Metabolic Status Influences Probiotic Efficacy for Depression-PRO-DEMET Randomized Clinical Trial Results.

Probiotics may represent a safe and easy-to-use treatment option for depression or its metabolic comorbidities. However, it is not known whether metabolic features can influence the efficacy of probiotics treatments for depression. This trial involved a parallel-group, prospective, randomized, double-blind, controlled design. In total, 116 participants with depression received a probiotic preparation containing Lactobacillus helveticus Rosell®-52 and Bifidobacterium longum Rosell®-175 or placebo over 60 days. The psychometric data were assessed longitudinally at five time-points. Data for blood pressure, body weight, waist circumference, complete blood count, serum levels of C-reactive protein, cholesterol, triglycerides, and fasting glucose were measured at the beginning of the intervention period. There was no advantage of probiotics usage over placebo in the depression score overall (PRO vs. PLC: F(1.92) = 0.58; p = 0.45). However, we found a higher rate of minimum clinically important differences in patients supplemented with probiotics than those allocated to placebo generally (74.5 vs. 53.5%; X2(1,n = 94) = 4.53; p = 0.03; NNT = 4.03), as well as in the antidepressant-treated subgroup. Moreover, we found that the more advanced the pre-intervention metabolic abnormalities (such as overweight, excessive central adipose tissue, and liver steatosis), the lower the improvements in psychometric scores. A higher baseline stress level was correlated with better improvements. The current probiotic formulations may only be used as complementary treatments for depressive disorders. Metabolic abnormalities may require more complex treatments. ClinicalTrials.gov identifier: NCT04756544.

Resilience and Psychological Well-Being of Polish Women in the Perinatal Period during the COVID-19 Pandemic.

PURPOSE: The COVID-19 pandemic, with its multidimensional consequences, is the most serious threat of the 21st century affecting the mental health of women in the perinatal period around the world. Resilience, which assumes the flexible use of an individual's resources in facing adversity, is an important, protective factor influencing mental well-being. The presented study aimed to determine to what extent psychological resilience, mitigates the relationship between adverse consequences of the COVID-19 pandemic and symptoms of depression and anxiety in women in the perinatal period. METHODS: We recruited pregnant women from 17 February to 13 October 2021, using social media, the parenting portal, and the snowball method. To assess mental well-being, we used: The Edinburgh Postnatal Depression Scale (EPDS), The Beck Depression Inventory (BDI-2), Self-report Labour Anxiety Questionnaire-LAQ and the self-developed COVID-19 Pandemic Anxiety Questionnaire (CRAQ). Resilience was measured usingthe Resilience Measure Questionnaire (KOP26). Multiple Correspondence Analysis (MCA), an independent t-test, and a Pearson correlation analysis were performed. RESULTS: Low resilience was significantly associated with depressive symptoms (r = -0.46; p < 0.05) and anxiety related to childbirth (r = -0.21; p < 0.05). No associations were found for resilience and pandemic-related stress. Very high and high perinatal anxiety along with the lowest level of resilience clustered with EPDS and BDI-2 scores indicating depression. CONCLUSIONS: Our study provides evidence that lower levels of resilience during pregnancy may be a significant predictor of increased severity of depressive symptoms and higher levels of anxiety related to childbirth among the perinatal population.

Resilience and Strategic Emotional Intelligence as Mediators between the Disconnection and Rejection Domain and Negative Parenting among Female Intimate Partner Violence Victims.

(1) Background: The exposure of children to intimate partner violence (IPV) is associated with a wide range of negative effects on children's development, where as parenting practice is considered to be one of the key factors mediating and mitigating this. Studies have found mixed results regarding the impact of female IPV victimization on maternal parenting practice; however, the most frequently tested hypothesis suggests that the cumulative stress of the IPV experience may emotionally deregulate the mother, contributing to an increased risk of neglected and abusive parenting practices. Little is still known about the factors determining the observed differences in maternal parenting practices among IPV victims. Thus, in our study, we use mediation models to provide preliminary results exploring the role of resilience and strategic emotional intelligence in the relationship between women's disconnection and rejection (D/R) schema domain and maternal parenting practice among IPV victims. (2) Methods: A total of 48 female survivors of IPV and 48 age-matched women with no prior experience of IPV completed a set of tests examining parenting practices, the D/R domain, resilience and emotional intelligence. (3) Results: IPV victimization was associated with significantly higher rates of negative parenting practices. The D/R domain was found to be a significant predictor of parental autonomy attitude and level of parental competence, and these relationships were fully mediated by resilience with strategic emotional intelligence and resilience, respectively. (4) Conclusions: The results shed light on the under-researched relationship between early maladaptive schemas and parenting behavior in the context of IPV. The implications for clinical practice and further research can be drawn based on the study findings.

Cognitive-Affective Risk Factors of Female Intimate Partner Violence Victimization: The Role of Early Maladaptive Schemas and Strategic Emotional Intelligence.

(1) Background: Intimate partner violence (IPV) is a pervasive and destructive phenomenon. There is a need for an integrated and comprehensive approach to IPV in order to align prevention, support and treatment. Still little is known about the cognitive and affective markers of IPV that are modifiable. Such knowledge, therefore, can support the effectiveness of prevention and intervention programs. In this study, we put forward a hypothesis that, after accounting for the influence of sociodemographic variables, the domains of early maladaptive schemas (EMS) and strategic emotional intelligence would provide additional information for predicting female IPV victimization. (2) Methods: 48 female survivors of IPV and 48 age-matched women with no prior experience of IPV completed the Young Schema Questionnaire-Short Form 3 (YSQ-SF3) and The Emotional Understanding Test (TRE). (3) Results: The domains of disconnection and rejection and impaired limits were significant predictors of IPV victimization, but the results did not support the predictive value for impaired autonomy, other-directedness and strategic emotional intelligence. (4) Conclusions: Our findings add to the emerging evidence of a link between disconnection and rejection domain and IPV victimization. As a consequence, maladaptive beliefs that interpersonal relationships are unstable and insecure and expose to the risk of humiliation and harm, and that basic emotional needs cannot be satisfied in close relationships, are associated with a higher risk of intimate partner violence. In this context, schema therapy appears to be a promising support for IPV victims.

PRO-DEMET Randomized Controlled Trial on Probiotics in Depression-Pilot Study Results.

There is a pressing need to identify new treatment options for depression and its comorbidities. Depression often coexists with metabolic complications, and the two may share a pathophysiological overlap, including inflammation and microbiota changes. Microbiota interventions (e.g., probiotics) may represent a safe and easy-to-use treatment option as an adjunctive therapy in patients only partially responsive to pharmacologic treatment. (1) Objective: The paper presents the results of a feasibility and pilot study. The study is an internal part of a randomized controlled trail (RCT) of the effect of probiotic supplementation on psychometric, anthropometric, metabolic, and inflammatory parameters in adult patients with depressive disorders depending on the presence of metabolic syndrome. (2) Methods: The trial has a four-arm, parallel-group, prospective, randomized, double-blind, controlled design. Sixty participants received a probiotic preparation containing Lactobacillus helveticus Rosell®-52 and Bifidobacterium longum Rosell®-175 over 60 days. The feasibility of the study design was assessed, as well as the rates of recruitment, eligibility, consent, and study completion. The following were assessed: depressive, anxiety and stress symptoms, quality of life, blood pressure, body mass index and waist circumference, complete blood count with differential, serum levels of C-reactive protein, high-density lipoprotein cholesterol, triglycerides, fasting glucose, some secondary markers of inflammation and metabolic health, as well as noninvasive biomarkers of liver fibrosis (APRI and FIB-4). (3) Results: The study was found to be generally feasible. The eligibility rate was 52% of recruited participants with 80% completing the study protocol. No differences in sociodemographic or anthropometric factors or basic laboratory findings were found between the placebo and probiotic group at the start of the intervention period. Importantly, the proportion of recruited participants fulfilling the criteria of metabolic syndrome was too low. (4) Conclusions: Whilst the whole study protocol was feasible, some different timepoint procedures require modification. The major weakness of the recruitment methods was that the percentage of metabolic arms participants was insufficient. Overall, the full RCT design on probiotics in depression with vs. without metabolic syndrome was shown to be feasible with little modification.

The Influence of Probiotic Supplementation on the Severity of Anxiety and Depressive Symptoms; Function and Composition of Gut Microbiota; and Metabolic, Inflammation, and Oxidative Stress Markers in Patients with Depression-A Study Protocol.

This article aims to present the theoretical basis, methodology, and design of a clinical trial we will conduct. The study will be prospective, randomized, placebo-controlled, and double-blind. Each intervention period will last 8 weeks and the trial will be conducted on 100 patients in total, who will be randomly divided into two groups consisting of 50 patients each. We plan to investigate the impact of Lactobacillus helveticus Rosell and Bifidobacterium longum Rosell on the depressive, anxiety, and stress levels in patients with depressive disorders with possible comorbid anxiety. In addition to assessing the influence of probiotics on the clinical condition, we also plan to study the clinical and biochemical parameters of metabolic syndrome, which often coexists with depression. Both depressive and metabolic issues may have part of their etiopathology in common, e.g., inflammation, oxidative stress, and dysbiosis. This is why we will additionally investigate the parameters related to gut microbiota, inflammatory, and oxidative statuses. Thus, the primary endpoint of the study will be the change in depression score measured with the Montgomery-Åsberg Depression Rating Scale. The secondary endpoints will include changes in anxiety and stress levels, as well as metabolic, inflammation, and oxidative stress parameters.

"Leaky Gut" as a Keystone of the Connection between Depression and Obstructive Sleep Apnea Syndrome? A Rationale and Study Design.

Obstructive sleep apnea (OSA) and depression are highly comorbid. Immune alterations, oxidative stress or microbiota dysfunction have been proposed as some mechanisms underlying this association. The aim of the proposed study is to assess the severity and profile of OSA and depressive symptoms in the context of serum microbiota metabolites, biomarkers of intestinal permeability, inflammation and oxidative stress in adult patients diagnosed with OSA syndrome. The study population consists of 200 subjects. An apnoea-hypopnoea index ≥ 5/hour is used for the diagnosis. Depressive symptoms are assessed with Beck Depression Inventory. Measured serum markers are: tumour necrosis factor-alpha and interleukin-6 for inflammation, total antioxidant capacity and malondialdehyde concentration for oxidative stress, zonulin, calprotectin, lipopolisaccharide-binding protein and intestinal fatty acids-binding protein for intestinal permeability. All of the above will be measured by enzyme-linked immunosorbent assay (ELISA). Associations between clinical symptoms profile and severity and the above markers levels will be tested. It would be valuable to seek for overlap indicators of depression and OSA to create this endophenotype possible biomarkers and form new prophylactic or therapeutic methods. The results may be useful to establish a subpopulation of patients sensitive to microbiota therapeutic interventions (probiotics, prebiotics, and microbiota transplantation).

Comparison of thyroid-stimulating hormone levels in adolescents with schizophrenia, bipolar disorder, unipolar depression, conduct disorders, and hyperkinetic disorders.

ABSTRACT: The aim of this study was to retrospectively compare values of thyroid-stimulating hormone (TSH) in adolescent patients diagnosed with schizophrenia, bipolar disorder, unipolar depression (UNI-DEP), conduct disorders (CD), and hyperkinetic disorders.The research involved 1122 patients (718 women, 64%); aged 12 to 18 hospitalized in the Department of Adolescent Psychiatry, Medical University of Lodz. We analyzed TSH levels in the whole study population and compared it between the above-mentioned subgroups of diagnoses.Mean serum TSH concentration in the studied population (n = 1122) was 2.06 µIU/mL. The values of percentiles were as follows: 2.5th - 0.53 µIU/mL, 10th - 0.89 µIU/mL, 25th - 1.31 µIU/mL, 50th - 1.9 µIU/mL, 75th - 2.6 µIU/mL, 90th - 3.43 µIU/mL, 97.5th - 4.72 µIU/mL. TSH values were negatively correlated with patients' age (P = .00001). Patients with bipolar depression had higher TSH levels than patients with CD (P = .002). Also, when male and female groups were examined separately we found that female patients with UNI-DEP and bipolar disorder had higher TSH levels than female patients with CD (P = .001; P = .001).Our results confirm that there may be a higher prevalence of thyroid dysfunctions in bipolar and UNI-DEP subgroups among adolescents and that it is worthy to consider some kind of interventions regarding thyroid function in depressed individuals.

The Influence of Probiotic Supplementation on Depressive Symptoms, Inflammation, and Oxidative Stress Parameters and Fecal Microbiota in Patients with Depression Depending on Metabolic Syndrome Comorbidity-PRO-DEMET Randomized Study Protocol.

There is a huge need to search for new treatment options and potential biomarkers of therapeutic response to antidepressant treatment. Depression and metabolic syndrome often coexist, while a pathophysiological overlap, including microbiota changes, may play a role. The paper presents a study protocol that aims to assess the effect of probiotic supplementation on symptoms of depression, anxiety and stress, metabolic parameters, inflammatory and oxidative stress markers, as well as fecal microbiota in adult patients with depressive disorders depending on the co-occurrence of metabolic syndrome. The trial will be a four-arm, parallel-group, prospective, randomized, double-blind, controlled design that will include 200 participants and will last 20 weeks (ClinicalTrials.gov identifier: NCT04756544). The probiotic preparation will contain Lactobacillus helveticus Rosell®-52, Bifidobacterium longum Rosell®-175. We will assess the level of depression, anxiety and stress, quality of life, blood pressure, body mass index and waist circumference, white blood cells count, serum levels of C-reactive protein, high-density lipoprotein (HDL) cholesterol, triglycerides, fasting glucose, fecal microbiota composition and the level of some fecal microbiota metabolites, as well as serum inflammatory markers and oxidative stress parameters. The proposed trial may establish a safe and easy-to-use adjunctive treatment option in a subpopulation of depressive patients only partially responsive to pharmacologic therapy.

Does metabolic status affect serum levels of BDNF and MMP-9 in patients with schizophrenia?

The purpose of the article: Brain-derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (MMP-9) are involved in the processes of neurogenesis, synaptic plasticity, learning and memory. Growing number of studies shows a relationship between BDNF or MMP-9 and schizophrenia. Also, BDNF and MMP-9 levels may be affected by metabolic parameters, such as obesity or dyslipidemia. Our hypothesis is that alterations of BDNF or MMP-9 levels in schizophrenia might be secondary to metabolic abnormalities, often found among schizophrenia patients. Materials and methods: We have compared BDNF and MMP-9 between patients with schizophrenia (n = 64, age 49 ± 8.2 y) and healthy controls (n = 32, age 51 ± 8.9 y) in the context of cardio-metabolic parameters. Serum levels of BDNF and MMP-9 were measured using ELISA test, body composition parameters were determined using bioelectric impedance analysis. Results and conclusions: Our results showed significantly lowered serum BDNF concentration in the schizophrenia group (schizophrenia: 23.8 ± 7.83 ng/mL, control: 27.69 ± 8.11 ng/mL, p = 0.03). Serum MMP-9 concentration in schizophrenia group did not differ compared with the control group (schizophrenia: 456.8 ± 278.4 ng/mL, control: 341.5 ± 162.4 ng/mL, p = 0.07). After adjusting for age, all anthropometric parameters, body composition and laboratory tests BDNF were still significantly lower in the schizophrenia group. However, MMP-9 became significantly elevated in the schizophrenia group after adjusting for several anthropometric and body composition covariates. Our results confirmed reduced serum BDNF concentration in patients with schizophrenia. Also, this reduction seems to be independent of metabolic abnormalities. On the other hand, our hypothesis that MMP-9 level in schizophrenia is altered due to metabolic abnormalities might be true.

Serum level of cathelicidin LL-37 is increased in euthymic patients with bipolar disorder irrespective of their cardio-metabolic status

Abstract Background Antimicrobial peptides are components of the innate immune system. Cathelicidin LL-37 plays an important role in antimicrobial defense, exerts proinflammatory effect and strongly affects the immune system functioning. Our recent study revealed that serum concentration of LL-37 is increased in patients with bipolar disorder. Objectives The aim of this study is to re-evaluate serum LL-37 levels in patients with euthymic bipolar disorder and in healthy controls, matched for anthropometric and body composition parameters. Methods 36 adult patients with euthymic bipolar disorder and 68 non-depressed adults were included into the study. Concentration of LL-37 in serum was assessed using ELISA method. Detailed anthropometric measurements, body composition and biochemical analyses were performed. Results There was a statistically significant difference (p = 0.01) in serum LL-37 level between patients with bipolar disorder (4.97 ± 7.98 ng/mL) and control subjects (1.78 ± 2.69 ng/mL). Discussion Results of this study indicate that LL-37 serum level is increased in euthymic bipolar disorder patients. We found that this increase could not be attributed to analyzed anthropometric or body composition parameters.

Human cathelicidin LL-37 - Does it influence the homeostatic imbalance in mental disorders?

In addition to killing pathogens and influencing immunological processes, cathelicidin LL-37 is a multifunctional host defense peptide with a role in homeostasis. It has been suggested that imbalances in homeostatic signaling from inflammatory/ immune, endocrine and metabolic cascades and oxidative stress may partially contribute to the pathogenesis of mental disorders. The purpose of the study was to identify any differences in LL-37 levels between patients with schizophrenia, euthymic bipolar disorder, bacterial pneumonia, pulmonary tuberculosis, and healthy controls. Thirty-five patients with chronic paranoid schizophrenia, 40 patients with chronic, euthymic bipolar disorder, 30 patients with bacterial pneumonia, 32 patients with pulmonary tuberculosis, and 38 healthy volunteers were included in this study. The patients with schizophrenia demonstrated a significantly lower level of LL-37 than those with bipolar disorder (p=0.006) and those with pulmonary TB (p less than 0.001). Significant differences in LL-37 levels were found between patients with bipolar disorder, bacterial pneumonia (p less than 0.001) and pulmonary TB (p=0.004). Our findings suggest that changes observed in the serum level of LL-37 in psychiatric patients enrolled in this study could be a result of homeostatic imbalance.

Effect of clozapine dose and concentration on fasting concentration of appetite regulating peptides.

The aim of this study is to analyze whether clozapine serum concentration may affect fasting serum levels of several appetite regulating peptides: CART, PYY(1-36), NPY, AgRP, des-acylated ghrelin, leptin and obestatin. Serum concentration of clozapine and fasting serum levels of des-acylated ghrelin, neuropeptide Y (NPY), agouti-related protein (AgRP), peptide YY (PYY(1-36)), cocaine- and amphetamine-regulated transcript (CART), leptin and obestatin were measured in 30 subjects with schizophrenia on clozapine monotherapy. Leptin concentration was negatively correlated with clozapine dose (r = -0.53, p = 0.002), while NPY concentration was negatively correlated with clozapine concentration (r = -0.55, p = 0.01). Correlations with other peptides were not significant. We cannot conclude that serum concentration of clozapine is directly associated with increased or decreased level of appetite-regulating peptides.

Circulating cathelicidin LL-37 level is increased in euthymic patients with bipolar disorder.

More and more data seems to imply that immune mechanisms are involved in the pathomechanism of bipolar disorder (BD). However, the primary role of cathelicidin LL-37 is defense against pathogens, more and more data indicated that this peptide strongly modulates immune system functioning and contributes to immune pathology of chronic and inflammatory diseases. No data is available on the level of LL-37 in bipolar patients. The aim of the study was to examine the circulating levels of cathelicidin LL-37 in euthymic patients with BD. Forty patients with BD and fifty-nine healthy volunteers were enrolled into the study. Concentration of LL-37 in serum was assessed using immunoenzymatic test ELISA. The mean LL-37 concentration in bipolar patients and in healthy subjects were 4.60 ±â€¯7.65 ng/mL and 1.92 ±â€¯2.89 ng/mL, respectively, and the difference was statistically significant (p = 0.035). Within the BD group LL-37 level was significantly higher in women than in men (p = 0.045). The evaluation of serum LL-37 concentration during stable 8 week treatment indicated that at baseline (T1) mean level of LL-37 was 5.82 ±â€¯10.59 ng/mL; and after treatment (T2) was 4.33 ±â€¯5.87 ng/mL; the difference between T1 and T2 was not significant. Elevated serum levels of LL-37 in bipolar patients may suggest the role of this peptide in the pathomechanism of BD.

Levels of C-reactive protein (CRP) in patients with schizophrenia, unipolar depression and bipolar disorder.

OBJECTIVE: C-reactive protein (CRP) is the major acute-phase plasma protein. Studies show that patients with various mental disorders have elevated levels of CRP. The aim of the study was to determine differences in CRP serum level in patients with acute schizophrenia, unipolar depression, bipolar depression and bipolar mania. METHOD: Serum level of CRP was measured in 950 Caucasian inpatients (589 women, 62.0%; mean age 50.3 years). RESULTS: Mean concentration of CRP in study groups was: schizophrenia (n = 485) 5.30 mg/l, unipolar depression (n = 319) 5.61 mg/l, bipolar disorder (n = 146) 4.65 mg/l, bipolar depression (n = 114) 3.82 mg/l and bipolar mania (n = 32) 7.36 mg/l. There was no difference for CRP levels between patients with schizophrenia, unipolar depression, bipolar depression and bipolar mania (P = 0.58). The overall rate of being above the high level of CRP (set at 3.0 mg/l) was 35.7% for schizophrenia, 38.6% for unipolar depression, 40.4% for bipolar disorder, 40.4% for bipolar depression and 40.6% for bipolar mania. There were no significant differences in the risk of having high level of CRP between the clinical groups. The rate of patients being above high level was higher in women. We also found that in whole study group CRP level was positively correlated with age (P = 0.002). CONCLUSIONS: Although there is no statistically significant difference in CRP serum level between patients with schizophrenia, unipolar depression, bipolar depression and bipolar mania, our results show that more than one-third (37.4%) of all subjects had CRP level > 3 mg/l, which is the cut-off point for high cardiovascular risk.