The concept of "metabolic jet lag" in the pathophysiology of bipolar disorder: implications for research and clinical care.

Bipolar disorder (BD) is a potentially chronic mental disorder marked by recurrent depressive and manic episodes, circadian rhythm disruption, and changes in energetic metabolism. "Metabolic jet lag" refers to a state of shift in circadian patterns of energy homeostasis, affecting neuroendocrine, immune, and adipose tissue function, expressed through behavioral changes such as irregularities in sleep and appetite. Risk factors include genetic variation, mitochondrial dysfunction, lifestyle factors, poor gut microbiome health and abnormalities in hunger, satiety, and hedonistic function. Evidence suggests metabolic jet lag is a core component of BD pathophysiology, as individuals with BD frequently exhibit irregular eating rhythms and circadian desynchronization of their energetic metabolism, which is associated with unfavorable clinical outcomes. Although current diagnostic criteria lack any assessment of eating rhythms, technological advancements including mobile phone applications and ecological momentary assessment allow for the reliable tracking of biological rhythms. Overall, methodological refinement of metabolic jet lag assessment will increase knowledge in this field and stimulate the development of interventions targeting metabolic rhythms, such as time-restricted eating.

Effects of the ketogenic diet on cognition: a systematic review.

INTRODUCTION: Ketogenic diet (KD) therapy has been used as a dietary intervention in drug-resistant epilepsy for several years. Research currently suggests that KD therapy may carry neuroprotective and cognition enhancing effects for individuals with non-epileptic conditions as well as for healthy individuals. Therefore, KD may have potential as a non-invasive, nutritional treatment approach for difficult to manage conditions such as neurodegenerative illnesses or mood disorders. The aim of this review is to summarize the available evidence on ketogenic interventions and the resulting cognitive outcomes. MATERIALS AND METHODS: The paper was based on PRISMA 2020 guidelines. The search was conducted in June 2021 on the following databases: CENTRAL, PubMed, EMBASE, PsycInfo, Web of Science. The search yielded 2014 studies, of which 49 were included. RESULTS: There were 22 animal studies assessing murine models and 27 studies on humans. The primary indications in these studies were epileptic conditions, neurodegenerative disorders, cognitive impairment, and healthy populations. DISCUSSION: Administration of KD seems to confer cognitive-enhancing effects in areas such as working memory, reference memory and attention. Studies found that KD treatment in animals has the potential to alleviate age-related cognitive decline. Over 80% of the 27 human studies reported a favourable effect of intervention, and none reported a detrimental effect of KD. While these findings suggest that KD may improve the functioning of certain cognitive domains, definitive conclusions were limited by studies with small sample sizes, the absence of controls and randomization, and the lack of objective measures of cognition.

Characterizing eating behavioral phenotypes in mood disorders: a narrative review.

Mood disorders, including depressive and bipolar disorders, represent a multidimensional and prevalent group of psychiatric illnesses characterized by disturbances in emotion, cognition and metabolism. Maladaptive eating behaviors in mood disorders are diverse and warrant characterization in order to increase the precision of diagnostic criteria, identify subtypes and improve treatment strategies. The current narrative review synthesizes evidence for Eating Behavioral Phenotypes (EBP) in mood disorders as well as advancements in pathophysiological conceptual frameworks relevant to each phenotype. Phenotypes include maladaptive eating behaviors related to appetite, emotion, reward, impulsivity, diet style and circadian rhythm disruption. Potential treatment strategies for each phenotype are also discussed, including psychotherapeutic, pharmacological and nutritional interventions. Maladaptive eating behaviors related to mood disorders are relevant from both clinical and research perspectives, yet have been somewhat overlooked thus far. A better understanding of this aspect of mood disorders holds promise to improve clinical care in this patient group and contribute to the subtyping of these currently subjectively diagnosed and treated disorders.

The Influence of Stakeholder Interests on Safety Outcome Reporting in Psychedelic Research and Implications for Science Communication.

Psychedelics are a group of psychoactive substances which produce complex and subjective changes to consciousness and carry unique safety considerations. There is a growing body of work investigating the use of psychedelics for mental health treatment alongside increasing socio-cultural and political acceptance. This rapid evolution has prompted corporations to fund psychedelic clinical trials, leading to a potential rise in conflicts of interest in relevant studies and publications. However, the body of evidence for the safety and efficacy of psychedelic-assisted psychotherapy for psychiatric illnesses is early. There is concern regarding the introduction of bias in psychedelic clinical trials and the selective reporting of results amidst and beyond corporate involvement. At a crucial time in psychedelic drug reform, this paper explores the safety concerns associated with psychedelics, the potential influences of financial stakeholders on safety outcome reporting and the importance of balanced science communication in maintaining public health and safety.

Psilocybin-Assisted Psychotherapy as a Potential Treatment for Eating Disorders: a Narrative Review of Preliminary Evidence.

Eating disorders (ED) are a group of potentially severe mental disorders characterized by abnormal energy balance, cognitive dysfunction and emotional distress. Cognitive inflexibility is a major challenge to successful ED treatment and dysregulated serotonergic function has been implicated in this symptomatic dimension. Moreover, there are few effective treatment options and long-term remission of ED symptoms is difficult to achieve. There is emerging evidence for the use of psychedelic-assisted psychotherapy for a range of mental disorders. Psilocybin is a serotonergic psychedelic which has demonstrated therapeutic benefit to a variety of psychiatric illnesses characterized by rigid thought patterns and treatment resistance. The current paper presents a narrative review of the hypothesis that psilocybin may be an effective adjunctive treatment for individuals with EDs, based on biological plausibility, transdiagnostic evidence and preliminary results. Limitations of the psychedelic-assisted psychotherapy model and proposed future directions for the application to eating behavior are also discussed. Although the literature to date is not sufficient to propose the incorporation of psilocybin in the treatment of disordered eating behaviors, preliminary evidence supports the need for more rigorous clinical trials as an important avenue for future investigation.

A Comparison of Functional Connectivity in the Human Brainstem and Spinal Cord Associated with Noxious and Innocuous Thermal Stimulation Identified by Means of Functional MRI.

The somatosensory system is multidimensional and processes important information for survival, including the experience of pain. The brainstem and spinal cord serve pivotal roles in both transmitting and modulating pain signals from the periphery; although, they are studied less frequently with neuroimaging when compared to the brain. In addition, imaging studies of pain often lack a sensory control condition, failing to differentiate the neural processes associated with pain versus innocuous sensations. The purpose of this study was to investigate neural connectivity between key regions involved in descending modulation of pain in response to a hot, noxious stimulus as compared to a warm, innocuous stimulus. This was achieved with functional magnetic resonance imaging (fMRI) of the brainstem and spinal cord in 20 healthy men and women. Functional connectivity was observed to vary between specific regions across painful and innocuous conditions. However, the same variations were not observed in the period of anticipation prior to the onset of stimulation. Specific connections varied with individual pain scores only during the noxious stimulation condition, indicating a significant role of individual differences in the experience of pain which are distinct from that of innocuous sensation. The results also illustrate significant differences in descending modulation before and during stimulation in both conditions. These findings contribute to a deeper understanding of the mechanisms underlying pain processing at the level of the brainstem and spinal cord, and how pain is modulated.

The effect of lifestyle interventions on depressive symptom severity in individuals with type-2 diabetes: A meta-analysis of randomized controlled trials.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a severe metabolic condition which is commonly comorbid with depression. Lifestyle factors are involved in the pathophysiology of both conditions; however, the role of lifestyle interventions remains unclear. OBJECTIVE: The objective of this study is to systematically review the literature on randomized controlled trials evaluating the effect of lifestyle interventions on depressive scores in patients with T2DM. METHODS: A systematic search was conducted in computerized databases before October 2022. A random-effects model was used to investigate the effect of lifestyle interventions on depression scores and meta-regression was conducted to assess the influence of age and disease onset. RESULTS: Six trials met the eligibility criteria for inclusion. A statistically significant reduction in depression scores was found for groups receiving lifestyle interventions compared to controls (SMD = -0.49 [95%CI -0.89 to -0.08]; p = 0.0269]). Interventions increased in efficacy with the age of the participants but no significant correlation was found with years since disease onset. Participants in a control group receiving a less intense lifestyle intervention demonstrated improved depression scores when compared to those who received standard care or no intervention at all. Trial design and outcome measurement tools were heterogeneous between studies and limited data on antidepressant use was available which may introduce bias into the results. CONCLUSION: Lifestyle interventions were effective at improving depressive symptom severity in patients with T2DM.

Effects of nutritional interventions on the severity of depressive and anxiety symptoms of women in the menopausal transition and menopause: a systematic review, meta-analysis, and meta-regression.

IMPORTANCE: Depression and anxiety may significantly affect women during the menopausal transition. In addition to traditional treatment strategies such as hormone therapy, antidepressants, and psychotherapy, nutritional interventions have been increasingly studied, but there is no consensus about their role in this patient population. OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the effect of nutritional interventions on the severity of depressive (DS) and anxiety (AS) symptoms in women during the menopausal transition or menopausal years. EVIDENCE REVIEW: Electronic search using databases PubMed, Cochrane, and Embase to identify articles indexed until January 31, 2021, focusing on randomized placebo-controlled trials documenting the effect of diet, food supplements, and nutraceuticals on DS and AS. FINDINGS: Thirty-two studies were included (DS, n = 15; AS, n = 1; DS and AS combined, n = 16). We found two studies that demonstrated data combined with other interventions: one with lifestyle interventions (vitamin D plus lifestyle-based weight-loss program) and another with exercise (omega 3 plus exercise). The pooled effect size favored the intervention group over placebo for both DS and AS (DS: standardized mean difference, -0.35 [95% confidence interval, -0.68 to -0.03; P = 0.0351]; AS: standardized mean difference, -0.74 [95% CI, -1.37 to -0.11; P = 0.0229]). There was significant heterogeneity in the pooled results, which can be attributed to differences in assessment tools for depression and anxiety as well as the variety of nutritional interventions studied. The subgroup analysis showed a statistically significant effect of menopausal status (perimenopausal or menopausal) but not the type or duration of nutritional intervention. Older age was the only significant predictor of the effect size of nutritional interventions in the meta-regression. CONCLUSIONS AND RELEVANCE: Nutritional interventions are promising tools for the management of mood/anxiety symptoms in women during the menopausal transition and in postmenopausal years. Because of significant heterogeneity and risk of bias among studies, the actual effect of different approaches is still unclear.

Is there a place for dietetic interventions in adult ADHD?

Current treatments for Attention-Deficit/Hyperactivity Disorder (ADHD) in adults are limited by lack of response and side effects in about one third of the individuals. Changes towards a healthier lifestyle could have a positive impact beyond the relief of specific symptoms. However, it is not clear if nutritional interventions influence mental health and cognition. The objective of this study was to summarize the available literature addressing the impact of different diets in ADHD. The most promising dietetic approaches in ADHD are diets considered to be healthy (Mediterranean-type; DASH) and the Few-Foods Diet for children. Studies should take into account the presence of multiple confounders, biases associated with difficulties in blinding participants and researchers, and search for possible mechanisms of action, so we can have better evidence to guide clinical mental care of adults with ADHD.

A Possible Antidepressive Effect of Dietary Interventions: Emergent Findings and Research Challenges.

Purpose: Despite recent advancements in the treatment of depression, the prevalence of affected individuals continues to grow. The development of new strategies has been required and emerging evidence has linked a possible antidepressant effect with dietary interventions. In this review, we discuss recent findings about the possible antidepressant effect of dietary interventions with an emphasis on the results of randomized controlled trials. Recent findings: A high consumption of refined sugars and saturated fat and a low dietary content of fruits and vegetables has been associated with the development of depression. There is evidence supporting a small to moderate beneficial effect of a Mediterranean-type diet in depression. In addition, new dietary protocols are being studied for their use as possible interventions, such as the ketogenic diet, Nordic diet, and plant-based diet. Summary: Lifestyle interventions surrounding diet and nutrition are a relatively affordable way to enhance response to treatment and to be employed as an adjunct in mental health care. Most studies, however, are limited by the difficulty in controlling for the placebo effect. Mediterranean-style diets seem to be the most promising as an adjunctive treatment for mood disorders. Larger randomized controlled trials that could assess predictors of response to dietary interventions are needed to establish a clear positive effect of diet and guide clinical care and nutritional recommendations concerning mental health care.