Comorbid Alcohol Dependence Research Articles

Influence of Alcohol Dependence on the Clinical and Dynamic Characteristics of Bipolar Disorder with Their Comorbidity in Psychiatric Hospital Patients

Background: numerous studies indicate a high level of comorbidity of bipolar disorder with other psychiatric disorders. Alcohol dependence is one of the most common comorbid pathologies, along with anxiety disorders and personality disorders. Objective: determination of the frequency of comorbidity of BAR with alcohol dependence in patients of a specialized psychiatric hospital and identiашcation of clinical and dynamic features of BAR with this comorbidity. Patients and methods: in the psychiatric unit, 188 patients with bipolar disorder diagnosed according to ICD-10 (136 women and 52 men) were examined. The age of female patients was 41.6 ± 14.4 years, male — 39.4 ± 14.0 years. Depending on the current affective disorder, patients were distributed as follows: a depressive episode — 62.2 % (n = 117), a hypomanic episode — 2.7 % (n = 5), a manic episode (ME) — 1.6 % (n = 3), mixed episode — 33.5 % (n = 63). A comparative assessment of the clinical and dynamic characteristics of bipolar disorder was carried out in 2 groups of patients: with bipolar disorder and comorbid alcohol dependence — 30 individuals (14 women and 16 men), aged 43 years [29; 55] and without comorbidity with alcohol dependence — 59 individuals (39 women and 20 men), age 36 years [29; 50]. During the study, clinical-psychopathological, clinical-catamnestic, psychometric, statistical methods were used. Results and discussion: the level of comorbidity of bipolar disorder with alcohol dependence was determined — 15.9 %. It was found that in BD with comorbid alcohol dependence, compared with BD without alcohol dependence, patients have an early onset age of BD, more often have mixed episodes during an affective disorder. In addition, such patients have a higher risk of suicidal behavior, bipolar-I, and exacerbation of affective symptoms. It has also been shown that alcohol dependence makes it difficult to recognize bipolar disorder during the primary visit to specialized psychiatric care. Conclusion: addition of alcohol dependence to bipolar disorder affects negatively its main clinical and dynamic parameters and delays the terms of its diagnostics.

Sociodemographic profiles and determinants of relapse risks among people with substance use disorders in the Philippines: A survey in community and residential care settings

BackgroundMethamphetamine use is a major social and health issue in the Philippines. Former president Rodrigo Duterte prioritized combating illicit drugs, and the government launched an anti-drug campaign. People with substance use disorders (SUD) receive treatment and care in the community or residential treatment at Treatment and Rehabilitation Centers (TRCs) established by the Department of Health. However, since the content and quality of service are not sufficient, there is an urgent need for improvement. To this end, it is necessary to understand demographic characteristics, the severity of drug use, and treatment needs of this population. MethodsWe conducted a questionnaire survey of people with SUD in the community (n=308) and all TRC patients (n=1770) to obtain their demographic profiles. We also used the Drug Abuse Screening Test-20 (DAST-20) and the Stimulant Relapse Risk Scale (SRRS). ResultsBased on DAST-20 scores, the severity of dependence was not well-matched to the care provided; 12.4% of the community sample was in the severe or substantial categories and 14.2% of the TRC sample was in the low category. The TRC sample had a significantly higher relapse risk than the community sample, which was associated with a lower educational attainment level and comorbid alcohol dependence. ConclusionsIt is important to use standardized psychometric tools to match treatment with the severity of drug dependence. In addition, a wide variety of medical and social services need to be provided based on consideration of treatment needs to improve the well-being of this population.

Schema therapy for patients with borderline personality disorder and comorbid alcohol dependence: A multiple-baseline case series design study.

This study tested the effectiveness of schema therapy (ST) for borderline personality disorder (BPD) and comorbid alcohol dependence (AD). Twenty patients participated in a case series study with multiple baselines. The baseline phase consisted of treatment as usual. It was followed by a case conceptualization phase, an experiential techniques phase and a behavioural change phase. Patients showed a significant decrease in BPD and AD symptoms; change was mainly accomplished in the experiential techniques phase, with medium to large effect sizes. Three months after termination of therapy, 68% of the patients had remitted from BPD, and the number of drinking days decreased clearly. This study shows that, although treatment is challenging in this group of patients, meaningful change can be obtained in patients with BPD and AD using ST.

Concurrent use of alcohol and cocaine: which is the best drug choice?

IntroductionPatients with comorbid cocaine and alcohol dependence have a worse prognosis with lack of adherence to follow-up and treatment, frequent psychosocial problems, and higher rates of relapse [1]. Concurrent use of both substances produces cocaethylene, which is associated with more toxicity than cocaine alone [2].ObjectivesTo determine the efficacy of disulfiram compared to nalmefene in the treatment of comorbid cocaine and alcohol use.MethodsA quasi-experimental open study was designed on 41 outpatients, with a follow-up of at least 1 year at the Mental Health Unit, aged between 18 and 65 years, diagnosed with cocaine and alcohol dependence (ICD-10). A minimum simultaneous weekly consumption of 2 grams of cocaine and 12 SD (Standard Drink) of alcohol during the month before, described by self-records was established. Treatment with oral disulfiram 250mg/day was assigned to 21 patients, and with oral nalmefene 18mg/day to 20 individuals. Observation period was for 6 months. Urinalysis and alcohol breath test were carried out twice a week. Abstinence was defined by obtaining negative results for at least 4 consecutive weeks. Statistical analysis were performed using SPSS v21.0 (significance p<0.05).Results61.9% of patients treated with disulfiram achieved a minimum of 4 consecutive weeks of abstinence from cocaine and alcohol, compared to 40% in the nalmefene group (χ²=1.188; gl=1; p=0.276). There were no significant differences.ConclusionsDisulfiram or nalmefene monotherapy seems clinically ineffective or insufficient in reducing the combined use of cocaine and alcohol. Further research is needed to assess the effect of both drugs simultaneously.DisclosureNo significant relationships.

The Role of Posttraumatic Stress Symptoms and Negative Affect in Predicting Substantiated Intimate Partner Violence Incidents Among Military Personnel

Increasing rates of posttraumatic stress disorder (PTSD) in military populations during recent conflicts have sparked concerns regarding the incidence of other commonly associated problems, such as intimate partner violence (IPV). From a clinical perspective, it is important to understand patterns of PTSD symptomology that may indicate heightened risk for such aggression. To address this, among a longitudinal cohort of U.S. military personnel, we evaluated the association of PTSD symptom clusters and comorbid conditions as predictors of any subsequent Department of Defense Family Advocacy Program incidents of IPV meeting full definitional criteria for physical or psychological abuse. Results suggested that general symptoms of negative affect common in PTSD (e.g., anger/irritability, sleep disruption) and comorbid alcohol dependence were stronger predictors of IPV than trauma-specific PTSD symptomology (e.g., reexperiencing, hypervigilance). Clinical implications and recommendations for future research are discussed.

Параметры когерентности биоэлектрической активности мозга и уровень фосфорилированных нейрофиламентов в сыворотке крови при коморбидном течении алкогольной зависимости и аффективных расстройств

Введение. Наряду со многими психическими расстройствами алкогольная зависимость и аффективные расстройства являются результатом взаимодействия генетических, социальных и экологических факторов, что сопровождается морфофункциональными изменениями в центральной нервной системе. Тем не менее, основные причины и механизмы развития коморбидности алкоголизма и аффективных расстройств остаются не до конца ясны. Цель исследования - определение функциональной связности и уровня фосфорилированных нейрофиламентов у пациентов с алкогольной зависимостью и коморбидностью алкогольной зависимости и аффективного расстройства. Методика. Обследовано 60 пациентов после детоксикации: 30 пациентов с алкогольной зависимостью и 30 пациентов с коморбидным течением алкогольной зависимости и аффективного расстройства. Контрольную группу составили 20 психически и соматически здоровых лиц, сопоставимых по полу и возрасту. Исследование биоэлектрической активности головного мозга проводилось при помощи 16-канального энцефалографа. Анализировались общие усредненные значения внутри - и межполушарной когерентности. В сыворотках крови определяли содержание фосфорилированных нейрофиламентов методом твердофазного иммуноферментного анализа на полистироловых планшетах, предварительно покрытых куриными пoликлональными антителами. Результаты. При межгрупповом анализе были выявлены статистически значимо более низкие значения когерентности в правой гемисфере у пациентов с коморбидностью алкогольной зависимости и аффективного расстройства по сравнению с пациентами, страдающими только алкогольной зависимостью. Были обнаружены также статистически значимо более высокие значения концентрации нейрофиламентов в группе пациентов с коморбидностью алкогольной зависимости и аффективного расстройства по сравнению со здоровой группой контроля. При сравнении групп пациентов между собой были обнаружены боле высокие значения концентрации нейрофиламентов у пациентов с коморбидностью алкогольной зависимости и аффективного расстройства на уровне тенденции. Заключение. Наличие коморбидности алкоголизма и аффективных расстройств приводят к нейрофизиологическим изменениям в виде снижения функциональной связности коры головного мозга, особенно в правой гемисфере, а также увеличению степени нейронального повреждения. Background. Similar to many mental disorders, alcohol dependence and affective disorders result from interaction of genetic, social, and environmental factors associated with morpho-functional alterations in the central nervous system. However, major causes and mechanisms of the development of comorbid alcoholism and affective disorders are not fully clear. The aim of this study was to determine the functional connectivity and levels of phosphorylated neurofilaments in patients with alcohol dependence and comorbid alcohol dependence and affective disorder. Methods. 60 patients were evaluated after detoxification, including 30 patients with alcohol dependence and 30 patients with comorbid alcohol dependence and affective disorder. The control group consisted of 20 sex- and age-matched, mentally and somatically healthy individuals. Brain bioelectric activity was recorded with a 16-channel encephalograph. Overall average values of intra- and inter-hemispheric coherence were analyzed. Blood serum concentration of phosphorylated neurofilaments was measured by solid-phase enzyme immunoassay on polystyrene plates pre-coated with chicken polyclonal antibodies. Results. The intergroup analysis showed that coherence values for the right hemisphere were significantly lower in patients with comorbid alcohol dependence and affective disorder compared to patients with alcohol dependence alone (p=0.018). Also, concentrations of neurofilaments were significantly higher in the patient group with comorbid alcohol dependence and affective disorder compared to the healthy control group (p=0.042). Comparison of patient groups showed that neurofilament concentrations had a tendency toward higher values in patients with comorbid alcohol dependence and affective disorder (p=0.092). Conclusion. The presence of comorbid alcoholism and affective disorders leads to neurophysiological alterations evident as reduced functional connectivity of the cerebral cortex, particularly in the right hemisphere, as well as to the increased degree of neuronal damage.

A systematic review on genome-wide association studies exploring comorbidity in bipolar disorder

• We identified six GWAS with bipolar disorder I (BDI) and comorbid conditions (migraine, externalizing disorders and eating disorders) • Some genes involved in neurotransmission, stress response, neurogenesis and synaptic plasticity may be specifically associated with comorbid BDI. • Evidence from these GWAS is too weak to consider new endophenotypes in BDI. The comorbidities associated with bipolar disorder (BD) can worsen patients’ prognosis and increase economic costs to society. Currently, efforts are being made to identify new endophenotypes characterized by the presence of BD and another concomitant condition. We performed a search on PubMed and GWAS catalog databases to find genome-wide association studies carried out on patients with BD with any other comorbid condition. We extracted the associated SNPs that attained statistical significance and listed them to appraise their potential to define new BD endophenotypes based on the presence of comorbidities. Six articles fulfilled the inclusion criteria, and all included only patients with BD type-I (BDI). The identified comorbid conditions were migraine, externalizing disorders and eating disorders. BDI with comorbid migraine was associated with rs1160720 in the NBEA gene. BDI with comorbid anorexia or bulimia nervosa was associated with rs4854912 and rs13100379 in the SOX2-OT gene. BDI with comorbid substance abuse was associated with rs1039002 in the PDE10A gene, rs12563333 upstream of the MARK1 gene, and rs13220542 downstream of the MAP3K7 gene. BDI with comorbid alcohol dependence and substance abuse was associated with rs2727943, which is located between CNTN4 and CNTN6 . However, such associations were not strong enough to replicate. The main limitations are the small size and poor description of the samples used in the included articles. Some genes involved in neurotransmission, stress response, neurogenesis and synaptic plasticity may be associated with comorbid BDI. However, evidence is too weak to consider new endophenotypes in BDI.

Peripheral Markers of Nervous Tissue Damage in Addictive and Affective Disorders

Abstract—Studies on the pathophysiology of mental disorders indicate the involvement of neurobiological processes, including the neuroinflammatory response, neurogenesis, and neuronal degeneration, in the mechanisms of development of these disorders. We examined 135 patients with addictive and affective disorders (51 patients with alcohol dependence syndrome, 41 patients with a current depressive episode and 43 patients with comorbidity of alcohol dependence syndrome and affective disorder) and 46 mentally healthy donors. The content of neurospecific proteins (NSE, MBP, and GFAP) in the blood serum of patients and healthy people was determined by enzyme-linked immunosorbent assay. The study of peripheral markers of nerve tissue damage showed that all patients are characterized by signs of neuronal and glial distress. The results of analysis of variance and ROC analysis indicate the contribution of NSE and MBP to the development of affective disorders, while GFAP has a greater predictive efficiency in the case of addictive pathology. The tendency towards imbalance in the secretion of neurospecific proteins in the blood serum of patients with comorbidity of alcohol dependence and affective disorders is enhanced, which probably indicates a greater defect in neurobiological processes and neurodegeneration, and is also confirmed by data showing more severe clinical symptoms of patients in these cases of comorbidity.

Impact of alcohol abuse on suicide risk in schizophrenic patients

Suicide is one of the main causes of death among patients with mental illnesses. At the same time, alcohol consumption is associated with high risk of autoaggressive and suicidal behavior in population. On the other hand there is an opinion that alcohol may have an illusory-compensatory effect. In that case, alcohol consumption may be an attempt to decrease different symptoms such as depression, anxiety or hallucinations. An analysis of co-occurring schizophrenia and alcohol abuse is presented. Suicide statistics among patients with schizophrenia is studied. Different mechanisms contributing to suicide are highlighted. The correlations of other risk factors with suicide attempts with the assessment of the patient's social resources and environment were studied. The role of alcohol in the presence of other obvious risk factors has been assessed. Possible mechanisms of the protective role of alcohol in relation to suicides among patients with schizophrenia are presented. The authors outline topics of perspective research to clarify the risk of self-destructive behavior in patients with schizophrenia with comorbid alcohol dependence, to search for its predictors and to develop well-grounded complex preventive measures.

Medical Problems In Patients With Alcohol Dependence With Common Schizophrenia And Schizoaffective Disorder

Goal of this study of the relationship between alcohol use, severity of psychiatric symptoms and the number of verified medical diagnoses. The study was that self-reporting of medical history is less accurate in patients with comorbid alcohol dependence and schizophrenia compared with patients with alcohol dependence only or with control. 46 patients with schizophrenia or schizoaffective disorder and concomitant alcohol dependence recruited from the Bukhara Regional Psychoneurological Dispensary. 27 patients suffered from schizophrenia, and 19 patients from schizoaffective disorder.

A Prospective Comparison of Bipolar I and II Subjects With and Without Comorbid Alcohol Dependence From the COGA Dataset.

Objective: Comorbidity of alcohol use disorders in bipolar subjects is high as indicated by epidemiological and clinical studies. Though a more severe course of bipolar disorder in subjects with comorbid alcohol dependence has been reported, fewer studies considered the longitudinal course of alcohol dependence in bipolar subjects and the prospective course of comorbid bipolar II subjects. Beside baseline analysis, longitudinal data of the COGA (Collaborative Study on Genetics in Alcoholism) were used to evaluate the course of bipolar I and II disordered subjects with and without comorbid alcohol dependence over more than 5 years of follow-up.Methods: Characteristics of bipolar disorder, alcohol dependence and comorbid psychiatric disorders were assessed using semi-structured interviews (SSAGA) at baseline and at a 5-year follow-up. Two hundred twenty-eight bipolar I and II patients were subdivided into groups with and without comorbid alcohol dependence.Results: Of the 152 bipolar I and 76 bipolar II patients, 172 (75, 4%) had a comorbid diagnosis of alcohol dependence. Bipolar I patients with alcohol dependence, in particular women, had a more severe course of bipolar disorder, worse social functioning and more suicidal behavior than all other groups of subjects during the 5-year follow-up. In contrast, alcohol dependence improved significantly in both comorbid bipolar I and II individuals during this time.Conclusions: A 5-year prospective evaluation of bipolar patients with and without alcohol dependence confirmed previous investigations suggesting a more severe course of bipolar disorder in comorbid bipolar I individuals, whereas bipolar II individuals were less severely impaired by comorbid alcohol use disorder. While severity of alcohol dependence improved during this time in comorbid alcohol-dependent bipolar I patients, the unfavorable outcome for these individuals might be due to the higher comorbidity with personality and other substance use disorders which, together with alcohol dependence, eventually lead to poorer symptomatic and functional clinical outcomes.

Treatment Goals and Alcohol Use Outcomes in Veterans With Comorbid Alcohol Dependence and Posttraumatic Stress Disorder.

Previous research demonstrates the utility of goals in attaining improved drinking outcomes. Considerably less is known about the association between substance use goals and outcomes among persons with comorbid substance use disorder (SUD) and posttraumatic stress disorder (PTSD). This secondary analysis examined the association between alcohol use outcomes and participants' treatment entry substance use goals to either abstain or reduce substance use in the context of treatment for comorbid SUD/PTSD. Participants (N = 39) were treatment-seeking veterans with current alcohol dependence and PTSD. Participants completed self-report and clinician-rated measures of substance use and PTSD as part of a larger randomized controlled trial. Participants in both goal groups (abstain; reduce) achieved significant reductions in the likelihood of drinking and the likelihood of exceeding low-risk drinking levels. The primary analysis did not identify significant differences in outcome between goal groups; however, the exploratory analysis revealed that participants with reduced use goals were more likely to drink and more likely to exceed low-risk drinking levels. The findings suggest a moderately strong association between substance use goal and drinking outcome in the current study. Although the findings did not unequivocally support abstinence as a superior treatment goal, they offer a preliminary indication that abstinence may be an overall lower-risk option. These findings expand consideration of the utility of substance use goals and suggest that clinicians should invite consideration of abstinence but may need not limit integrated treatment for SUD/PTSD based on strict adherence to abstinence, particularly if low-risk use goals are targeted. (Am J Addict 2021;30:131-137).

Cognitive Changes in Comorbidity Alcohol Dependence and Affective Disorders

In this study, we sought to assess the level of cognitive functioning in patients with comorbid alcohol dependence and affective disorder, as well as to compare the detected changes with the indicators of cognitive tests in patients suffering only from alcoholism or affective disorder. It is suggested that patients with comorbidity may have a more severe cognitive deficit than patients with a single diagnosis.Materials and methods. We examined 100 patients aged 30–50 years before treatment: 30 patients with affective disorders, 40 patients with alcohol dependence and 30 patients with comorbid alcohol dependence and affective disorder. As a control group, 30 mentally and somatically healthy individuals were examined. The level of cognitive functioning was assessed using computer tests Go/No-go, Corsi and Stroop.Results. Statistically significantly lower indicators of cognitive functioning were found in patients with comorbid alcohol dependence and affective disorder in comparison with all the studied groups.Conclusion. The data obtained in the study indicate that the presence of comorbidity of alcohol dependence and affective disorder in patients leads to a significant deterioration in cognitive functions: Executive control, working memory, attention and cognitive flexibility compared to healthy individuals, as well as patients suffering only from alcohol dependence or affective disorder.

Depressive and Anxiety Symptoms Predict Obsessive and Compulsive Cravings among Depressed Alcoholics.

Alcohol craving is often associated with mood symptoms and predicts alcohol use in individuals with alcohol dependence. However, little is known about the impact of mood symptoms on alcohol craving in comorbid mood disorders and alcohol dependence. This study examines the predictive value of depressive and anxiety symptoms for obsessive and compulsive aspects of alcohol craving in adults with comorbid Major Depressive Disorder (MDD) and Alcohol Dependence. Fifty-five adults (47% female; mean age of 39.35 (SD=8.80)) with DSM-IV diagnoses of comorbid MDD and alcohol dependence were prospectively assessed over a six-month period. They completed the Hamilton Rating Scales for Depression and Anxiety, the Alcohol Timeline Followback, the Obsessive Compulsive Drinking Scale (OCDS), the Alcohol Dependence Scale (ADS), and the Addiction Severity Index (ASI). The linear mixed model analyses for repeated measures was used to test weather depressive and anxiety symptoms predict OCDS subscale scores. Depressive and anxiety symptoms were strongly associated with obsessive and compulsive subscales of the OCDS. Baseline ASI-alcohol scores were associated with both the obsessive and compulsive and with the obsessive subscale scores in the predictive model including depressive symptoms, and that including anxiety symptoms respectively. Results suggest that depressive and anxiety symptoms predict obsessive and compulsive aspects of alcohol craving in adults with comorbid MDD and alcohol dependence. Assessing the severity of depressive and anxiety symptoms and alcohol use in this population may identify those more likely to experience intense alcohol craving states and at increased risk of relapse.

Clinical-Dynamic Features of Affective Disorders Comorbid with Alcohol Dependence

Comorbidity of affective disorders (AD) and alcohol dependence (AlD) worsens prognosis and efficiency of therapy, exacerbates non-compliance in patients, and lowers their level of social adjustment. To study the influence of AlD on clinical-dynamic characteristics of AD, two groups of patients were examined and compared. The study group included 32 patients with AD and comorbid AlD. The comparison group included 31 AD patients without comorbid addictive pathology. The patients of compared groups did not have statistical differences (p > 0.05) according to sex, age, and AD. The Clinical Global Impression scale (CGI), Hamilton Depression Rating Scale (HDRS-17), Hamilton Anxiety Rating Scale (HARS), and Social Adaptation Self-evaluation Scale (SASS) were used. Compared to the group without comorbidity, the group of patients with comorbid AD and AlD had more frequent suicide attempts in their medical history, a high level of anxiety according to HARS, severe disorders according to CGI-S, and difficult and impaired social adaptation according to SASS; patients with recurrent depressive disorder (RDD) and bipolar disorder (BD) also experienced a larger number of affective episodes per year. AlD comorbid with AD affects clinical-dynamic indicators and levels of social adjustment in patients.

Clinical and electrophysiological parameters of alcohol dependence and its comorbidity with affective disorders

To identify characteristics of and possible differences in clinical and electroencephalographic parameters in patients with alcohol dependence with- and without comorbid affective disorders. Ninety-five patients, including 74 with an established diagnosis of alcohol dependence and 21 with alcohol dependence and affective disorders, were examined. Duration of alcohol dependence and affective disorder (years), number of hospitalizations and suicidal attempts were analyzed as anamnestic data. Hamilton's anxiety and depression scale (HDRS), the Alcohol Use Disorders Identification Test (AUDIT), the General clinical impression scale (CGI-s) were used as psychometric tools. The study of bioelectric activity of the brain was carried out using a 16-channel encephalograph. The background electroencephalogram was recorded, the values of absolute spectral power and coherence of theta, alpha and beta rhythms were analyzed. Patients with comorbidity of alcohol dependence and affective disorders have a significantly higher risk of suicidal behavior, a greater frequency of hospitalizations, higher levels of anxiety compared with patients without affective disorders. Electrophysiological data have shown that patients with comorbidity of alcohol dependence and affective disorders have higher values of spectral power of alpha-rhythm in all parts of the cerebral cortex (except for temporal lobes) and beta-rhythm in the occipital cortex, as well as an increase in interhemispheric coherence in all frequency ranges.

Neuroinvasion and cognitive impairment in comorbid alcohol dependence and chronic viral infection: An initial investigation

Viruses that invade the central nervous system (CNS) can cause neuropsychiatric impairments. Similarly, chronic alcohol exposure can induce inflammatory responses that alter brain function. However, the effects of a chronic viral infection and comorbid alcohol use on neuroinflammation and behavior are not well-defined. We investigated the role of heavy alcohol intake in regulating inflammatory responses and behavioral signs of cognitive impairments in mice infected with lymphocytic choriomeningitis virus (LCMV) clone 13. LCMV-infected mice exposed to alcohol had increased peripheral inflammation and impaired cognitive function (as indicated by performance on the novel object recognition test). Initial findings suggest that brain region-specific dysregulation of microglial response to viral infection may contribute to cognitive impairments in the context of heavy alcohol use.

Alcohol Abstainer Status and Prazosin Treatment in Association with Changes in Posttraumatic Stress Disorder Symptoms in Veterans with Comorbid Alcohol Use Disorder and Posttraumatic Stress Disorder.

The noradrenergic system has been implicated in alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD), with adrenergic agents reducing drinking in individuals with AUD and improving sleep disturbances in individuals with PTSD. In a recent clinical trial, prazosin, an α1-adrenergic antagonist, was not superior to placebo in reducing PTSD symptoms, sleep problems, or alcohol consumption in a comorbid population; however, patients in both treatment conditions improved in all symptom domains over the course of treatment. It remains unknown whether alcohol abstinence is related to changes in PTSD symptoms and medication effects in individuals with this comorbidity. Veterans with comorbid alcohol dependence and PTSD (n=96) were randomized to prazosin (16mg) or placebo in a 12-week outpatient, double-blind clinical trial. In this secondary data analysis, we examined main effects of alcohol abstainer status (abstainer vs. nonabstainer), treatment, and their interaction on changes in PTSD symptoms over time using linear mixed models. There was a main effect of alcohol abstainer status on symptoms of PTSD (p=0.03), such that nonabstainers had lower total Clinician-Administered PTSD Scale (CAPS) scores than abstainers. There was a significant treatment by alcohol abstainer status interaction (p=0.01); specifically, among placebo-treated individuals, those who did not abstain from alcohol had lower total CAPS scores compared to alcohol abstainers. Within the prazosin-treated group, abstainers and nonabstainers did not differ on total CAPS scores. Results were similar for the avoidance (p=0.02), reexperiencing (p=0.01), and hyperarousal (p=0.04) subscales, such that placebo-treated nonabstainers had lower CAPS scores overall. Overall, prazosin treatment was not significantly related to changes in PTSD symptoms over the course of the 12-week clinical trial in a comorbid population. Interestingly, placebo-treated alcohol nonabstainers had a significant reduction in PTSD symptoms. Whether placebo-treated individuals continued to use alcohol because of ongoing symptoms of PTSD is not known.

Ethanol normalizes glutamate-induced elevation of intracellular sodium in olfactory neuroepithelial progenitors from subjects with bipolar illness but not nonbipolar controls: Biologic evidence for the self-medication hypothesis.

Alcohol use disorders are quite common in bipolar patients with a prevalence of comorbidity that exceeds all other primary psychiatric diagnoses other than other substance use disorders1; over 60% of people with bipolar disorder type I (BD I) have comorbid alcohol dependence at some point in their lives.1 This intimate relationship has served as the basis of the proposed idea of “self-medication.”2 However, biological confirmation of “self-medication,” specifically, the correction of an abnormal biologic marker with alcohol, has never been demonstrated. Recently, we have succeeded in utilizing olfactory neuroepithelium biopsy to produce permanent cell lines of olfactory neuroepithelial progenitors (ONPs) from patients with BD and matched nonbipolar controls.3 These cells possess the genetic heritage of BD I and can be used for investigation of differential biological responses to ethanol. Ionic regulatory abnormalities have repeatedly been documented in patients with BD I.4 Most notably, intracellular sodium and calcium are elevated during both mania and depression, this distribution of cations alters transmembrane potential of lymphocytes—a phenomenon which may be a useful diagnostic marker (reviewed in references 4). Both pharmacologic and genetic animal models which inhibit the sodium pump to elevate intracellular sodium and calcium concentrations create mania-like behaviors (reviewed in 4). Similarly, altered-glutamate metabolism is a consistent finding in BD (reviewed in 4). Importantly, brain glutamate and glutamine are elevated in most brain areas in patients with bipolar illness during mania, depression, and euthymia. By extension, treating ONP cells with glutamate to increase both intracellular sodium and calcium may be a cellular model of bipolar illness, mania, and/or bipolar depression.

M31 - GENOME-WIDE ASSOCIATION STUDY OF COMORBID ALCOHOL DEPENDENCE AND MAJOR DEPRESSION

Background Alcohol Dependence (AD) and Major Depression (MD) are leading causes of disability, and they often co-occur. Genetic epidemiologic data have shown that they share, at least to some extent, a common genetic etiology. The molecular nature of this shared genetic basis is poorly understood. To detect genetic risk variants for comorbid AD and MD and to determine whether polygenic risk alleles are shared with neuropsychiatric traits or subcortical brain volumes. Methods This Genome-Wide Association Study (GWAS) analyzed criterion counts of comorbid AD and MD in data sets of African Americans (AA) and European Americans (EA) that were collected as part of the Yale-Penn study of the genetics of drug and alcohol dependence from 2000–2013. After excluding subjects who were never exposed to alcohol or had missing information for any diagnostic criterion, we performed GWAS on two samples (“Yale-Penn-1” and “Yale-Penn-2”) totaling 4,653 AAs and 3,169 EAs. AAs and EAs were analyzed separately. We then tested whether Polygenic Risk Scores (PRS) derived from potentially related traits in EAs could be used to predict comorbid AD and MD. Comorbid criterion counts (ranging from 0–14) comprised for DSM-IV AD (7 criteria) and MD (9 criteria, scaled to 7). Results Of the 7,882 participants, 42.7% were female. The median comorbid criterion count was 6.2 (interquartile range [IQR], 2.3–10.9). Under the linear regression model, rs139438618 at the Semaphorin 3A (SEMA3A) locus was significantly associated with AD-MD comorbidity in AAs in the Yale-Penn-1 sample (beta coefficient [β]=0.89, P=2.76×10-8). In the Yale-Penn-2 sample, the association was also significant (β=0.83, P=2.06×10-4). Meta-analysis of the two samples yielded a more robust association (β=0.87 [95% CI, 0.61–1.12], P=2.41×10–11). There was no significant association identified in EAs. PRS analyses showed that individuals with a higher risk of neuroticism (β=1.01 [95% CI, 0.50–1.52]) or depressive symptoms (β=0.87 [95% CI, 0.32–1.42]) and a lower level of subjective well-being (β=-0.94 [95% CI, -1.46 to -0.42]) and educational attainment (β=-1.00 [95% CI, -1.57 to -0.44]) were at higher level of AD+MD; while larger intracranial (β=1.07 [95% CI, 0.50–1.64]) and smaller putamen volumes (β=-1.16 [95% CI, -1.86 to -0.46]) predicted higher risks of AD+MD. Discussion SEMA3A variation is significantly associated with comorbid AD and MD in AAs. Using PRS analyses, we identified pleiotropy with neuropsychiatric traits and brain volumes. Further studies are warranted to understand the biological and genetic mechanisms of this comorbidity, which could facilitate medications development and other treatments for comorbid AD and MD.