Acta Neuropsychiatrica

In the EU project TRAJECTOME, we used a novel methodology to identify temporal disease maps of depression and highly prevalent co-occurring disease conditions. This information was combined with disability weights established by the Global Burden of Disease Study 2019 to create a depression-related health risk assessment tool, the Multimorbidity Adjusted Disability Score (MADS). MADS was used to stratify over one million cases from three different cohorts and evaluate the impact on utilisation of healthcare resources, mortality, pharmacological burden, healthcare expenditure and multimorbidity progression. Results indicate statistically significant associations between MADS and increased mortality rate (P <.001), heightened healthcare utilization (i.e. emergency room visits P <.001; hospitalizations P <.001; pharmaceutical prescriptions P <.001; total healthcare expenditure P <.001), and a higher risk of disease progression and incidence of new depression-related comorbidities. MADS seems to be a promising approach to predict depression-related health risk and depressions impact on individuals and healthcare systems, which can be tested in other diseases; nevertheless, clinical validation is still necessary.

Maes et al. (2008) published the first paper demonstrating that major depressive disorder (MDD) is accompanied by abnormalities in the microbiota-gut-brain axis, as evidenced by elevated serum IgM/IgA to lipopolysaccharides (LPS) of Gram-negative bacteria, such as Morganella morganii and Klebsiella Pneumoniae. The latter aberrations, which point to increased gut permeability (leaky gut), are linked to activated neuro-immune and oxidative pathways in MDD. To delineate the profile and composition of the gut microbiome in Thai patients with MDD, we examined fecal samples of 32 MDD patients and 37 controls using 16S rDNA sequencing and analyzed -(Chao and Shannon indices) and {beta}-diversity (Bray-Curtis dissimilarity) and conducted Linear discriminant analysis (LDA) Effect Size (LEfSe) analysis. Neither -nor {beta}-diversity differed significantly between MDD and controls. Rhodospirillaceae, Hungatella, Clostridium bolteae, Hungatella hathewayi, and Clostridium propionicum were significantly enriched in MDD, while Gracillibacteraceae family, Lutispora, and Ruminococcus genus, Ruminococcus callidus, Desulfovibrio piger, Coprococcus comes, and Gemmiger, were enriched in controls. Contradictory results have been reported for all these taxa, with the exception of Ruminococcus which is depleted in 6 different MDD studies (one study showed increased abundance), many medical disorders that show comorbidities with MDD, and animal MDD models. Our results may suggest a specific profile of compositional gut dysbiosis in Thai MDD patients with increases in some pathobionts and depletion of some beneficial microbiota. The results suggest that depletion of Ruminococcus may be a more universal biomarker of MDD that maybe contributes to increased enteral LPS load, LPS translocation, and gut-brain axis abnormalities.

BackgroundApproximately 10 to 20% of pregnant women worldwide experience perinatal depression (PND), a depressive episode with onset during pregnancy or after childbirth. We performed a systematic review to identify, summarize and discuss studies on inflammatory biomarkers described in relation to PND. MethodsInclusion criteria defined the selection of observational studies written in English, French, Spanish or Portuguese, that evaluate analytical levels of inflammatory molecules (protein levels) in biological fluids in women, with a diagnosis of depression using ICD/DSM diagnostic criteria or depressive symptoms assessed by standardized psychometric instruments, during pregnancy and/or postpartum. Case reports, experimental studies, reviews, qualitative analysis, meta-analysis, gray literature or replicated data were excluded. Three electronic databases were used for search (Pubmed, Web of Science and PsychInfo) and quality assessment of selected studies were performed using the Newcastle-Ottawa Scale. Data extraction included study design; number of subjects; obstetric information; tools and timepoints of depression and inflammatory markers assessment. Results56 studies where the major aim was to analyze the association between depression and inflammatory biomarkers during pregnancy and postpartum period were included in this systematic review. Overall, the findings of our systematic review lend support to the hypothesis that several inflammatory markers may be associated with peripartum depressive symptoms. The associations were somewhat different looking at pregnancy compared to the delivery time-point and postpartum, and mainly referred to increased levels of IL-6, IL-8, CRP and TNF- among depressed. DiscussionOur results revealed high heterogeneity in relation to the timing of biological sampling for markers, as well as timing and instruments used for depression assessment within the perinatal period for the different studies. Studies differed also in relation to use of biomarkers or depression as exposure and outcome respectively, and whether these were addressed at the same timepoint or separate ones. Given the high burden of PND on women, children and families, it is crucial to try to harmonize methods used in related studies, in order to be able to pool results that could give us insights into the pathophysiological mechanisms behind how the immune system and PND are connected; this could have great impact on early detection, prevention and even treatment of PND.

BackgroundAnxiety disorders are the most frequent mental comorbidity in people with functional GI difficulties, and abdominal discomfort is one of the most known physical signs of sadness. Successful top-down treatments using antidepressants and psychosocial therapies in the treatment of irritable bowel syndrome (IBS) further define personality illnesses as more than merely CNS disorders, but disorders with highly extensive systemic interconnections. Therefore, we recently conducted a systematic review of the observational literature comparing the gut microbiota composition of persons with personality difficulties with healthy control. MethodsThis review was written according to the guidelines established by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Not a single rule was broken, yet a more thorough search strategy did provide more relevant results. Pubmed, Scopus, Embase, Web of Science, Ovid, Global Health, PsycINFO, etc. were searched thoroughly using the phrases "gut microbiota, psychological disorders, personality disorders, composition, major depressive disorder, bipolar disorders, schizophrenia, etc." ResultsResearchers did discover widespread differences in the gut microbiota of patients and controls under each category of personality disorder. They also found that there are distinct bacterial taxa that had differing abundances in patients with these three psychiatric illnesses compared to healthy controls. They found a great deal of variation in study designs and reporting, such as in the inclusion and exclusion of study populations, sampling feces for study of gut microbiota; taking into account or adjusting for important factors known to impact gut microbiota composition; storing feces; processing feces; analyzing feces. ConclusionOur systematic review did find that psychological disorders appeared to exhibit different overall compositional differences compared to controls. There was a general trend toward the finding of increased abundances of bacteria involved in glutamate and GABA metabolism, and lower abundances of butyrate-producing bacteria in psychological disorders

The first publication demonstrating that major depressive disorder (MDD) is associated with alterations in the gut microbiota appeared in 2008 (Maes et al., 2008). The purpose of the present study is to delineate a) the microbiome signature of the phenome of depression, including suicidal behaviours and cognitive deficits; the effects of adverse childhood experiences (ACE) and recurrence of illness index (ROI) on the microbiome; and the microbiome signature of lowered high-density lipoprotein cholesterol (HDLc). We determined isometric log-ratio abundances or prevalence of gut microbiome phyla, genera, and species by analyzing stool samples from 37 healthy Thai controls and 32 MDD patients using 16S rDNA sequencing. Six microbiome taxa accounted for 36% of the variance in the depression phenome, namely Hungatella and Fusicatenibacter (positive associations) and Butyricicoccus, Clostridium, Parabacteroides merdae, and Desulfovibrio piger (inverse association). This profile (labeled enterotype 1) indicates compositional dysbiosis, is strongly predicted by ACE and ROI, and is linked to suicidal behaviours. A second enterotype was developed that predicted a decrease in HDLc and an increase in the atherogenic index of plasma (Bifidobacterium, P. merdae, and Romboutsia were positively associated, while Proteobacteria and Clostridium sensu stricto were negatively associated). Together, enterotypes 1 and 2 explained 40.4% of the variance in the depression phenome, and enterotype 1 in conjunction with HDLc explained 39.9% of the variance in current suicidal behaviours. In conclusion, the microimmuneoxysome is a potential new drug target for the treatment of severe depression and suicidal behaviours, and possibly for the prevention of future episodes.

ImportanceScreening for anxiety and depression is important but especially difficult during pregnancy. Identification and quantification of the variation of maternal biologic dimensions during the dynamic pregnancy period, e.g. immune and microbiome profiles, have the potential to greatly improve mental heath screening and patient stratification. ObjectiveTo determine if specific immune and microbiome profiles align with features of mental distress during pregnancy. DesignProspective case-control study from two cohorts in US followed from 2017 to 2019 in the second and third trimesters. SettingFor the urban cohort, recruitment from an obstetric clinic; for the suburbian group, recruitment from advertisements in the hospital and surrounding communities. ParticipantsA total of 90 pregnant women from two distinct geographic regions, with contrasting race, age, marital status, education and urban vs suburban settings. ExposuresSelf-reported mental health symptoms (anxiety, preceptions of stress and depression) and sociodemographic characteristics; blood was obtained for cytokine profiles and stool for microbiota analysis. Main Outcomes and MeasuresDimensionality reduction clustered the symptom scores from the three self-report tools. Phenotypes based on these features were then defined. ResultsFactor analysis revealed four features: Burn-out, Low Self-Esteem, Mixed State, and Suicidal/Self-Harm; six phenotypes: severe, with and without suicidal thoughts, depressed with low self-steem, hyperactive, and healthy. Factors and phenotype groups were statistically associated with immune and microbiota profiles and sociodemography. The hyperactive phenotype, despite having low self-reported symptoms, had elevated inflammatory cytokines and a microbiota profile similar to the severe phenotype. Elevated T-helper cell 17 (Th17), inducer of inflammation, is related to anxiety in these cohorts. Variance in socioeconomic factors and and the gut microbiota profile can account for 50% of the variance in phenotype. ConclusionBetter stratification of biological charateristics is essential for understanding complex perinatal mental disorders and can be achieved by including microbiota and immune data. Our preliminary results suggest that variance in microbial and immune factors can describe differences in mental health phenotype, and could be predictive of the womens current or future risk for future diagnosis. These findings form testable hypotheses for larger longitudinal studies. KEY POINTSO_ST_ABSQuestionC_ST_ABSDoes self-reported mental distress in late pregnancy align with specific immune and microbiome patterns? FindingsWe show potential limitations in sole reliance on self-reported symptoms of mental distress in 90 subjects from two prospective cohorts. The most different groups based on symptom-based factors presented statistically similar inflammation and microbiome profiles that may reflect underreporting of mental distress symptoms. MeaningA systems biology approach identified risk immune and microbiome profiles with potential advantages to augment self-report. These biological charateristics high risk for mental distress in pregnancy should be confirmed in larger cohorts and may improve understanding of perinatal mood disorders.

BackgroundTourette syndrome is a childhood-onset neuropsychiatric disorder characterised by recurrent motor and vocal tics. It shows a marked male predominance and is frequently associated with comorbid conditions such as attention-deficit/hyperactivity disorder (ADHD) and obsessive- compulsive disorder (OCD). Histaminergic dysregulation in the brain has been proposed as one of the mechanisms underlying Tourette syndrome. Vitamin B6, a key cofactor in histamine metabolism, may therefore play a contributory role in its pathophysiology. MethodThe clinical features of 25 children diagnosed with Tourette syndrome were assessed using the Yale Global Tic Severity Scale. Plasma vitamin B6 levels were measured using enzyme-linked immunosorbent assay (ELISA) and compared with those of a control group. ResultMost participants were males, and 16% had comorbid ADHD or OCD. The most common motor tics were eye blinking, shoulder shrugging, head jerking, and orofacial movements. Frequent vocal tics included throat clearing, sniffing, uttering syllables, and breathing-related tics. Coprolalia was observed in four children. The median plasma vitamin B6 level in the Tourette syndrome group was 25.01ng/ml, which was significantly lower than the 36.33ng/ml in the control group (Mann-Whitney U = 225, p = 0.03). The rank-biserial correlation indicated a moderate effect size (r = 0.35). ConclusionTourette syndrome in children predominantly affects males and is commonly associated with ADHD and OCD. Coprolalia-a clinically distressing symptom - was present only in a small subgroup. The lower plasma vitamin B6 levels observed in children with Tourette syndrome suggest a possible role for vitamin B6 in disease pathogenesis, potentially through its involvement in histaminergic and GABAergic neurotransmission, as well as in the modulation of neuroinflammatory processes.

BackgroundContrary to the negative acute-phase protein (APP) response, there is no consistent correlation between serum pentameric C-reactive protein (pCRP) and major depression (MDD). Monomeric CRP (mCRP), a dissociation product of pCRP under immune-inflammatory conditions, exhibits pro-inflammatory effects; however, it has not been investigated in MDD or its subtypes, major dysmood disorder (MDMD) and simple dysmood disorder (SDMD). ObjectiveTo examine serum mCRP, albumin, transferrin, M1 macrophage and Thelper-17 immune profiles, and adverse childhood experiences (ACEs) in MDD, MDMD and SDMD. MethodsSeventy-nine MDMD patients, 30 SDMD patients, and 40 controls were included. Serum mCRP was measured by ELISA; albumin, transferrin, and pCRP by biochemical assays; and cytokines using Luminex technology. ResultsMDMD patients showed significantly higher mCRP compared with SDMD and controls, while both patient groups exhibited reduced albumin and transferrin. Combining mCRP with albumin and transferrin showed an adequate accuracy for MDD (area under the ROC Curve = 0.793). Adding IL-17A and ACEs improved accuracy (ROC=0.855). Serum mCRP levels are additionally associated with pCRP, M1 macrophage profile, body mass index, and ACEs. Up to 36.6% of the variance in overall severity of depression was explained by mCRP, T-helper-17 profile, ACEs (all positively), albumin and transferrin (both inversely). ConclusionFuture research in MDD should employ mCRP rather than pCRP as a biomarker of depression/MDMD. Combining mCRP with biomarkers of the negative AP response shows that around 63.7% of MDD patients have a smoldering acute phase response with high specificity.

BackgroundPatients with transfusion-dependent thalassemia (TDT) are vulnerable to neurotoxicity due to frequent blood transfusions and the subsequent iron overload (IO) and inflammation. As a result, affective (depression and anxiety) and chronic fatigue syndrome (CFS) symptoms may develop. AimsTo investigate the potential association between TDT and neuronal injury, as assessed with serum concentrations of neuronal damage biomarkers, including neurofilament light (NFL), glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), and nestin. MethodsWe investigated the associations between those CNS injury biomarkers, neuro-immune markers (C-reactive protein (CRP), interleukin (IL)-6, and IL-10), calcium, magnesium, copper and zinc, and the Fibro-Fatigue (FF), the Childrens Depression Inventory (CDI), and the Spence Childrens Anxiety Scale (SCAS) scores in 126 children with TDT and 41 healthy children. ResultsTDT children show significant increases in IO, FF, CDI, and SCAS scores, serum NSE, GFAP, NF-L, CRP, copper, IL-6, and IL-10, and lowered magnesium, zinc, and calcium as compared with healthy children. There were significant correlations between the CDI score and NFL, NSE and GFAP; SCAS score and NFL, and FF score and NFL and GFAP. The neuronal damage biomarkers (except nestin) were significantly associated with inflammatory, erythron (hematocrit and hemoglobin) and IO (iron and ferritin) biomarkers. ConclusionsTDT is characterized by intertwined increases in neuronal injury biomarkers and neuropsychiatric symptoms suggesting that TDT-associated neurotoxicity plays a role in affective symptoms and CFS due to TDT. Inflammation and neurotoxicity are novel drug targets for the prevention of affective symptoms and CFS due to TDT.

BackgroundCritical COVID-19 disease is accompanied by depletion of plasma tryptophan (TRY) and increases in indoleamine-dioxygenase (IDO)-stimulated production of neuroactive tryptophan catabolites (TRYCATs), including kynurenine (KYN) and quinolinic acid. The TRYCAT pathway has not been studied extensively in association with the physiosomatic and affective symptoms of Long COVID. MethodsIn the present study, we measured serum tryptophan (TRY), TRYCATs, insulin resistance (using the HOMA2-IR index), C-reactive protein (CRP), physiosomatic, depression and anxiety symptoms in 90 Long COVID patients, 3-10 months after remission of acute infection. ResultsWe were able to construct an endophenotypic class of severe Long COVID (22% of the patients) with very low TRY and oxygen saturation (SpO2, during acute infection), increased kynurenine, KYN/TRY ratio, CRP, and very high ratings on all symptom domains. One factor could be extracted from physiosomatic symptoms (including chronic fatigue-fibromyalgia), depression, and anxiety symptoms, indicating that all domains are manifestations of the common physio-affective phenome. Three Long COVID biomarkers (CRP, KYN/TRY, IR) explained around 40% of the variance in the physio-affective phenome. The latter and the KYN/TRY ratio were significantly predicted by peak body temperature (PBT) and lowered SpO2 during acute infection. One validated latent vector could be extracted from the three symptom domains and a composite based on CRP, KYN/TRY, IR (Long COVID), and PBT and SpO2 (acute COVID-19). ConclusionThe physio-affective phenome of Long COVID is a manifestation of inflammatory responses during acute and Long COVID and lowered plasma tryptophan and increased kynurenine may contribute to these effects.

ObjectivePediatric acute-onset neuropsychiatric syndrome (PANS) is a complex neuropsychiatric syndrome characterized by an abrupt onset of obsessive-compulsive symptoms and/or severe eating restrictions, along with at least two concomitant debilitating cognitive, behavioral, or neurological symptoms. A wide range of pharmacological interventions along with behavioral and environmental modifications, and psychotherapies have been adopted to treat symptoms and underlying etiologies. Our goal was to develop a data-driven approach to identify treatment patterns in this cohort. Materials and MethodsIn this cohort study, we extracted medical prescription histories from electronic health records. We developed a modified dynamic programming approach to perform global alignment of those medication histories. Our approach is unique since it considers time gaps in prescription patterns as part of the similarity strategy. ResultsThis study included 43 consecutive new-onset pre-pubertal patients who had at least 3 clinic visits. Our algorithm identified six clusters with distinct medication usage history which may represent clinicians practice of treating PANS of different severities and etiologies i.e., two most severe groups requiring high dose intravenous steroids; two arthritic or inflammatory groups requiring prolonged nonsteroidal anti-inflammatory drug (NSAID); and two mild relapsing/remitting group treated with a short course of NSAID. The psychometric scores as outcomes in each cluster generally improved within the first two years. Discussion and conclusionOur algorithm shows potential to improve our knowledge of treatment patterns in the PANS cohort, while helping clinicians understand how patients respond to a combination of drugs.

Despite the hardships of major depressive disorder (MDD), biomarkers for the diagnosis and pharmacological management of this condition are lacking. MicroRNAs are epigenetic mechanisms that could provide promising MDD biomarkers. Our aim was to summarize the findings and provide validation for the selection and use of specific microRNAs as biomarkers in the diagnosis and treatment of MDD. A systematic review was conducted using the PubMed/MEDLINE, Cochrane, PsycINFO, Embase, and LILACS databases from March to May 2022, with clusters of terms based on "microRNA" and "antidepressant". Studies involving human subjects, animal models, and cell cultures were included, whereas those that evaluated herbal medicines, non-pharmacological therapies, or epigenetic mechanisms other than miRNA were excluded. The review revealed differences in the expression of various microRNAs when considering the time of assessment (before or after antidepressant treatment) and the population studied. However, due to the heterogeneity of the microRNAs investigated, the limited size of the samples, and the wide variety of antidepressants used, few conclusions could be made. Despite the observed heterogeneity, the following microRNAs were determined to be important factors in MDD and the antidepressant response: mir-1202, mir-135, mir-124, and mir-16. The findings indicate the potential for the use of microRNAs as biomarkers for the diagnosis and treatment of MDD; however, more homogeneous studies are needed.

BackgroundCell deformability of all major blood cell types is increased in depressive disorders (DD). Furthermore, impaired glucocorticoid secretion is causally related to DD. Nevertheless, there are no longitudinal studies examining changes in glucocorticoid output and depressive symptoms regarding cell deformability in DD. AimTo investigate, whether changes in depressive symptoms or hair glucocorticoids predict cell deformability in DD. MethodsIn 136 individuals, depressive symptoms (PHQ-9) and hair glucocorticoids (cortisol and cortisone) were measured at timepoint one (T1), while one year later (T2) depressive symptoms and hair glucocorticoids were remeasured and additionally cell deformability of peripheral blood cells was assessed and DD status was determined by clinical interview. ResultsDepression severity at T1 predicted higher cell deformability in monocytes and lymphocytes over the entire sample. Subjects with continuously high depressive symptoms at T1 and T2 showed elevated monocyte deformability as compared to subjects with low depressive symptoms. Depression severity at T1 of subjects with a lifetime persistent depressive disorder (PDD) was associated with elevated monocyte, neutrophil, and granulo-monocyte deformability. Depression severity at T1 of subjects with a 12-month PDD was positively associated with monocyte deformability. Furthermore, increases in glucocorticoid concentrations from T1 to T2 tended to be associated with higher immune cell deformability, while strongest associations emerged for the increase in cortisone with elevated neutrophil and granulo-monocyte deformability in the 12-month PDD group. ConclusionContinuously elevated depressive symptomatology as well as an increase in glucocorticoid levels over one year are associated with higher immune cell deformability, particularly in PDD. These findings suggest, that persistent depressive symptomatology associated with increased glucocorticoid secretion may lead to increased immune cell deformability thereby compromising immune cell function and likely contributing to the perpetuation of PDD.

One of the most promising areas of research into the biological underpinnings of depression is genetic studies. However, the absence of generally accepted phenotyping methods leads to the difficulties in generalizing their results due to the heterogeneity of the samples. Thus, the development of a reliable and convenient phenotyping method that allows large sample sizes to be included in studies remains a top priority for the further development of genetic studies of depression. The aim of this study was to evaluate the applicability of the online version of the depression subscale of Hospital Anxiety and Depression Scale (HADS-D) for depression phenotype screening in the general population. Using online HADS-D we performed screening of depressive symptoms and compared results with known population patterns of depression. We conducted an online survey of 2610 Russian-speaking respondents over the age of 18. The overall HADS-D score was higher in women (p=0.003), in individuals under 30 y.o compared to participants over 42 y.o. (p=0.004) and in individuals reporting cardiovascular diseases (CVD) symptoms (p<0.0001). Linear regression showed that the presence of CVD leads to higher HADS-D scores (p<0.001), male gender (p=0.002) and older age (p<0.001) led to lower scores. Logistic regression showed that CVD increases the risk of having depression symptoms by HADS-D (p=0.033, OR=1.29), older age (p=0.015, OR=0.87) and male sex (as a trend, p=0.052, OR=0.80) decrease this risk. These results are consistent with the known data on the association of sex, age, and the presence of CVD with the prevalence of depression. The online version of HADS-D, given the ease of its usage, can be regarded as an effective tool for phenotyping depression in the general population.

IntroductionBipolar Disorder (BD) is associated with thyroid dysfunction, and literature on the clinical impact of Lithium on thyroid function in BD patients remains inconsistent. Thus, we aimed to systematically estimate the prevalence of thyroid dysfunction in Lithium treated BD patients, explore the clinical factors associated with the development of hypothyroidism and time to detection of thyroid dysfunction after Lithium initiation. MethodsA retrospective review of BD patients with a follow-up between Jan to Dec 2019 was conducted. Patients with no pre-existing thyroid dysfunction and at least six months of cumulative exposure to Lithium were included. For the included 444 patients, sociodemographic, clinical variables and laboratory assessment values were charted systematically. Patients with TSH > 5 mIU/L were classified as hypothyroid. Results27.7% (n=123) developed thyroid dysfunction; 27.3% (n=121) developed hypothyroidism after Lithium exposure. The median duration of detection of hypothyroidism was 33.6 months for females and 38.4 months for males, with no significant difference across genders (p=.52). A significantly higher proportion of females (49.5%) developed hypothyroidism as opposed to males (23.7%). Hypothyroid females differed significantly with respect to comorbid diabetes mellitus and hypertension; from euthyroid females. First-episode depression was associated with hypothyroidism in males. However, multivariate analyses did not detect any associations. DiscussionOne-fourth of Lithium-treated patients developed hypothyroidism. This risk was higher in female patients, with onset close to 33 months, indicating the need for closer monitoring for long durations. The impact of hypothyroidism on prognosis and response to treatment needs further exploration.

IntroductionCommon diseases are influenced by a variety of factors that can enhance one persons susceptibility to developing a specific condition. Complex traits have been investigated in several biological levels. One that reflects the high interconnectivity and interaction of genes, proteins and transcription factors is the transcriptome. In this study, we disclose the protocol for a systematic review and meta-analysis aiming at summarizing the available evidence regarding transcriptomic gene expression levels of peripheral blood samples comparing subjects with psychiatric, neurological and other common disorders to healthy controls. Methods and analysisThe investigation of the transcriptomic levels in the peripheral blood enables the unique opportunity to unravel the etiology of common diseases in patients ex-vivo. However, the experimental results should be minimally consistent across studies for them to be considered as the best approximation of the true effect. In order to test this, we will systematically identify all transcriptome studies that compared subjects with common disorders to their respective control samples. We will apply meta-analyses to assess the overall differentially expressed genes throughout the studies of each condition. Ethics and disseminationThe data that will be used to conduct this study are available online and have already been published following their own ethical laws. Therefore this study requires no further ethical approval. The results of this study will be published in leading peer-reviewed journals of the area and also presented at relevant national and international conferences. Strengths and limitations of this study We present a new and systematically centered method to assess the overall effect of transcriptomic levels in the blood of subjects with common conditions. Meta-analyses are a robust statistical method to assess effect sizes across studies. The analysis is limited by the availability of studies, as well as their quality and comprehensiveness. Subgroup and meta-regression analyses will be also limited by the amount and quality of sample characterization variables made available by original studies.

The link between weather elements and mental disorders is often described in high-income countries, with hardly any data from low-and middle-income countries where the resources to cope with the negative mental health impacts of climate change are extremely constrained. In this paper, we examined the association between weather elements and the incident presentation with a mental disorder at Butabika National Referral Mental Hospital. We used secondary data from two datasets: i) a mental health data set collated from all patients presenting at Butabika National Referral Mental Hospital in 2019; and ii) a climatic dataset for the geographic location of Butabika National Referral Mental Hospital for the same year (2019). The mental health data set included socio-demographic variables and mental disorder diagnoses, while the climatic data set included data on, atmospheric pressure (hPa), rainfall (mm), sunshine (hours/month), humidity (%), temperature ({degrees}C) and wind speed (m/s). We performed descriptive statistical analyses to summarize the frequency of mental disorder diagnoses and the monthly averages of weather variables. We then undertook correlation and multiple logistic regression analyses to investigate the associations between specific weather elements and the incident presentation of different mental disorders. In the mental health data, we had 2,827 participants, males were 56.1%(n=1,584), and the median age was 29 years (IQR 23-38). Psychotic disorders were the most common diagnosis at 43.8% (n=1,239). Overall, various weather elements correlated at different strengths with incident presentation of various mental disorders, particularly humidity and rainfall. On controlling for age and sex in the multiple regression models, the strongest associations were between heat elements and incident presentation for psychotic disorders [AOR1.12, 95%CI (1.04; 1.27) p<0.001]. No associations were demonstrated between weather elements and incident presentation for neurocognitive and neurodevelopmental disorders. These preliminary findings point to a possible relationship between incident presentation of mental disorders to a tertiary psychiatric hospital in Uganda and various weather elements. There is need for longitudinal studies to confirm these associations and to explore underlying social and biological mechanisms.

BackgroundMajor depressive disorder (MDD) and its most severe phenotype, major dysmood disorder (MDMD), are distinguished by the activation of the immune-inflammatory response system, T cell activation, and a relative T regulatory cell suppression. Nevertheless, these immune data were not used to characterize the features of the immune protein-protein interaction (PPI) network of MDMD. ObjectivesTo identify the networks nodes and bottlenecks as well as the biological processes that are overrepresented in the PPI network, we conducted PPI network, annotation, and enrichment analyses. ResultsThe PPI network analysis has identified the following backbone genes: tumor necrosis factor- (TNF), interleukin (IL)6, CXCL12, CXCL10, CCL5, cluster of differentiation (CD)4, CD8A, human leukocyte antigen (HLA)-DR, and FOXP3. A "cellular and defense response", an "immune response system response", and "a viral process that involves viral protein interaction with cytokines and cytokine receptors" were all highly associated with the network. The chemokine network and TNF and nuclear factor-{kappa}B (NFKB) pathways are additional biological pathways that are enriched in the PPI network. Molecular complex detection extracted one component from the data, including viral protein interaction with cytokine and cytokine receptors and "regulated by RELA" (an NFKB subunit). ConclusionsViral processes may underlie the activation of T cells and the cytokine and chemokine networks that are associated with MDMD. Future research on the pathogenesis of MDMD and MDD should examine whether and which viral infections are associated with the onset of these conditions, or whether viral reactivation is associated with the recurrence of illness.

BackgroundLongitudinal data on the course of somatic symptom disorder (SSD) in ulcerative colitis (UC) and irritable bowel syndrome (IBS) are lacking. Understanding SSD trajectories and predictors in IBS and UC may clarify clinical relevance and guide psychological treatment decisions. This study examined the 12-month course and biopsychosocial predictors of interview-based SSD in patients with UC or IBS. MethodsLongitudinal data from a randomised controlled trial were analysed. SSD was assessed using DSM-5-based structured interviews at baseline and 12 months. SSD Criteria A (Somatic symptom severity) and B (symptom-related distress) were measured with the Patient Health Questionnaire-15 (PHQ-15) and the Somatic Symptom Disorder - B Criteria Scale-12 (SSD-12), respectively. Further variables included gastrointestinal symptom severity, inflammatory markers, depression severity, illness perceptions, and neuroticism. Logistic and linear regression models identified baseline predictors of SSD diagnosis and Criteria A and B at 12 months. ResultsThe sample included 213 patients (73.7% female; Mage=40.5, SD=13.98) with UC (n=110) or IBS (n=103). SSD was present in 42.3% (95%CI: 35.2-49.3) at baseline and in 15.5% (95%CI: 11.3- 20.7) at follow-up. Baseline SSD and depression severity predicted follow-up SSD. Criterion A was predicted by somatic symptom severity, female gender, and neuroticism; the B criterion by symptom-related distress, somatic symptom severity, neuroticism, and negative illness perceptions. Inflammatory markers and gastrointestinal symptom severity showed no predictive value. ConclusionStructured interview-based SSD was frequent in patients with UC or IBS at baseline and declined over time. Psychosocial rather than disease-related variables predicted SSD, highlighting modifiable targets for early detection and tailored interventions. Results should be interpreted in light of the studys interventional context.

BackgroundRecently, it was suggested that serum high-sensitive C-reactive protein (hsCRP) serves as a biomarker for "inflammatory major depression (MDD)" when serum hsCRP exceeds > 3.0 mg/L. Since 1991-1992, it has been known that MDD is characterized by a negative acute phase protein (APP) response with lowered serum albumin and transferrin levels. AimsTo compare hsCRP with negative APPs as biomarkers of MDD and the severity of physio-affective symptoms and to clarify their relationship with immune and metabolic variables. MethodsThis case-control study included 125 MDD patients and 40 healthy controls and assessed serum hsCRP, albumin, transferrin, M1 macrophage profile, and the compensatory immunoregulatory system (CIRS). ResultsNo significant elevations in hsCRP levels in MDD compared to controls were found. A minority of MDD patients (15.2%) had hsCRP values higher than 3 mg/L, and 78.9% of those had concentrations between 3 and 7 mg/L. Serum hsCRP is largely associated with metabolic parameters, including metabolic syndrome and body mass index (BMI), and with adverse childhood experiences (ACEs), M1 macrophage profile (all positively), and CIRS (inversely). Serum transferrin and albumin are significantly reduced in MDD with an accuracy of 77.3%. Both proteins are strongly and inversely correlated with the physio-affective phenome of MDD, ACEs, and immune activation. ConclusionsMDD is accompanied by non-classical inflammation with a negative APP response associated with immune activation and ACEs. Many MDD patients with hsCRP values <3 mg/L show indicants of a smoldering negative acute phase response. Increased hsCRP does not indicate "inflammatory depression."