Sex differences in the effects of alcohol on brain structure

OBJECTIVE: This study investigated whether alcoholic women manifest deficits in cortical gray and white matter volumes and ventricular enlargement similar to those seen in alcoholic men. METHOD: Volumetric measures of intracranium, cortical gray matter, white matter and sulci, and lateral and third ventricles were obtained from magnetic resonance images of 42 women and 44 men with DSM-III-R alcoholism and age-matched healthy comparison groups (37 women and 48 men). Groups of alcoholic men and women were matched on age and length of sobriety, but men had a 2.5 times higher lifetime alcohol consumption than women. RESULTS: Women, regardless of diagnosis, had less cortical gray and white matter and smaller third ventricles than men, consistent with sex-related differences in intracranial volume. Alcoholics had larger volumes of cortical sulci and lateral and third ventricles than comparison subjects. Diagnosis-by-sex interactions for cortical white matter and sulcal volumes were due to abnormalities in alcoholic men but not alcoholic women, relative to same-sex comparison subjects. This interaction persisted for cortical sulci after covarying for lifetime alcohol consumption. Slopes relating cortical gray matter and sulcal volumes to age were steeper in alcoholic than in comparison men. Slopes relating lateral ventricle volume to age were steeper in alcoholic than in comparison women. In alcoholic women, longer sobriety was associated with larger white matter volumes. CONCLUSIONS: Alcoholic men and women show different brain morphological deficits, relative to same-sex comparison subjects. However, age and alcoholism interact in both sexes, which puts all older alcoholics at particular risk for the negative sequelae of alcoholism.     

N400 as an index of semantic expectancies: differential effects of alcohol and cocaine dependence

BACKGROUND: Chronic substance abuse has been associated with decrements in the processing and expression of language. The present study utilized the N400 event-related electroencephalographic potential to index semantic processing in 133 adults with (n=49) or without (n=84) a history of alcohol and/or cocaine dependence. The contributions of age, gender, and comorbid marijuana and nicotine dependence, and antisocial symptomology to N400 decrements were either covaried or controlled. METHODS: A continuous series of 300 stimuli was presented for 150 ms each (interstimulus interval=1475 ms) on a computer screen. The series was arranged such that a word (approximately 17% of stimuli) immediately preceded presentations of its antonym (primed condition; approximately 17% of stimuli), or a semantically unrelated word (unprimed condition; approximately 17% of stimuli). The remaining 50% of stimuli consisted of unpronounceable letter combinations (non-word condition). EEG responses to the antonyms, unrelated words, and letter jumbles were retained for analysis. Throughout the task, the subject pressed response keys to discriminate words from non-words. RESULTS: Analyses revealed a detrimental effect of alcohol dependence on N400 amplitude and no significant main or interactive effects of cocaine dependence. CONCLUSION: The present findings suggest that alcohol-dependent individuals may exhibit verbal processing decrements. These findings also challenge hypotheses suggesting that the combined use of cocaine and alcohol is more deleterious to brain function than alcohol use alone.     

Compounded brain volume deficits in schizophrenia-alcoholism comorbidity

BACKGROUND: Schizophrenia and alcoholism are characterized by brain volume abnormalities. Despite the frequent comorbidity of these conditions, the potentially compounded effects of comorbidity on brain structure have seldom been rigorously assessed. METHODS: To determine the compounding effect of schizophrenia and alcoholism on regional brain volumes, we performed retrospective quantitative analysis of magnetic resonance images from men who participated in research protocols at the Veterans Affairs Palo Alto Health Care System, Palo Alto, Calif. Participants were selected on the basis of diagnostic criteria, yielding 4 comparison groups: 35 men comorbid for DSM-III-R schizophrenia or schizoaffective disorder and lifetime alcohol abuse or dependence; 64 men with DSM-III-R schizophrenia or schizoaffective disorder; 62 men with Research Diagnostic Criteria alcoholism; and 62 healthy men screened to exclude any Axis I diagnosis or heavy alcohol use. The comorbid group matched the schizophrenia group on age and illness severity but was younger and drank 5 times less alcohol in their lifetimes than the alcoholism group. Gray and white matter volumes from 6 cortical regions were expressed as age- and head size-corrected z scores and were subjected to multivariate profile analyses. RESULTS: Gray matter volume deficits were present in all 3 patient groups but were greatest in the comorbid group. In the comorbid group, the most prominent volume deficits were in the prefrontal and anterior superior temporal regions. CONCLUSIONS: Despite lower alcohol exposure than in pure alcoholism, the comorbidity of schizophrenia with alcoholism has a particularly profound effect on prefrontal gray matter volume, compounding the prominent prefrontal deficits present independently in schizophrenia and alcoholism.     

Alcohol and Drug Use and the Developing Brain

Adolescence is an important neurodevelopmental period marked by rapidly escalating rates of alcohol and drug use. Over the past decade, research has attempted to disentangle pre- and post-substance use effects on brain development by using sophisticated longitudinal designs. This review focuses on recent, prospective studies and addresses the following important questions: (1) what neuropsychological and neural features predate adolescent substance use, making youth more vulnerable to engage in heavy alcohol or drug use, and (2) how does heavy alcohol and drug use affect normal neural development and cognitive functioning? Findings suggest that pre-existing neural features that relate to increased substance use during adolescence include poorer neuropsychological functioning on tests of inhibition and working memory, smaller gray and white matter volume, changes in white matter integrity, and altered brain activation during inhibition, working memory, reward, and resting state. After substance use is initiated, alcohol and marijuana use are associated with poorer cognitive functioning on tests of verbal memory, visuospatial functioning, psychomotor speed, working memory, attention, cognitive control, and overall IQ. Heavy alcohol use during adolescence is related to accelerated decreases in gray matter and attenuated increases in white matter volume, as well as increased brain activation during tasks of inhibition and working memory, relative to controls. Larger longitudinal studies with more diverse samples are needed to better understand the interactive effects of alcohol, marijuana, and other substances, as well as the role of sex, co-occurring psychopathology, genetics, sleep, and age of initiation on substance use.     

Disordered Eating in Female Alcohol-Dependent Inpatients: Prevalence and Associated Psychopathology

This study's aims were twofold: to examine the prevalence rate of eating disorders in women hospitalized for substance abuse treatment and to analyze differences in psychopathology of three patient groups: 25 alcohol-dependent women without comorbid eating disorders, 15 alcohol-dependent women with partial syndromes of eating disorders, and 41 eating-disordered women without comorbid psychoactive substance use disorders. A higher prevalence rate of eating disorder synptomatology (38%) was detected among inpatient alcohol-dependent women than is found in studies examining community samples. Subjects diagnosed with comorbid eating disorder symptoms and alcohol dependence scored signijicantly higher than those with alcohol dependence alone on scales measuring borderline personality disorder. Subjects with comorbidity also scored significantly higher on bonlerline, antisocial, and bbolar scales than those with single diagnoses of eating disorders. Results indicate that, for better assessment and treatment, close attention must be paid to comorbidity in both p u p s of eating-disordered and substance-a busing women. Future research should focus on defining the mechanisms by which these disorders coexist.     

Cortical gray matter deficit in patients with bipolar disorder

Background: cortical gray matter volume deficit and ventricular enlargement are well documented in schizophrenia, but their presence in bipolar disorder is less well established.

Methods: global cortical gray matter, white matter and sulcal CSF, as well as lateral and third ventricular volume measures, were derived from axial MRI brain images obtained on age-matched bipolar (n=9), schizophrenic (n=9), and control (n=16) subjects. All subjects were free of history of alcohol or other substance dependence.

Results: relative to controls, bipolar patients had widespread volume deficits of cortical gray matter but not of cortical white matter. Schizophrenic patients had an even more severe cortical gray matter deficit and greater sulcal and lateral ventricular enlargement than the bipolar patients.

Conclusions: this group of patients with bipolar disorder had a widespread deficit of cortical gray matter similar to, but less pronounced than, that observed in patients with schizophrenia.     

A family study of alcohol dependence: coaggregation of multiple disorders in relatives of alcohol-dependent probands

BACKGROUND: Alcohol dependence tends to aggregate within families. We analyzed data from the family collection of the Collaborative Study on the Genetics of Alcoholism to quantify familial aggregation using several different criterion sets. We also assessed the aggregation of other psychiatric disorders in the same sample to identify areas of possible shared genetic vulnerability. DESIGN: Age-corrected lifetime morbid risk was estimated in adult first-degree relatives of affected probands and control subjects for selected disorders. Diagnostic data were gathered by semistructured interview (the Semi-Structured Assessment for the Genetics of Alcoholism), family history, and medical records. Rates of illness were corrected by validating interview and family history reports against senior clinicians' all sources best estimate diagnoses. Sex, ethnicity, comorbidity, cohort effects, and site of ascertainment were also taken into account. RESULTS: Including data from 8296 relatives of alcoholic probands and 1654 controls, we report lifetime risk rates of 28.8% and 14.4% for DSM-IV alcohol dependence in relatives of probands and controls, respectively; respective rates were 37.0% and 20.5% for the less stringent DSM-III-R alcohol dependence, 20.9% and 9.7% for any DSM-III-R diagnosis of nonalcohol nonnicotine substance dependence, and 8.1% and 5.2% for antisocial personality disorder. Rates of specific substance dependence were markedly increased in relatives of alcohol-dependent probands for cocaine, marijuana, opiates, sedatives, stimulants, and tobacco. Aggregation was also seen for panic disorder, obsessive-compulsive disorder, posttraumatic stress disorder, and major depression. CONCLUSIONS: The risk of alcohol dependence in relatives of probands compared with controls is increased about 2-fold. The aggregation of antisocial personality disorder, drug dependence, anxiety disorders, and mood disorders suggests common mechanisms for these disorders and alcohol dependence within some families. These data suggest new phenotypes for molecular genetic studies and alternative strategies for studying the heterogeneity of alcohol dependence.     

Predictors and correlates of suicide attempts over 5 years in 1,237 alcohol-dependent men and women

OBJECTIVE: In previous studies, factors related to a history of suicide attempts in persons with alcohol dependence have included sociodemographic variables, a more severe course of alcoholism, additional substance use disorders, and psychiatric comorbidity. This 5-year prospective study evaluated attributes associated with suicide attempts in a group of treatment-seeking persons with alcohol dependence. Psychiatric comorbidity was examined in terms of a distinction between substance-induced and independent psychiatric disorders. METHOD: Semistructured interviews were conducted with 1,237 alcohol-dependent subjects from the Collaborative Study on the Genetics of Alcoholism both at an initial evaluation and at a 5-year follow-up. Clinically relevant information was gathered at baseline, and suicidal behavior, aspects of alcohol dependence, and drug use were evaluated at the follow-up interview. RESULTS: Alcohol-dependent subjects (N=56) with suicide attempts during the follow-up period were more likely than subjects with no suicide attempts (N=1,181) to have made prior attempts. Other factors related to future suicide attempts in univariate analyses included younger age, being separated or divorced, other drug dependence, substance-induced psychiatric disorders, and indicators of a more severe course of alcoholism. Gender did not predict future attempts. CONCLUSIONS: A 5-year prospective evaluation of attributes associated with suicide attempts among alcohol-dependent persons identified factors that contributed to a small but significant proportion of the variance for future suicidal behavior.     

Effect of comorbid substance use on neuropsychological performance in subjects with psychotic or mood disorders

Objective - Patients presenting with psychotic or mood disorders present with neuropsychological deficits such as executive and memory disturbance. Deficits of these functions have also been reported in patients presenting with alcohol use or substance use disorders. A large percentage of patients with non-affective psychotic or mood disorders present with a comorbid substance use disorder. These subjects are often a priori excluded from most neuropsychological studies. However, using such an exclusion criterion may induce a selection bias linked to the high prevalence of this dual diagnosis. It is therefore necessary to further explore the impact of substance abuse on neuropsychological performance in subjects with psychotic or mood disorders. Method - Patients consecutively hospitalized for a non-affective psychotic disorder or a mood disorder were included. A standardised method was used to collect information on addictive behaviour, clinical and social characteristics. DSM IV diagnoses, including those of substance use, were made using a structured diagnostic interview and all other available clinical and historical information collected during the hospital stay. Memory performance was tested using the Batterie d'Efficience Mnésique 84 (Battery of memory efficiency 84 items, BEM 84). Executive abilities were explored using the Wisconsin Card Sorting Test (WCST) and the Stroop test. ANCOVAs with cannabis use disorder or alcohol use disorder as main factor were used to examine associations with neuropsychological test scores. Results - We have included 77 patients fulfilling the diagnostic criteria for non-affective psychotic disorders (schizophrenia, schizoaffective disorder, delusional disorder, other psychotic disorder, n=35) or mood disorders (n=42). Among these patients, 27.3% presented with a lifetime history of alcohol abuse/dependence (current prevalence: 14.3%) and 23.4% presented with a lifetime history of cannabis abuse/dependence (current prevalence: 11.7%). We have assessed the specific impact of alcohol and cannabis use on neuropsychological performance. No significant differences on memory and executive performance were found between patients presenting with and without a lifetime history of alcohol abuse/dependence. These results were not modified after adjustement for potential confounding factors (age, gender, educational level, age at onset, diagnosis, current versus past addictive behaviour). Patients with a lifetime history of cannabis abuse/dependence had significantly higher (i.e. better performance) general BEM 84 score (F=3.89, df=1, p=0.05), higher complex figure delayed recall scores (F=6.62, df=1, p=0.01) and higher recognition scores (F=3.9, df=1, p=0.05) than patients presenting without a lifetime history of cannabis use. After adjustment on covariables (age, gender, educational level, age at onset, diagnosis, current versus past addictive behaviour), the differences on memory performance between the two groups were no longer significant, the differences found before adjustment were mainly explained by the confounding effect of age. Patients presenting with a lifetime history of cannabis abuse/dependence had significantly lower interference scores on the Stroop test than subjects without cannabis use (F=5.67, df=1, p=0.02). This finding was not modified after adjustment for confounding factors. Information on substance use was collected by interviewing the patient and was completed by using all other available source of information, but no urine testing was performed. Thus, substance use could have been underestimated or unrecognized in some patients. We did not distinguish patients who presented with substance abuse from those who presented with dependence because there were few of the latter. Distinguishing these two populations would be of interest because dependence may have a more deleterious effect than abuse in neuropsychological performances. Finally, we did not included normal control subjects so we can not assess if our cohort present with memory and executive deficits compared to normal subjects. Conclusion - Comorbid alcohol or cannabis abuse/dependence has limited effects on memory and executive abilities in subjects with psychotic or mood disorder. The only significant difference between subjects with and without a dual diagnosis was that subjects with cannabis use disorder performed poorly on the Stroop test. No other significant difference in executive and memory performance was found after adjustment for confounding factors. Since there is a high prevalence of a comorbid substance use disorder in subjects with psychotic or mood disorder, the exclusion of these patients in neuropsychological studies may not be systematically justified.     

Hippocampal volume in adolescent-onset alcohol use disorders

OBJECTIVE: Alcohol use disorders (defined as DSM-IV alcohol dependence or abuse) are prevalent and serious problems among adolescents. As adolescence is marked by progressive hippocampal development, this brain region may be particularly susceptible to the adverse effects of adolescent alcohol use disorders. This study compared the hippocampal volumes of adolescents and young adults with adolescent-onset alcohol use disorders to those of healthy matched comparison subjects. METHOD: Magnetic resonance imaging was used to measure the hippocampal volumes and volumes of comparison brain regions in 12 subjects with alcohol use disorders and 24 comparison subjects matched on age, sex, and handedness. RESULTS: Both left and right hippocampal volumes were significantly smaller in subjects with alcohol use disorders than in comparison subjects. Total hippocampal volume correlated positively with the age at onset and negatively with the duration of the alcohol use disorder. Intracranial, cerebral, and cortical gray and white matter volumes and measures of the mid-sagittal area of the corpus callosum did not differ between groups. CONCLUSIONS: In the mature brain, chronic alcohol use disorders are associated with graded global brain dysmorphology. Although the etiology, neuropsychological consequences, and permanence of these hippocampal findings need to be further examined, these findings suggest that, during adolescence, the hippocampus may be particularly susceptible to the adverse effects of alcohol.     

Lifetime posttraumatic stress disorder in Turkish alcohol-dependent inpatients: relationship with depression, anxiety and erectile dysfunction

The aim of the present study was to evaluate the prevalence of lifetime posttraumatic stress disorder (PTSD) in Turkish male alcohol-dependent inpatients, and to investigate the relationship of lifetime PTSD diagnosis with anxiety, depression, hopelessness, erectile dysfunction and psychosocial problems related with alcohol dependency. Eighty-two male inpatients who met DSM-IV criteria for alcohol dependence and 48 subjects without substance use disorder as a control group were included in the study. Subjects were applied the Hamilton Depression Rating Scale (HAM-D), the Hamilton Anxiety Rating Scale (HAM-A), the Michigan Alcoholism Screening Test (MAST), the Beck Hopelessness Scale (BHS) and the International Index of Erectile Function (IIEF). Rate of lifetime PTSD diagnosis was found to be 26.8% among alcohol-dependent inpatients. The mean age of patients with lifetime PTSD was lower than in patients without this diagnosis, while there were no significant differences between these two groups in terms of age of first alcohol use, lifetime major depression, current depression, presence and severity of erectile dysfunction. Mean scores of HAM-D, HAM-A, BHS and MAST in the group with lifetime PTSD were significantly higher than the group without this diagnosis. There was a positive relationship between lifetime PTSD diagnosis and depression, anxiety, hopelessness and severity of psychosocial problems related to alcohol dependency, while there was no relationship between lifetime PTSD comorbidity and erectile dysfunction in alcohol-dependent patients.     

Developmental sequence from disruptive behavior diagnosis to adolescent alcohol dependence.

OBJECTIVE: The authors sought to clinically describe the relationship of disruptive behavior disorders with both alcohol dependence and the use of a variety of substances. METHOD: The Child Semi-Structured Assessment for the Genetics of Alcoholism was used to collect data on 54 adolescents with a diagnosis of alcohol dependence. The frequency and age at onset of the disruptive behavior disorder diagnoses were examined as well as age at first use of alcohol, tobacco, marijuana, and other street drugs. RESULTS: Nearly three-quarters of the alcohol-dependent adolescents had at least one disruptive behavior disorder diagnosis. Attention deficit hyperactivity disorder (ADHD) typically occurred first, followed by conduct disorder. Substance use began with alcohol or tobacco, followed by marijuana and then other street drugs. Alcohol dependence began significantly later than the onset of either ADHD or conduct disorder and significantly later than the first use of tobacco. CONCLUSIONS: Disruptive behavior diagnoses, particularly conduct disorder, typically precede the initiation of use of a variety of substances that, in turn, precede the diagnosis of alcohol dependence in adolescents.     

Gender effects on persistent cerebral metabolite changes in the frontal lobes of abstinent cocaine users.

OBJECTIVE: Previous studies found functional changes in the frontal brain region and regions with projections to the frontal lobe in cocaine users. The aim of this study was to investigate persistent neurochemical changes in the frontal lobes of subjects with a history of crack cocaine dependence and to determine whether these changes are different in male and female users. METHOD: The frontal gray and white matter of 64 young asymptomatic and abstinent (> 5 months) cocaine users (34 male and 30 female) and 58 healthy comparison subjects without a history of drug abuse was evaluated with localized proton magnetic resonance spectroscopy (1H-MRS). RESULTS: Two-way analysis of variance showed significant cocaine effects on the concentration of frontal gray matter N-acetyl compounds, on the ratio of frontal white matter N-acetyl compounds to creatine levels, on frontal gray and white matter myoinositol levels, and on the ratio of myoinositol to creatine. Significant gender effects were observed for frontal gray matter choline-containing compounds, the ratio of choline-containing compounds to creatine, and the percentage of CSF in both gray and white matter. Interaction effects of cocaine and gender were observed for creatine, N-acetyl/creatine ratio, and myoinositol/creatine ratio in frontal white matter. CONCLUSIONS: Cocaine use is associated with neuronal injury (with decreased N-acetyl compounds) in the frontal cortex and glial activation (with increased myoinositol) in both frontal gray and white matter. In the frontal lobe, cocaine affects male users differently than female users. Future studies on the effects of cocaine abuse should control for the effects of gender-specific neurotoxicity.     

Serotonin transporter gene regulatory region polymorphism (5-HTTLPR), [3H]paroxetine binding in healthy control subjects and alcohol-dependent patients and their relationships to impulsivity

The aim of this study was to investigate [3H]paroxetine binding and impulsivity in alcohol-dependent and age-matched control subjects in relation to a 5'-promoter region serotonin transporter (5-HTT) polymorphism (5-HTTLPR). Alcohol-dependent subjects were hypothesized to show a decreased number of bindings sites and a lower dissociation constant. 5-HTTLPR S-genotype carriers in both alcohol-dependent and control subjects were expected to show significantly fewer binding sites and a lower dissociation constant. Influences of impulsive traits, chronic daily alcohol intake, duration of alcohol dependence, age of onset and age on [3H]paroxetine binding were also investigated. Inpatients meeting DSM IV alcohol dependence criteria and of German descent were recruited to avoid ethnic stratification effects. One hundred and seventeen control subjects of similar social status were recruited from a town community. Blood samples were taken from both alcohol-dependent and control subjects to determine 5-HTTLPR genotypes using PCR of lymphocyte DNA, and to perform platelet [3H]paroxetine binding (binding capacity: B(max); and dissociation constant: K(D)). Impulsivity was assessed using the Barratt impulsiveness scale version 5 (BIS-5) in alcohol-dependent subjects only. Alcohol-dependent subjects were subdivided into low or high impulsivity groups using a median-split of the BIS-5 scale. The control group was slightly older than the alcohol-dependent group (not statistically significant). [3H]paroxetine binding was investigated in 72 control subjects and 72 patients, of which five patients met type 2 alcohol dependence criteria. Genotyping was carried out in all patients and control subjects. A significant influence of duration of alcohol dependence was found on the [3H]paroxetine binding K(D) but not B(max.) Neither alcohol-dependent nor control subjects showed any differences in B(max) or K(D). S-allele carriers did not show a decreased binding or lower dissociation constant. Furthermore, no significant interaction between B(max) and K(D) with either 5-HTTLPR genotype or impulsivity was revealed. This was the first study to investigate platelet [3H]paroxetine binding in alcohol-dependent and age-matched control subjects in relation to the 5-HTTLPR genotype. No differences concerning 5-HTTLPR-alleles were found in these groups Furthermore, no significant interaction between these parameters and impulsivity was shown in alcohol-dependent subjects. These results do not support previous results of altered [3H]paroxetine binding sites in alcohol-dependent subjects or 5-HTTLPR S-allele carriers. K(D) might be influenced by duration of alcohol dependence, but not sufficiently to yield differences between alcohol-dependent and control subjects.     

Substance use disorders in individuals with body dysmorphic disorder

BACKGROUND: Little is known about substance use disorders (SUDs) in individuals with body dysmorphic disorder (BDD). Although studies have examined SUD comorbidity in BDD, no previous studies have examined clinical correlates of SUD comorbidity. METHOD: We examined rates and clinical correlates of comorbid SUDs in 176 consecutive subjects with DSM-IV BDD (71% female; mean +/- SD age = 32.5 +/- 12.3 years). Comorbidity data were obtained with the Structured Clinical Interview for DSM-IV. BDD severity was assessed with the Yale-Brown Obsessive Compulsive Scale Modified for BDD, and delusionality (insight) was assessed with the Brown Assessment of Beliefs Scale. Quality of life and social/occupational functioning were examined using the Social Adjustment Scale, Quality of Life Enjoyment and Satisfaction Questionnaire, Medical Outcomes Study 36-Item Short-Form Health Survey, and Range of Impaired Functioning Tool. All variables were compared in BDD subjects with and without lifetime and current SUDs. Data were collected from January 2001 to June 2003. RESULTS: 48.9% of BDD subjects (N = 86) had a lifetime SUD, 29.5% had lifetime substance abuse, and 35.8% had lifetime substance dependence (most commonly, alcohol dependence [29.0%]). 17% (N = 30) had current substance abuse or dependence (9.1% reported current substance abuse, and 9.7% reported current dependence). 68% of subjects with a lifetime SUD reported that BDD contributed to their SUD. There were far more similarities than differences between subjects with a comorbid SUD and those without an SUD, although those with a lifetime SUD had a significantly higher rate of suicide attempts (p = .004). CONCLUSION: These preliminary results suggest that SUDs are very common in individuals with BDD. Subjects with and without a comorbid SUD were similar in most domains that were examined.     

Characteristics of subgroups of individuals with psychotic illness and a comorbid substance use disorder

OBJECTIVES: The co-occurrence of severe mental illness and substance use disorder, or dual diagnosis, is prevalent and is associated with significant clinical and social problems. Most studies have treated persons with a dual diagnosis as a homogeneous population, grouping together different substances of misuse. This study investigated whether subgroups defined by their main substances of misuse were heterogeneous. The primary hypothesis was that users of stimulants, such as cocaine or amphetamines, would be characterized by especially high rates of inpatient admission, violence, and self-harm. METHODS: Case managers' ratings were used to identify individuals with serious mental illness and comorbid substance abuse or dependence who were being treated by 13 community mental health teams in South London. Standardized instruments were used to elicit sociodemographic, clinical, social, and service use data. RESULTS: A total of 233 cases of comorbid substance use disorder and psychotic illness were identified. On the basis of best available information, 78 (34 percent) patients were classified as alcohol misusers only, 52 (22 percent) as alcohol and cannabis users, 29 (12 percent) as users of cannabis only, and 55 (24 percent) as stimulant users; 19 patients (8 percent) were excluded from the analysis. No significant differences were found between subgroups in the use of inpatient services and lifetime history of self-harm, but there was a significant difference in lifetime history of violence, which was more frequent among stimulant users. The alcohol users were older and more likely to be white, but otherwise few differences between subgroups were suggested by exploratory analyses. CONCLUSIONS: Apart from differences in history of violence, little heterogeneity was found among subgroups of patients with different types of substance misuse.     

Axis II comorbidity of substance use disorders among patients referred for treatment of personality disorders.

OBJECTIVE: The purpose of this study was to determine the extent of comorbid substance use disorders in patients referred for treatment of personality disorders. METHOD: Two hundred inpatients and outpatients were assessed by semistructured interviews for substance use and personality disorders. Univariate odds ratios were calculated for groups of substance use disorders and each DSM-III-R axis II disorder; comorbidity among axis II disorders was controlled in multivariate models predicting current or lifetime substance use disorder groups. The impact of personality disorder on chronicity and overall impairment associated with substance use disorders was evaluated. RESULTS: Close to 60% of subjects with substance use disorders had personality disorders. Borderline personality disorder was significantly associated with current substance use disorders, excluding alcohol and cannabis, and with lifetime alcohol, stimulant, and other substance use disorders, excluding cannabis. Antisocial personality disorder was associated with lifetime substance use disorders other than alcohol, cannabis, and stimulants. These relationships remained significant after controlling for the presence of all other personality disorders. There was no evidence that personality disorders increased the chronicity of substance use disorders, but comorbid personality disorders were associated with greater global impairment. CONCLUSIONS: Borderline personality disorder may be associated with a wide variety of substance use disorders, especially among patients seeking treatment for personality problems.     

Reduced hippocampal volume and total white matter volume in posttraumatic stress disorder.

BACKGROUND: Reduced hippocampal volumes in posttraumatic stress disorder (PTSD) patients are thought to reflect specific changes of this structure. Previous magnetic resonance imaging (MRI) studies have not consistently examined indices of overall brain atrophy, therefore it cannot be completely ruled out that hippocampal changes are explained by whole-brain atrophy. The purpose of this study was to assess hippocampal and whole-brain volume in civilian PTSD. METHODS: Twelve subjects with PTSD and 10 control subjects underwent brain MRI. Hippocampal volumes were visually quantified using a computerized volumetric program. Whole-brain volumes were obtained with automated k-means-based segmentation. RESULTS: No differences were found in intracranial volumes (ICV). Subjects with PTSD had higher cerebrospinal fluid (CSF)/ICV ratios and lower white matter/ICV ratios, consistent with generalized white matter (WM) atrophy. The effect of age on CSF/ICV was more pronounced in the PTSD group. Subjects with PTSD had smaller absolute and normalized bilateral hippocampal volumes. These differences persisted after adjusting for lifetime weeks of alcohol intoxication. Posttraumatic stress disorder and depression scores correlated negatively with left hippocampal volume, but PTSD scores were a better predictor of hippocampal volumes. CONCLUSIONS: Our results replicate previous findings of reduced hippocampal volume in PTSD but also suggest independent, generalized, white matter atrophy.     

Comorbidity of DSM-IV pathological gambling and other psychiatric disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions

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. METHOD: 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). CONCLUSION: 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.     

Brain maturation may be arrested in chronic cocaine addicts.

BACKGROUND: Animal and human newborn studies suggest that exposure to cocaine in utero delays glial maturation and white matter myelination. Postmortem data show that in the frontal and temporal lobes, white matter myelination continues into middle age. Recent magnetic resonance imaging (MRI) data have confirmed continued white matter volume increase in these regions, reaching a maximum at age 47. METHODS: Thirty-seven male cocaine dependent (CD) and 52 normal control subjects between ages 19 and 47 were evaluated with MRI. Coronal images focused on the frontal and temporal lobes were acquired using pulse sequences that maximized gray/white matter contrast. RESULTS: Highly significant positive correlations between white matter volume and age were observed in both the frontal and temporal lobes of the control group (r =.52, p =.0001 and r =.54, p =.0001, respectively); however, CD subjects did not demonstrate any age-related increase in white matter volume of the frontal (r = -.001; p =.99) and temporal (r = -.07; p =.67) lobes in this age range. CONCLUSIONS: The age-related expansion in white matter volume occurring in normal control subjects was absent in CD subjects. The findings suggest that in adults, cocaine dependence may arrest normal white matter maturation in the frontal and temporal lobes of addicts who continue using cocaine.