Comorbidity, smoking behavior and treatment outcome

BACKGROUND: A sizeable sector of the population continues to smoke cigarettes despite our efforts to prevent and treat this addiction. We explored the relationships between lifetime comorbidity, psychiatric symptomatology, smoking behavior and treatment outcome to better understand vulnerability to smoking and treatment response. METHODS: One hundred and twenty smokers at two sites were enrolled in a multicenter, double-blind, randomized, 10-week smoking cessation trial with fluoxetine and behavioral treatment. The Structured Clinical Interview for DSM-III-R and Hamilton Depression Rating Scale were administered prior to treatment initiation. Self-report measures were used to assess psychiatric symptoms throughout treatment and during a 6-month follow-up period. RESULTS: Overall 62.3% of our sample were diagnosed with a lifetime mood, anxiety or substance use disorder despite stringent study exclusion criteria. Lifetime comorbidity was shown to be related to higher smoking rates and nicotine dependence, depressed mood and greater self-report of anxiety and stress. Lifetime comorbidity, however, alone or in combination with treatment condition, failed to predict treatment outcome (at posttreatment or follow-up). Baseline depression scores (Beck Depression Inventory, BDI) were related to treatment outcome only for smokers without a positive history of any psychiatric disorder or depression, with lower BDI scores more frequent in those who were abstinent. CONCLUSIONS: High prevalence rates of lifetime psychiatric illness and substance use disorders are reported for chronic smokers. Subsyndromal psychiatric symptoms may play a role in smoking behavior in combination with diagnosable disorders. Clinicians need to carefully assess both psychiatric diagnoses and symptoms in chronic smokers to optimize patient-treatment matching.     

Self-reported hay fever and panic attacks in the community.

OBJECTIVE: The objective of this study was to determine the relationship between self-reported hay fever and common mental disorders among adults in the general population. METHODS: Data were drawn from the Midlife Development in the United States Survey, a representative household survey of the adult US population (25 to 74 years old; n = 3,032). Multivariate logistic regression analyses were used to determine the relationship between self-reported hay fever and current major depression, panic attacks, generalized anxiety disorder, and alcohol/substance use disorders. RESULTS: Self-reported hay fever was associated with a significantly increased odds of panic attack (odds ratio = 1.8 [1.2, 2.6]), which persisted after adjusting for differences in sociodemographic characteristics and comorbid mental disorders. Self-reported hay fever was not associated with a significantly increased likelihood of major depression, generalized anxiety disorder, or alcohol/substance use disorders. CONCLUSIONS: Consistent with previous findings, these data show a relationship between self-reported hay fever and increased likelihood of panic attacks among adults in the general population. The mechanism of the observed association remains unknown. Future work that examines the relationship between hay fever and panic attacks, as well as other mental disorders using both self-report and objective measurement of allergic response in prospective, longitudinal, epidemiologic data may be useful in improving our understanding of this observed link.     

Electrodermal reactivity and its association to substance use disorders

Poor electrodermal response modulation is associated with substance use disorders, but the specificity of the relationship has not been tested. To test this, 112 college students were assessed for psychiatric symptoms using structured interviews and for ability to modulate skin conductance responses to 2-s 92- or 110-dB white noise blasts that varied in temporal predictability. Twenty-eight good and 28 poor modulators were compared on symptoms of alcohol and illicit drug use disorders, personality disorders (antisocial, borderline, histrionic, and narcissistic), social and specific phobia, and depression. As expected, poor modulators had significantly more symptoms of substance use disorders than good modulators. Groups did not differ in symptoms of anxiety disorder, depression, or personality disorders marked by disinhibition. Poor electrodermal response modulation may reflect a biological risk factor for substance use disorders in particular.     

P300 amplitude reduction is associated with early‐onset and late‐onset pathological substance use in a prospectively studied cohort of 14‐year‐old adolescents

P3 amplitude reduction (P3AR) is associated with risk for adolescent‐onset pathological substance use (PSU). In this longitudinal study, data from over 1,100 adolescent twins were used to examine P3AR in relation to early adolescent onset PSU (i.e., by age 14), late adolescent onset PSU (i.e., ages 14–18), misuse of different classes of substances (PSU‐nicotine, PSU‐alcohol, PSU‐illicit), degree of PSU comorbidity, and gender differences. P3 amplitude was recorded at age 14 from two midline electrodes during a visual oddball paradigm. PSU was defined as meeting criteria for any symptom of a substance use disorder assessed using semistructured clinical interviews. P3AR was associated with degree of drug class comorbidity, early adolescent onset PSU for all three substance classes, and late adolescent onset PSU for alcohol and illicit PSU. Gender differences in P3AR were not statistically significant. These findings provide further evidence that P3AR indexes a nonspecific diathesis for adolescent‐onset PSU.     

Comorbid disorders in patients with bipolar disorder and concomitant substance dependence

OBJECTIVE: Substance dependence is common in bipolar disorder and is associated with an increase in Axis I and II comorbidity. Little research has compared the relative rates of comorbidity among bipolar patients with dependence on different substances. METHODS: The Mini International Neuropsychiatric Interview (MINI) was used to assess 166 outpatients involved in one of three clinical trials of medications for bipolar disorder and substance dependence. Patients had concurrent alcohol dependence, cocaine dependence, or both conditions. RESULTS: Generalized anxiety disorder and current depressed mood were significantly more common in bipolar patients with alcohol dependence than bipolar patients with cocaine dependence. Those with cocaine dependence had significantly higher rates of post-traumatic stress disorder and antisocial personality disorder and were more likely to present in a mixed mood state than patients dependent on alcohol. Cocaine ENC dependent patients were more likely than alcohol dependent patients to have Bipolar I relative to Bipolar II. LIMITATIONS: This is a retrospective, cross-sectional data analysis using the MINI for diagnosis. CONCLUSIONS: Cocaine dependence and alcohol dependence were associated with different clinical features and comorbid disorders in bipolar patients. The results may help confirm the validity of integrative models of mood, behavioral, anxiety, and personality disorders. Further studies on the causal relationship between substance dependence and concurrent and lifetime Axis I disorders for patients with bipolar disorders are indicated.     

Nicotine dependence and mental disorders among adults in the USA: evaluating the role of the mode of administration

BACKGROUND: To investigate the association between nicotine dependence (ND), by cigarette smoking and use of smokeless tobacco (UST), and mental disorders. METHOD: Face-to-face surveys (n=43 093) were conducted in the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Nicotine use, ND, and mental disorders were assessed using DSM-IV criteria. RESULTS: UST-ND was associated with a significantly increased likelihood of any anxiety disorder, specific phobia, alcohol abuse and dependence. Consistent with previous findings, cigarette smoking-ND was associated with an increased likelihood of all mental disorders examined. Among those without ND, cigarette smoking was specifically associated with panic attacks and panic disorder; non-dependent UST was not associated with mental disorders. CONCLUSIONS: Our findings suggest that the association between ND and mental disorders is relatively specific to the mode of nicotine administration. Among those who are nicotine dependent, cigarette use is associated with most major psychiatric disorders, whereas UST is associated with dysthymia and specific phobia. Among those who use tobacco but are not nicotine dependent, cigarette use is associated with dysthymia and panic disorder; UST is not associated with any major mood or anxiety disorders. The link between mental disorders and nicotine is complex, and is associated primarily with dependence, and not with non-dependent use.     

Race/ethnic differences in the prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders: Results from the National Epidemiologic Survey on Alcohol and Related Conditions

BACKGROUND: Very few large national epidemiologic surveys have examined the prevalence of psychiatric disorders among Asians and Native Americans due to small sample sizes. Very little is also known about the co-occurrences between substance use disorders and mood and anxiety disorders among these two minority groups and how their rates compare to Whites, Blacks, and Hispanics. METHOD: Analyses were based on a large (n = 43093) nationally representative survey of the adult (18+ years), U.S. population supplemented by a group quarters sampling frame. Prevalences and associations of major DSM-IV mood, anxiety and substance use disorders were examined among all major race/ethnic subgroups of the population. RESULTS: Twelve-month rates of most mood, anxiety and substance use disorders were generally greatest among Native Americans and lowest among Asians. For most race/ethnic subgroups, alcohol and drug dependence, but not abuse, were significantly associated with mood disorders. With few exceptions, there were no significant associations between alcohol and drug abuse and anxiety disorders. In contrast, alcohol dependence was associated with most anxiety disorders among Whites, Blacks and Asians, but not among Native Americans. CONCLUSIONS: The 12-month prevalence of substance use, mood, and anxiety disorders varied greatly across the five major race/ethnic subgroups of the population. Twelve-month co-occurrence of substance use disorders and mood and anxiety disorders was pervasive among all race/ethnic subgroups. Future research is also needed to understand race/ethnic differentials in prevalence and co-occurrence of these disorders with a particular focus on factors that may give rise to them.     

Indirect Associations of Anxiety Sensitivity with Tobacco,Alcohol, and Other Drug Use Problems Through Emotional Disorder Symptoms in Adolescents

Abstract

Theoretically, anxiety sensitivity—fear of anxiety symptoms—enhances perception of and emotional reactivity to autonomic arousal and mental distress, thereby increasing negative affect and motivation to use substances for negative reinforcement. Because no prior study of adolescents has tested if anxiety sensitivity is indirectly associated with substance use problems through symptoms of emotional disorders (i.e., disorders involving high levels of negative affect), the current cross-sectional study examined this theoretical pathway. Participants included ninth-grade students from 10 different high schools in the Los Angeles metropolitan area (N?=?3005; 54.3% female). Self-report measures of anxiety sensitivity, emotional disorder symptoms, tobacco dependence, and alcohol and other drug problems were administered. Controlling for sex, race/ethnicity, parental education, school, and impulsiveness, we tested the associations of anxiety sensitivity with tobacco, alcohol, and other drug use problems as well as the indirect effects of anxiety sensitivity on each domain of substance use problems through emotional disorder symptoms. Anxiety sensitivity was associated with more severe tobacco dependence and greater alcohol problems and other drug problems, and anxiety sensitivity further was indirectly associated with all three domains of substance use problems through emotional disorder symptoms. Current findings suggest that adolescents high in anxiety sensitivity tend to experience emotional disorder symptoms, which may increase risk for substance use problems. Interventions that target anxiety sensitivity and enhance negative-affect coping skills may assist in preventing and reducing adolescent substance use problems.     

Relationship of social phobia with other psychiatric illness.

Fifty-seven social phobic patients were studied to identify the comorbidity with other psychiatric illnesses and their temporal relationships. Mood disorders, particularly major depression, was the most common other lifetime diagnosis (70.2%). A large majority (70.2%) suffered from, at least, one other anxiety disorder in their lifetime and, in particular, panic disorder with or without agoraphobia (49.1%). Alcohol (28.1%) and substance (15.8%) abuse or dependence were also common lifetime diagnoses. Social phobia usually predated any episode of mood disorder (81.7%) or any other anxiety disorder (62.7%). Social phobia may predispose individuals to other psychiatric illnesses, in particular major depression.     

Self-Reported Zygosity and the Equal-Environments Assumption for Psychiatric Disorders in the Vietnam Era Twin Registry

The equal-environments assumption (EEA) in twin studies of psychiatric disorders assumes that the family environment which contributes to risk for a disorder is equally correlated between monozygotic (MZ) and dizygotic (DZ) twin pairs. In a study of psychiatric disorders in female twins, Kendler and colleagues (1993) have demonstrated the utility of a test of the EEA which includes a specified family environmental factor defined by using measures of perceived zygosity. We tested the EEA assumption among 3155 male—male twin pair members of the Vietnam Era Twin Registry for the following DSM-III-R lifetime disorders: alcohol dependence, marijuana dependence, any illicit drug dependence, nicotine dependence, major depression, and posttraumatic stress disorder. The majority of MZ (81.6%; n = 1593) and DZ (90.2%; n = 1086) twin pairs agreed with the investigator's assigned zygosity. The best-fitting model for each of these disorders did not allow for a specified family environmental influence. These results support the usefulness of perceived zygosity in tests of the EEA. In male twin pairs, perceived zygosity has little impact on twin similarity for common psychiatric disorders.     

Pathways to comorbidity: the transition of pure mood, anxiety and substance use disorders into comorbid conditions in a longitudinal population-based study

BACKGROUND: To describe transitions to comorbidity within a 3-year period in three cohorts of subjects with at baseline a 12-month pure mood, anxiety or substance use disorder but no lifetime history of any other disorder category. To assess the role of personal and social vulnerability factors, life events, clinical factors and functional disability in the pathway to comorbidity. METHODS: Data were derived from the Netherlands Mental Health Survey and Incidence Study (NEMESIS), a prospective epidemiologic study of a representative sample of 7076 adults aged 18-65, interviewed in three waves (baseline, 1 and 3 years after baseline) with the Composite International Diagnostic Interview. RESULTS: 15.2% of 99 pure mood, 10.5% of 220 anxiety and 6.8% of 192 substance use disorder cases became comorbid. Comorbid transition from pure mood disorder was multivariately associated with higher age, external mastery and severity of the disorder. Comorbidity developing from pure anxiety disorder was associated with past and recent stressful life circumstances (childhood trauma, negative life events) and physical functional disability. Predictors of comorbid transition from pure substance use disorder were personal and social vulnerability variables only (high neuroticism, low social support). LIMITATIONS: Although NEMESIS was performed among a substantial number of cases, the number of cases with a pure disorder at baseline subsequently developing comorbidity was low. This limited analysing determinants of different comorbid conditions. CONCLUSIONS: Risk factors for comorbid transitions vary depending on whether subjects have a primary mood, anxiety or substance use disorder. Interventions aimed at primary prevention of comorbidity to reduce psychiatric burden in populations with a history of pure disorders are indicated in response to clearly identified risk factors.     

Comorbid mental disorders among the patients with alcohol abuse and dependence in Korea

This study investigated the patterns of alcohol disorder comorbidity with other psychiatric disorders, using Korean nationwide epidemiological data. By two-stage cluster sampling, 5,176 adult household residents of Korea were interviewed using the Korean version of the Diagnostic Interview Schedule. Psychiatric disorders strongly associated with alcohol disorders were, other drug abuse or dependence, major depression, simple phobia, antisocial personality disorder, tobacco dependence, and pathological gambling. Male alcoholics had a tendency to begin with tobacco dependence, and some male pathological gamblers first had alcohol disorders. The presence of comorbid psychiatric disorders was associated with a more severe form and the later onset of alcohol disorders, and associated with help-seeking for alcohol abuse/dependence.     

The moderating influence of nicotine and smoking on resting-state mood and EEG changes in remitted depressed patients during tryptophan depletion

Comorbidity between depression and tobacco use may reflect self-medication of serotonergically mediated mood dysregulation, which has been associated with aberrant cortical activation and hemispheric asymmetry in patients with major depressive disorders (MDD). This randomized, double-blind study in 28 remitted MDD patients examined the moderating effects of acute nicotine and smoker vs. nonsmoker status on mood and EEG changes accompanying transient reductions in serotonin induced by acute tryptophan depletion (ATD). In smokers, who exhibited greater posterior high alpha power and increased left frontal low alpha power (signs of deactivation) compared to nonsmokers, ATD increased self-ratings of depressed mood and elevated left frontal and right parietal high alpha power (i.e. further cortical deactivation). Smokers were not affected by nicotine administration. In nonsmokers, ATD did not influence depression ratings, but it reduced vigor ratings and increased frontal and posterior theta power; both of which were blocked by acute nicotine. These findings indicate a role for nicotinic receptors in disordered mood.     

Prospective association of childhood attention-deficit/hyperactivity disorder (ADHD) and substance use and abuse/dependence: a meta-analytic review

Given the clinical and public health significance of substance disorders and the need to identify their early risk factors, we examined the association of childhood attention-deficit/hyperactivity disorder (ADHD) with substance use (nicotine, alcohol, marijuana) and abuse/dependence outcomes (nicotine, alcohol, marijuana, cocaine, other). To strengthen a potential causal inference, we meta-analyzed longitudinal studies that prospectively followed children with and without ADHD into adolescence or adulthood. Children with ADHD were significantly more likely to have ever used nicotine and other substances, but not alcohol. Children with ADHD were also more likely to develop disorders of abuse/dependence for nicotine, alcohol, marijuana, cocaine, and other substances (i.e., unspecified). Sex, age, race, publication year, sample source, and version of the Diagnostic and Statistical Manual of Mental Disorders (DSM) used to diagnose ADHD did not significantly moderate the associations with substance outcomes that yielded heterogeneous effect sizes. These findings suggest that children with ADHD are significantly more likely to develop substance use disorders than children without ADHD and that this increased risk is robust to demographic and methodological differences that varied across the studies. Finally, few studies addressed ADHD and comorbid disruptive behavior disorders (DBD), thus preventing a formal meta-analytic review. However, we qualitatively summarize the results of these studies and conclude that comorbid DBD complicates inferences about the specificity of ADHD effects on substance use outcomes.     

Childhood sexual abuse and risks for licit and illicit drug-related outcomes: a twin study

BACKGROUND: This study examined the relationships between self-reported childhood sexual abuse (CSA) and drug-related outcomes in an Australian twin panel. METHOD: A semi-structured psychiatric interview was conducted in 1996-2000 by telephone with young adult Australian twins (mean age 29.9 years). Data reported here are from 6050 twins who responded to both CSA and drug-related items. RESULTS: A history of CSA was associated with significant risk for subsequently occurring regular smoking and use of each illicit drug class. Further CSA-associated risk was found among regular users, for nicotine and alcohol dependence, and among illicit drug users, for abuse/dependence of most drug classes. In same-sex discordant pairs, significant risk for regular smoking and illicit drug use was found in twins with a history of CSA compared to their non-abused co-twins. Similar analyses for abuse/dependence found significant risk for opioids, any illicit drug, and any non-cannabis illicit drug. CSA was associated with significantly earlier drug use. Despite the association of CSA with risk for early-onset cannabis use and regular smoking, risks for illicit drug outcomes associated with CSA and with either form of early-onset use combine in near-additive fashion. CONCLUSIONS: CSA is associated with risk for subsequently occurring regular smoking and illicit drug use and abuse/dependence. Risks for drug use are mildly attenuated with control for familial contributions; similar risks for abuse/dependence remain significant for opioids and for illicit drugs combined across classes. Although we found evidence of earlier onset drug use with CSA, risks associated with CSA and with early-onset use combine in a largely additive manner.     

Primary anxiety disorders and the development of subsequent alcohol use disorders: a 4-year community study of adolescents and young adults

BACKGROUND: Cross-sectional findings in community surveys of adults suggest that adolescent anxiety disorders are strong predictors of the subsequent onset of alcohol use, abuse and dependence. However, prospective data that follow a sample of adolescents into adulthood are needed to confirm these associations. METHOD: Baseline and 4-year follow-up data from the EDSP-Study, a prospective community survey of 3021 (2548 at follow-up) adolescents and young adults aged 14 to 24 years at baseline carried out in Munich, were used. DSM-IV anxiety disorders, alcohol use and alcohol use disorders were assessed with the Munich-Composite-International-Diagnostic-Interview (M-CIDI). Multiple logistic regression analysis, controlling for age, gender, other mental disorders, substance use disorders and antisocial behaviour was used to study the associations of baseline anxiety disorders with the subsequent onset and course of alcohol use and alcohol disorders. RESULTS: Baseline social phobia significantly predicts the onsets of regular use and hazardous use and the persistence of dependence. Panic attacks significantly predict the onsets of hazardous use and abuse as well as the persistence of combined abuse/dependence. Panic disorder significantly predicts the persistence of combined abuse/dependence. Other anxiety disorders do not significantly predict any of the outcomes. CONCLUSIONS: Panic and social phobia are predictors of subsequent alcohol problems among adolescents and young adults. Further studies are needed to investigate the underlying mechanisms and the potential value of targeted early treatment of primary panic and social phobia to prevent secondary alcohol use disorders.     

Alcoholism in 274 patients with panic disorder in Spain,one of the main producers of wine worldwide

BACKGROUND: Though panic disorder (PD) and alcoholism have been found in epidemiologic studies to often co-occur, the influence of cultural factors on the order of onset of the disorders has not been frequently addressed. METHODS: A sample of 274 patients with PD was assessed and compared according to the presence of alcohol use disorder (AUD) (alcohol abuse or dependence), employing several clinical scales. RESULTS: A total of 26 subjects were diagnosed from AUD. In 73.1% of patients, onset of alcohol use was previous to PD onset. PD subjects with AUD were found to have an earlier age at PD onset. They were more likely to be males, to have a family history of alcoholism, to abuse other drugs and to experience a more severe PD (more attacks in the last month, higher scores in anticipatory anxiety). CONCLUSIONS: Patients with PD and alcoholism may represent a distinct clinical subgroup. Our finding of an uncommon order of onset for both disorders may reflect cultural influences. CLINICAL IMPLICATIONS: (i)The study of panic disorder patients with comorbid alcoholism may help to better characterize this subgroup of patients. (ii) Patterns of alcohol use and the order of onset of both disorders may be influenced by cultural factors, with important practical implications. (iii) Patients with panic disorder and alcoholism may represent a distinct clinical subgroup, with an earlier age at panic disorder onset and greater clinical severity of anxiety. LIMITATIONS: (i) Our results refer to a clinical sample, which may not be representative of the general population. (ii) Alcoholic patients with a history of other drug abuse or dependence were not excluded. (iii) Owing to the small sample size, patients with alcohol dependence and with alcohol abuse were not separated.     

Changes in plasma brain-derived neurotrophic factor levels in smokers after smoking cessation

Several studies have reported that brain-derived neurotrophic factor (BDNF) might be associated with nicotine dependence. However, there are few studies on BDNF levels in humans with nicotine dependence. In the present study, we compared the differences in plasma BDNF levels in patients with nicotine dependence and in healthy nonsmokers, and we investigated serial changes in plasma BDNF levels in patients with nicotine dependence following smoking cessation. Forty-five voluntary smokers and 66 nonsmokers were recruited in this study. Of the 45 smokers, 12 were taking varenicline, 21 were using a nicotine patch, and 12 were unaided in their cessation effort by their own choice. Plasma BDNF levels were measured at baseline using an enzyme-linked immunosorbent assay (both smokers and nonsmokers) and at weeks 4 and 12 after smoking cessation (abstinent smokers only). A total of 19 smokers were able to remain abstinent during the entire study period. Baseline plasma BDNF levels were significantly lower in smokers compared to nonsmokers (F = 4.410, p = 0.002). The plasma BDNF levels in the abstinent smokers significantly increased from baseline after 4 weeks of smoking cessation (z = −2.86, p = 0.004) but had a tendency of decrease in the period between weeks 4 and 12. We could not find differences in the plasma BDNF levels among the three smoker subgroups at week 12 following cessation. Changes in plasma BDNF levels might be related to the process of abstinence and the pathophysiology of nicotine dependence.     

Alcohol abuse in social phobic patients: is there a bipolar connection?

BACKGROUND: Epidemiological and clinical studies have reported the frequent co-occurrence of social phobia (SP) and alcohol use disorders. Patients with SP often use alcohol to cope with the social situations they fear, and to lessen anticipatory anxiety, behavioral inhibition, and phobic avoidance. We investigated whether the presence of lifetime comorbidity with alcohol abuse was associated with significant differences as regards demographic and clinical features, family history and pattern of comorbidity in a large clinical sample of SP outpatients. METHOD: The sample comprised 153 outpatients who met DSM-III-R diagnostic criteria for SP. Demographic, family history and course characteristics were investigated by a semi-structured interview. Social phobic symptoms and the severity of the illness have been assessed by the Liebowitz Social Anxiety Scale (LSAS) and the Liebowitz Social Phobic Disorders Rating Scale, Severity (LSPDRS). Patients completed the Hopkins Symptom Checklist (HSCL 90). RESULTS: Thirty-four patients (22.2%) had a past or current history of alcohol abuse for at least 1 year. There were no significant differences between these patients and those without a history of alcohol abuse, as regards demographic features and lifetime comorbidity with major depression and other anxiety disorders. Bipolar disorder type II was found almost exclusively among patients with alcohol abuse, as well as family history for bipolar disorders. LIMITATIONS: Retrospective study. CONCLUSIONS: Our data indicate a strong relationship between bipolar II disorder and alcohol abuse comorbidity in patients with SP. The socializing and disinhibiting effect that many social phobics report might be mediated by mood elation induced by alcohol. The presence of bipolar diathesis in patients presenting with social anxiety might explain their increased susceptibility to alcohol, as they might undertake alcohol abuse as an attempt to overcome social difficulties.