Clinical characterization of patients with bipolar disorder and a history of asthma: An exploratory study.

INTRODUCTION: Bipolar disorder (BD) and asthma are leading causes of morbidity in the US and frequently co-occur. OBJECTIVES: We evaluated the clinical features and comorbidities of patients with BD and a history of asthma. METHODS: In a cross-sectional analysis from the Mayo Clinic Bipolar Biobank, we explored the clinical characteristics of the BD and an asthma phenotype and fitted a multivariable regression model to identify risk factors for asthma. RESULTS: A total of 721 individuals with BD were included. From these, 140 (19%) had a history of asthma. In a multivariable model only sex and evening chronotype were significant predictors of asthma with the odds ratios and 95% confidence intervals being 1.65 (1.00, 2.72; p=0.05) and 1.99 (1.25, 3.17; p < 0.01), respectively. Individuals with asthma had higher odds of having other medical comorbidities after adjusting for age, sex, and site including hypertension (OR = 2.29 (95% CI 1.42, 3.71); p < 0.01), fibromyalgia (2.29 (1.16, 4.51); p=0.02), obstructive sleep apnea (2.03 (1.18, 3.50); p=0.01), migraine (1.98 (1.31, 3.00); p < 0.01), osteoarthritis (2.08 (1.20, 3.61); p < 0.01), and COPD (2.80 (1.14, 6.84); p=0.02). Finally, individuals currently on lithium were less likely to have a history of asthma (0.48 (0.32, 0.71); p < 0.01). CONCLUSION: A history of asthma is common among patients with BD and is associated with being female and having an evening chronotype, as well as with increased odds of having other medical comorbidities. A lower likelihood of a history of asthma among those currently on lithium is an intriguing finding with potential clinical implications that warrants further study.

Revisiting the bipolar disorder with migraine phenotype: Clinical features and comorbidity.

INTRODUCTION: To evaluate the prevalence and clinical correlates of lifetime migraine among patients with bipolar disorder (BD). METHODS: In a cross-sectional study, we evaluated 721 adults with BD from the Mayo Clinic Bipolar Disorder Biobank and compared clinical correlates of those with and without a lifetime history of migraine. A structured clinical interview (DSM-IV) and a clinician-assessed questionnaire were utilized to establish a BD diagnosis, lifetime history of migraine, and clinical correlates. RESULTS: Two hundred and seven (29%) BD patients had a lifetime history of migraine. BD patients with migraine were younger and more likely to be female as compared to those without migraine (p values <0.01). In a multivariate logistic regression model, younger age (OR=0.98, p<0.01), female sex (OR=2.02, p<0.01), higher shape/weight concern (OR=1.04, p=0.02), greater anxiety disorder comorbidities (OR=1.24, p<0.01), and evening chronotype (OR=1.65, p=0.03) were associated with migraine. In separate regression models for each general medical comorbidity (controlled for age, sex, and site), migraines were significantly associated with fibromyalgia (OR=3.17, p<0.01), psoriasis (OR=2.65, p=0.03), and asthma (OR=2.0, p<0.01). Participants with migraine were receiving ADHD medication (OR=1.53, p=0.05) or compounds associated with weight loss (OR=1.53, p=0.02) at higher rates compared to those without migraine. LIMITATIONS: Study design precludes determination of causality. Migraine subtypes and features were not assessed. CONCLUSIONS: Migraine prevalence is high in BD and is associated with a more severe clinical burden that includes increased comorbidity with pain and inflammatory conditions. Further study of the BD-migraine phenotype may provide insight into common underlying neurobiological mechanisms.

Body mass index and blood pressure in bipolar patients: Target cardiometabolic markers for clinical practice.

OBJECTIVE: To evaluate the association between cardiometabolic markers and bipolar disorder (BD), examining the impact of sex and cardiometabolic medication use, from a large case-control biorepository of more than 1300 participants. PATIENTS AND METHODS: Recruited from July 2009 through September 2017, cardiometabolic markers were harvested from electronic health records (EHR) of participants (n=661) from the Mayo Clinic Individualized Medicine Biobank for Bipolar Disorder and Mayo Clinic Biobank age-sex-matched controls (n=706). Markers were compared between cases and controls using logistic regression, stratified by sex, adjusting for cardiometabolic medications and current smoking status. We studied the effect of psychotropics in case-only analyses. RESULTS: The mean age of the sample was 52.5 ± 11.6 years and 55% were female. BD patients had higher rates of smoking, but lower utilization of lipid-lowering medication compared with controls. After adjustment, BD was associated with obesity [Odds ratio (CI) 1.62 (1.22-2.15)], elevated systolic blood pressure (SBP) [2.18 (1.55-3.06)] and elevated triglycerides [1.58 (1.13-2.2)]. When stratified by sex, obesity [1.8 (1.23-2.66)] and systolic blood pressure [2.32 (1.46-3.7)] were associated with BD females compared to female controls; however, only systolic blood pressure [2.04 (1.23-3.42)] was associated with male bipolars compared to male controls. Psychotropics were marginally associated with mean BMI, abnormal triglycerides, and HbA1c. LIMITATIONS: EHR cross-sectional data CONCLUSION: To our knowledge, this is the largest case controlled study to date to explore the association between cardiometabolic markers and bipolar disorder adjusting for utilization of cardiometabolic medication. Identification of significant, non-laboratory based cardiometabolic markers that are associated with increased risk of major cardiovascular adverse events in patients with bipolar disorder, underscores, both the utility and importance of risk monitoring that can be easily done in community mental health centers.

Progress in Developing Pharmacologic Agents to Treat Bulimia Nervosa.

This paper reviews past and current progress in developing pharmacologic agents for the treatment of individuals with bulimia nervosa (BN). We searched the literature and clinical trial registries for compounds studied in BN, the related condition, binge eating disorder (BED), and preclinical models of binge-eating behavior. Drug classes evaluated included antidepressants, antiepileptic drugs, stimulants and other medications for attention-deficit/hyperactivity disorder, opioid antagonists, and weight loss agents, among others. The only available drugs with established efficacy in BN at this time include antidepressants (especially selective serotonin reuptake inhibitors [SSRIs]) and the antiepileptic topiramate, though the efficacy of these compounds is modest at best. The only medications we found currently receiving empirical study in people with BN were fluoxetine, other serotonergic antidepressants, intranasal naloxone, lisdexamfetamine dimesylate, phentermine-topiramate combination, the antiandrogenic oral contraceptive ethinyl estradiol plus drospirenone, and prazosin. Preclinical models suggest that nociceptin receptor antagonists, the selective serotonin 5-HT2C receptor agonist lorcaserin, monoamine stabilizers, and selective orexin-1 receptor antagonists might be helpful. We found no evidence of a drug developed specifically for the treatment of individuals with BN. Future areas for research in the pharmacotherapy of BN are suggested. Importantly, until drugs are developed specifically for eating disorders, drugs developed for other conditions that are centrally acting and associated with beneficial psychotropic effects and/or reduced appetite or weight loss might be considered for repurposing in BN.

Olanzapine-induced early cardiovascular effects are mediated by the biological clock and prevented by melatonin.

Second generation antipsychotics (SGA) are associated with adverse cardiometabolic side effects contributing to premature mortality in patients. While mechanisms mediating these cardiometabolic side effects remain poorly understood, three independent studies recently demonstrated that melatonin was protective against cardiometabolic risk in SGA-treated patients. As one of the main target areas of circulating melatonin in the brain is the suprachiasmatic nucleus (SCN), we hypothesized that the SCN is involved in SGA-induced early cardiovascular effects in Wistar rats. We evaluated the acute effects of olanzapine and melatonin in the biological clock, paraventricular nucleus and autonomic nervous system using immunohistochemistry, invasive cardiovascular measurements, and Western blot. Olanzapine induced c-Fos immunoreactivity in the SCN followed by the paraventricular nucleus and dorsal motor nucleus of the vagus indicating a potent induction of parasympathetic tone. The involvement of a SCN-parasympathetic neuronal pathway after olanzapine administration was further documented using cholera toxin-B retrograde tracing and vasoactive intestinal peptide immunohistochemistry. Olanzapine-induced decrease in blood pressure and heart rate confirmed this. Melatonin abolished olanzapine-induced SCN c-Fos immunoreactivity, including the parasympathetic pathway and cardiovascular effects while brain areas associated with olanzapine beneficial effects including the striatum, ventral tegmental area, and nucleus accumbens remained activated. In the SCN, olanzapine phosphorylated the GSK-3ß, a regulator of clock activity, which melatonin prevented. Bilateral lesions of the SCN prevented the effects of olanzapine on parasympathetic activity. Collectively, results demonstrate the SCN as a key region mediating the early effects of olanzapine on cardiovascular function and show melatonin has opposing and potentially protective effects warranting additional investigation.

The Circadian System: A Regulatory Feedback Network of Periphery and Brain.

Circadian rhythms are generated by the autonomous circadian clock, the suprachiasmatic nucleus (SCN), and clock genes that are present in all tissues. The SCN times these peripheral clocks, as well as behavioral and physiological processes. Recent studies show that frequent violations of conditions set by our biological clock, such as shift work, jet lag, sleep deprivation, or simply eating at the wrong time of the day, may have deleterious effects on health. This infringement, also known as circadian desynchronization, is associated with chronic diseases like diabetes, hypertension, cancer, and psychiatric disorders. In this review, we will evaluate evidence that these diseases stem from the need of the SCN for peripheral feedback to fine-tune its output and adjust physiological processes to the requirements of the moment. This feedback can vary from neuronal or hormonal signals from the liver to changes in blood pressure. Desynchronization renders the circadian network dysfunctional, resulting in a breakdown of many functions driven by the SCN, disrupting core clock rhythms in the periphery and disorganizing cellular processes that are normally driven by the synchrony between behavior and peripheral signals with neuronal and humoral output of the hypothalamus. Consequently, we propose that the loss of synchrony between the different elements of this circadian network as may occur during shiftwork and jet lag is the reason for the occurrence of health problems.

Estudio comparativo sobre depresión y los factores asociados en alumnos del primer año de la Facultad de Medicina y del Internado / A Comparative study on depression and associated factors between medical student of first and last academic years

The prevalence of depression in Medical Students (MS) is higher than in the general population and changes with time. It is not known whether the prevalence of depression is higher and the associated factors different between students that initiate the last and first academic years in Medical School. Objective To compare the prevalence of depression and the associated factors in MS that start their academic courses in the first and the last academic years. Methods This is a cross sectional, observational and analytical study. A total of 1871 MS participated: 1240 were in the initiation of the first academic year, and 631 in the initiation of the last academic year. Participants answered a written survey conformed by a questionnaire about risk factors for depression and assessed for current depression with the Patients Health Questionnaire-9 (PHQ-9). Results The prevalence of depression (PHQ-9>10) was significantly higher in last year MS compared to first year MS (5.7 vs. 3.5%). The percentage of MS with a personal history of depression was higher in last year compared to first year MS (12.1% vs. 7.1%), as was the mean for previous depressive episodes (3.2 vs. 1.6). The age of onset for depressive episodes was higher in the last year group. Conclussions The prevalence of depression in MS that initiated the academic year is higher in the last year than at the beginning of the first year of the career, and could be attributed, among other factors, to a cumulative phenomenon resulting from the allostatic load that this academic process currently generates. A personal history of depression and other situational factors are associated to the presence of depression in a differential manner according to the academic year and should be considered in future studies.

La prevalencia de depresión en estudiantes de la Facultad de Medicina (EM) es mayor que en la población general y cambia a lo largo del tiempo. No se conoce si la prevalencia de depresión es mayor y los factores asociados son diferentes en estudiantes que inician el último y el primer año académico de la carrera de Medicina. Objetivo Comparar la prevalencia de Depresión y los factores asociados en EM que inician el año académico en primer año y aquellos que realizan el año de internado. Método Este es un estudio observacional, transversal y analítico. Participaron un total de 1871 EM: 1240 que iniciaban el primer año de la carrera y 631 que iniciaban el año de internado. Los alumnos contestaron una encuesta en papel compuesta por el Cuestionario sobre Factores de riesgo para Depresión y el Cuestionario sobre la Salud del Paciente (PHQ-9, por sus siglas en inglés) para evaluar la presencia actual de depresión. Resultados La prevalencia de Depresión (PHQ-9>10) resultó significativamente mayor en los estudiantes de internado comparados con los de primer año (5.7 vs. 3.5%). El porcentaje de alumnos con antecedente personal de depresión fue mayor en los alumnos de internado con respecto a los de primer año (12.1% vs. 7.1%), como lo fue el promedio de episodios depresivos previos (3.2 vs. 1.6). La edad de inicio del primer episodio depresivo fue significativamente mayor para los del quinto año. Conclusiones La prevalencia de Depresión en EM que inician el año académico es mayor en la etapa final de la carrera y puede ser atribuible, entre otros factores, a un fenómeno acumulativo de carga alostática que actualmente genera este proceso educativo. Los antecedentes personales para depresión y los factores situacionales se asocian a la presencia de depresión de una forma diferente de acuerdo al año académico y deben de ser considerados en futuros estudios.