Background
Many individuals with eating disorders remain symptomatic after a course of psychotherapy and pharmacotherapy; therefore, the development of innovative treatments is essential.
Method
To ...learn more about the current evidence for treating eating disorders with stimulants, we searched for original articles and reviews published up to April 29, 2021 in PubMed and MEDLINE using the following search terms: eating disorders, anorexia, bulimia, binge eating, stimulants, amphetamine, lisdexamfetamine, methylphenidate, and phentermine.
Results
We propose that stimulant medications represent a novel avenue for future research based on the following: (a) the relationship between eating disorders and attention deficit/hyperactivity disorder (ADHD); (b) a neurobiological rationale; and (c) the current (but limited) evidence for stimulants as treatments for some eating disorders. Despite the possible benefits of such medications, there are also risks to consider such as medication misuse, adverse cardiovascular events, and reduction of appetite and pathological weight loss. With those risks in mind, we propose several directions for future research including: (a) randomized controlled trials to study stimulant treatment in those with bulimia nervosa (with guidance on strategies to mitigate risk); (b) examining stimulant treatment in conjunction with psychotherapy; (c) investigating the impact of stimulants on “loss of control” eating in youth with ADHD; and (d) exploring relevant neurobiological mechanisms. We also propose specific directions for exploring mediators and moderators in future clinical trials.
Discussion
Although this line of investigation may be viewed as controversial by some in the field, we believe that the topic warrants careful consideration for future research.
Polygenic prediction of bipolar disorder in a Latin American sample Cuellar-Barboza, Alfredo B; Prieto, Miguel L; Coombes, Brandon J ...
American journal of medical genetics. Part B, Neuropsychiatric genetics,
2023 Oct-Dec, 2023-10-00, 20231001, Volume:
192, Issue:
7-8
Journal Article
Peer reviewed
To date, bipolar disorder (BD) genetic studies and polygenic risk scores (PRSs) for BD are based primarily on populations of European descent (EUR) and lack representation from other ancestries ...including Latin American (LAT). Here, we describe a new LAT cohort from the Mayo Clinic Bipolar Biobank (MCBB), a multisite collaboration with recruitment sites in the United States (EUR; 1,443 cases and 777 controls) and Mexico and Chile (LAT; 211 cases and 161 controls) and use the sample to explore the performance of a BD-PRS in a LAT population. Using results from the largest genome-wide association study of BD in EUR individuals, PRSice2 and LDpred2 were used to compute BD-PRSs in the LAT and EUR samples from the MCBB. PRSs explained up to 1.4% (PRSice) and 4% (LDpred2) of the phenotypic variance on the liability scale in the LAT sample compared to 3.8% (PRSice2) and 3.4% (LDpred2) in the EUR samples. Future larger studies should further explore the differential performance of different PRS approaches across ancestries. International multisite studies, such as this one, have the potential to address diversity-related limitations of prior genomic studies and ultimately contribute to the reduction of health disparities.
Objective
The aim of this study was to evaluate the efficacy and safety of the dopaminergic‐enhancing agent modafinil/armodafinil (MoArm) as adjunctive treatment for bipolar depression.
Methods
A ...comprehensive search of major electronic databases was conducted to identify randomized controlled trials (RCTs) of adjunctive MoArm that included patients with bipolar I (BP‐I) or bipolar II (BP‐II) depression. Data for response/remission and all‐cause discontinuation were analyzed. Effect size was summarized by relative risk (RR) using a random effect model.
Results
Of 58 studies, five RCTs (N = 795 drug, N = 792 placebo) met inclusion criteria. Four armodafinil studies included only BP‐I patients and one modafinil study included both bipolar subtypes with limited heterogeneity (I2 = 34%, P = .19; I2 = 18%, P = .30). Compared to placebo, augmentation with MoArm was associated with significantly greater rates of treatment response (RR, 1.18; 95% CI, 1.01‐1.37; P = .03) and remission (RR, 1.38; 95% CI, 1.10‐1.73; P = .005). All‐cause discontinuation was not different than placebo (RR, 1.08; 95% CI, 0.89‐1.30; P = .45) with no evidence of increased risk of mood switch or suicide attempts with MoArm (RR, 0.99; 95% CI, 0.39‐2.5; P = .98; RR, 1.02; 95% CI, 0.37‐2.85; P = .97).
Conclusion
This narrower scope meta‐analysis of one drug for one disease suggests that adjunctive MoArm may represent a novel therapeutic intervention. Further studies delineating the subtypes of bipolar depression responsive to these novel dopaminergic‐enhancing agents are encouraged.
Objective
Second‐generation antipsychotics (SGAs) are among the first‐line treatments for bipolar disorder and schizophrenia, but have a tendency to generate metabolic disturbances. These features ...resemble a metabolic syndrome for which a central autonomic imbalance has been proposed that may originate from the hypothalamic suprachiasmatic nuclei. In a clinical trial, we hypothesized that melatonin, a hormone that regulates the suprachiasmatic nucleus, could attenuate SGA‐induced adverse metabolic effects.
Methods
In an eight‐week, double‐blind, randomized, placebo‐controlled, parallel‐group clinical trial, we evaluated the metabolic effect of melatonin in SGA‐treated patients in terms of weight, blood pressure, lipid, glucose, body composition, and anthropometric measures. A total of 44 patients treated with SGAs, 20 with bipolar disorder and 24 with schizophrenia, randomly received placebo (n = 24) or melatonin 5 mg (n = 20).
Results
The melatonin group showed a decrease in diastolic blood pressure (5.1 versus 1.1 mmHg for placebo, p = 0.003) and attenuated weight gain (1.5 versus 2.2 kg for placebo, F = 4.512, p = 0.040) compared to the placebo group. The strong beneficial metabolic effects of melatonin in comparison to placebo on fat mass (0.2 versus 2.7 kg, respectively, p = 0.032) and diastolic blood pressure (5.7 versus 5.5 mmHg, respectively, p = 0.001) were observed in the bipolar disorder and not in the schizophrenia group. No adverse events were reported.
Conclusions
Our results show that melatonin is effective in attenuating SGAs' adverse metabolic effects, particularly in bipolar disorder. The clinical findings allow us to propose that SGAs may disturb a centrally mediated metabolic balance that causes adverse metabolic effects and that nightly administration of melatonin helps to restore. Melatonin could become a safe and cost‐effective therapeutic option to attenuate or prevent SGA metabolic effects.
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‐3β, 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.
OBJECTIVES/GOALS: Cognitive dysfunction and/or depressionfollowing ischemic stroke results in loss of independence in daily functioning. The objective of this work is to assess neural correlates of ...post-stroke cognitive deficits and the effect of left frontal transcranial electrical stimulation on cognitive control and associated brain rhythms. METHODS/STUDY POPULATION: We recorded midfrontal scalp EEG from 15 healthy and 13 participants with stroke while they performed a multi-source interference task (MSIT). The stroke cohort also performed additional MSIT sessions where they received active and sham transcranial direct current stimulation (tDCS) on the left prefrontal cortex (PFC). The EEG was pre-processed to get rid of eye movement and other channel noise artifacts and filtered to retain 0.5-55 Hz components. A Morlet wavelet was used to estimate power in theta (4-8 Hz), alpha (8-15 Hz) and gamma (35-50 Hz) frequency bands over a period of 2 seconds following MSIT image presentation. A generalized linear mixed effects model was used to find effect of group on behavior and EEG oscillations. A GLME was also used to find effects of active tDCS on behavior and EEG. RESULTS/ANTICIPATED RESULTS: We found Group (healthy v stroke) as a significant predictor of both response time (behavior) and conflict evoked theta power in the frontal channels (F1-Fz, F2-Fz). We also found that active tDCS significantly improved MSIT performance as compared to sham, after accounting for cognitive load. Active tDCS also induced low frequency oscillations in frontal EEG channels compared to sham. Preliminary results indicate that mid-frontal theta oscillations are a potential neural correlate of post-stroke cognitive deficit and tDCS of the left PFC might be a promising therapeutic intervention to ameliorate this. DISCUSSION/SIGNIFICANCE: Current therapeutic approaches often do not alleviate post stroke executive dysfunction, hence a better understanding of the brain network changes underlying such deficit can elucidate neural correlates of post stroke cognitive deficit to inform the development of neuromodulation interventions.
Depression is a multifactorial illness that is highly prevalent among medical students (MS). Chronotypes, which reflect circadian preference in humans, as well as academic stress have been associated ...with depression in different populations. However, it is not known how chronotype and stress might alone or in combination, associate with depression in MS. Thus, we aimed to evaluate the association between stress, chronotype and depression in MS. In a cross-sectional study, we evaluated a total of 1068 medical students from a public Medical School in Mexico City. The Patient Health Questionnaire-9 (PHQ-9) was used to evaluate depressive symptom severity and the presence of a current depressive episode with a cutoff score of 10 or higher. The Morning-Evening Questionnaire (MEQ) was used to establish chronotype and the Academic Stress Inventory was used to measure perceived academic stress (PAS). We observed that depressive symptom severity was higher in non-morning chronotypes and moderate/severe PAS groups. A factorial ANOVA showed an association between PAS groups and depressive symptom severity. Linear regression showed an association between depressive symptom severity and variables such as PAS scores (p = 0.001), family history of depression (p = 0.001), gender (p = 0.001) and academic year (p = 0.029). Logistic regression analysis showed that evening chronotype (OR: 2.3, 95% CI: 1.2-4.3, p = 0.01) and severe PAS (OR: 4.4, 95% CI: 2.8-7.0, p = 0.0001) were associated with depression. Further, MS with the combination of severe PAS and morning (OR: 5.9, 95% CI: 1.6-22.2, p = 0.01), intermediate (OR: 7.5, 95% CI: 2.3-24.4, p = 0.001) or evening (OR: 10.6, 95% CI: 2.8-40.0, p = 0.001) chronotypes showed a greater association with depression than any PAS or chronotype group alone. Being female, perceiving restricted or limited economic resources, having severe scores of academic stress, and evening chronotype were associated with an increased probability to suffer a current depressive episode. Collectively, these results show that chronotype and PAS are factors associated with depression in MS, and when combined promote this association. Our results might aid in early identification of MS susceptible to depression. Future research could focus on the implementation of simple, low cost preventive strategies, such as chronotype-oriented academic schedules.
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