Pathophysiology Of Depression Research Articles

Tocilizumab Reduces Depression Risk in Rheumatoid Arthritis Patients: A Systematic Review and Meta-Analysis.

Depression is a possible cause of the increased mental health risks associated with rheumatoid arthritis (RA), including depression-related complications. Biological disease-modifying antirheumatic drug (bDMARDs) therapies have emerged as innovative anti-inflammatory drugs with positive effects on mental well-being. Tocilizumab is a bDMARDs commonly used to treat RA and its influence on depression needs to be studied. It targets interleukin-6 (IL-6) receptors, reducing inflammation, which may also alleviate depressive symptoms due to the role of inflammation in the pathophysiology of depression. Thus, its influence on depression needs to be studied. To assess the strength of the association between exposure to tocilizumab and the rate of development of depression in patients with RA and to evaluate tocilizumab as an exposure and depression as an outcome in these patients, a search was conducted in the MEDLINE, PreMEDLINE, Cochrane, and Scopus databases from January 1980 to April 2024. Inclusion criteria were studies that diagnosed RA according to the latest American College of Rheumatology/European League Against Rheumatism guidelines or a rheumatologist and provided information on tocilizumab exposure and diagnosed depression as an outcome. The present meta-analysis was conducted following the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. These studies were assessed for eligibility by the author and an independent assessor. To summarize the findings, the meta-analysis combined the relative risk estimates from each study with raw data counts. Twelve studies in the meta-analysis fulfilled the inclusion criteria. Tocilizumab monotherapy exhibited a promising beneficial effect on the risk of depression, indicated by the decreased risk in RA patients (Relative risk 0.68, 95% CI 0.20, 2.31). Patients with RA on tocilizumab treatment had a lower risk of developing depression compared to those unexposed to tocilizumab treatment. Therefore, future longitudinal studies are needed to confirm the beneficial effect of tocilizumab on depression in the RA population.

Use of Levosimendan in Right Ventricular Dysfunction due to Sepsis and Septic Shock: A Research Protocol

Introduction: Sepsis is a clinical condition that results from infection and systemic inflammatory response syndrome, which can progress to severe sepsis and septic shock. This condition leads to myocardial dysfunction and increased mortality rates, particularly in cases of septic shock. Inotropic agents are beneficial in improving cardiac contractility and cardiac output in septic shock. Need for the study: It is important to address myocardial dysfunction in sepsis and septic shock, as these conditions significantly contribute to patient morbidity and mortality. Calcium desensitisation is a key factor in the pathophysiology of septic myocardial depression, leading to impaired cardiac function. Levosimendan, a novel calcium sensitiser, offers a promising therapeutic option due to its unique pharmacologic and biologic profile. By enhancing calcium sensitivity in cardiac myocytes, levosimendan may improve cardiac function without the detrimental side-effects associated with traditional inotropic agents. Aim: The research protocol was planned with an aim to analyse the impact of intravenous levosimendan on Right Ventricular (RV) dysfunction in patients with septic shock. Materials and Methods: This prospective observational study aims to assess the effect of levosimendan on the improvement of RV dysfunction in patients with septic shock who are admitted to the intensive care unit of Acharya Vinoba Bhave Rural Hospital, DMIHER (DU) Sawangi (Meghe), Wardha, Maharashtra, India from July 2023 to March 2025, 45 patients who meet the inclusion criteria will be recruited. Transthoracic Echocardiography (TTE) will be performed using standard measures to calculate RV function. Patients diagnosed with RV dysfunction will be administered levosimendan, followed by a re-evaluation of RV function at designated intervals. Statistical analysis will be conducted using R software, and a paired t-test will be employed to determine significant differences at pre- and post-intervention timelines for the outcome variables of echocardiographic parameters, including Tricuspid Annular Plane Systolic Excursion (TAPSE), EF, RV Fractional Area Change (FAC), and Tricuspid Regurgitant jet Velocity (TRV), at a 5% level of significance.

Is the acquired hypothyroidism a risk factor for developing psychiatric disorders?

Hypothyroidism is a prevalent thyroid condition in which the thyroid gland fails to secrete an adequate amount of thyroid hormone into the bloodstream. This condition may develop due to genetic or acquired factors. The most frequent cause of acquired hypothyroidism is chronic autoimmune thyroiditis, also known as Hashimoto's disease. Acquired hypothyroidism is diagnosed when patients present with overt hypothyroidism (also known as clinical hypothyroidism), as they exhibit increased TSH and decreased T3 and T4 serum levels. This article examines the prevalence of psychiatric disorders among patients diagnosed with acquired hypothyroidism with or without Levothyroxine treatment. We discuss the available evidence indicating that acquired hypothyroidism may be a risk factor for psychiatric disorders, and the effectiveness of thyroid treatment in relieving psychiatric symptoms. Additionally, we provide critical details on thyroid hormone cutoff values reported in the literature, their potential clinical importance, and their correlation with psychiatric symptoms. Finally, we examined the various mechanisms by which acquired hypothyroidism can lead to depression. The high rate of comorbidity between hypothyroidism and psychiatric disorders deserves special attention, indicating the importance of consistent monitoring and timely identification of psychiatric symptoms to prevent disease exacerbation and facilitate therapeutic management. On the other hand, several mechanisms underlie the strong association between depression and acquired hypothyroidism. Deeper research into these mechanisms will allow knowledge of the pathophysiology of depression in patients with acquired hypothyroidism and will provide clues to design more precise therapeutic strategies for these patients.

Plasma amino acids in major depressive disorder: between pathology to pharmacology.

Addressing the formidable challenge posed by the development of effective and personalized interventions for major depressive disorder (MDD) necessitates a comprehensive comprehension of the intricate role that plasma amino acids play and their implications in MDD pathology and pharmacology. Amino acids, owing to their indispensable functions in neurotransmission, metabolism, and immune regulation, emerge as pivotal entities in this intricate disorder. Our primary objective entails unraveling the underlying mechanisms and unveiling tailored treatments through a meticulous investigation into the interplay between plasma amino acids, MDD, and pharmacological strategies. By conducting a thorough and exhaustive review of the existing literature, we have identified pertinent studies on plasma amino acids in MDD, thereby uncovering noteworthy disturbances in the profiles of amino acids among individuals afflicted by MDD when compared to their healthy counterparts. Specifically, disruptions in the metabolism of tryptophan, phenylalanine, and tyrosine, which serve as precursors to essential neurotransmitters, have emerged as prospective biomarkers and critical contributors to the pathophysiology of depression. Amnio acids play an essential role in MDD and could represent an attractive pharmacological target, more studies are further required to fully reveal their underlying mechanisms.

Locus Coeruleus-Dorsolateral Septum Projections Modulate Depression-Like Behaviors via BDNF But Not Norepinephrine.

Locus coeruleus (LC) dysfunction is involved in the pathophysiology of depression; however, the neural circuits and specific molecular mechanisms responsible for this dysfunction remain unclear. Here, it is shown that activation of tyrosine hydroxylase (TH) neurons in the LC alleviates depression-like behaviors in susceptible mice. The dorsolateral septum (dLS) is the most physiologically relevant output from the LC under stress. Stimulation of the LCTH -dLSSST innervation with optogenetic and chemogenetic tools bidirectionally can regulate depression-like behaviors in both male and female mice. Mechanistically, it is found that brain-derived neurotrophic factor (BDNF), but not norepinephrine, is required for the circuit to produce antidepressant-like effects. Genetic overexpression of BDNF in the circuit or supplementation with BDNF protein in the dLS is sufficient to produce antidepressant-like effects. Furthermore, viral knockdown of BDNF in this circuit abolishes the antidepressant-like effect of ketamine, but not fluoxetine. Collectively, these findings underscore the notable antidepressant-like role of the LCTH -dLSSST pathway in depression via BDNF-TrkB signaling.

Limbic System Response to Psilocybin and Ketamine Administration in Rats: A Neurochemical and Behavioral Study.

The pathophysiology of depression is related to the reduced volume of the hippocampus and amygdala and hypertrophy of the nucleus accumbens. The mechanism of these changes is not well understood; however, clinical studies have shown that the administration of the fast-acting antidepressant ketamine reversed the decrease in hippocampus and amygdala volume in depressed patients, and the magnitude of this effect correlated with the reduction in depressive symptoms. In the present study, we attempted to find out whether the psychedelic substance psilocybin affects neurotransmission in the limbic system in comparison to ketamine. Psilocybin and ketamine increased the release of dopamine (DA) and serotonin (5-HT) in the nucleus accumbens of naive rats as demonstrated using microdialysis. Both drugs influenced glutamate and GABA release in the nucleus accumbens, hippocampus and amygdala and increased ACh levels in the hippocampus. The changes in D2, 5-HT1A and 5-HT2A receptor density in the nucleus accumbens and hippocampus were observed as a long-lasting effect. A marked anxiolytic effect of psilocybin in the acute phase and 24 h post-treatment was shown in the open field test. These data provide the neurobiological background for psilocybin's effect on stress, anxiety and structural changes in the limbic system and translate into the antidepressant effect of psilocybin in depressed patients.

Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

The role of the hypothalamic-pituitary-adrenal axis in depression across the female reproductive lifecycle: current knowledge and future directions.

The aim of this narrative review is to consolidate knowledge on the role of the hypothalamic-pituitary-adrenal (HPA) axis in depression pathophysiology at different reproductive stages across the female lifespan. Despite growing evidence about the impact of gonadal hormones on mood disorders, no previous review has examined the interaction between such hormonal changes and the HPA axis within the context of depressive disorders in women. We will focus on HPA axis function in depressive disorders at different reproductive stages including the menstrual cycle (e.g., premenstrual dysphoric disorder [PMDD]), perinatally (e.g., postpartum depression), and in perimenopausal depression. Each of these reproductive stages is characterized by vast physiological changes and presents major neuroendocrine reorganization. The HPA axis is one of the main targets of such functional alterations, and with its key role in stress response, it is an etiological factor in vulnerable windows for depression across the female lifespan. We begin with an overview of the HPA axis and a brief summary of techniques for measuring HPA axis parameters. We then describe the hormonal milieu of each of these key reproductive stages, and integrate information about HPA axis function in depression across these reproductive stages, describing similarities and differences. The role of a history of stress and trauma exposure as a contributor to female depression in the context of HPA axis involvement across the reproductive stages is also presented. This review advances the pursuit of understanding common biological mechanisms across depressive disorders among women. Our overarching goal is to identify unmet needs in characterizing stress-related markers of depression in women in the context of hormonal changes across the lifespan, and to support future research in women's mental health as it pertains to pathophysiology, early diagnosis, and treatment targets.

The hypothalamic steroidogenic pathway mediates susceptibility to inflammation-evoked depression in female mice

BackgroundDepression is two-to-three times more frequent among women. The hypothalamus, a sexually dimorphic area, has been implicated in the pathophysiology of depression. Neuroinflammation-induced hypothalamic dysfunction underlies behaviors associated with depression. The lipopolysaccharide (LPS)-induced mouse model of depression has been well-validated in numerous laboratories, including our own, and is widely used to investigate the relationship between neuroinflammation and depression. However, the sex-specific differences in metabolic alterations underlying depression-associated hypothalamic neuroinflammation remain unknown.MethodsHere, we employed the LPS-induced mouse model of depression to investigate hypothalamic metabolic changes in both male and female mice using a metabolomics approach. Through bioinformatics analysis, we confirmed the molecular pathways and biological processes associated with the identified metabolites. Furthermore, we employed quantitative real-time PCR, enzyme-linked immunosorbent assay, western blotting, and pharmacological interventions to further elucidate the underlying mechanisms.ResultsA total of 124 and 61 differential metabolites (DMs) were detected in male and female mice with depressive-like behavior, respectively, compared to their respective sex-matched control groups. Moreover, a comparison between female and male model mice identified 37 DMs. We capitalized on biochemical clustering and functional enrichment analyses to define the major metabolic changes in these DMs. More than 55% of the DMs clustered into lipids and lipid-like molecules, and an imbalance in lipids metabolism was presented in the hypothalamus. Furthermore, steroidogenic pathway was confirmed as a potential sex-specific pathway in the hypothalamus of female mice with depression. Pregnenolone, an upstream component of the steroid hormone biosynthesis pathway, was downregulated in female mice with depressive-like phenotypes but not in males and had considerable relevance to depressive-like behaviors in females. Moreover, exogenous pregnenolone infusion reversed depressive-like behaviors in female mice with depression. The 5α-reductase type I (SRD5A1), a steroidogenic hub enzyme involved in pregnenolone metabolism, was increased in the hypothalamus of female mice with depression. Its inhibition increased hypothalamic pregnenolone levels and ameliorated depressive-like behaviors in female mice with depression.ConclusionsOur study findings demonstrate a marked sexual dimorphism at the metabolic level in depression, particularly in hypothalamic steroidogenic metabolism, identifying a potential sex-specific pathway in female mice with depressive-like behaviors.

Zuranolone - synthetic neurosteroid in treatment of mental disorders: narrative review.

With each passing year, the number of people suffering from mental disorders grows at a disturbing speed. Neuroactive steroids are a new promising group of drugs with the potential for use in many diseases like postpartum depression, postnatal psychosis, major depression, insomnia, bipolar disorder, and Parkinson's tremor, due to their ability to modulate the activity of GABAA receptor. Neurosteroids are progesterone metabolites that are synthesized from cholesterol or steroid hormones in various brain regions. They regulate neuronal development, regeneration, and neurotransmission. They are implicated in mood disorders, anxiety disorders, schizophrenia, PTSD, and impulsive aggression. Neurosteroids have been studied for their potential to prevent or treat neurodegenerative diseases such as Alzheimer's disease and HIV-associated dementia. They can promote neurogenesis, neuronal survival, myelination, and memory function. They can also affect the growth and sensitivity of hormone-dependent brain tumors such as gliomas. Zuranolone, a newly registered neurosteroid drug has shown huge flexibility in both clinical and ambulatory treatment thanks to its pharmacokinetic traits, especially the possibility for oral administration, unlike its predecessor Brexanolone. Zuranolone is a synthetic positive allosteric modulator of the GABAA receptor that can be taken orally. The review aims to summarize the current knowledge on zuranolone as a novel neurosteroid drug for various mental disorders, especially for postpartum mental disorders for which this drug was meant originally. It covers studies indexed in the PubMed, Scopus, and Web of Science databases published since 2017. Keywords used in the search, as well as inclusion and exclusion criteria, are given in the aims and methodology section. The review explains the evidence for the role of neurosteroids, especially allopregnanolone, in the pathophysiology and treatment of postpartum depression. It discusses the mechanisms of neurosteroid action, the changes in neurosteroid levels during pregnancy and postpartum, and the clinical trials of brexanolone and zuranolone, two synthetic analogs of allopregnanolone, for postpartum depression. It provides an overview of the biosynthesis and metabolism of neurosteroids in the central and peripheral nervous system. Furthermore, it explains the different sources and pathways of neurosteroid production and the factors that influence their synthesis and regulation, such as stress, hormones, drugs, and genetic variations. The review also explores the potential relevance of neurosteroids for other psychiatric disorders, such as major depression, bipolar disorder, post-traumatic stress disorder (PTSD), schizophrenia, and premenstrual dysphoric disorder. Finally, it highlights the associations between neurosteroid levels and symptom severity and the effects of neurosteroid modulation on mood, cognition, and neuroplasticity.

Development of a blood‐based biomarker signature for detection of cognitive impairment through a targeted metabolomics approach deciphering the association with depression

AbstractBackgroundA series of pathological episodes set off the development of cognitive impairment, which precede years before the onset of clinical symptoms. Disrupted glucose and fatty acid metabolism notably contributes to the development of cognitive impairment and further advancement to clinical dementia. Disrupted metabolism leads to the secretion of various inflammatory eicosanoids leading to neuroinflammation. Alteration of some specific metabolites in plasma are noted during these metabolic changes. Depression is a key risk factor of cognitive impairment, and similar changes in plasma metabolites have observed in the pathophysiology of depression. This aim of this project is to establish a blood‐based biomarker signature for early detection of cognitive impairment in individuals with depression through quantifying plasma levels of metabolites associated with glucose and fatty acid metabolism in plasma samples from the participants of the Sydney Memory and Ageing Study (MAS).MethodSamples of 275 participants were randomly collected from baseline and 251 from an 8 year follow up study. At baseline there were 130 healthy participants, 93 participants with MCI, 36 participants with depression and 16 participants had both MCI and depression. Plasma samples were analysed to quantify the levels of fatty acids and carnitines using chemical derivatization – UPLC‐MRM/MS.ResultSignificant correlations were observed between the biomarkers like FA040 butyric acid (P: 0.034), FA224 (P: 0.032), acotinic acid (P:0.027) with MMSE. Biomarkers like C70carnitine (P:0.010), C90carnitine (P: 0.033), C150carnitine (P: 0.016), C160 carnitines (P: 0.004) significantly correlated with GDS scales. Linear regression showed significance between C90 carnitine (P: 0.021; β: 0.139) ad GDS scale. Whereas linear regression showed significant relationship between FA224 (P: 040, β: ‐.122), acotinic acid (P: 0.042, β: ‐.122), FA040 butyric acid (P: 0.036, β: ‐.193) with MMSE indicative of cognitive impairment.ConclusionThe study will help to identify candidate metabolites of perturbed fatty acid metabolism and establish a plasma biomarker signature of early cognitive impairment, by deciphering the association with depression as a risk factor. An association will be established between central AD pathology and peripheral metabolic changes, and potential treatment options targeting the right biochemical pathways will be identified.

MiR-182-5p: A Novel Biomarker in the Treatment of Depression in CSDS-Induced Mice.

Depression is a neuropsychiatric disease with a high disability rate and mainly caused by the chronic stress or genetic factors. There is increasing evidence that microRNAs (miRNAs) play a critical role in the pathogenesis of depression. However, the underlying molecular mechanism for the pathophysiology of depression of miRNA remains entirely unclear so far. We first established a chronic social defeat stress (CSDS) mice model of depression, and depression-like behaviors of mice were evaluated by a series of behavioral tests. Next, we detected several abundantly expressive miRNAs suggested in previous reports to be involved in depression and found miR-182-5p was selected as a candidate for analysis in the hippocampus. Then western blotting and immunofluorescence were used together to examine whether adeno-associated virus (AAV)-siR-182-5p treatment alleviated chronic stress-induced decrease in hippocampal Akt/GSK3β/cAMP-response element binding protein (CREB) signaling pathway and increase in neurogenesis impairment and neuroinflammation. Furthermore, CREB inhibitor was adopted to examine if blockade of Akt/GSK3β/CREB signaling pathway abolished the antidepressant actions of AAV-siR-182-5p in mice. Knockdown of miR-182-5p alleviated depression-like behaviors and impaired neurogenesis of CSDS-induced mice. Intriguingly, the usage of agomiR-182-5p produced significant increases in immobility times and aggravated neuronal neurogenesis damage of mice. More importantly, it suggested that 666-15 blocked the reversal effects of AAV-siR-182-5p on the CSDS-induced depressive-like behaviors in behavioral testing and neuronal neurogenesis within hippocampus of mice. These findings indicated that hippocampal miR-182-5p/Akt/GSK3β/CREB signaling pathway participated in the pathogenesis of depression, and it might give more opportunities for new drug developments based on the miRNA target in the clinic.

Distinct Neural Correlates of Anxiety and Depression in Subjective Cognitive Decline versus Healthy Aging, a Microstructural Diffusion MRI Study

AbstractBackgroundA common criticism of considering Subjective Cognitive Decline (SCD) as a preclinical stage of Alzheimer’s Disease is that it may be explained by depression or anxiety1. We used NODDI, a diffusion microstructural model2, to explore the pathophysiology of depression and anxiety in SCD versus controls.Method325 participants in the Cam‐CAN study 3 (127 SCD) older than 55 were included in the analysis. Diffusion imaging data was collected on a 3T Siemens TIM Trio scanner with a 32‐channel head coil for 0, 1000 and 2000 s/mm2 b‐values and 30 gradient directions. Preprocessing and calculation of the NODDI metric Intracellular Volume Fraction (ICVF) were completed using MRTrix3, AMICO and MATLAB. The hippocampal cingulum bundle and fornix regions of interest (ROIs)4 were extracted from the ICBM‐DTI‐81 atlas. Depression and anxiety were assessed using the Hamilton Anxiety and Depression Scale (HADS). Linear regression models were completed in R. Gender and age were included as nuisance variables.ResultThere were no differences in gender or age distribution between cohorts, however participants with SCD were more depressed and anxious on average (Table 1). There was a significant interaction effect between depression and cohort in the fornix (Figure 1), as well as between anxiety and cohort in the hippocampal cingulum (Figure 2). In post‐hoc analyses, only the SCD group showed a correlation between depression and ICVF in the fornix (Figure 1) while only controls showed a correlation between anxiety and ICVF in the hippocampal cingulum (Figure 2), indicating different pathophysiology underlying psychiatric symptoms in the two groups.ConclusionAnxiety and depression appear to be associated with different microstructural features in SCD versus controls, suggesting anxiety and depression in SCD is a phenomenon distinct from anxiety and depression in healthy aging. Future work will explore the relationship between anxiety and depression and risk of conversion to mild cognitive impairment.1. Mitchell AJ, Beaumont H, Ferguson D, et al. Acta Psychiatrica Scandinavica. 2014;130(6):439‐51.2. Daducci A, Canales‐Rodriguez EJ, Zhang H, et al. Neuroimage. 2015;105:32‐44.3. Shafto MA, Tyler LK, Dixon M, et al. BMC neurology. 2014;14(1):1‐25.4. Kantarci K. Frontiers in Aging Neuroscience. 2014;6.

Distinct Neural Correlates of Anxiety and Depression in Subjective Cognitive Decline versus Healthy Aging, a Microstructural Diffusion MRI Study

AbstractBackgroundA common criticism of considering Subjective Cognitive Decline (SCD) as a preclinical stage of Alzheimer’s Disease is that it may be explained by depression or anxiety1. We used NODDI, a diffusion microstructural model2, to explore the pathophysiology of depression and anxiety in SCD versus controls.Method325 participants in the Cam‐CAN study 3 (127 SCD) older than 55 were included in the analysis. Diffusion imaging data was collected on a 3T Siemens TIM Trio scanner with a 32‐channel head coil for 0, 1000 and 2000 s/mm2 b‐values and 30 gradient directions. Preprocessing and calculation of the NODDI metric Intracellular Volume Fraction (ICVF) were completed using MRTrix3, AMICO and MATLAB. The hippocampal cingulum bundle and fornix regions of interest (ROIs)4 were extracted from the ICBM‐DTI‐81 atlas. Depression and anxiety were assessed using the Hamilton Anxiety and Depression Scale (HADS). Linear regression models were completed in R. Gender and age were included as nuisance variables.ResultThere were no differences in gender or age distribution between cohorts, however participants with SCD were more depressed and anxious on average (Table 1). There was a significant interaction effect between depression and cohort in the fornix (Figure 1), as well as between anxiety and cohort in the hippocampal cingulum (Figure 2). In post‐hoc analyses, only the SCD group showed a correlation between depression and ICVF in the fornix (Figure 1) while only controls showed a correlation between anxiety and ICVF in the hippocampal cingulum (Figure 2), indicating different pathophysiology underlying psychiatric symptoms in the two groups.ConclusionAnxiety and depression appear to be associated with different microstructural features in SCD versus controls, suggesting anxiety and depression in SCD is a phenomenon distinct from anxiety and depression in healthy aging. Future work will explore the relationship between anxiety and depression and risk of conversion to mild cognitive impairment. • Mitchell AJ, Beaumont H, Ferguson D, et al. Acta Psychiatrica Scandinavica. 2014;130(6):439‐51. • Daducci A, Canales‐Rodriguez EJ, Zhang H, et al. Neuroimage. 2015;105:32‐44. • Shafto MA, Tyler LK, Dixon M, et al. BMC neurology. 2014;14(1):1‐25. • Kantarci K. Frontiers in Aging Neuroscience. 2014;6.

Antidepressant Effect of Sodium Butyrate is Accompanied by Brain Epigenetic Modulation in Rats Subjected to Early or Late Life Stress.

Major depression has a complex and multifactorial etiology constituted by the interaction between genetic and environmental factors in its development. The aim of this study was to evaluate the effects of sodium butyrate (SD) on epigenetic enzyme alterations in rats subjected to animal models of depression induced by maternal deprivation (MD) or chronic mild stress (CMS). To induce MD, male Wistar rats were deprived of maternal care during the first 10 days of life. To induce CMS, rats were subjected to the CMS for 40 days. Adult rats were then treated with daily injections of SD for 7 days. Animals were subjected to the forced swimming test (FST), and then, histone deacetylase (HDAC), histone acetyltransferase (HAT), and DNA methyltransferase (DNMT) activities were evaluated in the brain. MD and CMS increased immobility time in FST and increased HDAC and DNMT activity in the animal brains. SD reversed increased immobility induced by both animal models and the alterations in HDAC and DNMT activities. There was a positive correlation between enzyme activities and immobility time for both models. HDAC and DNMT activities also presented a positive correlation between themselves. These results suggest that epigenetics can play an important role in major depression pathophysiology triggered by early or late life stress and its treatment.

Potential Effects of Anthocyanin on Depression: A Review

Nutrition is helpful in preventing depression and reducing its symptoms in depressed patients. This is because when the pathophysiology of depression is examined, deficiencies in certain nutrients are observed. Oxidative stress is also known to cause inflammation, which can contribute to the pathophysiology of the disease. We examined the effectiveness of anthocyanin, which is known to be an antioxidant, on depression. Related articles were searched in the Web of Science database. The combinations of the following terms were used for the search: “Anthocyanidin” OR “Anthocyanidins” OR “Anthocyanin” OR “Leucoanthocyanidins” AND “depression”. 71 abstracts were reviewed, 55 full-text articles were examined, and 7 papers met all of the inclusion criteria. According to these studies, anthocyanin may offer protection against depression and can alleviate its symptoms. Oxidative stress and deterioration in neurogenesis are the mechanisms behind inflammation. Various human, animal, and in vitro studies demonstrate that anthocyanins possess strong anti-inflammatory and antioxidant properties.

Reduction of p11 in dorsal raphe nucleus serotonergic neurons mediates depression-like behaviors

The pathology of depression is related to the imbalance of various neurotransmitters. The dorsal raphe nucleus (DRN), the main brain region producing 5-HT, is crucially involved in the pathophysiology of depression. It contains several neuron types, in which GABAergic neurons are activated by stimuli associated with negative experiences and 5-HT neurons are activated by reward signals. However, little is known about its underlying molecular mechanisms. Here, we found that p11, a multifunctional protein associated with depression, was down-regulated by chronic social defeat stress in 5-HTDRN neurons. Knockdown of p11 in DRN induced depression-like behaviors, while its overexpression in 5-HTDRN neurons alleviated depression-like behavior caused by chronic social defeat stress. Further, p11 regulates membrane trafficking of glutamate receptors in 5-HTDRN neurons, suggesting a possible molecular mechanism underlying the participation of p11 in the pathological process of depression. This may facilitate the understanding of the molecular and cellular basis of depression.

Neuroimaging Genomics a Predictor of Major Depressive Disorder (MDD).

Depression is a complex psychiatric disorder influenced by various genetic and environmental factors. Strong evidence has established the contribution of genetic factors in depression through twin studies and the heritability rate for depression has been reported to be 37%. Genetic studies have identified genetic variations associated with an increased risk of developing depression. Imaging genetics is an integrated approach where imaging measures are combined with genetic information to explore how specific genetic variants contribute to brain abnormalities. Neuroimaging studies allow us to examine both structural and functional abnormalities in individuals with depression. This review has been designed to study the correlation of the significant genetic variants with different regions of neural activity, connectivity, and structural alteration in the brain as detected by imaging techniques to understand the scope of biomarkers in depression. This might help in developing novel therapeutic interventions targeting specific genetic pathways or brain circuits and the underlying pathophysiology of depression based on this integrated approach can be established at length.

Perinatal Depression and the Role of Synaptic Plasticity in Its Pathogenesis and Treatment.

Emerging evidence indicates that synaptic plasticity is significantly involved in the pathophysiology and treatment of perinatal depression. Animal models have demonstrated the effects of overstimulated or weakened synapses in various circuits of the brain in causing affective disturbances. GABAergic theory of depression, stress, and the neuroplasticity model of depression indicate the role of synaptic plasticity in the pathogenesis of depression. Multiple factors related to perinatal depression like hormonal shifts, newer antidepressants, mood stabilizers, monoamine systems, biomarkers, neurotrophins, cytokines, psychotherapy and electroconvulsive therapy have demonstrated direct and indirect effects on synaptic plasticity. In this review, we discuss and summarize the various patho-physiology-related effects of synaptic plasticity in depression. We also discuss the association of treatment-related aspects related to psychotropics, electroconvulsive therapy, neuromodulation, psychotherapy, physical exercise and yoga with synaptic plasticity in perinatal depression. Future insights into newer methods of treatment directed towards the modulation of neuroplasticity for perinatal depression will be discussed.

Nutritional considerations in major depressive disorder: current evidence and functional testing for clinical practice.

Depression is a multifaceted condition with diverse underlying causes. Several contributing and inter-related factors such as genetic, nutritional, neurological, physiological, gut-brain-axis, metabolic and psychological stress factors play a role in the pathophysiology of depression. This review aims to highlight the role that nutritional factors play in the aetiology of depression. Secondly, we discuss the biomedical and functional pathology tests which measure these factors, and the current evidence supporting their use. Lastly, we make recommendations on how practitioners can incorporate the latest evidence-based research findings into clinical practice. This review highlights that diet and nutrition greatly affect the pathophysiology of depression. Nutrients influence gene expression, with folate and vitamin B12 playing vital roles in methylation reactions and homocysteine regulation. Nutrients are also involved in the tryptophan/kynurenine pathway and the expression of brain-derived neurotrophic factor (BDNF). Additionally, diet influences the hypothalamic-pituitary-adrenal (HPA) response and the composition and diversity of the gut microbiome, both of which have been implicated in depression. A comprehensive dietary assessment, combined with appropriate evaluation of biochemistry and blood pathology, may help uncover contributing factors to depressive symptoms. By employing such an approach, a more targeted and personalised treatment strategy can be devised, ultimately leading to improved patient outcomes.