There is increasing interest in individualizing treatment selection for more than 25 regulatory approved treatments for major depressive disorder (MDD). Despite an inconclusive efficacy evidence ...base, antidepressants (ADs) are prescribed for the depressive phase of bipolar disorder (BD) with oftentimes, an inadequate treatment response and or clinical concern for mood destabilization. This study explored the relationship between antidepressant response in MDD and antidepressant-associated treatment emergent mania (TEM) in BD. We conducted a genome-wide association study (GWAS) and polygenic score analysis of TEM and tested its association in a subset of BD-type I patients treated with SSRIs or SNRIs. Our results did not identify any genome-wide significant variants although, we found that a higher polygenic score (PGS) for antidepressant response in MDD was associated with higher odds of TEM in BD. Future studies with larger transdiagnostic depressed cohorts treated with antidepressants are encouraged to identify a neurobiological mechanism associated with a spectrum of depression improvement from response to emergent mania.
Objectives
The prevalence of obesity has dramatically increased in many countries and it is particularly high in patients with bipolar disorder (BD). A region in the first intron of the fat mass‐ and ...obesity‐associated (FTO) gene, encompassing markers rs9939973, rs8050136, and rs9939609, has been consistently associated with obesity and body mass index (BMI) in different populations. We sought to determine whether FTO is associated with BMI and/or obesity in patients with BD.
Methods
The sample included 129 Mexican Mestizo patients with bipolar I or bipolar II disorder. After obtaining informed consent, participants were evaluated with the Structured Clinical Interview for DSM‐IV Axis I Disorders and weight, height, and body measurements were recorded. DNA was extracted from a 5‐mL blood sample and real‐time polymerase chain reaction was performed. The results were analyzed with Haploview v4.2 and SPSS v21.
Results
Differences in mean BMI were explained by rs8050136 and rs9939609 genotypes, especially by comparing non‐carriers and carriers of two copies of the risk allele (Tukey's p ≤ 0.019), with a mean difference in BMI as high as 7.81 kg/m2. Differences in BMI were also explained by the interaction of the genotype (rs8050136 and/or rs9939609), the use of second‐generation antipsychotics, and the use of mood stabilizers (p ≤ 0.41). Obesity was also associated with these two markers when patients with and without obesity were compared.
Conclusions
In patients with BD, differences in BMI may be affected by the presence of FTO risk alleles, especially in homozygous individuals for these variants. Besides evaluating the possible metabolic effects of certain antipsychotics or mood stabilizers, it is important to evaluate the role of other factors such as FTO risk alleles.
Psychostimulants are FDA-approved for treating attention deficit hyperactivity disorder (ADHD). They are often prescribed off-label for mood disorders (in the majority of cases for augmentation of ...major depressive disorder MDD or treatment-resistant cases) with particular concerns in patients with comorbid ADHD and bipolar disorder (BD). We aimed to systematically appraise the current knowledge on genetic associations of psychostimulant treatment responses for mood disorders and ADHD.
A comprehensive search was conducted from database inception until March 21st, 2023. We included randomized controlled studies and non-randomized studies of intervention in adults (>18 years) with a DSM-IV/DSM-5 diagnosis of MDD, BD, or ADHD. We specifically included studies that reported the use of psychostimulants (e.g., methylphenidate MPH) and explored genetic associations with dopamine receptors and transporters (DRD4, DRD2, SLC6A3) reuptake inhibitors, norepinephrine transporters (SLC6A2) and serotonin transporters (SLC6A4).
We identified and screened 1,479 abstracts and selected 17 articles for full-text review. Five studies met the inclusion criteria (N=498; mean age 37.13±12.26), including two randomized controlled trials (n= 121, mean age 41.16±14.86) which analyzed genetic polymorphisms in SLC6A3 and SLC6A4. Three non-randomized intervention studies were included: one study (n=171, mean age 35±11) analyzed several SLC6A3 variants, and two studies (n=206, mean age 36.5±11.01) analyzed DRD4, SLC6A3, and SLC6A4 variants. Evidence from the selected studies did not consistently show statistically significant differences in treatment response for either MDD or ADHD in association with genetic polymorphisms. No studies evaluating BD were found, and MPH was the only psychostimulant assessed in the selected articles. The most reported adverse events were moderate nausea, anxiety, and polyuria, with a higher percentage for headaches (38.1%), gastrointestinal complaints (21.2%), and decreased appetite (19.08%). None of the included studies reported serious adverse events which required discontinuation.
Further research is necessary to determine the implications of genetic polymorphisms on clinical response to stimulants with mood disorders and ADHD. Moreover, studies examining a broader range of stimulant medications as well as duration/dose of treatment, including individuals with BD, are crucial to understanding possible genetic influences on treatment response with the potential to inform personalized treatment strategies-optimization of interventions for individuals with mood disorders and ADHD.
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 ano 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 ano de la carrera y 631 que iniciaban el ano 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 ingles) para evaluar la presencia actual de depresión. Resultados. La prevalencia de Depresión (PHQ-9=10) resulto 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 alostatica 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.
Bipolar disorder (BD) with co-occurring attention deficit-hyperactivity disorder (ADHD) is associated with an unfavorable course of illness. We aimed to identify potential clinical and genetic ...correlates of BD with and without ADHD.
Among patients with BD (
= 2,198) enrolled in the Mayo Clinic Bipolar Biobank we identified those with ADHD diagnosed in childhood (BD+cADHD;
= 350), those with adult-onset attention deficit symptoms (BD+aAD;
= 254), and those without ADHD (
= 1,594). We compared the groups using linear or logistic regression adjusting for age, sex, and recruitment site. For genotyped patients (
= 1,443), logistic regression was used to compare ADHD and BD polygenic risk scores (PRSs) between the BD groups, as well as to non-BD controls (
= 777).
Compared to the non-ADHD BD group, BD+cADHD patients were younger, more often men and had a greater number of co-occurring anxiety and substance use disorders (all
< 0.001). Additionally, BD+cADHD patients had poorer responses to lithium and lamotrigine (
= 0.005 and
= 0.007, respectively). In PRS analyses, all BD patient subsets had greater genetic risk for BD and ADHD when compared to non-BD controls (
< 0.001 in all comparisons). BD+cADHD patients had a higher ADHD-PRS than non-ADHD BD patients (
= 0.012). However, BD+aAD patients showed no evidence of higher ADHD-PRS than non-ADHD BD patients (
= 0.38).
BD+cADHD was associated with a greater number of comorbidities and reduced response to mood stabilizing treatments. The higher ADHD PRS for the BD+cADHD group may reflect a greater influence of genetic factors on early presentation of ADHD symptoms.
Oral presentation of 10 patients with Cowden syndrome Flores, Isadora Luana, DDS, MSc; Romo, Saray Aranda, DDS, MSc, PhD; Tejeda Nava, Francisco Javier, DDS, MSc, PhD ...
Oral surgery, oral medicine, oral pathology and oral radiology,
04/2014, Volume:
117, Issue:
4
Journal Article
Peer reviewed
Cowden syndrome (CS) is an autosomal dominant genodermatosis that frequently affects several tissues with hamartomatous growth. The oral cavity is quite commonly involved with papillomatous lesions, ...which can be crucial to early diagnosis of this disease. In this series, 10 patients with a great diversity of manifestations associated with CS are presented, in whom oral papillomatosis was a constant and relevant finding to establish the diagnosis of CS. The role of the dentist in recognizing the oral lesions, the other diagnostic criteria, the risk for the development of malignancies, and the importance of lifetime follow-up are discussed.
Emerging research suggests that food intake timing, eating behavior and food preference are associated with aspects of the circadian system function but the role that the circadian system may play in ...binge eating (BE) behavior in humans remains unclear.
To systematically evaluate the evidence for circadian system involvement in BE behavior.
Systematic searches of PubMed, EMBASE, and Scopus were performed for reports published from inception until May 2020 (PROSPERO Registration CRD42020186325). Searches were conducted by combining Medical Subject Headings related to the circadian system, BE behavior, and/or interventions. Observational and interventional studies in humans with BE behavior published in peer-review journals in the English language were included. Studies were assessed using quality and risk of bias tools (AXIS, ROB 2.0, or ROBINS).
The search produced 660 articles, 51 of which were included in this review. Of these articles, 46 were observational studies and 5 were interventional trials. Evidence from these studies suggests that individuals with BE behavior tend to have more food intake, more binge cravings, and more BE episodes later in the day. Hormonal and day/night locomotor activity rhythm disturbances may be associated with BE behavior. Furthermore, late diurnal preference ("eveningness") was associated with BE behavior and chronobiological interventions that shift the circadian clock earlier (e.g., morning bright light therapy) were found to possibly decrease BE behavior. Substantive clinical overlap exists between BE and night eating behavior. However, there is a significant knowledge gap regarding their potential relationship with the circadian system. Limitations include the lack of studies that use best-established techniques to assess the chronobiology of BE behavior, heterogeneity of participants, diagnostic criteria, and study design, which preclude a meta-analytic approach.
Current evidence, although limited, suggests that the circadian system may play a role in the etiology of BE behavior. Further mechanistic studies are needed to fully characterize a potential role of the circadian system in BE behavior. A chronobiological approach to studying BE behavior may lead to identification of its neurobiological components and development of novel therapeutic interventions.
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020186325, identifier CRD42020186325.
Lithium has been a cornerstone treatment for bipolar disorder (BD). Despite descriptions in the literature regarding associations between long-term lithium therapy (LTLT) and development of a thyroid ...disorder (overt/subclinical hypo/hyperthyroidism, thyroid nodule, and goiter) in BD, factors such as time to onset of thyroid abnormalities and impact on clinical outcomes in the course of illness have not been fully characterized. In this study we aimed to compare clinical characteristics of adult BD patients with and without thyroid disorders who were on LTLT. We aimed to identify the incidence of thyroid disorders in patients with BD on LTLT and response to lithium between patients with and without thyroid disorders in BD. The Cox proportional model was used to find the median time to the development of a thyroid disorder. Our results showed that up to 32% of patients with BD on LTLT developed a thyroid disorder, of which 79% developed hypothyroidism, which was corrected with thyroid hormone replacement. We did not find significant differences in lithium response between patients with or without thyroid disorders in BD. Findings from this study suggest that patients with BD and comorbid thyroid disorders when adequately treated have a response to lithium similar to patients with BD and no thyroid disorders.
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.
Abstract
We report a 12-day-old male who was admitted with vomiting because of an unusual early complication of Marfan's syndrome (MS): a sliding hiatal hernia. Initial ultrasound showed no stomach ...at its normal position and the chest X-ray presented an intrathoracic gas bubble with the nasogastric tube inside. An upper gastrointestinal contrast study confirmed the complete herniation of the stomach into the thorax. Via an exploratory laparotomy it was carefully reintroduced into the abdomen, following a hiatal reconstruction. A Thal fundoplication and a gastrostomy were also performed to guarantee its fixation. Although characterized by cardiac/aortic abnormalities, MS should be considered in any infant with hiatal/paraesophageal hernia, which should be repaired early to avoid gastric ischemia/volvulus.
PDF
