The Harvard Twin Study of Substance Abuse: what we have learned

The Harvard Twin Study of Substance Abuse was carried out with the members of the Vietnam Era Twin (VET) Registry. The VET Registry comprises over 8000 male twins who served in the United States military between 1965 and 1975 and were subsequently interviewed regarding their use of licit and illicit substances, as well as various types of psychopathology. Our research has demonstrated significant influences by genetic, shared environmental, and unique environmental factors on the abuse of illicit substances. Multivariate analyses have indicated that the co-occurrence of abuse of various types of illicit drugs reflects a common vulnerability, influenced by both genetic and environmental factors, that cuts across all categories of illicit drugs. We have also demonstrated that some drugs have unique determinants, both genetic and environmental, that are not shared with other drugs. In part, the genetic influence on marijuana abuse is mediated by genetic influence on subjective effects in response to the drug. The determinants of transitions from one stage of drug use to another differ depending on which drug or which transition is examined. We determined significant genetic influences on several aspects of nicotine and alcohol use separately, as well as genetic influences shared by both substances. We found that the co-occurrence of illicit drug abuse and major depression is due to unique environmental influences. The phenotypic association between symptoms of conduct disorder and alcohol and marijuana dependence is due largely to shared environmental influences. Our results, thus far, indicate a complex pattern of genetic and environmental influences on substance use and abuse.     

Illicit drug use and dependence in a New Zealand birth cohort

OBJECTIVE: To describe the patterns of illicit drug use in a birth cohort studied to the age of 25 years. METHOD: The data were gathered during the Christchurch Health and Development Study. In this study a cohort of 1265 children born in the Christchurch, New Zealand urban region in mid-1977 have been studied to the age of 25 years. Information was gathered on patterns of illicit drug use and dependence during the period 15-25 years. RESULTS: By age 25 years, 76.7% of the cohort had used cannabis, while 43.5% had used other illicit drugs on at least one occasion. In addition, 12.5% of the cohort met DSM-IV criteria for dependence on cannabis, and 3.6% of the cohort met criteria for dependence on other illicit drugs at some time by age 25. There was also evidence of substantial poly-drug use among the cohort, with hallucinogens and amphetamines being the most commonly used illicit drugs (excluding cannabis). Illicit drug use and dependence was higher in males, in Māori, and in those leaving school without qualifications. Key risk factors for illicit drug use and dependence included adolescent risk-taking behaviours including cigarette smoking and alcohol consumption, affiliation with substance-using peers, novelty-seeking, and conduct problems in adolescence. Other key risk factors included parental history of illicit drug use and childhood sexual abuse. CONCLUSIONS: Levels of cumulative illicit drug use in this cohort were relatively high, with the majority of respondents having tried illicit drugs by age 25. For the majority of illicit drug users, drug use did not lead to problems of dependence. Nonetheless, nearly 15% of the cohort showed symptoms of illicit drug dependence by the age of 25 years, with cannabis dependence accounting for the majority of illicit drug dependence.     

Maternal Substance Abuse and the Later Risk of Fractures in Offspring: L’abus maternel de substances et le risque ultérieur de fractures chez les enfants

Objective:To assess the association of maternal illicit drug abuse before or during pregnancy with future fractures in offspring.Methods:We performed a longitudinal cohort study of 792,022 infants born in hospitals of Quebec, Canada, between 2006 and 2016, with 5,457,634 person-years of follow-up. The main exposure was maternal substance abuse before or during pregnancy, including cocaine, opioid, cannabis, and other illicit drugs. The main outcome measure was hospitalization for traumatic fracture in offspring up to 12 years of age. We used adjusted Cox regression models to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association of maternal drug abuse with the subsequent risk of fracture in children.Results:The incidence of child fractures was higher for maternal illicit drug abuse than no drug abuse (21.2 vs. 15.4 per 10,000 person-years). Maternal drug abuse before or during pregnancy was associated with 2.35 times the risk of assault-related fractures (95% CI, 1.29 to 4.27) and 2.21 times the risk of transport accident-related fractures (95% CI, 1.34 to 3.66), compared with no drug abuse. Associations were strongest before 6 months of age for assault-related fractures (HR = 2.14; 95% CI, 0.97 to 4.72) and after 6 years for transport-related fractures (HR = 2.86; 95% CI, 1.35 to 6.05). Compared with no drug abuse, associations with assault and transport-related fractures were elevated for all drugs including cocaine, opioids, and cannabis.Conclusions:Maternal illicit drug abuse is associated with future child fractures due to assault and transport accidents.     

Specificity of genetic and environmental risk factors for use and abuse/dependence of cannabis,cocaine, hallucinogens,sedatives, stimulants,and opiates in male twins

OBJECTIVE: Data on use and misuse of six classes of illicit substances by male twin pairs were used to examine whether genetic and shared environmental risk factors for substance use disorders are substance-specific or -nonspecific in their effect. METHOD: Lifetime history of use and abuse/dependence of cannabis, cocaine, hallucinogens, sedatives, stimulants, and opiates was assessed at personal interview in both members of 1,196 male-male twin pairs ascertained by the Virginia Twin Registry. Multivariate twin modeling of substance-nonspecific (common) and substance-specific genetic, shared environmental, and unique environmental risk factors was performed by using the program Mx. RESULTS: High levels of comorbidity involving the different substance categories were observed for both use and abuse/dependence. One common genetic factor was found to have a strong influence on risk for illicit use and abuse/dependence for all six substance classes. A modest influence of substance-specific genetic factors was seen for use but not for abuse/dependence. Shared environmental factors were more important for use than for abuse/dependence and were mediated entirely through a single common factor. CONCLUSIONS: In an adult population-based sample of male twins, both the genetic and the shared environmental effects on risk for the use and misuse of six classes of illicit substances were largely or entirely nonspecific in their effect. Environmental experiences unique to the person largely determine whether predisposed individuals will use or misuse one class of psychoactive substances rather than another.     

Self-injury in Japanese junior and senior high-school students: Prevalence and association with substance use

The present study examined the prevalence of self-injury and its association with substance abuse in 2974 junior and senior high-school students, by self-reporting questionnaires. Consequently, 9.9% of students (boys, 7.5%; girls, 12.1%) reported an experience of self-injury at least once. Significant differences were found in substance use-related problems including alcohol abuse, smoking, and illicit drug use ( P  < 0.001) between students with and without an experience of self-injury. The results also suggest that self-injuring students may more easily gain access to illicit drugs even if they had not yet experienced the use of illicit drugs. Self-injury in adolescence may be associated with substance use and is considered to be a risk factor predicting future illicit drug use.     

The impact of alcohol and illicit drugs on people with psychosis: The second Australian national survey of psychosis

Objective: To provide the most up-to-date prevalence estimates of alcohol and illicit drug use among individuals with psychosis in Australia, and explore correlates associated with a lifetime diagnosis of both alcohol abuse/dependence and cannabis abuse/dependence. Method: This paper uses data from the Survey of High Impact Psychosis (SHIP), conducted as a follow-up to the first Australian National Low Prevalence (Psychotic) Disorders Study (1997-1998). The SHIP was a national study, carried out across five states, in which a sample of 1825 individuals was recruited through a two-phase sampling framework. Results: Alcohol and illicit drug use was highly prevalent for the entire sample. There were few significant differences in the prevalence or frequency of use across the diagnostic categories examined. Substantial increases in substance abuse/dependence were noted since the 1997-1998 survey (51% diagnosed with alcohol abuse/dependence, 51% with cannabis abuse/dependence and 32% with other illicit drug abuse/dependence, compared to 28%, 23% and 12% respectively, in the 1997-1998 survey by Kavanagh et al., 2004). Factors significantly associated with both lifetime alcohol and cannabis dependence included male gender, younger age, single marital status, lower educational attainment, shorter duration of illness, lifetime presence of hallucinations, higher negative syndrome score and lower body mass index (BMI). A number of other factors were found to be differentially associated with either lifetime alcohol or cannabis dependence. Conclusions: The use of alcohol and illicit substances is common among people with a psychotic illness, with a concerning upward trend in rates of substance abuse/dependence since the 1997-1998 survey. Clinicians should be aware of the potential impact of concurrent substance use and provide integrated treatment for individuals presenting with psychotic illnesses. More research and investment in new intervention programs is required.     

American Indian substance use: the hazards for substance use initiation and progression for adolescents aged 14 to 20 years

OBJECTIVE: To describe the risks and risk factors for substance use initiation and progression among a large sample of American Indian (AI) adolescents. METHOD: Data came from surveys completed by 2,356 AI adolescents aged 14 to 20 years who participated in two or more consecutive waves of a longitudinal study between 1993 and 1996 (response rate 74%). Discrete-time survival analysis was used to describe the risks and risk factors for substance use initiation and progression. RESULTS: The risk for initiating use of any substance accelerated in early adolescence and peaked at age 18. The risk for progression from use of alcohol, marijuana, and/or inhalants to the use of other illicit drugs (e.g., cocaine) increased over the first 4.5 years after initiating substance use, then diminished in subsequent years. The risk of substance use initiation and progression varied across the four participating communities and by season of the year. Compared to adolescents who initiated substance use with alcohol only, adolescents who initiated substance use with marijuana or inhalants were more likely to progress to use other illicit drugs. CONCLUSIONS: Prevention programs for AI communities should be designed to address these community, age, and seasonal variations in the risks for substance use initiation and progression.     

Prospective effects of attention-deficit/hyperactivity disorder, conduct disorder, and sex on adolescent substance use and abuse

CONTEXT: Attention-deficit/hyperactivity disorder (ADHD), an early manifestation of externalizing behavior, may identify children at high risk for later substance abuse. However, the ADHD-substance abuse relationship often disappears when co-occurring conduct disorder (CD) is considered. OBJECTIVE: To determine whether there is a prospective relationship between ADHD and the initiation of substance use and disorders, and whether this relationship depends on the ADHD subtype (hyperactive/impulsive or inattentive), CD, or sex. DESIGN, SETTING, AND PARTICIPANTS: Dimensional and categorical measures of ADHD and CD were examined via logistic regression analyses in relation to subsequent initiation of tobacco, alcohol, and illicit drug use by 14 years of age and onset of substance use disorders by 18 years of age in a population-based sample of 11-year-old twins (760 female and 752 male twins) from the Minnesota Twin Family Study. MAIN OUTCOME MEASURES: Structured interviews were administered to adolescents and their mothers regarding substance use and to generate diagnoses. RESULTS: For boys and girls, hyperactivity/impulsivity predicted initiation of all types of substance use, nicotine dependence, and cannabis abuse/dependence (for all, P < .05), even when controlling for CD at 2 time points. By contrast, relationships between inattention and substance outcomes disappeared when hyperactivity/impulsivity and CD were controlled for, with the possible exception of nicotine dependence. A categorical diagnosis of ADHD significantly predicted tobacco and illicit drug use only (adjusted odds ratios, 2.01 and 2.82, respectively). A diagnosis of CD between 11 and 14 years of age was a powerful predictor of substance disorders by 18 years of age (all odds ratios, > 4.27). CONCLUSIONS: Hyperactivity/impulsivity predicts later substance problems, even after growth in later-emerging CD is considered, whereas inattention alone poses less risk. Even a single symptom of ADHD or CD is associated with increased risk. Failure in previous research to consistently observe relationships between ADHD and substance use and abuse outcomes could be due to reliance on less-sensitive categorical diagnoses.     

3-Year Follow-up of Lower Risk Cannabis Use Patterns: Evidence from a Longitudinal Survey

Objectives:Following recommendations from the Lower Risk Cannabis Use Guidelines, we evaluated how lower risk cannabis use (late initiation and low use frequency) was associated with the risk of developing cannabis abuse/dependence over a 3-year follow-up period compared to 12-month abstinence (controls) or higher risk cannabis use (early initiation and higher use frequency). We also explored the effect of cannabis quantity.Methods:Data were obtained from the U.S. nationally representative survey, National Epidemiologic Survey on Alcohol and Related Conditions wave I (2001 to 2002) and wave II (2004 to 2005), which included 31,464 respondents with no lifetime history of cannabis abuse/dependence at the first interview. We applied multiple logistic regression and propensity score matching analyses to examine the association between different use patterns at wave I and cannabis abuse/dependence at wave II, adjusting for covariates. Lower risk cannabis use and the transition to higher use frequency were also assessed.Results:For propensity score analysis, lower risk cannabis use at wave I was associated with higher risk of cannabis use/dependence at wave II compared to controls (odds ratio [OR]: 4.27; 95% confidence interval [95% CI], 1.57 to 11.61); however, there was no association with use frequency increase (OR: 2.52; 95% CI, 0.88 to 7.17). Higher risk use had a greater risk of cannabis use/dependence than controls (OR: 6.27; 95% CI, 2.56 to 15.38) and lower risk use (OR: 2.69; 95% CI, 1.12 to 6.47). Logistic regression analyses showed similar results, except that lower risk use was significantly associated with use frequency increase (OR: 2.49; 95% CI, 1.22 to 5.08). For the lower risk use group, 1 to 3 joints/day of use was significantly associated with cannabis abuse/dependence.Conclusions:We found that following recommended use patterns can significantly lower one’s risk of cannabis abuse/dependence. However, risk of cannabis abuse/dependence is still 4 times higher than staying abstinent. Updated recommendations on safe cannabis exposure levels are needed to guide cannabis use in the general population after cannabis legalization.     

Substance use among Danish psychiatric patients: a cross-sectional study

Background: Patients with psychiatric disorders have a greater risk of mortality than the general population. Use or abuse of substances, including alcohol, play a crucial part in this context. Moreover, it is well known that drug use can worsen psychopathology and reduce treatment compliance. However, the magnitude of these problems among Danish psychiatric patients has not been studied previously.

Aims: The aim of this study is to investigate substance use among psychiatric patients in the Capital Region of Denmark.

Methods: Outpatients from five psychiatric units were asked to complete a questionnaire regarding their use of alcohol and other drugs of abuse. The questionnaire was based on the Alcohol Use Disorder Identification Test (AUDIT), supplemented by questions regarding use of tobacco and illicit drugs. The results were compared with those uses in the general population.

Results: In total, 412 psychiatric patients participated in the study, and 33% had an AUDIT-score ≥8, indicating problematic alcohol use according to the AUDIT guidelines. The mean weekly alcohol intake was 9.7?±?28.3 standard drinks, and 47% were current smokers with a mean daily use of 19.9?±?13.8 cigarette equivalents. Compared to the general population, the psychiatric patients had higher odds of being current smokers and having used illicit drugs within the past month. Women with psychiatric disorders were twice as likely to binge drink on a monthly basis. No significant difference was found in the patients’ AUDIT scores compared to the general population.

Conclusions: Our findings demonstrate a substantial and problematic use of tobacco and illicit drugs among Danish psychiatric patients, greater than in the general population.     

Sex differences in drug abuse

Sex differences are present for all of the phases of drug abuse (initiation, escalation of use, addiction, and relapse following abstinence). While there are some differences among specific classes of abused drugs, the general pattern of sex differences is the same for all drugs of abuse. Females begin regularly self-administering licit and illicit drugs of abuse at lower doses than do males, use escalates more rapidly to addiction, and females are at greater risk for relapse following abstinence. In this review, sex differences in drug abuse are discussed for humans and in animal models. The possible neuroendocrine mechanisms mediating these sex differences are discussed.     

Association between psychiatric disorders and the progression of tobacco use behaviors

OBJECTIVE: To examine the progression of tobacco use and the patterns of comorbidity of tobacco use and psychiatric disorders. METHOD: The authors conducted analyses of prospective and retrospective reports, collected from 1988 to 1998, of a sample of high- and low-risk youths identified on the basis of the presence or absence of a parental history of substance abuse or dependence. RESULTS: A parental history of substance use disorders was associated with regular tobacco use and nicotine dependence, but not with experimentation for all youths. Individual and composite psychiatric diagnoses were strongly associated with nicotine dependence, but not with regular use or experimentation. While the presence of an affective disorder and drug abuse/dependence generally increased the risk for co-occurring nicotine dependence, analyses based on the temporal onset of disorders showed that it was the initiation of alcohol or drug use that predicted the progression to nicotine dependence. For low-risk youths, oppositional defiant disorder was the single psychiatric risk factor that predicted the transition to nicotine dependence. CONCLUSIONS: This study adds to the accumulating evidence that has implicated comorbid psychiatric disorders in the etiology and subsequent course of nicotine dependence. In addition, family history may represent an important indicator of an increased risk for nicotine dependence.     

Is cigarette smoking a gateway to alcohol and illicit drug use disorders? A study of youths with and without attention deficit hyperactivity disorder.

BACKGROUND: The goal of this study was to assess whether cigarette smoking is a gateway drug for subsequent alcohol and illicit drug abuse and dependence in youth with Attention Deficit Hyperactivity Disorder (ADHD), and to test if this association is stronger in ADHD youth relative to controls. METHODS: We used data from a case-control family study of female youth with and without ADHD. We studied 97 ADHD and 203 control youth of both sexes, aged at least 12 years. We assessed ADHD, smoking, and substance use status using structured diagnostic interviews. We tested the association between cigarette smoking and subsequent substance use outcomes using Cox proportional hazard regression models. RESULTS: ADHD youth who smoked cigarettes (n = 15) were significantly more likely to subsequently use alcohol and illicit drugs as well as to develop abuse and dependence compared to ADHD youth who did not smoke (n = 76; p < .05). CONCLUSIONS: These results extend the gateway hypothesis to an ADHD sample and provide evidence that this effect may be particularly robust in ADHD youth. If replicated in larger, community-based samples, these findings have important public health consequences, and underscore the already pressing need to prevent smoking in ADHD children.     

Do initial responses to drugs predict future use or abuse?

Individuals vary in their initial reactions to drugs of abuse in ways that may contribute to the likelihood of subsequent drug use. In humans, most drugs of abuse produce positive subjective states such as euphoria and feelings of well-being, which may facilitate repeated use. In nonhumans, many drugs initially increase locomotor activity and produce discriminative stimulus effects, both of which have been considered to be models of human stimulant and subjective states. Both humans and nonhumans vary in their sensitivity to early acute drug effects in ways that may predict future use or self-administration, and some of these variations appear to be genetic in origin. However, it is not known exactly how the initial responses to drugs in either humans or nonhumans relate to subsequent use or abuse. In humans, positive effects of drugs facilitate continued use of a drug while negative effects discourage use, and in nonhumans, greater genetic risk for drug intake is predicted by reduced sensitivity to drug aversive effects; but whether these initial responses affect escalation of drug use, and the development of dependence is currently unknown. Although early use of a drug is a necessary step in the progression to abuse and dependence, other variables may be of greater importance in the transition from use to abuse. Alternatively, the same variables that predict initial acute drug effects and early use may significantly contribute to continued use, escalation and dependence. Here we review the existing evidence for relations between initial direct drug effects, early use, and continued use. Ultimately, these relations can only be determined from systematic longitudinal studies with comprehensive assessments from early drug responses to progression of problem drug use. In parallel, additional investigation of initial responses in animal models as predictors of drug use will shed light on the underlying mechanisms.     

Opioid abuse and hospitalization rates in patients with schizophrenia

Background: Substance abuse worsens the course of schizophrenia, but it is not known whether or not there are differences between specific substances concerning their association with the hospitalizations of patients with schizophrenia. Aims: The primary aims of this study were to examine the possible associations between amphetamine, cannabis, and opioid abuse, and the risk of hospitalizations among patients with schizophrenia. Methods: The study population consisted of 146 patients with ICD-defined schizophrenia from two different geographical sites in Finland, and it included both inpatients and outpatients. Data were collected retrospectively from the patients’ medical files. Substance abuse was defined as either harmful use or dependence according to ICD-10. Results: The cumulative prevalence of substance abuse was 10.9% (16/146) for cannabis, 8.9% (13/146) for amphetamine, and 4.1% (6/146) for opioids. Among patients with schizophrenia and abuse of any substance, the number of hospitalizations was about 1.5-fold when compared to those without substance abuse. The incidence rate ratio for hospitalizations was 2.9 (95% CI 2.47–3.63) for opioids, 2.0 (1.71–2.41) for amphetamine, and 1.6 (1.33–1.84) for cannabis, when compared with no abuse of each substance. The risk of hospitalizations was significantly higher for opioids when compared with amphetamine (p < 0.001) or cannabis (p < 0.001). Conclusions: Harmful use or dependence of opioids among patients with schizophrenia is associated with significantly higher risk of hospitalizations than either harmful use or dependence of amphetamine or cannabis.     

Épidémiologie des usages de substances addictives : résultats d’études réalisées en France et perspectives internationales

Addiction to drugs is an important public health concern. Describing the frequency of dependence, abuse and use of substances in a country allows a monitoring and helps in the design of an appropriate healthcare system. We will present studies describing the prevalence of use of tobacco, alcohol, and illicit drugs in France, with a comparison to European or International studies. They show a decrease in the use of tobacco and cannabis, while there is an increase in alcohol use in young adults. We also observe that the difference in substances use between females and males is tightening, especially in young people. We have less studies of analytic epidemiology trying to describe risk or protective factors associated with substances’ use in France. Further studies on addicted people's pathway (from use to abuse and to dependence, as well as from dependence to recovery, with or without medical support) are warranted.     

The level of illicit drug use is related to symptoms and premorbid functioning in severe mental illness

Objective: There is conflicting data on drug abuse and outcome in severe mental illness. This study aims to investigate if the amount of illicit psychoactive drug use is related to symptom load or premorbid functioning across diagnosis in patients with severe mental illness. Method: Symptom load, sociodemographic status, premorbid functioning and the level of use of illicit psychoactive drugs were assessed in 423 subjects with schizophrenia or bipolar disorder in a cross‐sectional study. Results: High amount of illicit drug use was associated with poorer premorbid academic functioning. In schizophrenia, there was a significant positive association between amount of drug use and severity of psychiatric symptoms. The association between symptom load and drug use was significant after controlling for premorbid functioning. Conclusion: The results suggest a direct association between the quantity of current drug use and more severe symptoms in schizophrenia. Poor premorbid functioning was related to high amount of use, but did not explain the difference in symptom load.     

Cerebellar Lingula Size and Experiential Risk Factors Associated with High Levels of Alcohol and Drug Use in Young Adults

Previous studies have reported cerebellar abnormalities or static ataxia associated with risk for chronic use of alcohol and drugs. Adverse childhood experience is another strong risk factor for later substance abuse. We therefore sought to ascertain the relationship between morphological phenotypes of the lingula (lobule I) of the anterior cerebellar vermis, and exposure to emotional (EM) versus physical (PM) maltreatment, on the degree of ongoing alcohol or drug use. The study design consisted of a cross-sectional in vivo neuroimaging study, utilizing retrospective assessment of maltreatment history and self-reports of alcohol and substance use. Study participants were 153 subjects (54 M/99F, 21.9 ± 2.2 years) selected for imaging from a database of 1,402 community participants 18–25 years of age, who completed a detailed online screening instrument and met rigorous inclusion/exclusion criteria. Subjects were exposed to only physical abuse or harsh corporal punishment (HCP; PM group, n = 37) and parental verbal abuse and/or witnessing domestic violence (EM group, n = 58) or had no history of maltreatment or axis I disorders (n = 58). The main outcome measures consisted of the gray matter volume of lobule I as measured by manual tracing, number and type of alcoholic beverages consumed during a drinking session, number of sessions per month, and monthly drug use, along with family history of drug and alcohol abuse. Lingula thickness was not attenuated by alcohol use or maltreatment history. However, increased lingula thickness was associated with greater consumption of drugs and hard liquor, particularly in physically maltreated subjects who consumed 2.5- and 2.7-fold more alcohol and used drugs 6.1- and 7.8-fold more frequently than controls or EM subjects, respectively. In conclusion, physical maltreatment was observed to interact with cerebellar morphology resulting in a strong association with alcohol and substance use. Lingula thickness may represent a novel, experientially sensitive, phenotypic risk factor for enhanced alcohol and drug use that perhaps modulates sensitivity to these agents.     

Traumatic brain injury and alcohol/substance abuse: A Bayesian meta-analysis comparing the outcomes of people with and without a history of abuse

Alcohol and substance (drugs and/or alcohol) abuse are major risk factors for traumatic brain injury (TBI); however, it remains unclear whether outcomes differ for those with and without a history of preinjury abuse. A meta-analysis was performed to examine this issue. The PubMed, Embase, and PsycINFO databases were searched for research that compared the neuroradiological, cognitive, or psychological outcomes of adults with and without a documented history of alcohol and/or substance abuse who sustained nonpenetrating TBIs. Data from 22 studies were analyzed using a random-effects model: Hedges’s g effect sizes measured the mean difference in outcomes of individuals with/without a history of preinjury abuse, and Bayes factors assessed the probability that the outcomes differed. Patients with a history of alcohol and/or substance abuse had poorer neuroradiological outcomes, including reduced hippocampal (g = ?0.82) and gray matter volumes (g = ?0.46 to ?0.82), and enlarged cerebral ventricles (g = ?0.73 to ?0.80). There were limited differences in cognitive outcomes: Executive functioning (g = ?0.51) and memory (g = ?0.39 to ?0.43) were moderately affected, but attention and reasoning were not. The findings for fine motor ability, construction, perception, general cognition, and language were inconclusive. Postinjury substance and alcohol use (g = ?0.97 to ?1.07) and emotional functioning (g = ?0.29 to ?0.44) were worse in those with a history of alcohol and/or substance abuse (psychological outcomes). This study highlighted the type and extent of post-TBI differences between persons with and without a history of alcohol or substance abuse, many of which may hamper recovery. However, variation in the criteria for premorbid abuse, limited information regarding the history of abuse, and an absence of preinjury baseline data prevented an assessment of whether the differences predated the TBI, occurred as a result of ongoing alcohol/substance abuse, or reflected the cumulative impact of alcohol/substance abuse and TBI.