Racial differences in pathways to care preceding first episode mania or psychosis: a historical cohort prodromal study.

Background: There is evidence suggesting racial disparities in diagnosis and treatment in bipolar disorder (BD) and schizophrenia (SZ). The purpose of this study is to compare psychiatric diagnoses and psychotropic use preceding a first episode of mania (FEM) or psychosis (FEP) in racially diverse patients. Methods: Using a comprehensive medical records linkage system (Rochester Epidemiology Project, REP), we retrospectively identified individuals diagnosed with BD or SZ and a documented first episode of mania or psychosis. Illness trajectory before FEP/FEM were characterized as the time from first visit for a mental health complaint to incident case. Pathways to care and clinical events preceding FEP/FEM were compared based on subsequent incident case diagnosis (BD or SZ) and self-reported race (White vs. non-White). Results: A total of 205 (FEM = 74; FEP = 131) incident cases were identified in the REP. Duration of psychiatric antecedents was significantly shorter in non-White patients, compared to White patients (2.2 ± 4.3 vs. 7.4 ± 6.6 years; p < 0.001) with an older age at time of first visit for a mental health complaint (15.7 ± 6.3 vs. 11.1 ± 6.0 years; p = 0.005). There were no significant differences by race in FEM pathway to care or age of first seeking mental health. Overall non-White patients had lower rates of psychotropic use. Conclusion: These data are unable to ascertain reasons for shorter duration of psychiatric antecedents and later age of seeking care, and more broadly first age of initial symptom presentation. If symptoms are confirmed to be earlier than first time seeking care in both groups, it would be important to identify barriers that racial minorities face to access timely psychiatric care and optimize early intervention strategies.

Potential pharmacogenomic targets in bipolar disorder: considerations for current testing and the development of decision support tools to individualize treatment selection.

BACKGROUND: Treatment in bipolar disorder (BD) is commonly applied as a multimodal therapy based on decision algorithms that lack an integrative understanding of molecular mechanisms or a biomarker associated clinical outcome measure. Pharmacogenetics/genomics study the individual genetic variation associated with drug response. This selective review of pharmacogenomics and pharmacogenomic testing (PGT) in BD will focus on candidate genes and genome wide association studies of pharmacokinetic drug metabolism and pharmacodynamic drug response/adverse event, and the potential role of decision support tools that incorporate multiple genotype/phenotype drug recommendations. MAIN BODY: We searched PubMed from January 2013 to May 2019, to identify studies reporting on BD and pharmacogenetics, pharmacogenomics and PGT. Studies were selected considering their contribution to the field. We summarize our findings in: targeted candidate genes of pharmacokinetic and pharmacodynamic pathways, genome-wide association studies and, PGT platforms, related to BD treatment. This field has grown from studies of metabolizing enzymes (i.e., pharmacokinetics) and drug transporters (i.e., pharmacodynamics), to untargeted investigations across the entire genome with the potential to merge genomic data with additional biological information. CONCLUSIONS: The complexity of BD genetics and, the heterogeneity in BD drug-related phenotypes, are important considerations for the design and interpretation of BD PGT. The clinical applicability of PGT in psychiatry is in its infancy and is far from reaching the robust impact it has in other medical disciplines. Nonetheless, promising findings are discovered with increasing frequency with remarkable relevance in neuroscience, pharmacology and biology.

Clinical phenotype and genetic risk factors for bipolar disorder with binge eating: an update.

Introduction: Clinical and genetic study of psychiatric conditions has underscored the co-occurrence of complex phenotypes and the need to refine them. Bipolar Disorder (BD) and Binge Eating (BE) behavior are common psychiatric conditions that have high heritability and high co-occurrence, such that at least one quarter of BD patients have BE (BD + BE). Genetic studies of BD alone and of BE alone suggest complex polygenic risk models, with many genetic risk loci yet to be identified. Areas covered: We review studies of the epidemiology of BD+BE, its clinical features (cognitive traits, psychiatric comorbidity, and role of obesity), genomic studies (of BD, eating disorders (ED) defined by BE, and BD + BE), and therapeutic implications of BD + BE. Expert opinion: Subphenotyping of complex psychiatric disorders reduces heterogeneity and increases statistical power and effect size; thus, it enhances our capacity to find missing genetic (and other) risk factors. BD + BE has a severe clinical picture and genetic studies suggests a distinct genetic architecture. Differential therapeutic interventions may be needed for patients with BD + BE compared with BD patients without BE. Recognizing the BD + BE subphenotype is an example of moving towards more precise clinical and genetic entities.

Long-term risk of myocardial infarction and stroke in bipolar I disorder: A population-based Cohort Study.

OBJECTIVES: To estimate the risk of fatal and non-fatal myocardial infarction (MI) and stroke in patients with bipolar I disorder compared to people without bipolar I disorder. METHOD: Utilizing a records-linkage system spanning 30 years (1966-1996), a population-based cohort of 334 subjects with bipolar I disorder and 334 age and sex-matched referents from Olmsted County, Minnesota, U.S. was identified. Longitudinal follow-up continued until incident MI or stroke (confirmed by board-certified cardiologist/neurologist), death, or study end date (December 31, 2013). Cox proportional hazards models assessed the hazard ratio (HR) for MI or stroke, adjusting for potential confounders. RESULTS: There was an increased risk of fatal or non-fatal MI or stroke (as a composite outcome) in patients with bipolar I disorder [HR 1.54, 95% confidence interval (CI) 1.02, 2.33; p=0.04]. However, after adjusting for baseline cardiovascular risk factors (alcoholism, hypertension, diabetes, and smoking), the risk was no longer significantly increased (HR 1.19, 95% CI 0.76, 1.86; p=0.46). LIMITATIONS: Small sample size for the study design. Findings were not retained after adjustment for cardiovascular disease risk factors. Psychotropic medication use during the follow-up was not ascertained and was not included in the analyses. CONCLUSION: This study in a geographically defined region in the U.S. demonstrated a significant increased risk of MI or stroke in bipolar I disorder, which was no longer significant after adjustment for cardiovascular risk factors.

Female smokers have the highest alcohol craving in a residential alcoholism treatment cohort.

BACKGROUND: Cigarette smoking among female and male alcoholics has not been extensively studied as a factor related to intensity of alcohol craving during residential treatment and corresponding sobriety length. METHODS: This retrospective cohort study assessed self-reported sobriety outcomes in patients with alcohol dependence at 3-month intervals over 12 months after completion of a 30-day residential treatment program. Demographic and clinical variables were collected including smoking status, alcohol craving utilizing the Penn Alcohol Craving Scale (PACS), and alcohol relapse. Statistical analyses included Chi-square, ANOVA, Tukey's test, Kaplan-Meier plots and Cox proportional hazards models as appropriate. RESULTS: Of the 761 alcohol-dependent study subjects, 355 (47%) were current smokers. Alcohol craving intensity was higher in smoking females compared to nonsmoking females (p=0.0096), smoking males (p<0.0001), and nonsmoking males (p<0.0001). Smoking status-by-sex interaction was not associated with post-treatment relapse. After controlling for other variables, higher PACS scores at admission were associated with higher probability of relapse (p=0.0003). CONCLUSIONS: In this study, female alcoholic smokers experienced the highest level of alcohol craving in an alcohol treatment setting. Interestingly, this did not translate into higher rates of post-treatment relapse. Further research is warranted to explore the neurobiological basis for sex differences in this highly prevalent comorbidity.

Change in consumption patterns for treatment-seeking patients with alcohol use disorder post-bariatric surgery.

OBJECTIVE: The aim of this study is to describe the clinical phenotype of alcohol use disorder (AUD) treatment-seeking patients with Roux-en-Y Gastric Bypass Surgery (RYGB) history; and to compare it to AUD obese non-RYGB controls. METHODS: Retrospective study of electronic medical records for all patients 30-60years treated at the Mayo Clinic Addiction Treatment Program, between June, 2004 and July, 2012. Comparisons were performed with consumption patterns pre-RYGB and at time of treatment; excluding patients with AUD treatments pre-RYGB. RESULTS: Forty-one out of 823 patients had a RYGB history (4.9%); 122 controls were selected. Compared to controls, the RYGB group had significantly more females [n=29 (70.7%) vs. n=35 (28.7%) p<0.0001]; and met AUD criteria at a significantly earlier age (19.1±0.4 vs. 25.0±1years old, p=0.002). On average, RYGB patients reported resuming alcohol consumption 1.4±0.2years post-surgery, meeting criteria for AUD at 3.1±0.5years and seeking treatment at 5.4±0.3years postoperatively. Pre-surgical drinks per day were significantly fewer compared to post-surgical consumption [2.5±0.4 vs. 8.1±1.3, p=0.009]. Prior to admission, RYGB patients reported fewer drinking days per week vs. controls (4.7±0.3 vs. 5.5±1.8days, p=0.02). Neither RYGB, gender, age nor BMI was associated with differential drinking patterns. CONCLUSION: The results of this study suggest that some patients develop progressive AUD several years following RYGB. This observation has important clinical implications, calling for AUD-preventive measures following RYGB. Further large-scale longitudinal studies are needed to clarify the association between RYGB and AUD onset.

The poor prognosis of childhood-onset bipolar disorder.

OBJECTIVE: We examined age of onset of bipolar disorder as a potential course-of-illness modifier with the hypothesis that early onset will engender more severe illness. STUDY DESIGN: A total of 480 carefully diagnosed adult outpatients with bipolar disorder (mean age, 42.5 +/- 11.6 years) were retrospectively rated for age of illness onset, time to first pharmacotherapy, and course of illness. Clinicians prospectively rated daily mood fluctuations over 1 year. RESULTS: Of the 480 patients, 14% experienced onset in childhood (12 years or younger); 36% in adolescence (13 to 18 years); 32% in early adulthood (19 to 29 years); and 19% in late adulthood (after 30 years). Childhood-onset bipolar illness was associated with long delays to first treatment, averaging more than 16 years. The patients with childhood or adolescent onset reported more episodes, more comorbidities, and rapid cycling retrospectively; prospectively, they demonstrated more severe mania, depression, and fewer days well. CONCLUSIONS: This study demonstrates that childhood onset of bipolar disorder is common and is associated with long delays to first treatment. Physicians and clinicians should be alert to a possible bipolar diagnosis in children in hopes of shortening the time to initiating treatment and perhaps ameliorating the otherwise adverse course of illness.