Comorbid Bipolar and Alcohol Use Disorder-A Therapeutic Challenge.
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ABSTRACT:
SUBMITTER: Grunze H
PROVIDER: S-EPMC8021702 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Comorbidity of psychiatric and substance use disorders represents a significant complication in the clinical course of both disorders. Bipolar Disorder (BD) is a psychiatric disorder characterized by severe mood swings, ranging from mania to depression, and up to a 70% rate of comorbid Tobacco Use Disorder (TUD). We found epidemiological evidence consistent with a common underlying etiology for BD and TUD, as well as evidence of both genetic and environmental influences on BD and TUD. Therefore, we hypothesized a common underlying genetic etiology, interacting with nicotine exposure, influencing susceptibility to both BD and TUD.Using meta-analysis, we compared TUD rates for BD patients and the general population. We identified candidate genes showing statistically significant, replicated, evidence of association with both BD and TUD. We assessed commonality among these candidate genes and hypothesized broader, multi-gene network influences on the comorbidity. Using Fisher Exact tests we tested our hypothesized genetic networks for association with the comorbidity, then compared the inferences drawn with those derived from the commonality assessment. Finally, we prioritized candidate SNPs for validation.We estimate risk for TUD among BD patients at 2.4 times that of the general population. We found three candidate genes associated with both BD and TUD (COMT, SLC6A3, and SLC6A4) and commonality analysis suggests that these genes interact in predisposing psychiatric and substance use disorders. We identified a 69 gene network that influences neurotransmitter signaling and shows significant over-representation of genes associated with BD and TUD, as well as genes differentially expressed with exposure to tobacco smoke. Twenty four of these genes are known drug targets.This work highlights novel bioinformatics resources and demonstrates the effectiveness of using an integrated bioinformatics approach to improve our understanding of complex disease etiology. We illustrate the development and testing of hypotheses for a comorbidity predisposed by both genetic and environmental influences. Consistent with our hypothesis, the selected network models multiple interacting genetic influences on comorbid BD with TUD, as well as the environmental influence of nicotine. This network nominates candidate genes for validation and drug testing, and we offer a panel of SNPs prioritized for follow-up.
| S-EPMC2823619 | biostudies-literature
Project description:To explore the relationship between binge eating disorder (BED) and obesity in patients with bipolar disorder (BP).717 patients participating in the Mayo Clinic Bipolar Biobank completed structured diagnostic interviews and questionnaires for demographic and illness-related variables. They also had weight and height measured to determine body mass index (BMI). The effects of BED and obesity (BMI?30 kg/m(2)), as well as their interaction, were assessed on one measure of general medical burden and six proxies of psychiatric illness burden.9.5% of patients received a clinical diagnosis of BED and 42.8% were obese. BED was associated with a significantly elevated BMI. Both BED and obesity were associated with greater psychiatric and general illness burden, but illness burden profiles differed. After controlling for obesity, BED was associated with suicidality, psychosis, mood instability, anxiety disorder comorbidity, and substance abuse comorbidity. After controlling for BED status, obesity was associated with greater general medical comorbidity, but lower substance abuse comorbidity. There were no significant interaction effects between obesity and BED, or BMI and BED, on any illness burden outcome.There may have been insufficient power to detect interactions between BED and obesity.Among patients with BP, BED and obesity are highly prevalent and correlated, but associated with different profiles of enhanced illness burden. As the association of BED with greater psychiatric illness burden remained significant even after accounting for the effect of obesity, BP with BED may represent a clinically important sub-phenotype.
| S-EPMC5551039 | biostudies-literature
Project description:Propensity for alcohol misuse may be linked to an individuals' response to alcohol. This study examined the role of alcohol response phenotypes to future drinking problems.One hundred four young heavy social drinkers participated in a within-subject, double-blind, placebo-controlled laboratory alcohol challenge study with 6-year follow-up. Participants were examined for subjective responses before and after receiving an intoxicating dose of alcohol (.8 g/kg) or a placebo beverage, given in random order. Follow-up was conducted in 5 waves over 6 years after the sessions to assess drinking behaviors and alcohol use disorder (AUD) symptoms. Retention was high with 98% (509 of 520) of possible follow-ups completed.Greater sensitivity to alcohol, in terms of stimulation and rewarding effects (like, want more) and lower sensitivity to alcohol sedation predicted greater number of AUD symptoms through 6 years of follow-up. Cluster analyses revealed that for half the sample, increasing levels of stimulation and liking were predictors of more AUD symptoms with the other half divided between those showing like and want more and want more alone as significant predictors.The findings extend previous findings and offer new empirical insights into the propensity for excessive drinking and alcohol problems. Heightened alcohol stimulation and reward sensitivity robustly predicted more alcohol use disorder symptoms over time associated with greater binge-drinking frequency. These drinking problems were maintained and progressed as these participants were entering their third decade of life, a developmental interval when continued alcohol misuse becomes more deviant.
| S-EPMC4280017 | biostudies-literature
Project description:Anxiety disorders (AD) and substance use disorders (SUD) commonly co-occur with bipolar disorder. This study was undertaken to assess AD-SUD-bipolar subtype interactions.Extensive clinical interview and MINI were used to ascertain DSM-IV diagnoses of rapid cycling bipolar I (RCBPDI) or II (RCBPDII) disorder, SUDs, and ADs including generalized anxiety disorder (GAD), panic disorder (PD), and obsessive-compulsive disorder (OCD). Data at the initial assessment of four studies was used to compare the prevalence differences in ADs between RCBPDI and RCBPDII by using protocol-defined SUD categories, "Never," "Lifetime, but not recent," or "Recent."Five-hundred sixty-six of 568 patients (RCBPDI n=320, RCBPDII n=246) were eligible for analyses. In the "Never" group (n=191), patients with RCBPDI and RCBPDII had similar risk for ADs. In the "Lifetime, but not recent" group (n=195), RCBPDI patients had significantly higher risks for GAD (OR=3.29), PD (OR=2.95), but not OCD, compared with their RCBPDII counterparts. Similarly, in the "Recent" group (n=180), RCBPDI patients also had significantly higher risks for GAD (OR=3.6), PD (OR=3.8), but not OCD, compared with their RCBPDII counterparts.Data were cross-sectional and not all ADs were included.In this large cohort of patients with rapid cycling bipolar disorder, risk for having GAD, PD, but not OCD increased significantly in patients with bipolar I disorder compared to their bipolar II counterparts when a history of SUD was present. However, there were no significant differences in the risk for GAD, PD, or OCD between the subtypes among patients without a history of SUD.
| S-EPMC2561239 | biostudies-literature
Project description:BACKGROUND:Alcohol use is risky for patients with hepatitis C virus (HCV) and/or human immunodeficiency virus (HIV) infection, but alcohol use disorder (AUD) treatment is underutilized in these populations. Comorbid drug use disorders (DUD) are common, but their influence on AUD treatment receipt is understudied. We evaluated the association between DUD and AUD treatment receipt in two national samples of patients with AUD, those with HIV and those with HCV, in the U.S. Veterans Health Administration. METHODS:Samples included patients with AUD and HCV and/or HIV among positive alcohol screens (AUDIT-C?5) documented 10/01/09-5/30/13 in the national electronic health record. Poisson regression models estimated incidence rate ratios for receiving specialty treatment (stop codes) and pharmacotherapy (filled prescription for naltrexone, disulfiram, acamprosate, or topiramate) within 365 days of positive alcohol screening for patients with DUD versus those without. Models were clustered on patient and adjusted for potential confounders. RESULTS:Among 22,039 patients with HCV/AUD, 45.2% (N?=?9,964) had DUD, which was associated with receiving specialty treatment [adjusted incidence rate ratio: 1.89 (95% confidence interval 1.82-1.96)] and pharmacotherapy [aIRR: 1.50 (1.37-1.65)]. Among 1,834 patients with HIV/AUD, 56.9% (N?=?1,043) had DUD, which was associated with receiving specialty treatment [aIRR: 1.94 (1.68-2.24)], but not pharmacotherapy. CONCLUSIONS:Rates of AUD treatment receipt among patients with AUD and HCV and/or HIV were low overall, but likelihood of treatment receipt was generally higher among those with comorbid DUD. Future research should investigate mechanisms underlying these associations, such as enhanced readiness for treatment or differential provider prescribing or referral practices.
| S-EPMC6312483 | biostudies-literature
Project description:Bipolar disorder (BD) and premenstrual dysphoric disorder (PMDD) are two cyclic mood illnesses, sometimes presenting together. Their comorbidity appears to be linked to common biological mechanisms and usually results in more severity of mood symptoms and a poorer long-term outcome. Nevertheless, the management of comorbid PMDD/BD has been scarcely studied. Therefore, the aim of the present paper was to review the published literature on the treatment of comorbid PMDD/BD and to provide point-by-point hypotheses to address these complex clinical cases. We searched PubMed to identify the studies focused on the treatment and management of comorbid PMDD/BD using the following search words, alone and in combination: premenstrual dysphoric disorder, bipolar disorder, comorbid, treatment, management, pharmacotherapy, psychotherapy. The search was conducted on the 1st of June 2019 and yielded 55 records. Four papers met our inclusion/exclusion criteria and were therefore included in our qualitative synthesis. Integrating the few data pertaining to the treatment of comorbid PMDD/BD with the large amount of published data on the two conditions separately, we can suggest that the management of comorbid PMDD/BD needs as a first step to stabilize the bipolar symptoms by means of optimal dosages of mood stabilizers. Then, in euthymic BD patients, the PMDD symptoms could be treated with estroprogestins (first-line treatment). On the contrary, during acute phases of BD, antidepressants (for major depressive episodes) and atypical antipsychotics/hormonal modulators (for manic episodes) could be considered as promising add-on treatments to mood stabilizers. In case of resistant PMDD/BD symptoms, combined strategies should be taken into account, as well as alternative treatments, such as lifestyle changes. In conclusion, RCTs on comorbid PMDD/BD are still lacking. The management of this complex condition is therefore challenging and it requires a tailored treatment.
| S-EPMC7020916 | biostudies-literature
Project description:Bipolar disorder (BD) is a severe psychiatric disorder characterized by recurrent episodes of manic/hypomanic or depressive symptoms and euthymic periods, with some patients suffering a gradual deterioration of illness and consequent cognitive deficits during the late stage. Migraine is a disease generally without abnormal medical examinations, neurological examinations or laboratory studies, and the diagnosis is made based on the retrospective demonstration of headache features and groupings of disease-associated symptoms. The epidemiology of comorbid BD and migraine is high and it is obligatory to find effective treatments to improve the prognosis. Recent investigations demonstrated that the close relationship between BD and migraine significantly increased the rapid cycling rates of both BD and migraine in patients. Although the detailed mechanism is complex and largely unclear in comorbid BD and migrain, genetic factors, neurotransmitters, altered signaling pathways, disturbances of inflammatory cytokines, and mitochondrial dysfunction are risk factors of BD and migraine. Particularly these two diseases share some overlapping mechanisms according to previous studies. To this end, we call for further investigations of the potential mechanisms, and more efforts are underway to improve the treatment of people with comorbid BD and migraine. In this review, we provide an overview of the potential mechanisms in patients with BD or migraine and we further discuss the treatment strategies for comorbid BD and migraine and it is obligatory to find effective treatments to improve the prognosis. This work will provide insights for us to know more about the mechanisms of comorbid BD and migraine, provides new therapeutic targets for the treatment and give clinicians some guidance for more appropriate and beneficial treatment.
| S-EPMC7829298 | biostudies-literature
Project description:BACKGROUND:Bipolar disorder (BD), especially BD-II, is frequently comorbid with alcohol dependence. Because BD-II and alcohol dependence are neurodegenerative disorders, agents with anti-inflammatory and neurotrophic effects might provide effective therapy. We investigated whether add-on memantine to regular valproic acid treatment ameliorated clinical symptoms, reduced alcohol use, and cytokine levels, and increased plasma brain-derived neurotrophic factor (BDNF) in BD-II patients with comorbid alcohol dependence. METHODS:In a single-arm 12-week clinical trial, BD-II patients with comorbid alcohol dependence (n = 45) undergoing regular valproic acid treatments were given add-on memantine (5 mg/d). Symptom severity, alcohol use, cytokine (plasma tumor necrosis factor-? and C-reactive protein [CRP], transforming growth factor-?1 [TGF-?1], interleukin-8 [IL-8], IL-10), and plasma BDNF levels were regularly assessed. RESULTS:Mean within-group decreases in Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) scores, alcohol use, CRP, BDNF, and IL-8 levels were significantly different from baseline after 12 weeks of treatment. We found no significant correlation between alcohol use levels and changes in HDRS or YMRS scores. The correlation between reduced alcohol use and reduced TGF-?1 level was significant (B = 0.003, p = 0.019). CONCLUSIONS:BD-II comorbid with alcohol dependence might benefit from add-on memantine treatment, which significantly reduced clinical severity, alcohol use, and plasma cytokine levels, and increased BDNF levels.
| S-EPMC6473794 | biostudies-literature
Project description:Bipolar disorder and alcohol use disorder (AUD) have a high rate of comorbidity, more than 50% of individuals with bipolar disorder also receive a diagnosis of AUD in their lifetimes. Although both disorders are heritable, it is unclear if the same genetic factors mediate risk for bipolar disorder and AUD. We examined 733 Costa Rican individuals from 61 bipolar pedigrees. Based on a best estimate process, 32% of the sample met criteria for bipolar disorder, 17% had a lifetime AUD diagnosis, 32% met criteria for lifetime nicotine dependence, and 21% had an anxiety disorder. AUD, nicotine dependence and anxiety disorders were relatively more common among individuals with bipolar disorder than in their non-bipolar relatives. All illnesses were shown to be heritable and bipolar disorder was genetically correlated with AUD, nicotine dependence and anxiety disorders. The genetic correlation between bipolar and AUD remained when controlling for anxiety, suggesting that unique genetic factors influence the risk for comorbid bipolar and AUD independent of anxiety. Our findings provide evidence for shared genetic effects on bipolar disorder and AUD risk. Demonstrating that common genetic factors influence these independent diagnostic constructs could help to refine our diagnostic nosology.
| S-EPMC4160878 | biostudies-literature
Project description:BACKGROUND AND AIMS:Alcohol use disorder (AUD) and problem gambling are highly comorbid disorders. This study aims to explore the role of four aspects of impulsivity (trait concept of impulsivity, choice impulsivity, impulsive aggression and response inhibition/decision-making) in long-term chronic AUD patients with and without problem or pathological gambling symptoms. METHODS:Cognitively intact chronic AUD patients were enrolled with (n = 32) and without (n = 71) problem gambling symptoms in an inpatient clinic for chronic alcohol users. Multiple facets of impulsivity, cognitive ability, psychopathological symptoms, alcohol and gambling severity were measured. RESULTS:Chronic AUD patients with gambling disorder symptoms showed longer lifetime alcohol consumption, more severe alcohol use and higher psychopathological symptom severity than AUD patients without gambling symptoms. Gambling severity correlated with overall trait impulsivity, but not with choice impulsivity, impulsive aggression or cognitive impulsivity with controlling for lifetime alcohol consumption, lifetime alcohol use and psychopathological symptom severity. High trait impulsivity and non-planning was associated with comorbid gambling symptoms in AUD patients, which was independent of the level of intelligence, age and psychopathological symptoms. CONCLUSION:Comorbid gambling disorder symptoms in chronic AUD was connected to more severe alcohol-related variables. Higher trait impulsivity was also linked with gambling disorder symptoms in patients with chronic AUD. This accents the need of special focus on comorbid GD symptoms in AUD, since prognosis and treatment for them may vary.
| S-EPMC6992191 | biostudies-literature