LD block disorder-specific pleiotropic roles of novel CRHR1 in type 2 diabetes and depression disorder comorbidity.

Major depressive disorder (MDD) and type 2 diabetes (T2D) are complex disorders whose comorbidity can be due to hypercortisolism and may be explained by dysfunction of the corticotropin-releasing hormone receptor 1 (CRHR1) and cortisol feedback within the hypothalamic-pituitary-adrenal axis (HPA axis). To investigate the role of the CRHR1 gene in familial T2D, MDD, and MDD-T2D comorbidity, we tested 152 CRHR1 single-nucleotide-polymorphisms (SNPs), via 2-point parametric linkage and linkage disequilibrium (LD; i.e., association) analyses using 4 models, in 212 peninsular families with T2D and MDD. We detected linkage/LD/association to/with MDD and T2D with 122 (116 novel) SNPs. MDD and T2D had 4 and 3 disorder-specific novel risk LD blocks, respectively, whose risk variants reciprocally confirm one another. Comorbidity was conferred by 3 novel independent SNPs. In silico analyses reported novel functional changes, including the binding site of glucocorticoid receptor-alpha [GR-α] on CRHR1 for transcription regulation. This is the first report of CRHR1 pleiotropic linkage/LD/association with peninsular familial MDD and T2D. CRHR1 contribution to MDD is stronger than to T2D and may antecede T2D onset. Our findings suggest a new molecular-based clinical entity of MDD-T2D and should be replicated in other ethnic groups.

Association of serotonin transporter gene polymorphism with efficacy of the antidepressant drugs sertraline and mirtazapine in newly diagnosed patients with major depressive disorders.

OBJECTIVE: We examined the association of serotonin receptor transporter gene polymorphism in patients with MDD with the clinical efficacy of mirtazapine (MZ) and sertraline (ST). METHOD: Newly diagnosed, treatment naïve, 80 MDD patients (aged 18-45) diagnosed using DSM-5 criteria and with Beck's depression inventory score (BDI) score ≥21 were included and randomly divided into two groups of 40 participants and were administered MZ 15-45 mg/day or ST 25-200 mg/day respectively. Patients were followed up for 6 weeks for evaluation of BDI scores. Genotypic evaluation was done and three allele variants were identified based on the polymerase chain reaction fragment sizes: short (S; 486 bp), long (L; 529 bp), or extralong (XL; 612 or 654 bp) and classified into five genotypes: S/S,S/L, L/L, S/XL, and L/XL. RESULT: We found that 32.5% patients belonged to the S/S genotype, suggesting that individuals with the SS genotype are at higher risk of developing MDD. No statistically significant association was seen with ST or MZ groups on the basis of genotypes. Clinically significant improvement was observed with a more than 50% reduction in BDI scores at 6 weeks of treatment with both drugs. CONCLUSION: Identification of risk population can be carried out by genotype testing. Prior genotyping in MDD patients might help to predict a better clinical outcome with antidepressants.

The Genetic Basis for the Increased Prevalence of Metabolic Syndrome among Post-Traumatic Stress Disorder Patients.

Post-traumatic stress disorder (PTSD) is a highly debilitating psychiatric disorder that can be triggered by exposure to extreme trauma. Even if PTSD is primarily a psychiatric condition, it is also characterized by adverse somatic comorbidities. One illness commonly co-occurring with PTSD is Metabolic syndrome (MetS), which is defined by a set of health risk/resilience factors including obesity, elevated blood pressure, lower high-density lipoprotein cholesterol, higher low-density lipoprotein cholesterol, higher triglycerides, higher fasting blood glucose and insulin resistance. Here, phenotypic association between PTSD and components of MetS are tested on a military veteran cohort comprising chronic PTSD presentation (n = 310, 47% cases, 83% male). Consistent with previous observations, we found significant phenotypic correlation between the various components of MetS and PTSD severity scores. To examine if this observed symptom correlations stem from a shared genetic background, we conducted genetic correlation analysis using summary statistics data from large-scale genetic studies. Our results show robust positive genetic correlation between PTSD and MetS (rg[SE] = 0.33 [0.056], p = 4.74E-09), and obesity-related components of MetS (rg = 0.25, SE = 0.05, p = 6.4E-08). Prioritizing genomic regions with larger local genetic correlation implicate three significant loci. Overall, these findings show significant genetic overlap between PTSD and MetS, which may in part account for the markedly increased occurrence of MetS among PTSD patients.

Implementation and clinical characteristics of a posttraumatic stress disorder brain collection.

A postmortem human brain collection to study posttraumatic stress disorder (PTSD) is critical for uncovering the molecular mechanisms that contribute to this psychiatric disorder. We describe here the PTSD brain collection at the Lieber Institute for Brain Development in Baltimore, Maryland, consisting of postmortem brain donations acquired between 2012 and 2017. Thus far, 87 brains from individuals meeting DSM-5 criteria for PTSD were collected after consent was obtained from legal next-of-kin, and subsequently clinically characterized for molecular studies. PTSD brain donors had high rates of comorbid diagnoses, including depression (62.1%), substance abuse (74.7%), drug-related death (69.0%), and suicide completion (17.2%). PTSD cases were subdivided into two categories: combat-related PTSD (n = 24) and noncombat/domestic PTSD (n = 63). The major differences between the combat-related and domestic PTSD cohorts were sex, drug-related death, and the prevalence of bipolar disorder (BPD) comorbidity. The combat-related group was entirely male, with only one BPD subject (4.2%), and had significantly fewer drug-related deaths (45.8%) in contrast to the domestic group (31.8% male, 36.5% bipolar, and 77.8% drug-related deaths). Medical examiners' offices, particularly in areas with higher military populations, are an excellent source for PTSD brain donations of both combat-related and domestic PTSD.

Relationship between serum inflammatory cytokines and suicide risk in patients with major depressive disorder.

Background: Studies have shown that increased inflammatory cytokines are associated with suicide risk, but the relationship between suicide risk and inflammatory cytokines is not clear. This study aimed to investigate the relationship between specific inflammatory markers and suicide risk in patients with MDD. Methods: This is a cross-sectional study. Firstly, we measured and compared psychological characteristics and 10 peripheral inflammatory cytokines in 130 MDD patients and 130 healthy controls(HC). Secondly, MDD patients were divided into 4 groups according to the severity of suicide risk for comparison between groups. Finally, multiple linear regression analysis was used to explore the predictors of suicide risk. Results: We found that the group with higher suicide risk had higher levels of IL-6, CRP, TNF-α, CXCL-2, and IFN-γ, and lower levels of IL-2 and IL-8 (all p<0.01). However, we found no difference in CRP between MIS and LS groups (p=0.337). Regression models were well-fitted. IL-2,IL-8 negatively predicted suicide risk (all p<0.05),IL-6,CRP,TNF-α,CXCL-2, and IFN-γ can positively predict the risk of suicide (all p<0.05). Limitations: This study employed a self-assessment scale. Conclusions: The higher the levels of IL-6, CRP, TNF-α, CXCL-2, and IFN-γ and the lower the levels of IL-2 and IL-8 of MDD patients, the higher the risk of suicide.

Personalized Approach in the Management of Difficult-to-Treat and Treatment-Resistant Depression With Second-Generation Antipsychotics: A Delphi Statement.

Background Major depressive disorder (MDD) has many facets including mixed or atypical depression that requires personalized care to improve treatment-related outcomes. Second-generation antipsychotics (SGAs) offer complementary mechanisms for clinical roles in difficult-to-treat depression and treatment-resistant depression cases. Aim/objective To further delineate a consensus on the clinical positioning of SGAs for MDD, mixed, or atypical depression, a Knowledge Attitude Perception (KAP)-mediated Delphi Statement was planned. Material/methods A literature review for the definition, diagnosis, and management of MDD, mixed, and atypical depression as treatment-resistant depression (TRD) or difficult-to-treat depression (DTD) was conducted by a steering committee of academic and clinical experts (n=6) while developing a validated KAP questionnaire. Scientific statements as clinical recommendations were evolved using the Delphi methodology before building a clinical expert consensus with an online survey (n=24). Results Twenty-four psychiatrists highlighted DTD to offer a multidimensional approach to assess treatment strategies involving selective serotonin reuptake inhibitors (SSRIs) or SGAs, while ensuring symptom, functional, and quality of life (QoL) domain improvement for improved outcomes and remission rates. MDD cases with anxiety, anhedonia, comorbidities, and risk traits require personalized care with early induction of SGAs for severe cases or symptom persisters with functional impairment. Early augmentation with SGAs including aripiprazole or cariprazine can provide a favorable risk-benefit profile for clinical cases of MDD with or without the antecedent of mixed depression or personality disorder.  Conclusion The literature review and KAP responses emphasize the importance of early identification for personalized care strategies with SGAs for DTD. Large-scale real-world evidence needs to evolve with due recognition of different phenotypes as TRD or DTD with partial or functional impairment to understand the impact of appropriate treatment pathways with SGAs.

Differences in the prevalence and clinical correlates of comorbid suicide attempts in patients with early- and late-onset major depressive disorder.

Objective: There are many studies on differences in the onset age of major depressive disorder (MDD) patients. However, study on differences in clinical correlates of suicide attempts between early- and late-onset MDD patients is limited. The aim of this study was to investigate the differences in the prevalence and clinical correlates of suicide attempts in patients with early- and late-onset MDD in China. Methods: A total of 1718 adult outpatients with MDD were recruited. Demographic and clinical data were collected. The 17-item Hamilton Rating Scale for Depression (HAMD-17), Hamilton Anxiety Rating Scale (HAMA), Positive and Negative Syndrome Scale (PANSS) positive subscale, and Clinical Global Impression-Severity (CGI-S) Scales were used to assess their depressive, anxiety, psychotic symptoms, and the severity of the clinical symptoms, respectively. Results: The prevalence of suicide attempts was higher in late-onset MDD patients (291/1369, 21.3%) than in early-onset MDD patients (55/349, 15.8%) (p = 0.023). However after Bonferroni correction no significant difference was found in the prevalence of suicide attempts in late-onset and late-onset MDD patients (p > 0.05). In both early- and late-onset groups, univariate analysis showed that the following characteristics were significantly associated with suicide attempts: HAMA, HAMD and PANSS positive subscale scores, thyroid stimulating hormone (TSH) levels, blood glucose levels, systolic blood pressure (SBP), and diastolic blood pressure (DBP). In both the early- and late-onset groups, the prevalence rates of severe anxiety disorder and psychotic symptoms were significantly higher in the suicide attempt group than in the non-suicide attempt group. In regression analysis, disease duration, TSH levels and HAMA score were independently associated with suicide attempts in the early-onset group, while TSH levels, HAMA and HAMD score were independently associated with suicide attempts in the late-onset group. Conclusion: This study suggests that suicide attempts are not frequent in early-onset outpatients with MDD compared with late-onset, and some clinical correlates are associated with suicide attempt in early- and late-onset MDD.

Determinants of Health-Seeking Behavior in Major Depressive Disorder: An Observational Study.

BACKGROUND: Major depressive disorder (MDD) is one of the most common illnesses in the world and a major cause of years lived with disability. It is necessary to diagnose and treat depression promptly. OBJECTIVES: To identify and compare factors affecting health-seeking behavior in patients suffering from MDD. METHODS: An observational cross-sectional study was conducted. The study population was divided into two groups: early and late health seekers (cut off: three months). Patient Health Questionnaire - 9 (PHQ-9) as well as Perceived and Personal Depression Stigma Scores were calculated. Data were analyzed and the chi-square test and z-test were used to calculate statistical significance. RESULTS: There were 102 participants. The majority were female (62.75%) and the maximum number of participants were from the age group of 26-45 years (65.69%). There were more early help seekers (61.76%) than late help seekers (38.24%). The majority of early help seekers were married individuals. Distance played a vital role in help-seeking behavior. A significant association was also found between participants' personal stigma and late treatment seeking. The most common reason for delaying medical attention was that patients thought that they could cure themselves, followed by a lack of awareness. CONCLUSION: Delay and hesitance observed concerning health-seeking behavior are assumed to be associated with factors such as gender, income, family or marital status, stigma, lack of awareness, beliefs and practices, and deficient health facilities causing delays in the diagnosis and management of MDD. The research supported that involving primary health care centers, spreading awareness about the disease, and increasing psychiatric facilities, along with a special emphasis on factors as mentioned like gender, marital status, stigma, and feasibility of reaching facility as distance plays a major role in causing delay, and can help decrease the duration of symptom from the onset, initiating appropriate treatment, and improving prognosis.

Overcoming the myths of esketamine administration: different and not difficult.

Intranasal esketamine for treatment-resistant depression has been introduced and approved by the FDA and EMA in 2019 and 2020, respectively. Since then, the administration practices were found different among countries. Major depression has a high impact on many humans lives worldwide and more than a third of treated people are not responding after several treatment attempts. Additional administration with esketamine closed this gap for more than the half of these non-responders. Guidelines for the treatment of major depression recommend starting with add-on esketamine after 2-4 serious attempts of treatment with standard antidepressants (SSRI/SNRI) irrespective of augmentation with others, e.g., second generation antipsychotics or lithium. Thus, intranasal esketamine became an important role in the evidence-based treatment of major depression. The authors review and critically evaluated published articles focusing on preparation, management and observation of intranasal esketamine treatment. There exists a clear recommendation for administrating intranasal esketamine in a medical environment, not limited to a clinical setting for selecting the dose, monitoring the improvements and managing adverse events. The administration of intranasal esketamine is considered as safe during the application itself and long-lasting or severe adverse events during long-term treatment are very rare. Since this is a new approach for treatment application psychiatrists face new different but not difficult treatment procedures compared to prescribing only a medication.

The Prevalence of Mood Disorders Among Health and Non-health Undergraduate Students in King Saud University, Riyadh, Saudi Arabia: A Cross-Sectional Study.

BACKGROUND: Mood disorders (MDs) are among the most common of all mental health diagnoses, with increasing prevalence and a devastating impact on individuals, families, and the community. This study aimed to estimate the frequency of MDs among health and non-health profession students. MATERIALS AND METHODS: A cross-sectional survey was conducted on 391 students to estimate the self-reported prevalence of different MDs and to screen for bipolar disorder (BD) using the mood disorder questionnaire (MDQ) and for depressive, anxiety, and stress symptoms using the Depression, Anxiety, and Stress Scale - 21 items (DASS-21). RESULTS: MDs were reported by 24.9% (n=50) of health profession students and 22.8% (n=31) of non-health profession students. For BD, it affected 35.3% of students in the health profession and 47.4% (n=46) of students without the health profession, although the difference was not statistically significant. The most reported MDs among health and non-health profession students were major depression (4.9% vs. 4.2%), seasonal affective disorder (SAD) (3.3% vs. 2.1%), dysthymia (2.4% vs. 2.8), and BD (2% vs. 2.8%), respectively. None of the observed differences between the two groups were statistically significant. According to DASS-21 scores for health and non-health profession students, severe depressive and severe anxiety symptoms were more common among non-health students (45.1% and 59.3%, respectively) than among health profession students (41.4% and 51.1%, respectively). However, stress was higher among health-related than non-health-related students (19.4% and 18.1%, respectively). CONCLUSIONS: MDs constitute a high burden among university students regardless of their field of study, creating an increased urgency to incorporate ways to promote the mental well-being of students and to manage those with an MD. Further research is needed to identify effective preventive strategies for depression in the future.

Differential symptom cluster responses to repetitive transcranial magnetic stimulation treatment in depression.

Background: Repetitive transcranial magnetic stimulation (rTMS) can target specific neural circuits, which may allow for personalized treatment of depression. Treatment outcome is typically determined using sum scores from validated measurement scales; however, this may obscure differential improvements within distinct symptom domains. The objectives for this work were to determine: (1) whether a standard depression measure can be represented using a four symptom cluster model and (2) whether these symptom clusters had a differential response to rTMS treatment. Methods: Data were obtained from two multi-centre randomized controlled trials of rTMS delivered to the left dorsolateral prefrontal cortex (DLPFC) for participants with treatment-resistant depression (TRD) conducted in Canada (THREE-D [Conducted between Sept 2013, and Oct 2016] and CARTBIND [Conducted between Apr 2016 and Feb 2018]). The first objective used confirmatory factor analytic techniques, and the second objective used a linear mixed effects model. Trial Registration: NCT01887782, NCT02729792. Findings: In the total sample of 596 participants with TRD, we found a model consisting of four symptom clusters adequately fit the data. The primary analysis using the THREE-D treatment trial found that symptom clusters demonstrated a differential response to rTMS treatment (F(3,5984) = 31.92, p < 0.001). The anxiety symptom cluster was significantly less responsive to treatment than other symptom clusters (t(6001) = -8.02, p < 0.001). These findings were replicated using data from the CARTBIND trial. Interpretation: There are distinct symptom clusters experienced by individuals with TRD that have a differential response to rTMS. Future work will determine whether differing rTMS treatment targets have distinct patterns of symptom cluster responses with the eventual goal of personalizing rTMS protocols based on an individual's clinical presentation. Funding: Canadian Institutes of Health Research, Brain Canada.

Lower Levels of GABAergic Function Markers in Corticotropin-Releasing Hormone-Expressing Neurons in the sgACC of Human Subjects With Depression.

Rationale: A previous transcriptome meta-analysis revealed significantly lower levels of corticotropin-releasing hormone (CRH) mRNA in corticolimbic brain regions in major depressive disorder (MDD) subjects, suggesting that cortical CRH-expressing (CRH+) cells are affected in MDD. Rodent studies show that cortical CRH is mostly expressed in GABAergic interneurons; however, the characteristic features of CRH+ cells in human brain cortex and their association with MDD are largely unknown. Methods: Subgenual anterior cingulate cortex (sgACC) of human subjects without brain disorders were labeled using fluorescent in situ hybridization (FISH) for CRH and markers of excitatory (SLC17A7), inhibitory (GAD1) neurons, as well as markers of other interneuron subpopulations (PVALB, SST, VIP). MDD-associated changes in CRH+ cell density and cellular CRH expression (n = 6/group) were analyzed. RNA-sequencing was performed on sgACC CRH+ interneurons from comparison and MDD subjects (n = 6/group), and analyzed for group differences. The effect of reduced BDNF on CRH expression was tested in mice with blocked TrkB function. Results: About 80% of CRH+ cells were GABAergic and 17.5% were glutamatergic. CRH+ GABAergic interneurons co-expressed VIP (52%), SST (7%), or PVALB (7%). MDD subjects displayed lower CRH mRNA levels in GABAergic interneurons relative to comparison subjects without changes in cell density. CRH+ interneurons show transcriptomic profile suggesting lower excitability and less GABA release and reuptake. Further analyses suggested that these molecular changes are not mediated by altered glucocorticoid feedback and potentially occur downstream for a common modulator of neurotrophic function. Summary: CRH+ cells in human sgACC are a heterogeneous population of GABAergic interneurons, although largely co-expressing VIP. Our data suggest that MDD is associated with reduced markers of inhibitory function in sgACC CRH+ interneurons, and provide further evidence for impaired GABAergic function in the cortex in MDD.

Mental health impacts of earthquake on Afghans amidst humanitarian crisis.

The deadly earthquake in southeast Afghanistan on June 22, 2022 was a tragedy amidst the country's humanitarian crisis. It cost more than a thousand people's lives, caused three times more injuries, and destroyed many houses, mainly in Spera, Giyan, and Barmal districts. WHO and other NGOs responded to incidence, focusing on physical injuries, food shortage, and shelter, while mental health was not adequately emphasized. Almost half of the Afghanistan population suffers from mental disorders due to decades of civil war, economic instability, and natural disasters. The recent earthquake further exacerbates the mental conditions among earthquake victims and their families, making them vulnerable to severe mental disorders. The absence of local mental facilities and proper roads delayed the early response and made the follow-up difficult leading to serious mental issues and costly management. Although WHO and HealthNet TPO sent their mental health professionals to consult the earthquake victims and train health care workers, the sociocultural beliefs made the approach difficult and its result suspicious. Moreover, the stigma around mental health and the lack of female HCWs stop people from seeking mental healthcare.

Food insecurity and symptoms of anxiety and depression disorder during the COVID- 19 pandemic: COVID-Inconfidentes, a population-based survey.

This study aimed to investigate the association between adult food insecurity (FI) and symptoms of generalized anxiety disorder (GAD) and major depressive disorder (MDD) in two Brazilian cities during the coronavirus disease (COVID-19) pandemic. This study used data derived from a cross-sectional survey of 1693 adults. Interviews were conducted using an electronic questionnaire. The FI was measured using the Brazilian Food Insecurity Scale. The Generalized Anxiety Disorder-7 was used to measure the symptoms of GAD. The Patient Health Questionnaire-9 was used for MDD symptoms. The association between FI, GAD, and MDD symptoms was investigated using a Poisson regression model with robust variance to estimate the prevalence ratio and 95% confidence interval (95% CI). In regression models, a linear association between FI levels and outcomes was observed, with severe food insecurity having a 3.56 higher prevalence of GAD symptoms (95% CI: 2.23, 5.68) and a 3.03 higher prevalence of MDD (95% CI: 1.55, 5.90). In the stratified analyses, worse results were observed for females and males, individuals with non-white race/skin color, those without children, and those with lower monthly family income. In conclusion, the FI was associated with symptoms of GAD and MDD, and the sociodemographic characteristics interfered in this association. Therefore, we recommend the improvement of public health and social protection policies for food-insecure people.

Neurotrophin Crosstalk in the Etiology and Treatment of Neuropsychiatric and Neurodegenerative Disease.

This article reviews the current progress in our understanding of the mechanisms by which growth factors, including brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), and select neurotrophin-regulated gene products, such as VGF (non-acronymic) and VGF-derived neuropeptides, function in the central nervous system (CNS) to modulate neuropsychiatric and neurodegenerative disorders, with a discussion of the possible therapeutic applications of these growth factors to major depressive disorder (MDD) and Alzheimer's disease (AD). BDNF and VEGF levels are generally decreased regionally in the brains of MDD subjects and in preclinical animal models of depression, changes that are associated with neuronal atrophy and reduced neurogenesis, and are reversed by conventional monoaminergic and novel ketamine-like antidepressants. Downstream of neurotrophins and their receptors, VGF was identified as a nerve growth factor (NGF)- and BDNF-inducible secreted protein and neuropeptide precursor that is produced and trafficked throughout the CNS, where its expression is greatly influenced by neuronal activity and exercise, and where several VGF-derived peptides modulate neuronal activity, function, proliferation, differentiation, and survival. Moreover, levels of VGF are reduced in the CSF of AD subjects, where it has been repetitively identified as a disease biomarker, and in the hippocampi of subjects with MDD, suggesting possible shared mechanisms by which reduced levels of VGF and other proteins that are similarly regulated by neurotrophin signaling pathways contribute to and potentially drive the pathogenesis and progression of co-morbid neuropsychiatric and neurodegenerative disorders, particularly MDD and AD, opening possible therapeutic windows.

Mood phenotypes in rodent models with circadian disturbances.

Many physiological functions with approximately 24-h rhythmicity (circadian rhythms) are generated by an internal time-measuring system of the circadian clock. While sleep/wake cycles, feeding patterns, and body temperature are the most widely known physiological functions under the regulation of the circadian clock, physiological regulation by the circadian clock extends to higher brain functions. Accumulating evidence suggests strong associations between the circadian clock and mood disorders such as depression, but the underlying mechanisms of the functional relationship between them are obscure. This review overviews rodent models with disrupted circadian rhythms on depression-related responses. The animal models with circadian disturbances (by clock gene mutations and artifactual interventions) will help understand the causal link between the circadian clock and depression.

Kamikihito rescued depressive-like behaviors and hippocampus neurogenesis in chronic restraint stress rats.

Background and aim: Substantial evidence suggests the effectiveness of plant-based medicine in stress-related diseases. Kamikihito (KKT), a Japanese traditional herbal medicine (Kampo), has been used for anemia, insomnia, and anxiety. Recent studies revealed its ameliorating effect on cognitive and memory dysfunction in several animal models. We, therefore, determined whether daily supplementation of KKT has an antidepressant-like effect on the stress-induced behavioral and neurological changes in rats. Experimental procedure: The effect of KKT against the stress-induced changes in anxiety- and depressive-like behaviors and hippocampal neurogenesis were determined using a rat model of chronic restraint stress (CRS). KKT was orally administered daily at 300 or 1000 mg/kg during 21 consecutive days of CRS (6 h/day). The effect of CRS and KKT on physiological parameters, including body weight gain, food/water consumptions, plasma corticosterone (CORT) levels, and percentage of adrenal gland weight to body weight, were firstly measured. Anxiety- and depressive-like behaviors in rats were assessed in the open field test (OFT), sucrose preference test (SPT), and forced swimming test (FST). Hippocampal neurogenesis was determined by immunohistochemistry. Results and conclusion: CRS for 21 days caused a significant decrease in body weight gain and increase in plasma CORT levels and percentage of adrenal gland weight to body weight, which were rescued by KKT treatment. KKT also suppressed the CRS-induced anxiety- and depressive-like behaviors and impairment of hippocampal neurogenesis. These results suggest that daily treatment of KKT has a protective effect against physiological, neurological, and behavioral changes in a rat model of depression.

The impact of physical conditions on the incidence of major depressive disorder in Chinese university students: Results from a longitudinal study.

BACKGROUND: Major depressive disorder (MDD) is prevalent, and highly comorbid with physical illnesses. Few longitudinal studies have investigated the relationship between physical health conditions and MDD. The objectives of this study were to investigate the comorbid relationship between physical conditions and MDD, and the association between physical conditions and the 2-year risk of MDD. METHODS: A study was conducted in first-year Chinese university students (n = 8,079) over two and half years, using a longitudinal design. An adapted version of the Composite International Diagnostic Interview (CIDI - 3.0) was used to assess for MDD. The presence of physician diagnosed physical conditions was assessed using ten self-report questions. Cross-sectional and longitudinal associations between self-reported physical conditions and MDD were estimated, adjusting for possible confounders. RESULTS: The most frequently reported physical conditions were migraines, chronic rhinitis, and gastritis. We found that migraines, gastritis, and stomach ulcers were associated with a significantly higher lifetime prevalence of MDD than those without any physical health conditions. In those without a lifetime MDD, migraines, gastritis and stomach ulcers were also found to be significant predictors for 2-year risk of new onset MDD. LIMITATIONS: Recall and selection biases are possible when using self-reporting measures. Additionally, the COVID-19 outbreak impacted the response rate at the second follow-up assessment. Lastly, the severity of the physical conditions was not measured. CONCLUSIONS: Physical conditions and MDD are highly prevalent and comorbid in university students. Migraines, gastritis and stomach ulcers are associated with the risk of developing MDD. Future studies should further investigate how this information can be used to prevent MDD.

Relationship between psychosocial stress-induced prefrontal cortex activity and gut microbiota in healthy Participants-A functional near-infrared spectroscopy study.

Brain and gut microbes communicate in a bidirectional manner with each affecting a person's response to psychosocial stress. Although human studies demonstrated that the intake of probiotics can alter stress-related behavior in both patients and healthy participants, the association between stress-related brain functions and the gut microbiota has mostly been investigated in patients with depression. However, the response to psychosocial stress differs, even among healthy individuals, and elucidating the natural state of the gut microbiota would broaden the understanding of responses to psychosocial stress. We investigated the relationship between psychosocial stress response in the prefrontal cortex and the abundance of gut microbes in healthy male participants. The participants were exposed to psychosocial stress during a task while brain activation data were recorded using functional near-infrared spectroscopy. The heart rate and subjective stress were recorded, and fecal samples were collected. The stressful condition was accompanied by high subjective stress, high heart rate, and higher prefrontal activation in the right pre-motor cortex/supplementary motor area, right dorsolateral prefrontal cortex, right frontal pole, and right inferior prefrontal gyrus. The psychosocial stress response in the prefrontal cortex was also associated with changes in the gut microbiota abundance. The abundance of Alistipes, Clostridium IV, Clostridium XI, Faecalibacterium, and Blautia in healthy participants who had high psychosocial stress resembled that noted in patients with depression. These results suggest that the gut microbiota differs, among healthy participants, depending on the psychosocial stress response. We believe that this study is the first to report a direct relationship between brain function and the gut microbiota in healthy participants, and our findings would shed a new light on this field in the near future.

Economic evaluation alongside a randomized controlled trial of blended cognitive-behavioral therapy for patients suffering from major depressive disorder.

OBJECTIVE: This study aimed to investigate the cost-effectiveness of blended cognitive-behavioral therapy (CBT) compared to standard CBT for adult patients suffering from major depressive disorder (MDD). DESIGN: A cost-utility analysis alongside the randomized controlled ENTER trial. SETTING: Center for Telepsychiatry, Mental Health Services in the Region of Southern Denmark, Denmark. PARTICIPANTS: The study included 76 patients suffering from MDD. INTERVENTIONS: The patients in the intervention group received blended CBT treatment comprising a combination of online modules and face-to-face consultations with a psychologist. The patients in the control group received standard CBT treatment, that is, solely face-to-face consultations with a psychologist. The treatment period was 12 weeks. OUTCOME MEASURES: Cost-effectiveness was reported as incremental cost-effectiveness ratio. A micro-costing approach was applied to evaluate the savings derived. Changes in quality-adjusted life-years (QALYs) were estimated using the EuroQol 5-Dimensions 5-Levels questionnaire at the baseline and the six-month follow-up. RESULTS: Data for 74 patients were included in the primary analysis. The adjusted QALY difference between blended CBT and standard CBT was -0.0291 (95% CI: -0.0535 to -0.0047), and the adjusted difference in costs was -£226.32 (95% CI: -300.86 to -151.77). Blended CBT was estimated to have a 6.6% and 3.1% probability of being cost-effective based on thresholds of £20,000 and £30,000. CONCLUSION: Compared to standard CBT, blended CBT represents a cost-saving but also a loss in QALYs for patients suffering from MDD. However, results should be carefully interpreted, given the small sample size. Future research involving larger replication studies focusing on other aspects of blended CBT with more patient involvement is advised. TRIAL REGISTRATION NUMBER: ClinicalTrial.gov: S-20150150.