Investigation and Analysis of Emotional State and Oxytocin Level in Patients with Postpartum Depression.

BACKGROUND: Postpartum depression (PPD) is a common mental disorder in postpartum women, negatively impacting physical and mental health. Correlation analysis can predict the relationship between variables. By detecting the abnormal level of oxytocin, clinicians can timely know the emotional states of parturients to guide clinical practice. This study aimed to investigate the relationship between emotional states and oxytocin (OT) levels in patients with PPD. MATERIALS AND METHODS: The medical records of 166 PPD patients admitted to Cangzhou Central Hospital from May 2020 to March 2023 were retrospectively analyzed. After excluding 9 patients who did not meet the inclusion criteria, the remaining 157 patients were included in this study. The 7-item Generalized Anxiety Disorder Scale and Patient Health Questionaire-9 items were used to evaluate the emotional states of 157 patients, and the included subjects were grouped according to the results of the scale. The serum OT levels of patients was measured, and the relationship between the OT levels and emotional states was analyzed. RESULTS: In this study, 75 patients were included in the mild anxiety group, and 82 patients were included in the moderate and severe anxiety group. Seventy-nine patients were selected as the mild depression group, and 78 patients were included in the moderate and severe depression group. The mild anxiety group had a higher OT level than the moderate and severe anxiety group (Z = -10.121, p < 0.001). The mild depression group had a higher OT level than the moderate and severe depression group (Z = -9.758, p < 0.001). OT level was negatively correlated with anxiety and depression scores (r = -0.676, r = -0.665, p < 0.001). CONCLUSION: There is a specific relationship between the emotional states of PPD patients and the OT levels in the body, and active clinical management strategies need to be implemented.

Changes in peripheral oxytocin and vasopressin during a silent month-long Insight meditation retreat.

Background: Given its putative roles in mediating prosocial behavior, attachment bonds, and stress physiology, oxytocin modulation has been hypothesized to be a biological correlate of the salubrious effects of meditation practice. Here we investigated the effects of a month-long silent meditation retreat on changes in oxytocin, and the related hormone and vasopressin, in relation to psychosocial changes in attachment style, anxiety, personality measures, and feelings of social connectedness with fellow meditators. Methods: Plasma oxytocin and vasopressin and self-report questionnaires were measured in retreat participants (n = 28) at the beginning of, and 3 weeks into, a residential meditation retreat. Control participants (n = 34), who were similar in age, gender, and meditation experience, were also assessed across a 3-week interval. Linear mixed effects models were used to assess outcomes. Results: The retreat group showed a small but significant decrease in oxytocin compared to controls who showed no change. In the retreat group, higher openness to experience at Time 1 predicted greater reductions in oxytocin during the retreat, and lower oxytocin at Time 2 was related to stronger feelings of personal connection with fellow meditators. The changes in oxytocin were not related to attachment style or anxiety. Vasopressin decreased over time across both groups, suggesting no specific effect of retreat. Conclusion: These preliminary findings suggest that meditation training in the context of a silent residential retreat may reduce circulating levels of oxytocin. We interpret this finding from multiple theoretical perspectives, discussing key measurement limitations and proposing future study designs that may help to differentiate the effects of different meditation practices and contexts on oxytocin signaling.

Parkinson's disease with anxiety: clinical characteristics and their correlation with oxidative stress, inflammation, and pathological proteins.

OBJECTIVE: This study was performed to explore the differences in the clinical characteristics and oxidative stress indicators, inflammatory factors, and pathological proteins in serum between Parkinson's disease (PD) with anxiety (PD-A) and with no anxiety (PD-NA) patients, and further correlations among clinical characteristics and above variables were analyzed in PD-A and PD-NA groups. METHODS: A total of 121 patients with PD were enrolled in this study and assessed by the Hamilton Anxiety Scale (14 items) (HAMA-14). These patients were divided into PD-A and PD-NA groups according to a cut-off point of 7 of HAMA-14. Demographic variables were collected, and clinical symptoms were assessed by multiple rating scales. The levels of free radicals, inflammatory factors, and pathological proteins in serum were measured by chemical colorimetric method and enzyme-linked immunosorbent assay (ELISA). The differences of above variables were compared between PD-A and PD-NA groups, and the correlations of clinical symptoms with the abovevariables were analyzed in PD-A and PD-NA groups. RESULTS: The frequency of PD-A was 62.81%. PD-A group exhibited significantly impaired motor dysfunction and multiple non-motor symptoms, including fatigue, sleep behavior disorder, restless leg syndrome and autonomic dysfunction, and dramatically compromised activities of daily living compard with PD-NA group. PD-A group displayed prominently increasedlevels of hydroxyl radical (·OH) and tumor necrosis factor (TNF)-α, and a decreased nitric oxide (NO) level in serum compared with PD-NA group (P<0.001, P = 0.001, P= 0.027, respectively). ·OH, NO, and TNF-α were identified as the risk factors of PD-A (OR = 1.005, P = 0.036; OR = 0.956, P = 0.017; OR = 1.039, P = 0.033, respectively). In PD patients, HAMA-14 score was significantly and positively correlated with the levels of ·OH and TNF-α in serum (P<0.001, P = 0.002, respectively). In PD-A group, ·OH level was significantly and negatively correlated with Aß1-42 level, while TNF-α level was significantly and positively correlated with P-tau (S396) level in serum. CONCLUSIONS: The frequency of PD-A is high. PD-A patients present more severe motor dysfunction and multiple non-motor symptoms, and poorer activities of daily living. The increased levels of ·OH and TNF-α levels and the decreased NO level in serum are all associated with more severe anxiety in PD patients.Findings from this study may provide in-depth insights into the clinical characteristics, underlying mechanisms of PD-A, and potential correlations among anxiety, oxidative stress, inflammation, and cognitive decline in PD patients.

The influence of gender-specific factors influencing severe anxiety in psychotic major depression: role of thyroid hormones and depression severity.

BACKGROUND: Psychotic major depression (PMD) is characterized by major depressive disorder (MDD) accompanied by delusions or hallucinations. While the prevalence of PMD and its association with anxiety have been studied, gender-specific differences and the role of thyroid hormones in PMD-related anxiety remain less explored. METHODS: A total of 1718 first-episode and drug-naïve MDD patients was assessed for the presence of PMD and severe anxiety. Clinical assessments, including Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impressions-Severity (CGI-S) scale, were conducted to assess depression, anxiety, psychotic symptoms, and clinical severity, respectively. Blood samples were collected to measure thyroid function parameters. RESULTS: The prevalence of severe anxiety was higher in PMD patients compared to non-psychotic MDD patients (71.3% vs. 5.3%). No significant gender differences were observed in the prevalence of severe anxiety among PMD patients. However, elevated thyroid-stimulating hormone (TSH) levels and increased depression severity (HAMD scores) were identified as independent risk factors for severe anxiety in female PMD patients. In contrast, no significant risk factors were found in male PMD patients. The area under the receiver operating characteristic (AUCROC) analysis revealed that the HAMD score and TSH level showed acceptable discriminatory capacity for distinguishing between female PMD patients with and without severe anxiety. CONCLUSION: This study highlights the heightened prevalence of severe anxiety in PMD patients, with TSH levels and depression severity emerging as gender-specific risk factors for anxiety in females. These findings suggest the importance of thyroid hormone assessment and tailored interventions for managing anxiety in female PMD patients.

Human placental lactogen (human chorionic somatomammotropin) and oxytocin during pregnancy: Individual patterns and associations with maternal-fetal attachment, anxiety, and depression.

Previous studies support links among maternal-fetal attachment, psychological symptoms, and hormones during pregnancy and the post-partum period. Other studies connect maternal feelings and behaviors to oxytocin and suggest that an increase in oxytocin during pregnancy may prime maternal-fetal attachment. To date, researchers have not examined a possible association between maternal-fetal attachment with human placental lactogen although animal models are suggestive. In the current study, we sought to describe oxytocin and human placental lactogen levels as related to psychological constructs across pregnancy. Seventy women participated in the study. At each of three time-points (early, mid, and late pregnancy), the women had their blood drawn to assess oxytocin and human placental lactogen levels, and they completed psychological assessments measuring maternal-fetal attachment, anxiety, and depression. Our results indicate that oxytocin levels were statistically similar across pregnancy, but that human placental lactogen significantly increased across pregnancy. Results did not indicate significant associations of within-person (comparing individuals to themselves) oxytocin or human placental lactogen levels with maternal-fetal attachment. Additionally, results did not show between-person (comparing individuals to other individuals) oxytocin or human placental lactogen levels with maternal-fetal attachment. Oxytocin levels were not associated with anxiety; rather the stage of pregnancy moderated the effect of the within-person OT level on depression. Notably, increasing levels of human placental lactogen were significantly associated with increasing levels of both anxiety and depression in between subject analyses. The current study is important because it describes typical hormonal and maternal fetal attachment levels during each stage of pregnancy, and because it suggests an association between human placental lactogen and psychological symptoms during pregnancy. Future research should further elucidate these relationships.

Does brain-derived neurotrophic factor play a role in the association between maternal prenatal mental health and neurodevelopment in 2-year-old children?

OBJECTIVE: To evaluate the role of brain-derived neurotrophic factor (BDNF)-a crucial modulator of neural development and plasticity-in the association between prenatal maternal anxiety, depression, and perceived stress and child neurodevelopment in a prospective cohort study. METHODS: We included 526 eligible mother-child pairs from the Shanghai Birth Cohort in the study. Maternal mental health was assessed at mid-pregnancy using Zung's Self-Rating Anxiety Scale, Center for Epidemiologic Studies Depression Scale, and Perceived Stress Scale. The concentration of BDNF in cord blood was measured by ELISA. The offspring neurodevelopment at 24 months of age was assessed using the Bayley Scales. Linear and non-linear regression models were used. RESULTS: The average cord blood BDNF levels were higher in female newborns and those born via vaginal delivery, full term, and normal birth weight. Prenatal maternal anxiety (ß = -0.32; 95 % CI: -0.55, -0.09), depression (ß = -0.30; 95 % CI: -0.52, -0.08), and perceived stress (ß = -0.41; 95 % CI: -0.71, -0.12) scores were negatively associated with social-emotional performance at 24 months of age. However, no significant associations were found between prenatal maternal anxiety, depression, or perceived stress at mid-pregnancy and cord blood BDNF levels, as well as between cord blood BDNF levels and child neurodevelopment. LIMITATIONS: Maternal mental health at different timepoints during pregnancy and generalizability of the results warrant further assessment. CONCLUSIONS: Prenatal mental health was not associated with cord blood BDNF level and that BDNF may not be a mediator in the association between prenatal mental health and child neurodevelopment.

C-Reactive Protein Does Not Predict Future Depression Onset in Adolescents: Preliminary Findings from a Longitudinal Study.

Introduction: Neuroinflammatory processes have been extensively implicated in the underlying neurobiology of numerous neuropsychiatric disorders. Elevated C-reactive protein (CRP), an indicator of nonspecific inflammation commonly utilized in clinical practice, has been associated with depression in adults. In adolescents, our group previously found CRP to be associated with altered neural reward function but not with mood and anxiety symptoms assessed cross-sectionally. We hypothesized that the distinct CRP findings in adolescent versus adult depression may be due to chronicity, with neuroinflammatory effects on psychiatric disorders gradually accumulating over time. Here, we conducted a longitudinal study to evaluate if CRP levels predicted future onset or progression of depression in adolescents. Methods: Participants were 53 adolescents (age = 14.74 ± 1.92 years, 35 female), 40 with psychiatric symptoms and 13 healthy controls. At baseline, participants completed semistructured diagnostic evaluations; dimensional assessments for anxiety, depression, anhedonia, and suicidality severity; and bloodwork to quantify CRP levels. Clinical assessments were repeated at longitudinal follow-up after ∼1.5 years. Spearman's correlation between CRP levels and follow-up symptom severity were controlled for body mass index, age, sex, and follow-up interval and considered significant at the two-tailed, Bonferroni-adjusted p < 0.05 level. Results: After correction for multiple comparisons, no relationships were identified between baseline CRP levels and follow-up symptom severity. Conclusion: CRP levels were not significantly associated with future psychiatric symptoms in adolescents in this preliminary analysis. This may suggest that CRP is not a useful biomarker for adolescent depression and anxiety. However, future longitudinal studies with larger sample sizes and incorporating additional indicators of neuroinflammation are needed.

Stress during pregnancy and fetal serum BDNF in cord blood at birth.

INTRODUCTION: Adverse environments during pregnancy impact neurodevelopment including cognitive abilities of the developing children. The mediating biological alterations are not fully understood. Maternal stress may impact the neurotrophic regulation of the offspring as early as in utero and at birth. Brain-derived neurotrophic factor (BDNF) is essential for neurodevelopment. Short-term higher levels of BDNF in mice upon stressors associate with lower BDNF later in life, which itself associates with depression in animals and humans. Stress including glucocorticoids may impact BDNF, but there is a lack of data at birth. This study investigated if stress near term associates with fetal BDNF at birth in humans. METHODS: Pregnant women near term who underwent primary cesarean sections (at 38.80±0.64 weeks), were included in this study (n=41). Stress at the end of pregnancy was assessed before the cesarean section by determining maternal depressive symptoms (EDPS), maternal state and trait anxiety (STAI-S and STAI-T), maternal prenatal distress (PDQ), stress over the past month (PSS), prenatal attachment to the offspring (PAI), maternal social support (F-Sozu), maternal early life stress (CTQ), socioeconomic status, and the glucocorticoids cortisol and cortisone (n=40) in amniotic fluid at birth. The association with fetal BDNF was analyzed. Cord blood serum of n=34 newborns at birth was analyzed for BDNF and newborn anthropometrics (weight, length and head circumference per gestational age at birth) were assessed. The association of fetal BDNF with anthropometrics at birth was analyzed. RESULTS: After a BDNF-outlier (>3 SD) was removed, higher fetal BDNF associated significantly with maternal depressive symptoms (r=0.398, p=0.022), with lower socioeconomic status as assessed by the average number of people per room in the household (r=0.526, p=0.002) and with borderline significance with net income per person in the household (r=-0.313, p=0.087) in the bivariate analyses. In multivariable analysis, BDNF stayed positively associated with maternal depressive symptoms (ß=0.404, 95% CI [7.057, 306.041], p=0.041) and lower net income per person in the household (ß=-0.562, 95% CI [-914.511, -60.523], p=0.027) when controlling for maternal age, maternal pre-pregnancy BMI, fetal sex and gestational age. Fetal BDNF did not associate with newborn anthropometrics with the outlier removed in bivariate analyses or in multivariable analyses when controlling for maternal BMI and fetal sex. CONCLUSION: Maternal depressive symptoms and lower socioeconomic status associated with higher fetal BDNF when controlling for confounders. Fetal BDNF did not associate with newborn anthropometrics with the outlier removed. Further studies should investigate how early altered BDNF associate with the development and possibly psychopathology of the offspring.

Post-COVID Trajectory of Pentraxin 3 Plasma Levels Over 6 Months and Their Association with the Risk of Developing Post-Acute Depression and Anxiety.

BACKGROUND AND OBJECTIVES: Clinical manifestations of coronavirus disease 2019 (COVID-19) often persist after acute disease resolution. Underlying molecular mechanisms are unclear. The objective of this original article was to longitudinally measure plasma levels of markers of the innate immune response to investigate whether they associate with and predict post-COVID symptomatology. METHODS: Adult patients with previous severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection during the first pandemic wave who underwent the 6-month multidisciplinary follow-up were included. Plasma levels of pentraxin 3 (PTX3), the complement components C3a and C5a, and chitinase-3 like-protein-1 (CHI3L1) were measured at hospital admission during acute disease (baseline) and at 1 and 6 months after hospital discharge. Associations with post-COVID-19 sequelae at 6 months were investigated using descriptive statistic and multiple regression models. RESULTS: Ninety-four COVID-19 patients were included. Baseline PTX3, C5a, C3a, and CHI3L1 did not predict post-COVID-19 sequelae. The extent of the reduction of PTX3 over time (delta PTX3) was associated with lower depressive and anxiety symptoms at 6 months (both p < 0.05). When entering sex, age, need for intensive care unit or non-invasive ventilation during hospital stay, psychiatric history, and baseline PTX3 as nuisance covariates into a generalized linear model (GLM), the difference between baseline and 6-month PTX3 levels (delta PTX3) significantly predicted depression (χ2 = 4.66, p = 0.031) and anxiety (χ2 = 4.68, p = 0.031) at 6 months. No differences in PTX3 levels or PTX3 delta were found in patients with or without persistent or new-onset other COVID-19 symptoms or signs at 6 months. Plasma levels of C3a, C5a, and CHI3L1 did not correlate with PTX3 levels at either time point and failed to associate with residual or de novo respiratory or systemic clinical manifestations of the disease at 6 months. CONCLUSIONS: A lower reduction of plasma PTX3 after acute COVID-19 associates with the presence of depression and anxiety, suggesting an involvement of inflammation in post-COVID-19 psychopathology and a potential role of PTX3 as a biomarker.

Elevated neurotensin levels among obese adolescents may be related to emotion dysregulation and impulsivity: a cross-sectional, case-control study.

BACKGROUND: In this study, we aimed to evaluate the serum neurotensin (NT) levels and their relationships with self-reported anxiety, emotion regulation skills and impulsivity in healthy and obese adolescents. METHODS: Adolescents who gained weight between 12- 17 years of age and who were above the 95th percentile (p) for body mass index (BMI) > 95p were compared with age- and gender-matched healthy adolescents with a BMI of 3-85 p. Anthropometric measurements were performed, and serum NT levels were analyzed with ELISA method in all participants. Barrat Impulsivity Scale-11 (BIS-11), Screen for Child Anxiety Related Disorders (SCARED) and Difficulties in Emotion Regulation Scale (DERS) were used for evaluating self-reported impulsivity, anxiety and emotion regulation. MANOVA with follow-up univariate ANOVAs (Bonferroni corrected) were used for group comparisons. P was set at 0.05 (two-tailed). RESULTS: Sixty-five obese and 65 healthy adolescents were included in the study. In the obese group, NT levels were significantly elevated compared to the control group. Self-reported emotion-regulation difficulties, anxiety and impulsivity were significantly elevated among obese adolescents. Serum NT levels among the obese group were positively correlated with emotion dysregulation and impulsivity scores. CONCLUSIONS: In this study, we found emotional dysregulation, anxiety, impulsivity, and serum NT levels were significantly elevated among obese adolescents compared to controls. NT levels in the obese group correlated with impulsivity and emotion dysregulation. Further studies should evaluate the potential role of NT in the etiology of psychopathology among adolescents who are obese.

Blood-based biomarkers of agitation in Alzheimer's disease: Advances and future prospects.

Agitation is a common neuropsychiatric symptom that becomes more prevalent as Alzheimer's disease (AD) increases in severity. The treatment of agitation is an urgent and unmet need due to the poor outcomes associated with it, its disruptive impact on patients and caregivers, and the lack of efficacious and safe treatments. Recent research on agitation in AD with blood-based biomarkers has advanced the search for its biomarkers beyond the brain and provides new insights to understand its mechanisms and improve treatments. Here, we reviewed studies of blood-based biomarkers of agitation in AD, which show that inflammatory biomarkers are increased in patients with agitation, may predict the development of agitation, and are associated with symptom severity. In addition, they may also track symptom severity and response to treatment. Other biomarkers associated with agitation include markers of oxidative stress, brain cholesterol metabolism, motor activity, and clusterin, a chaperone protein. These results are promising and need to be replicated. Preliminary evidence suggests a role for these biomarkers in interventional studies for agitation to predict and monitor treatment response, which may eventually help enrich study samples and deliver therapy likely to benefit individual patients. Advances in blood-based biomarkers of AD including those identified in "-omic" studies and high sensitivity assays provide opportunities to identify new biomarkers of agitation. Future studies of agitation and its treatment should investigate blood-based biomarkers to yield novel insights into the neurobiological mechanisms of agitation, monitoring symptoms and response to treatment, and to identify patients likely to respond to treatments.

The association of in vitro fertilization/intracytoplasmic sperm injection results with anxiety levels and stress biomarkers: An observational, case-control study✰.

INTRODUCTION: Anxiety has been considered to exert a negative influence on fecundity. However, it remains unclear whether it is a cause or a consequence and whether it is associated with the treatment outcome. This observational case control study evaluated the levels of state anxiety and various stress biomarkers and assessed their association with in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes. MATERIALS AND METHODS: We allocated 109 infertile nulliparous women aged 25-45 years in their first IVF/ICSI fresh treatment cycle into two groups according to the final outcome: group A (PTP = pregnancy-test positive, n = 49) and group B (PTN = pregnancy-test negative, n = 60). State anxiety levels were measured with the Spielberger Trait Anxiety Inventory (STAI) questionnaire (Marteau and Bekker modification) on the days of oocyte retrieval (OR) and embryo transfer (ET). Serum stress biomarkers (cortisol, adrenaline, noradrenaline, α-amylase, and prolactin) were measured at the same time points. Blood samples were collected at 9 am. RESULTS: Most women in both groups showed comparable mild-to-moderate degrees of state anxiety on the days of OR and ET (p = 0.183 and p = 0.760, respectively). The stress biomarker measurements did not differ between the two groups, except for noradrenaline that was higher in group B (p = 0.015) and associated with significant cardiovascular changes. DISCUSSION: Women in both groups showed comparable levels of state anxiety, which were unlikely to influence the chance of pregnancy. Noradrenaline levels were higher in the non-pregnant group, with significant cardiovascular changes. Other stress biomarkers did not reflect the different treatment outcomes between the groups.

Low Anti-Mullerian Hormone Levels Are Associated with the Severity of Anxiety Experienced by Healthcare Professionals During the COVID-19 Pandemic.

The objective of this study is to investigate a possible correlation between anxiety status and anti-Mullerian hormone (AMH) levels among healthcare professionals who provide medical care directly to COVID-19-positive patients during the recent pandemic. Fifty-two healthcare professionals (nurses, midwives, and residents) who provide medical care directly to COVID-19-positive patients in inpatient clinics or intensive care units were enrolled in this study. Serum AMH levels were analyzed to reflect ovarian reserve. The Beck Anxiety Inventory (BAI) and the State-Trait Anxiety Inventory (STAI-S and STAI-T, respectively) were completed by participants to assess their anxiety status. A linear regression model with participant age as the constant variable was applied to analyze the relationship between inventory scale scores and AMH levels. P-values less than 0.05 were considered statistically significant. The mean AMH value was significantly lower for the participants in the moderate/severe anxiety group compared to the minimal/mild anxiety group (p = 0.007). A linear regression analysis revealed a significant negative correlation between AMH levels and both BAI (B = -0.030, standard error = 0.010, p = 0.004) and STAI-S and STAI-T scores when age was controlled (both p = 0.003). The severity of anxiety experienced during the recent COVID-19 pandemic among healthcare professionals, who provide medical care directly to COVID-19-positive patients, is found to be related to low AMH levels.

Effect of treadmill exercise on serum corticosterone, serum and hippocampal BDNF, hippocampal apoptosis and anxiety behavior in an ovariectomized rat model of post-traumatic stress disorder (PTSD).

There is a sex difference in vulnerability to PTSD and in response to therapeutic interventions. Since relation between gonadal hormones and PTSD has been revealed, this study aimed to understand the severity of PTSD-induced impairments after ovarian hormone deficiency and the influence of exercise on PTSD accompanied by ovarian hormone deficiency. Female adult Wistar rats were subjected to ovariectomy, PTSD, or combination ovariectomy plus PTSD. Twenty days after ovariectomy, PTSD was induced by single prolonged stress (SPS) model. The exercise started 14 days after SPS and continued for 4 weeks. Thirty minutes moderate treadmill exercise was planned for 5 days per week. On day 65, after assessing rats using the elevated plus-maze (EPM) test, corticosterone, BDNF, and apoptotic markers were tested. p < 0.05 was considered as significant level. The results showed that ovariectomy worsened the effect of SPS on hippocampal BDNF and led to greater increase in serum corticosterone and hippocampal caspase 3 and BAX in SPS rats. Also, ovariectomy exacerbated anxiety-like behavior in SPS rats. Exercise improved the alterations of hippocampal BDNF, corticosterone, caspase 3, and BAX in SPS ovariectomized rats. However, exercise had no statistically significant effect on anxiety-like behavior in this group. According to the results, exercise is effective to attenuate SPS-induced impairments in molecular and cellular responses even when the condition becomes more complicated due to ovarian hormone deficiency. However, exercise alone cannot help to improve behavior impairments in PTSD combined with an ovarian hormone deficiency. Therefore, exercise could likely be considered as a complementary intervention to strengthen other treatments.

Metabolite trajectories across the perinatal period and mental health: A preliminary study of tryptophan-related metabolites, bile acids and microbial composition.

Depression and anxiety during pregnancy and postpartum are common, but affected women differ in timing, trajectories, and extent of symptoms. The objective of this pilot, feasibility study is to analyze trajectories of serotonin and tryptophan-related metabolites, bile acid metabolites, and microbial composition, in relation to psychiatric history and current symptoms across the perinatal period. Serum and fecal samples were collected from 30 women at three times points in the perinatal period and assayed with LC-MS/MS and 16S sequencing respectively. We defined mean trajectories for each metabolite, clustered individuals by metabolite trajectories, tested associations between metabolites, and examined metabolite levels in relation to microbial composition. Findings of note include: (1) changes in kynurenine and the ratio of kynurenic acid to kynurenine from second trimester to third trimester were strongly associated with baseline primary and secondary bile acids. (2) Secondary bile acid UDCA and its conjugated forms were associated with lower bacterial diversity and levels of Lachnospiraceae, a taxa known to produce Short Chain Fatty Acids. (3) History of anxiety was associated with UDCA levels, but history of major depression was not associated with any of the bile acids. (4) There was a trend towards lower dietary fiber for those with history of anxiety or depression. Overall, our results reveal substantial temporal variation in tryptophan-related metabolites and in bile acid metabolites over the perinatal period, with marked inter-individual variability. Trajectories of TRP -related metabolites, primary and secondary bile acids, and the absence or presence of microbes that produce Short Chain Fatty Acids (SCFAs) considered in concert have the potential to differentiate individuals based on perinatal adaptations that may impact mental and overall health.

Depression and anxiety in patients with active ulcerative colitis: crosstalk of gut microbiota, metabolomics and proteomics.

Patients with ulcerative colitis (UC) have a high prevalence of mental disorders, such as depression and anxiety. Gut microbiota imbalance and disturbed metabolism have been suggested to play an important role in either UC or mental disorders. However, little is known about their detailed multi-omics characteristics in patients with UC and depression/anxiety. In this prospective observational study, 240 Chinese patients were enrolled, including 129 patients with active UC (69 in Phase 1 and 60 in Phase 2; divided into depression/non-depression or anxiety/non-anxiety groups), 49 patients with depression and anxiety (non-UC), and 62 healthy people. The gut microbiota of all subjects was analyzed using 16S rRNA sequencing. The serum metabolome and proteome of patients with UC in Phase 2 were analyzed using liquid chromatography/mass spectrometry. Associations between multi-omics were evaluated by correlation analysis. The prophylactic effect of candidate metabolites on the depressive-like behavior of mice with colitis was investigated. In total, 58% of patients with active UC had depression, while 50% had anxiety. Compared to patients with UC without depression/anxiety, patients with UC and depression/anxiety had lower fecal microbial community richness and diversity, with more Lactobacillales, Sellimonas, Streptococcus, and Enterococcus but less Prevotella_9 and Lachnospira. Most metabolites (e.g., glycochenodeoxycholate) were increased in the serum, while few metabolites, including 2'-deoxy-D-ribose and L-pipecolic acid, were decreased, accompanied by a general reduction in immunoglobulin proteins. These related bacteria, metabolites, and proteins were highly connected. A prophylactic administration of 2'-deoxy-D-ribose and L-pipecolic acid significantly reduced the depressive-like behaviors in mice with colitis and alleviated the inflammatory cytokine levels in their colon, blood and brain. This study has identified a comprehensive multi-omics network related to depression and anxiety in active UC. It is composed of a certain set of gut microbiota, metabolites, and proteins, which are potential targets for clinical intervention for patients with UC and depression/anxiety.

Effects of Importin α1/KPNA1 deletion and adolescent social isolation stress on psychiatric disorder-associated behaviors in mice.

Importin α1/KPNA1 is a member of the Importin α family widely present in the mammalian brain and has been characterized as a regulator of neuronal differentiation, synaptic functionality, and anxiety-like behavior. In humans, a de novo mutation of the KPNA1 (human Importin α5) gene has been linked with schizophrenia; however, the precise roles of KPNA1 in disorder-related behaviors are still unknown. Moreover, as recent studies have highlighted the importance of gene-environment interactions in the development of psychiatric disorders, we investigated the effects of Kpna1 deletion and social isolation stress, a paradigm that models social stress factors found in human patients, on psychiatric disorder-related behaviors in mice. Through assessment in a behavioral battery, we found that Kpna1 knockout resulted in the following behavioral phenotype: (1) decreased anxiety-like behavior in an elevated plus maze test, (2) short term memory deficits in novel object recognition test (3) impaired sensorimotor gating in a prepulse inhibition test. Importantly, exposure to social isolation stress resulted in additional behavioral abnormalities where isolated Kpna1 knockout mice exhibited: (1) impaired aversive learning and/or memory in the inhibitory avoidance test, as well as (2) increased depression-like behavior in the forced swim test. Furthermore, we investigated whether mice showed alterations in plasma levels of stress-associated signal molecules (corticosterone, cytokines, hormones, receptors), and found that Kpna1 knockout significantly altered levels of corticosterone and LIX (CXCL5). Moreover, significant decreases in the level of prolactin were found in all groups except for group-housed wild type mice. Our findings demonstrate that Kpna1 deletion can trigger widespread behavioral abnormalities associated with psychiatric disorders, some of which were further exacerbated by exposure to adolescent social isolation. The use of Kpna1 knockout mice as a model for psychiatric disorders may show promise for further investigation of gene-environment interactions involved in the pathogenesis of psychiatric disorders.

Influence of Vitamin D Supplementation on Mental Health in Diabetic Patients: A Systematic Review.

Diabetes is associated with a number of mental health consequences, including enhanced risk of depression and anxiety, as well as decreased quality of life, and vitamin D deficiency is considered to be one of the factors that influence these outcomes in diabetic patients. The aim of the present study was to conduct a systematic review of the literature presenting the data regarding the influence of vitamin D supplementation on mental health in diabetic adults. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (Registration number CRD42020155779). A systematic search of the PubMed and Web of Science databases was performed, and the intervention studies published until September 2021 were included in the review. The human studies were included if an adult sample of diabetic individuals received vitamin D supplementation during the intervention and its effect on any mental health aspect was assessed, but studies presenting the influence of combined supplementation of multiple nutrients were excluded. After removing duplicate records, a total of 8514 publications were screened and assessed independently by two researchers, based on their title, abstract, and full text. Finally, six studies were included in the current systematic review, and the risk of bias was evaluated using the Newcastle-Ottawa Scale (NOS). The included studies analyzed the influence of a specific dose of vitamin D, or different doses of vitamin D, or compared the results of supplementation with a specific dose of vitamin D against the placebo group. The supplementation was performed for at least 12 weeks. The mental health outcomes analyzed in these studies included health-related quality of life, depression, anxiety, stress, and general mental health status of adult diabetic patients. The results of the majority of the studies confirmed the positive influence of vitamin D supplementation on the mental health of diabetic individuals. Those studies that analyzed the influence of vitamin D supplementation on depression and anxiety established the beneficial effect of the vitamin. In some studies, the influence of vitamin D supplementation on the health-related quality of life was not considered unless combined with mindfulness training. However, it must be emphasized that different dosage regimens and intervention periods were followed in the reviewed studies, and only a small number of studies were randomized against placebo, which should be considered as a limitation of the present study. The findings of the conducted systematic review demonstrated the positive influence of vitamin D supplementation on the mental health of diabetic patients, which was proved for anxiety and depression, but in the case of health-related quality of life, the positive effect was observed only when the intervention included mindfulness training. These outcomes suggest that supplementation should be recommended to improve the vitamin D status and the mental health of patients in this group.

Indoxyl sulfate, a gut microbiome-derived uremic toxin, is associated with psychic anxiety and its functional magnetic resonance imaging-based neurologic signature.

It is unknown whether indoles, metabolites of tryptophan that are derived entirely from bacterial metabolism in the gut, are associated with symptoms of depression and anxiety. Serum samples (baseline, 12 weeks) were drawn from participants (n = 196) randomized to treatment with cognitive behavioral therapy (CBT), escitalopram, or duloxetine for major depressive disorder. Baseline indoxyl sulfate abundance was positively correlated with severity of psychic anxiety and total anxiety and with resting state functional connectivity to a network that processes aversive stimuli (which includes the subcallosal cingulate cortex (SCC-FC), bilateral anterior insula, right anterior midcingulate cortex, and the right premotor areas). The relation between indoxyl sulfate and psychic anxiety was mediated only through the metabolite's effect on the SCC-FC with the premotor area. Baseline indole abundances were unrelated to post-treatment outcome measures, and changes in symptoms were not correlated with changes in indole concentrations. These results suggest that CBT and antidepressant medications relieve anxiety via mechanisms unrelated to modulation of indoles derived from gut microbiota; it remains possible that treatment-related improvement stems from their impact on other aspects of the gut microbiome. A peripheral gut microbiome-derived metabolite was associated with altered neural processing and with psychiatric symptom (anxiety) in humans, which provides further evidence that gut microbiome disruption can contribute to neuropsychiatric disorders that may require different therapeutic approaches. Given the exploratory nature of this study, findings should be replicated in confirmatory studies.Clinical trial NCT00360399 "Predictors of Antidepressant Treatment Response: The Emory CIDAR" https://clinicaltrials.gov/ct2/show/NCT00360399 .

Vitamin D and the Risks of Depression and Anxiety: An Observational Analysis and Genome-Wide Environment Interaction Study.

Previous studies have suggested that vitamin D (VD) was associated with psychiatric diseases, but efforts to elucidate the functional relevance of VD with depression and anxiety from genetic perspective have been limited. Based on the UK Biobank cohort, we first calculated polygenic risk score (PRS) for VD from genome-wide association study (GWAS) data of VD. Linear and logistic regression analysis were conducted to evaluate the associations of VD traits with depression and anxiety traits, respectively. Then, using individual genotype and phenotype data from the UK Biobank, genome-wide environment interaction studies (GWEIS) were performed to identify the potential effects of gene × VD interactions on the risks of depression and anxiety traits. In the UK Biobank cohort, we observed significant associations of blood VD level with depression and anxiety traits, as well as significant associations of VD PRS and depression and anxiety traits. GWEIS identified multiple candidate loci, such as rs114086183 (p = 4.11 × 10-8, LRRTM4) for self-reported depression status and rs149760119 (p = 3.88 × 10-8, GNB5) for self-reported anxiety status. Our study results suggested that VD was negatively associated with depression and anxiety. GWEIS identified multiple candidate genes interacting with VD, providing novel clues for understanding the biological mechanism potential associations between VD and psychiatric disorders.