Metabolic disorders, metabolic syndrome and non-alcoholic fatty liver disease, and depression are those of the most common and debilitating disorders worldwide that often coexist further increasing mortality risks. Although the exact mechanisms underlying this association are poorly known, several hypotheses have been proposed: antipsychotic medication and antidepressants use, diet and physical activity or any other lifestyle factors. However, the high co-occurrence rate of depression and metabolic disorders suggests a possible pathophysiological overlap. In this paper I review several raised mechanisms for this overlap which are the hypothalamic-pituitary-adrenal axis dysregulation, immune alterations with chronic inflammation, as well as oxidative stress. In my view, there is one common thread running through all the aforementioned areas of pathophysiology which is microbiota alteration. So far, several possible interventions in our microbiota have been introduced into clinical practice - dietary and other lifestyle changes, supplementation with prebiotics or probiotics, fecal microbiota transplantation – but with vague indications. A better characterization of the above associations may represent a critical step at phenotyping, and a more targeted approach to the treatment of both depressive and metabolic disorders. At the end of the paper, I give several practical applications for future studies.

There is increasing evidence and recognition that Lyme borreliosis, and other associated tick-borne diseases (LB/TBD) cause mental symptoms. Data was drawn from databases, search engines and clinical experience to review current information on LB/TBD. LB/TBD infections cause immune and metabolic effects that result in a gradually developing spectrum of neuropsychiatric symptoms, usually presenting with significant comorbidity and may include developmental disorders, autism spectrum disorders, schizoaffective disorders, bipolar disorder, depression, anxiety disorders (panic disorder, social anxiety disorder, generalized anxiety disorder, posttraumatic stress disorder, intrusive symptoms), eating disorders, decreased libido, sleep disorders, addiction, opioid addiction, cognitive impairments, dementia, seizure disorders, suicide, violence, anhedonia, depersonalization, dissociative episodes, derealization and other impairments. Screening assessment followed by a comprehensive psychiatric clinical exam relevant to patient’s complaints and findings with a thorough history, mental status exam, review of systems, neurological exam, physical exam, a knowledgeable interpretation of laboratory findings, pattern recognition and clinical judgment facilitate diagnosis. Psychotropics and antibiotics may help improve functioning and prevent further disease progression. Awareness of the association between LB/TBD and neuropsychiatric impairments and studies of their prevalence in neuropsychiatric conditions can improve understanding of the causes of mental illness and violence and result in more effective prevention, diagnosis and treatment.

(1) Background: Adolescent girls have increasingly faced mental health challenges. We examined prevalence trends and associated risk factors for depression among adolescent girls. (2) Methods: Data for girls aged 12 to 17 years (N=4346) from the 2021 cross-sectional National Survey on Drug Use and Health were analyzed. Factors associated with depression were examined using multiple regression analysis. (3) Results: Rates of severe depression were significantly higher (p<.001) in older girls (adjusted odds ratio [AOR]: 1.63, 1.61, those who did not have authoritative parents (AOR: 3.40), and those with negative school experiences (AOR: 4.03). Black and Asian/Native Hawaiian or other Pacific Islanders were less likely to report severe depression than white girls. As previously reported, non-White girls were significantly less likely to receive treatment for depression (p<.05). Parents’ characteristics and school experiences had no effect on the likelihood of receiving mental health treatment. (4) Conclusion: Depression has become increasingly common among American adolescent girls, who are now three times as likely as adolescent boys to have had recent experiences with depression. Our results show that family structure, parenting style, and negative school experiences significantly contribute to the rate of depression and that treatment disparities exist with regard to race and ethnicity. The results of our research could be valuable for policymakers, healthcare professionals, and educators in developing specific preventative initiatives and support networks that effectively address these unique challenges.

Background: Depression presents with altered energy regulation and neural plasticity. Previous electroencephalography (EEG) studies showed that practice increases power in beta range (13-30 Hz) in healthy subjects but not in those with impaired plasticity. Here, we ascertain whether depression presents with alterations of spectral activity and connectivity before and after practice. Methods: We used publicly available resting state EEG (64 electrodes) of 122 subjects. Based on Beck Depression Inventory (BDI) score, they were assigned to either high BDI (hBDI, BDI>13, N=46) or control (CTL, BDI<7, N=75) group. We analyzed spectral activity, theta-beta and theta-gamma phase-amplitude coupling (PAC) of EEG recorded before and after a learning task. Results: At baseline, compared to CTL, hBDI group exhibited greater beta power over fronto-parietal regions and gamma over right parieto-occipital area. After practice, increases in all frequency ranges were observed only in CTL. Theta-beta and theta-gamma PAC were greater in hBDI before the task but not after the task. Conclusions: The lack of substantial post-task growth of beta power in depressed subjects likely represents power saturation due to greater baseline values. We speculate that inhibitory/excitatory imbalance, altered plasticity mechanisms, and energy dysregulation present in depression may contribute to this phenomenon.

Abstract: Background: chronotype is generally defined as the variability of the phase angle of en-trainment, while the latter reflects the relationship between the timing of a certain rhythm (e.g., sleep-wake cycle) and the timing of an external temporal cue. Individuals can be placed on a spectrum from "morning types" (M types), to "evening types" (E types). E-chronotype has been proposed as a transdiagnostic risk factor for psychiatric conditions and associated with psycho-pathological dimensions. Eveningness seems correlated with both suicidal ideation (SI) and suicidal behavioral (SB), through several possible mediating factors. Immunological alterations also have been linked to later chronotypes and SI/SB. Objective: This narrative review aims to summarize the evidence supporting the possible association between chronotypes and suicide, with the eventual mediating role of neuroinflammation and several psychopathological dimensions. Material and methods: A search of literature (2003-2023) was conducted, using various databases: PUBMED, EMBASE, Scopus, UpToDate, PsycINFO, Cochrane Library. English-language articles were col-lected and screened for eligibility. Results: Despite the apparent absence of a direct correlation between E-chronotype and suicidality, E-chronotype promotes a chain of effects that could be in-volved in an increased risk of SB, in which with neuroinflammation possibly play an intriguing role and some psychopathological dimensions may stand out.

Background: Depression, a multifaceted mental health condition, necessitates a multidimensional approach to treatment. This study aimed to elucidate the potential efficacy of various mitochondrial interventions, ranging from pharmacological treatments to lifestyle modifications, in alleviating depressive symptoms and enhancing overall mental well-being and assess the diverse range of mitochondrial assessments for managing depression by synthesizing findings from selected studies. Methods: A systematic compilation of studies, employing observational, interventional, and animal-based designs, was undertaken to elucidate the intricate relationship between mitochondrial function and depression as well as depressive signs and symptoms. The PRISMA guidelines were employed for conducting this review and a specific set of selection criterion were formulated by a team of reviewers for selection of relevant papers. Results: The synthesized results from the 21 selected papers highlighted the potential of these interventions to target diverse aspects of depression. Hyperbaric oxygen therapy and psychotherapy demonstrated significant reductions in depression and anxiety scores, with hyperbaric oxygen therapy particularly effective in improving nerve function and daily living activities. Whole-body cryotherapy displayed substantial improvements in depressive symptoms and quality of life. Frequent sauna bathing exhibited a lower risk of depressive symptoms in males. Dietary patterns, including Paleolithic and Mediterranean diets, showcased potential protective effects against depression, anxiety, and stress. The ketogenic diet revealed promise in ameliorating depression and psychosis symptoms alongside positive metabolic changes. Fasting interventions, though challenging, were associated with lower anxiety and depression levels without increased fatigue. Bright white light therapy enhanced remission rates and reduced depression scores in bipolar depression. Probiotic supplementation exhibited potential in reducing depression scores and improving metabolic markers, although further investigation is warranted. Conclusion: The diverse array of interventions explored in this study underlines the multifaceted nature of depression treatment. While these findings offer hope for more personalized and effective approaches, it is imperative to consider the variability in study designs, sample sizes, and methodologies among the selected papers. The mechanisms underlying the observed effects remain partially understood, emphasizing the need for continued mechanistic research. This study sets the stage for future investigations and clinical practices, showcasing the potential of various interventions in mitigating the challenges posed by depression and paving the way for more effective treatment strategies.

Geriatric decisional capacity assessment is a complex medico-legal activity that evaluates normal subjects involved in specific civil matter like wealth transfer, access to treatment or voluntary hospitalization. Our objective was to evaluate how geriatric extrajudicial capacity exams impacted a general psychiatric unit over a decade. We also assessed the value of a surrogate biomarker (neutrophils to lymphocyte ratio) as a screening factor in the capacity assessment process. 72 cases were assessed in one psychiatric unit over a decade (2009-2018). As population was fast ageing, the total number of capacity exams per year doubled in time. None of the subjects had an active diagnostic of severe cognitive impairment or active psychiatric disease. The percentage of subjects receiving an “absence of capacity” conclusion remained constant over time (approx. 20% of all cases). 81% of the subjects within this subgroup had a clinical diagnostic of mild cognitive impairment compared to 46% in the “presence of capacity” subgroup (p<0.001). The surrogate biomarker neutrophils to lymphocyte ratio was significantly higher in the “absence of capacity” subgroup, mainly related to a cognitive impairment diagnostic. The ratio has to be validated by larger studies before to be included in the capacity assessment process as an early screening tool.

We constructed a novel design integrating the administration of a clinical self-assessment scale with simultaneous acquisition of functional Magnetic Resonance Imaging (fMRI), aiming at cross-validation between psychopathology evaluation and neuroimaging techniques. We hypothesized that areas demonstrating differential activation in two groups of patients (paranoid and depressive) will have distinct connectivity patterns and structural differences.

This systematic review explores the cross-cultural validation of neuropsychological assessments and their clinical applications in cognitive behavioral therapy (CBT), focusing on culturally adapted CBT (CA-CBT) across diverse populations and settings. Methods: Following the PRISMA guidelines, a comprehensive search was conducted in multiple academic databases, including PubMed, PsycINFO, Scopus, and Web of Science. Keywords related to cognitive-behavioral therapy, cultural adaptation, and specific populations were used. Inclusion criteria encompassed randomized controlled trials (RCTs) and pilot studies that assessed CA-CBT for various mental health conditions. Results: The review included studies involving Chinese Americans, Latino caregivers, Syrian refugees, Jordanian children, Malaysian Muslims, Afghan refugees, Iraqi women, Japanese children and adolescents, and Tanzanian and Kenyan children. CA-CBT demonstrated significant effectiveness in reducing symptoms of depression, anxiety, PTSD, and psychosis. For instance, Research has shown that CA-CBT is more effective than standard CBT in reducing depressive symptoms among Chinese Americans and significantly lowering PTSD symptoms in Syrian refugee women. The method has been well-received and feasible in diverse populations, such as Jordanian children and Afghan refugees. Long-term benefits are promising, with sustained improvements reported in various studies. Additionally, digital and remote delivery methods have demonstrated potential for expanding the accessibility of CA-CBT. Conclusions: CA-CBT is a valuable and effective intervention for diverse cultural populations, significantly improving mental health outcomes. However, future research must address limitations such as small sample sizes, short follow-up periods, and variability in assessment tools. Studies should include larger and more diverse sample sizes, longer follow-up periods, rigorous control groups, and comprehensive outcome measures to further validate and enhance the application of CA-CBT across different cultural contexts.

Muscarinic acetylcholine receptors are well-known for their crucial involvement in hippocampus-dependent learning and memory, but the exact roles of the various receptor subtypes (M1-M5) are still not fully understood. Here, we studied how M1 and M3 receptors affect plasticity at the mossy fiber (MF)-CA3 pyramidal cell synapse. In hippocampal slices from M1/M3 receptor double knockout (M1/M3-dKO) mice, the signature short-term plasticity of the MF-CA3 synapse was not significantly affected. However, the rather unique, NMDA receptor-independent and presynaptic form of long-term potentiation (LTP) of this synapse was much larger in M1/M3-deficient slices compared to wild type slices, in both field potential and whole-cell recordings. Consistent with its presynaptic origin, induction of MF-LTP strongly enhanced the excitatory drive onto single CA3 pyramidal cells, with the effect being more pronounced in M1/M3-dKO cells. In an earlier study [1], we found that deletion of M2 receptors in mice disinhibits MF-LTP in a similar fashion, suggesting that endogenous acetylcholine employs both M1/M3 and M2 receptors to constrain MF-LTP. Importantly, such synergism was not observed for MF long-term depression (LTD). Low-frequency stimulation, which reliably induced LTD of MF synapses in control slices, failed to do so in M1/M3-dKO slices and gave rise to LTP instead. In striking contrast, loss of M2 augmented LTD when compared to control slices. Taken together, our data demonstrate convergence of M1/M3 and M2 receptors on MF-LTP, but functional divergence on MF-LTD, the net effect being well-balanced bidirectional plasticity of the MF-CA3 pyramidal cell synapse.

Recent research has identified the gut-brain axis as a key mechanistic pathway and potential therapeutic target in depression. In this paper, the potential role of gut hormones as potential treatments or predictors of response in depression is examined, with specific reference to the peptide hormone motilin. This possibility is explored through two methods: (a) a conceptual review of the possible links between motilin and depression, including evidence from animal and human research as well as clinical trials, and (b) an analysis of the relationship between a functional polymorphism (rs2281820) of the motilin (MLN) gene and cross-national variations in the prevalence of depression. It was observed that (a) there are several plausible mechanisms, including interactions with diet, monoamine, and neuroendocrine pathways, to suggest that motilin may be relevant to the pathophysiology and treatment of depression, and (b) there was a significant correlation between rs2281820 allele frequencies and the prevalence of depression after correcting for multiple confounding factors. These results suggest that further evaluation of the utility of motilin and related gut peptides as markers of antidepressant response is required, and that these molecular pathways represent potential future mechanisms for antidepressant drug development.

Inside hippocampal circuits, neuroplasticity events that individual cells may undergo during synaptic transmissions occur in the form of Long Term Potentiation (LTP) and Long Term Depression (LTD). The high density of NMDA receptors expressed on the surface of the dendritic CA1 spines confers to hippocampal CA3-CA1 synapses, the ability to easily undergo NMDA-mediated LTP and LTD, that is essential for some forms of explicit learning in mammals. Providing a comprehensive kinetic model that can be used for running computer simulations of the synaptic transmission process is currently a major challenge. Here, we propose a compartmentalized kinetic model for CA3-CA1 synaptic transmission. Our major goal was to tune our model in order to predict the functional impact caused by disease associated variants of NMDA receptors related to severe cognitive impairment. Indeed, for variants Glu413Gly and Cys461Phe, our model predicts negative shifts in the glutamate affinity and changes in the kinetic behavior, consistent with experimental data. These results pinpoint to the predictive power of this multiscale viewpoint, which aims to integrate the quantitative kinetic description of large interaction networks typical of system biology approaches with a focus on the quality of few, key, molecular interactions typical of structural biology ones.

The art of observing and describing behaviors has driven diagnosis and informed basic science in Psychiatry. In recent times, studies of mental illness are focused on understanding the brain’s neurobiology but there is a paucity of information on the potential contributions from peripheral activity to mental health. In Precision Medicine, this common practice leaves a gap between bodily behaviors and genomics that we here propose to address with a new layer of inquiry that includes genes’ expression on tissues inclusive of brain, heart, muscle-skeletal and organs for vital bodily functions. We interrogate genes’ expression on human tissue as a function of disease-associated genes. By removing genes linked to disease from the typical human set, and recomputing the genes’ expressions on the tissues, we can compare the outcomes across mental illnesses, well-known neurological conditions, and non-neurological ones. We find that major neuropsychiatric conditions that are behaviorally defined today (e.g. Autism, Schizophrenia, Depression) through DSM-observation criteria, have strong convergence with well-known neurological ones (e.g. Ataxias, Parkinson), but less overlap with non-neurological ones. Surprisingly, tissues majorly involved in the central control, coordination, adaptation and learning of movements, emotion and memory are maximally affected in psychiatric diagnoses along with peripheral heart and muscle-skeletal tissues. Our results underscore the importance of considering both the brain-body connection and the contributions of the peripheral nervous systems to mental health.

Keywords: bariatric surgery, sleeve gastrectomy, Roux-en-y gastric bypass, obesity, microbiota, gut-brain axis, beck scale, depression, diet, probiotics

Virtual reality (VR) describes a family of technologies which immerse users in sensorily-stimulating virtual environments. Such technologies have increasingly found applications in the treatment of neurological and mental health disorders. Depression, anxiety, and other mood abnormalities are of concern in the growing elderly population – especially those who reside in long-term care facilities (LTCFs). The transition from the familiar home environment to the foreign LTCF introduces a number of stressors that can precipitate depression. However, recent studies reveal that VR therapy (VRT) can promote positive emotionality and improve cognitive abilities in the elderly, both at home and in LTCFs. VR thus holds potential in allowing elderly individuals to gradually adapt to their new environments – thereby mitigating the detrimental effects of place attachment and social exclusion. Nevertheless, while the current psychological literature is promising, the implementation of VR in LTCFs faces many challenges. LTCF residents must gain trust in VR technologies, care providers require training to maximize the positive effects of VRT, and decision makers must evaluate both the opportunities and obstacles in adopting VR. Here, we concisely review the implications of depression related to place attachment in LTCFs, and explore the potential therapeutic applications of VR.

Environmental studies, metabolic research, and state of the art neurobiology point towards the reduced amount of natural day and sunlight exposure of the developing child’s organism as the consequence of increasingly long hours spent indoors online as the single unifying source of a whole set of health risks identified worldwide, as is made clear in this review of the current literature. Over exposure to digital environments, from abuse to addiction, now concerns even the youngest (ages 0 to 2), and triggers, as argued on the basis of clear examples herein, a chain of interdependent negative and potentially long-term metabolic changes. This leads to a deregulation of the serotonin and dopamine neurotransmitter pathways in the developing brain, currently associated with online activity abuse and/or internet addiction, and akin to that found in severe substance abuse syndromes. A general functional working model is proposed under the light of evidence brought to the forefront in this review.

Mitochondrial malfunction is supposed to be involved in the etiology and pathology of major depressive disorder (MDD). Here, we aimed to identify and characterize the molecular pathomechanisms related to mitochondrial disfunction in adult human skin fibroblasts which were derived from MDD patients or non-depressive control subjects. We found that MDD fibroblasts showed significantly impaired mitochondrial functioning: basal and maximal respiration, spare respiratory capacity, non-mitochondrial respiration and ATP-related oxygen consumption was lower. Moreover, MDD fibroblasts harbor lower ATP levels and showed hyperpolarized mitochondrial membrane potential. To investigate cellular resilience, we challenged both groups of fibroblasts with hormonal (dexamethasone) or metabolic (galactose) stress for one week, and found that both stressors increased oxygen consumption but lowered ATP content in MDD as well as in non-depressive control fibroblasts. Interestingly, the bioenergetic differences between fibroblasts from MDD or non-depressed subjects, which were observed under non-treated conditions, could not be detected after stress. Our findings support the hypothesis that altered mitochondrial function causes a bioenergetic imbalance which is associated with the molecular pathophysiology of MDD. The observed alterations in OXPHOS and other mitochondria-related properties represent a basis for further investigations of pathophysiological mechanisms and might open new ways to gain insight into antidepressant signaling pathways.

Background and objectives: Only a few studies analyzed the physical activity level of elderly people living alone in local communities and evaluated the relationship between it and mental health. The purpose of this study was to investigate the relationship between physical activity and depression in the elderly living alone and to provide basic data for the prevention of depression in the elderly. Materials and Methods: We analyzed 256 elderly people living alone aged 65 years or older who completed the 2014 Korea National Health and Nutrition Examination Survey. Depression was defined as a score of 10 or higher using Patient Health Questionnaire-10(PHQ-9). This study investigated walking per week, days of muscular strength exercise performance in the past one week, days of flexibility exercise in the past one week, mean hours in a sitting position per day, the numbers of days and hours conducting a high intensity physical activity in the past one week, and numbers of days and hours conducting a medium intensity physical activity in the past one week to define physical activity. Our study presented prevalence odds ratios (pOR) and 95% confidence interval (CI) by using complex sample logistic regression analysis in order to identify the relationship between physical activity and depression. Results: The results of complex sample logistic regression analysis showed that flexibility exercise was significantly related to depression (p <0.05). On the other hand, the mean hours in a sitting position per day, aerobic physical activity, walking, and muscular strength exercise were not significantly related to geriatric depression. Conclusions: The results of our study implied that persistent flexibility exercise might be more effective to maintain a healthy mental status than muscular strength exercise. A longitudinal study is required to prove the causal relationship between physical activity and depression in the old age.

The editorial explores the realm of emerging translational research in neurology and psychiatry, providing insights into various subjects, including neurodegenerative disorders and innovative therapeutic methods. The main objective is to study neurological and psychiatric disorders, such as Alzheimer's disease, with a particular emphasis on techniques for neural regeneration and repair. The editorial highlights the importance of taking a comprehensive approach to studying and treating complex neurological and psychiatric conditions. This involves thoroughly reviewing research papers on the causes, development, biomarkers, and treatment options for these conditions. The editorial emphasizes the necessity of using multidisciplinary and integrative methods to gain a deeper understanding and improve the treatment of these conditions. The development of an animal model for recurrent primary dysmenorrhea showcases the innovative techniques employed in the investigation of gynecological disorders, illustrating the capacity of translational research to connect fundamental scientific knowledge with practical medical applications. The cooperative endeavors of researchers and clinicians emphasized in this editorial lay the foundation for revolutionary advancements that hold the potential to enhance outcomes for individuals afflicted with neurological and psychiatric disorders globally.

Healthy diet interventions have been shown to improve depressive symptoms, but there is a need for randomized controlled trials (RCTs) that are double-blind and investigate biological mechanisms. The primary objectives of this randomized controlled pilot trial were to test the palatability of the meals and acceptability of the intervention in preparation for a future 8-week RCT which will investigate whether a healthy Nordic diet improves depressive symptoms in individuals with major depressive disorder, and associated biological mechanisms. Depressed (n=10) and non-depressed (n=6) women and men were randomized to receive either a healthy Nordic diet (ND) or a control diet (CD) for 8 days. Participants were blinded to diet allocation and study hypotheses. Health questionnaires were completed before and after the intervention, and, throughout the study, questionnaires assessed ratings of liking and sensory properties of the meals, adherence, and open-ended feedback. In the ND group, 75% of participants consumed no non-study foods, compared to 50% of CD participants. The meals of both diets, on average, received good ratings for liking and sensory properties, though the ND ratings were somewhat higher. Overall, results were positive and informative, indicating that the planned RCT will be feasible and well-accepted, with some proposed modifications.

Background and Objectives. To examine trends in the links between induced abortion and subsequent mental health problems for U.S. women approaching completed fertility. Materials and Methods. Panel data on a nationally-representative cohort of 3,842 ever-pregnant women assessed at mean ages of 15, 22, 28 and 37 years from the National Longitudinal Study of Adolescent to Adult Health (Add Health) were examined for pregnancy outcome-related mental health disorders, with extensive adjustment for confounders including sociodemographic dif-ferences, mental health history, and unwanted pregnancies. Outcomes were defined using pub-lished diagnostic criteria or validated index for depression, anxiety disorder, post-traumatic stress disorder (PTSD), and suicide ideation (affective problems); alcohol abuse, drug abuse, opioid abuse, and cannabis abuse (substance abuse problems); and summary counts of affective problems, substance abuse problems and total disorders. Results were adjusted for abortion under-reporting using cross-wave analysis. Results. The relative risk of mental health disorder with exposure to induced abortion followed an inverted “V” pattern as women aged to midlife, increasing from Wave III (age 22; IRR 1.41) to Wave IV (age 28; IRR 1.67), then dropping sharply by Wave V (age 37; IRR 1.20). The population at-tributable fraction of mental health disorder due to abortion dropped from 18.1% at Wave IV to 8.0% at Wave V. Unlike previous Waves, at Wave V mental health risk was more strongly reduced by exposure to childbirth (IRR 0.70, 95% CI .63, .78, p < .001). Reduced relative metrics at Wave V were not due to reduced prevalence of mental health disorders for ever-aborting women, which increased from Wave IV to Wave V by 1.7%, but increased much more, by 20.5%, for never-aborting women. Conclusion. At midlife approaching completed fertility, differential negative psychological out-comes for ever-aborting U.S. women remained elevated but reduced from younger ages.

Depression is one of the most severe sequelae of COVID-19, with major depressive disorder often characterized by disruption in white matter (WM) connectivity , stemming from changes in brain myelination. This study aimed to quantitatively assess brain myelination in clinically diagnosed post-COVID depression using recently proposed MRI method, macromolecular proton fraction (MPF) mapping. The study involved 63 recovered COVID-19 patients (52 mild, 11 moderate, 2 severe) at 13.5±10.0 months post-recovery, with matched controls without prior COVID-19 history (n=19). A post-COVID depression group (PCD, n=25) was identified based on psychiatric diagnosis, while a comparison group (noPCD, n=38) included participants with neurological COVID-19 complications, excluding clinical depression. Fast MPF mapping revealed extensive demyelination in PCD patients, particularly in juxtacortical WM (predominantly occipital lobe and medial surface), WM tracts (inferior fronto-occipital fasciculus (IFOF), posterior thalamic radiation, external capsule, sagittal stratum, tapetum), and grey matter (GM) structures (hippocampus, putamen, globus pallidus, and amygdala). The noPCD group also displayed notable demyelination but with less magnitude and propagation. Multiple regression analysis highlighted IFOF demyelination as the primary predictor of PCD presence and severity according to Hamilton scores. The number of post-COVID symptoms was a significant predictor of PCD presence while the number acute of symptoms was a significant predictor of PCD severity. This study, for the first time, reveals extensive demyelination in numerous WM and GM structures in PCD, outlining IFOF demyelination as a key biomarker.

We develop a machine learning (ML) approach for improving the accuracy of the horizontal dis-tribution of the aerosol optical depth (AOD) simulated by the CHIMERE chemistry-transport model over Northern Africa using Moderate-Resolution Imaging Spectroradiometer (MODIS) AOD satellite observations. These observations are used during the training phase of the ML method for deriving a regional bias correction of AODs simulated by CHIMERE. The results are daily maps of regional bias corrected AODs with full horizontal coverage over Northern Africa. We test four types of ML models: multiple linear regression (MLR), random forests (RF), gradi-ent boosting (XGB), and multiple layer perceptron networks (NN). We perform comparisons with satellite and independent ground-based observations of AOD that are not used in the training phase. They suggest that all models have overall comparable performances with a slight advantage of the RF model which expresses less spatial artifacts. While the method slightly underestimates the very high AODs, it significantly reduces biases and absolute errors, and clearly enhances linear correlations with respect to independent observations. This im-provement for deriving the AOD is particularly relevant for high dust pollution regions like the Sahara Desert, which dramatically lack ground-based measurements for validations of chemis-try-transport modeling which currently remains challenging and imprecise.

Background: The exacerbation of psychosocial problems among children and adolescents during the coronavirus disease 2019 (COVID-19) pandemic necessitates an assessment of the long-term mental health impact of pandemic interventions. Focusing on both pandemic-related factors and demographic variables, such as gender and daily habits, an analysis was conducted to under-stand how these elements continue to affect young populations in the post-pandemic era. Methods: In April 2023, a comprehensive online survey was administered to families in South Tyrol, Italy, with children aged 7–19 years, to ensure age and gender representation. The survey included par-ent ratings and adolescent (11–19 years) self-reports using standardized instruments to measure the symptoms of mental health problems (Strengths and Difficulties Questionnaire, SDQ), anxiety (Screen for Child Anxiety Related Emotional Disorders, SCARED), and depression (Patient Health Questionnaire-2, PHQ-2). Statistical analyses included descriptive statistics, chi-square tests, and unadjusted odds ratios (ORs). Results: Of the 4,525 valid responses, 1,831 were self-reported by adolescents. Notable gender differences in mental health outcomes were identified, along with significant demographic predictors, such as age, single parenthood, parental mental health problems, and immigrant background. Negative effects were associated with reduced family climate and increased screen time, whereas physical activity showed beneficial effects. Proxy reports overestimated adolescents' mental health problems, whereas self-report tended to underestimate them. Conclusions: Persistent mental health problems and gender disparities high-light the need for a public health approach. This should include accessible support services, resili-ence building, targeted support for vulnerable families and gender-specific interventions.

Epigenetics, the study of heritable changes in gene expression that do not involve alterations to the DNA sequence, is revolutionizing our understanding of psychiatric disorders. This article provides a comprehensive overview of the role of epigenetics in psychiatry, discussing its implications for genomics, evolution, inheritance patterns, and the development of biomarkers. Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs, are explored in the context of psychiatric conditions such as depression, schizophrenia, and post-traumatic stress disorder (PTSD). The discussion highlights how epigenetic modifications can influence brain dynamics, as measured by electroencephalography (EEG), and how artificial intelligence (AI) can accelerate the development of treatment options. The potential for epigenetic biomarkers to improve diagnosis, prognosis, and treatment is emphasized, along with the role of behavioral interventions in inducing beneficial epigenetic modifications. Future directions in epigenetic research, including the development of epigenetic therapies and the elucidation of molecular mechanisms underlying epigenetic inheritance, are also discussed. This article underscores the transformative potential of epigenetics in advancing our understanding of mental health and disease, paving the way for novel therapeutic interventions.

This study examines the association of sociodemographic risk factors and the comorbidities of COVID-19. Most COVID-19-related studies were conducted in inpatient settings among patients with severe infection during the first and second waves of the pandemic. The third wave with less severe Omicron variant presented a unique opportunity to observe the adult patients treated in outpatient settings. We conducted a cross-sectional study (117 patients aged &gt; 40 years presented with symptomatic COVID-19). We employed the Charlson Comorbidity Index (CCI) to compute comorbidity burden, Medical Outcomes Survey Short form (SF-12) to measure general health, and Self-care Self- Efficacy Scale (SCSES) to assess self-care ability. Fisher’s exact test and analysis of variance (ANOVA) were used to compute the relationship between comorbidities and demographics. This study report focuses on the distribution of the comorbidities and its relationship to demographic variables. The top five comorbidities were hypertension (42%), diabetes (31%), pulmonary disease/asthma (19%), depression (14%), and cancer (11%). Depression was significantly higher among younger age groups (p&lt;0.01) and women (p&lt;0.05). Age (p&lt;0.0001) and income (p&lt;0.01) were the most significantly associated demographics with the comorbidity burden. Incidence of pulmonary disease showed a positive association to educational status (p=0.05). This was the first study to report a significant prevalence of depression among adults with symptomatic COVID-19.

The tryptophan (TRP)-kynurenine (KYN) metabolic pathway is a main player of TRP metabolism through which more than 95% of TRP is catabolized. The pathway is activated by acute and chronic immune responses leading to a wide range of illnesses including cancer, immune diseases, neurodegenerative diseases, and psychiatric disorders. The TRP-KYN pathway synthesizes multifarious metabolites including oxidants, antioxidants, neurotoxins, neuroprotectants, and immunomodulators. The immunomodulators are known to facilitate the immune system towards a tolerogenic state, resulting in chronic low-grade inflammation (LGI) that is commonly present in obesity, poor nutrition, exposer to chemicals or allergens, prodromal stage of various illnesses, and chronic diseases. KYN, kynurenic acid, xanthurenic acid, and cinnabarinic acid are aryl hydrocarbon receptor ligands that serve as immunomodulators. Furthermore, TRP-KYN pathway enzymes are known to be activated by the stress hormone cortisol and inflammatory cytokines, and genotypic variants were observed to contribute to inflammation and thus various diseases. The tryptophan 2,3-dioxygenase, the indoleamine 2, 3-oxygenases, and the kynurenine-3-monooxygenase are main enzymes in the pathway. This review article discusses the TRP-KYN pathway with special emphasis on its interaction with the immune system and the tolerogenic shift towards chronic LGI and overviews the major symptoms, pro- and anti-inflammatory cytokines, and toxic and protective KYNs to explore the linkage between chronic LGI, KYNs, and major psychiatric, including depressive disorder, bipolar disorder, substance use disorder, post-traumatic stress disorder, schizophrenia, and autism spectrum disorder.

Abstract: Background: We previously found that forest bathing significantly reduced the scores for negative emotions and in-creased the score for vigor in the profile of mood states (POMS) test in both males and females and increased the sero-tonin level in males, indicating the potential for beneficial effect on depressive status. In the present study, we investi-gated the effects of forest bathing on the levels of serotonin, oxytocin and insulin-like growth factor I (IGF-1) in blood, Self-Rating Depression Scale (SDS) scores, POMS, subjective fatigue symptoms and subjective sleep quality in female subjects with depression/depressive tendencies. Methods: Thirty-one female subjects aged 40.1±2.4 years with depression/depressive tendencies were recruited after obtaining informed consent. These subjects took day trips to a forest park, the birthplace of forest bathing in Japan named Akasawa Shizen Kyuyourin in Nagano Prefecture, and to a city area of Nagano Prefecture as a control in June 2023. On both trips, they walked 2.2-2.5 km for two hours each in the morning and afternoon on Saturday and Sunday, respectively. Blood was sampled in the afternoon before and after each trip. Concentrations of serotonin, oxytocin, IGF-1 and lactic acid in blood were measured. The SDS scores, POMS test, and questionnaires for subjective fatigue symptoms and subjective sleep quality were conducted before and after the trips. Ambient temperature and humidity were monitoring during the trips. The Nippon Medical School Central Ethics Committee approved this study. Results: Forest bathing significantly decreased SDS scores and the effect lasted for one week after forest bathing. Forest bath-ing also significantly increased the level of serotonin in serum in subjects who were not taking antidepressants, significantly increased the levels of oxytocin and IGF-1 in blood, significantly increased the scores for vigor-activity and friendliness and de-creased the scores for anger-hostility, confusion-bewilderment, fatigue-inertia, tension-anxiety, depression-dejection and total mood disturbance compared with city walking (all p

Depression and cognitive impairment are recognized complications of COVID-19. This study aimed to assess cognitive performance in clinically diagnosed post-COVID depression (PCD) patients using neuropsychological testing. The study involved 71 post-COVID patients, with matched control groups: recovered COVID-19 individuals without complications (n=18) and individuals without prior COVID-19 history (n=19). A post-COVID depression group (PCD, n=25) was identified based on psychiatric diagnosis, a comparison group (noPCD, n=46) included participants with neurological COVID-19 complications, excluding clinical depression. The PCD patients showed significantly less scores in the MoCA test, decreased immediate memory recall in the Word Memory Test, decreased processing speed and higher accuracy in the Trail Making Test, and near to significant worse executive control and processing speed in the Stroop task compared to controls and the noPCD patients. The number of post-COVID symptoms negatively correlated with immediate word memory recall and processing speed among all post-COVID patients. In PCD patients, negative correlations between number of post-COVID symptoms and delayed recall, between time after recovery and immediate recall, and positive correlation between the number of acute symptoms and processing speed in the incongruent condition of the Stroop task were found. No differences between groups in Sniffin’s stick olfactory test was found. Overall, our study revealed cognitive impairment in PCD patients similar to those in major depressive disorder.

Nutrition, diabetes, and mental disorders are interconnected and significantly impact an individual's overall health and well-being. This comprehensive review aims to explore the complex interplay between nutrition, diabetes, and mental disorders, highlighting the latest research findings in this field. While the influence of nutrition on the development and management of both diabetes and mental disorders is widely recognized, there remains a gap in understanding the intricate interplay between nutrition, mental health, and diabetes. Diabetes is associated with an increased risk of mental disorders, including depression, anxiety, and cognitive decline. Mental disorders can also contribute to the development of diabetes through various mechanisms including increased stress, poor self-care behaviors, and adverse effects on glucose metabolism. Thus, the mechanisms linking nutrition, diabetes, and mental disorders are complex and multi-factorial. Inflammation, oxidative stress, gut microbiota alterations, and neuroendocrine dysregulation have emerged as potential pathways that may mediate the relationship between nutrition, diabetes, and mental disorders. Additionally, deficiencies in essential nutrients such as omega-3 fatty acids, vitamin D, B vitamins, zinc, chromium, magnesium, and selenium have been implicated in the pathogenesis of both diabetes and mental disorders. Our findings indicate that the use of personalized dietary interventions and targeted nutrient supplementation can improve metabolic and mental health outcomes in patients with type 2 diabetes.

The multidimensionality of chronic pain forces us to look beyond isolated pain assessment such as pain intensity, which does not consider multiple key parameters, particularly in patients suffering from post-operative Persistent Spinal Pain Syndrome (PSPS-T2). Our ambition was to provide a novel Multi-dimensional Clinical Response Index (MCRI), including not only pain intensity but also functional capacity, anxiety-depression, quality of life and objective quantitative pain mapping assessments, the objective being to capture patient condition instantaneously, using machine learning techniques. Two hundred PSPS-T2 patients were enrolled in a real-life observational prospective PREDIBACK study with 12-month follow-up and received various treatments. From a multitude of questionnaires/scores, specific items were combined using exploratory factor analyses to create an optimally accurate MCRI; as a single composite index, using pairwise correlations between measurements, it appeared to better represent all pain dimensions than any other classical score. It appeared to be the best compromise among all existing indexes, showing the highest sensitivity/specificity related to Patient Global Impression of Change (PGIC). Novel composite indexes could help to refine pain assessment by changing the physician’s perception of patient condition on the basis of objective and holistic metrics, and by providing new insights to therapy efficacy/patient outcome assessments, before ultimately being adapted to other pathologies.

The brain reciprocally communicates with the rest of the body via neural, endocrine, immune, and other systems. This is crucial for coordinating the complex behavioral and physiological responses needed to cope with the many challenges of life. The Anterior Cingulate Cortex (ACC) is a key brain structure involved in assessing rewards and threats, as well as activating appropriate responses. This is a dynamic process that depends on evolving needs and challenges. Important challenges include illness or injury. These typically involve inflammation and pain, which evoke neuroinflammatory processes in the brain to drive sickness behaviours. In the short term, sickness behaviours are considered adaptive, as they promote convalescence (e.g. low mood; lethargy, fatigue, social withdrawal), and enhanced threat appraisal (e.g. anxiety) to combat increased risk/vulnerability associated with sickness. Chronic inflammation, however, appears to remodel the system to inappropriately activate threat-coping responses, resulting in depressive and/or anxious phenotypes. These mood disorders are particularly pronounced in diseases and disorders associated with gut dysfunction, which feature chronic inflammation and altered ACC function. We propose that chronic inflammation remodels ACC physiology such that it errantly predicts heightened danger based on a mental model (a.k.a ‘schema’) of the world. This evokes chronic activation of threat-coping systems, including endocrine signaling (e.g. adrenaline), and anxiety. Inflammation can be driven by brain systems involving ACC, leading to a feedback-cycle that self-reinforces pathological states. This theory accounts for a wealth of clinical and preclinical data that implicate the ACC in disorders of mood and gastrointestinal function, and reveals a key player in the gut-brain axis that may represent a novel therapeutic target.

The literature on the causation of multiple sclerosis (MS), both genetic and environmental, extends over hundreds of years, with no firm conclusions on the exact role of autoimmunity and lifestyle. The epidemiology of MS was the basis for this review, but with a new, extensive examination of genes pertaining to each disorder, and disease of first, and second, degree relatives of those with MS. The author’s motivation was to discover some relationship between MS, and notable familial conditions, as the heredity of MS is concluded to be 30%, and the disorders had a chronic and/or idiopathic nature. This investigation hoped to further understand the randomness of MS- who acquires it, and what symptoms develop- after the author’s decades of observing several incidences of multiple members developing MS in a single family. Online databases for the human genome were used to link genes to MS, and symptoms, including excessive depression, fatigue and suicide rates, in coordination with linking genes for specific familial conditions including seizures, stroke, mental illness, bowel disorders, and thyroid conditions. Interesting associations were found, notably a cluster of Th2 cytokines, known to cure the animal model of MS, important receptors for neurotransmitters and hormones, a gene specific to Epstein Barr Virus, and potential genes for mitochondrial dysfunction. The results surprised the author, showing polygenic regions of chromosome 2 and 5, especially a cluster at loci 5q31-q33, may be dysregulated. The conclusion agrees with past hypotheses MS results not from a single gene, but from various genes, including those expressed in glial cells. The individual theories to the causation of MS, starting with Charcot may be explained by multiple pathways converging into a single disease outcome. In coordination with a sunlight factor, chromosome 2 appears to mediate the immune system, and inflammation, through ultraviolet radiation producing vitamin D3 in the skin, but additionally through peptides formed in the melanocyte stimulating and concentrating hormone class. The impact of stress in MS could be primary, given the loci of several stress-related and stress-modulated genes on these chromosomes, and calls for more appreciation of, and greater care for, the MS patients’ state of mind.