoking and the subsequent onset of psychiatric disorders.

BACKGROUND: Recent research has demonstrated that smokers are at an elevated risk for psychiatric disorders. This study extends the enquiry by examining: (1) the specificity of the psychiatric sequelae of smoking; and (2) the variability in the likelihood of these sequelae by proximity and intensity of smoking. METHOD: Data come from the National Comorbidity Survey (NCS), a representative sample of the US population 15-54 years of age. The Smoking Supplement was administered to a representative subset of 4414 respondents. A modified World Health Organization-Composite International Diagnostic Interview was used to measure DSM-III-R disorders. Survival analysis with smoking variables as time-dependent covariates was used to predict the subsequent onset of specific psychiatric disorders. RESULTS: The estimated effects of daily smoking varied across disorders. In the case of mood disorders, daily smoking predicted subsequent onset, with no variation between current versus past smokers or by smoking intensity. In the case of panic disorder and agoraphobia, current but not past smoking predicted subsequent onset; furthermore, the risk of these disorders in past smokers decreased with increasing time since quitting. In the case of substance use disorders, current but not past smoking predicted subsequent onset, with no variation by time since quitting or smoking intensity. CONCLUSIONS: The data suggest that smoking cessation programmes would not prevent the onset of mood disorder, as ex-smokers do not differ from current smokers in their risk for these disorders. In comparison, daily smoking might be a causal factor in panic disorder and agoraphobia, conditions that might be preventable by smoking cessation. Additionally, current smoking might serve as a marker for targeting interventions to prevent alcohol and drug disorders.

Comorbidity of migraine and depression: investigating potential etiology and prognosis.

BACKGROUND: An association between migraine and major depression has been observed in clinical and community samples. The factors that contribute to this association and their implications remain unclear. OBJECTIVE: To determine the factors contributing to the association of migraine and major depression. METHODS: A cohort study of persons aged 25 to 55 years with migraine (n = 496) or with other headaches of comparable severity (n = 151) and control subjects with no history of severe headaches (n = 539) randomly selected from the general community were interviewed first in 1997 and then reinterviewed in 1999. RESULTS: Major depression at baseline predicted the first-onset migraine during the 2-year follow-up period (odds ratio [OR] = 3.4; 95% CI = 1.4, 8.7) but not other severe headaches (OR = 0.6; 95% CI = 0.1, 4.6). Migraine at baseline predicted the first-onset major depression during follow-up (OR = 5.8; 95% CI = 2.7, 12.3); the prospective association from severe headaches to major depression was not significant (OR = 2.7; 95% CI = 0.9, 8.1). Comorbid major depression did not influence the frequency of migraine attacks, their persistence, or the progression of migraine-related disability over time. CONCLUSIONS: Major depression increased the risk for migraine, and migraine increased the risk for major depression. This bidirectional association, with each disorder increasing the risk for first onset of the other, was not observed in relation to other severe headaches. With respect to other severe headaches, there was no increased risk associated with pre-existing major depression, although the possibility of an influence in the reverse direction (i.e., from severe headaches to depression) cannot be securely ruled out.

The stressor criterion in DSM-IV posttraumatic stress disorder: an empirical investigation.

BACKGROUND: The DSM-IV two-part definition of posttraumatic stress disorder (PTSD) widened the variety of stressors (A1) and added a subjective component (A2). The effects of the revised stressor criterion on estimates of exposure and PTSD in a community sample are evaluated. METHODS: A representative sample of 2181 persons in southeast Michigan were interviewed about lifetime history of traumatic events and PTSD. The evaluation of the revised two-part definition is based on a randomly selected sample of events that represents the total pool of traumatic events experienced in the community. RESULTS: The enlarged definition of stressors in A1 increased the total number of events that can be used to diagnose PTSD by 59%. The majority of A1 events (76.6%) involved the emotional response in A2. Females were more likely than males to endorse A2 (adjusted odds ratio = 2.66; 95% confidence interval 1.92, 3.71). Of all PTSD cases resulting from the representative sample of events, 38% were attributable to the expansion of qualifying events in A1. The identification of exposures that lead to PTSD were not improved materially by A2 however, events that did not involve A2 rarely resulted in PTSD. CONCLUSIONS: Compared to previous definitions, the wider variety of stressors in A1 markedly increased the number of events experienced in the community that can be used to diagnose PTSD. Furthermore, A2 might be useful as a separate criterion, an acute response necessary for the emergence of PTSD, and might serve as an early screen for identifying a subset of recently exposed persons at virtually no risk for PTSD. The utility of A2 as a screen must be tested prospectively.

Stability and change in children's intelligence quotient scores: a comparison of two socioeconomically disparate communities.

The authors estimated the influence of familial factors and community disadvantage on changes in children's intelligence quotient (IQ) scores from age 6 years to age 11 years. Data were obtained from a longitudinal study of the neuropsychiatric sequelae of low birth weight in two socioeconomically disparate, geographically defined communities in the Detroit, Michigan, metropolitan area. Representative samples of low birth weight and normal birth weight children from the City of Detroit (urban) and nearby middle-class suburbs (suburban) were assessed at age 6 years (in 1990-1992) and age 11 years (in 1995-1997) (n = 717). Children's IQs were measured using the Wechsler Intelligence Scale for Children-Revised. The familial factors considered included maternal IQ, education, and marital status. Multiple regression analysis applying generalized estimating equations was used. The IQs of urban children, regardless of birth weight, declined from age 6 years to age 11 years. The downward shift increased by 50% the proportion of urban children scoring 1 standard deviation below the standardized IQ mean of 100. A negligible change was observed in suburban children. Maternal IQ, education, and marital status and low birth weight predicted IQ at age 6 years but were unrelated to IQ change. Growing up in a racially segregated and disadvantaged community, more than individual and familial factors, may contribute to a decline in IQ score in the early school years.

Nicotine dependence in the United States: prevalence, trends, and smoking persistence.

BACKGROUND: The prevalence of smoking in the United States has been closely monitored. However, little is known about the epidemiology of nicotine dependence. We studied DSM-III-R nicotine dependence in the United States, trends across cohorts, and the role of nicotine dependence in smoking persistence. METHODS: The Tobacco Supplement to the National Comorbidity Survey was administered to a representative subset of 4414 persons aged 15 to 54 years. The World Health Organization's Composite International Diagnostic Interview was used to assess nicotine dependence. RESULTS: Lifetime prevalence of nicotine dependence was 24%, nearly half of those who had ever smoked daily for a month or more. The highest risk for nicotine dependence occurred in the first 16 years after daily smoking began, at which point the rate declined and continued at a slower pace for several years. Nicotine dependence increased the risk of smoking persistence, with an odds ratio (OR) of 2.2 (95% confidence interval [CI], 1.6-3.0). Members of the most recent cohort, who were 15 to 24 years of age at the time of the survey, were the least likely to smoke daily, but those who smoked had the highest risk of dependence: OR for daily smoking in the most recent vs earliest cohort was 0.7 (95% CI, 0.5-0.9), and for dependence among smokers, 7.2 (95% CI, 5.0-10.4). CONCLUSIONS: Despite evidence that nicotine dependence is the leading preventable cause of death and morbidity, it remains a common psychiatric disorder. Smoking cessation and the decline in uptake in recent years varied across subgroups of the population.

The epidemiology of posttraumatic stress disorder: what is the extent of the problem?

Until recently, our understanding of posttraumatic stress disorder (PTSD) relied almost entirely on studies of war veterans and disaster victims. A handful of epidemiologic studies have now been conducted that investigate the natural course of PTSD as it occurs in the general population. Estimates of PTSD prevalence have tended to vary according to the diagnostic criteria used to define the disorder, assessment procedures, sample characteristics, and the definition of qualifying traumatic events. This article reviews key findings from these studies to provide insight into the burden of PTSD in the general population. Possible reasons for the observed difference in lifetime prevalence of PTSD between the sexes (a female-to-male lifetime prevalence ratio of 2:1 is typically reported) and factors thought to be associated with an increased risk for the disorder after exposure to trauma are reviewed.

Outcomes of posttraumatic stress disorder.

The typical reaction to a life-threatening experience is one of distress, anxiety, and fear. This is characteristic of the basic survival instinct; these emotions enhance the individual's memory of the traumatic experience and thus serve to help in the recognition and avoidance of similarly dangerous situations in the future. In a significant minority of individuals, however, the natural reaction to trauma becomes uncontrollably and disastrously intensified, resulting in the symptoms of posttraumatic stress disorder (PTSD). PTSD varies in severity and duration between individuals, often relating to personal characteristics and the nature of the trauma to which a person is subjected. However, several factors, namely, chronicity, impairment, comorbidity, and somatization, are significantly related to and can influence the course of PTSD and subsequent outcome. This article briefly reviews each of these factors.