Biomarkers of Depression among Adolescent Girls: BDNF and Epigenetics.

Alterations in brain-derived neurotrophic factor (BDNF) expression have been suggested to mediate the influence of environmental factors on the emergence of depression through epigenetic modifications. However, research on this subject in the developmental population is lacking and the pathophysiology of adolescent depression remains unclear. We aimed to investigate the alterations in BDNF expression and global DNA methylation in depression among adolescent girls. Thirty female inpatients with the initial diagnosis of depression were assessed before and after the period of antidepressant treatment and compared with thirty age-matched healthy controls. The assessment involved BDNF and proBDNF serum levels, the BDNF gene exon IV promoter methylation, and global DNA methylation. The methylation level in the BDNF gene exon IV promoter was significantly lower in the studied group compared with the control and correlated negatively with the severity of depression. The test distinguished the studied group from the controls with a sensitivity of 37% and specificity of 90%. The differences were no longer present after the period of antidepressant treatment. No differences in the global DNA methylation, BDNF, and proBDNF levels were found. We concluded that decreased methylation in the BDNF exon IV promoter could be considered as a biomarker of a depression state among adolescent girls.

Expression Biomarkers of Pharmacological Treatment Outcomes in Women with Unipolar and Bipolar Depression.

INTRODUCTION: This study aimed to find the expression biomarkers of pharmacological treatment response in a naturalistic hospital setting. Through gene expression profiling, we were able to find differentially-expressed genes (DEGs) in unipolar (UD) and bipolar (BD) depressed women. METHODS: We performed gene expression profiling in hospitalized women with unipolar (n=24) and bipolar depression (n=32) who achieved clinical improvement after pharmacological treatment (without any restriction). To identify DEGs in peripheral blood mononuclear cells (PBMCs), we used the SurePrint G3 Microarray and GeneSpring software. RESULTS: After pharmacological treatment, UD and BD varied in the number of regulated genes and ontological pathways. Also, the pathways of neurogenesis and synaptic transmission were significantly up-regulated. Our research focused on DEGs with a minimum fold change (FC) of more than 2. For both types of depression, 2 up-regulated genes, OPRM1 and CELF4 (p=0.013), were significantly associated with treatment response (defined as a 50% reduction on the Hamilton Depression Rating Scale [HDRS]). We also uncovered the SHANK3 (p=0.001) gene that is unique for UD and found that the RASGRF1 (p=0.010) gene may be a potential specific biomarker of treatment response for BD. CONCLUSION: Based on transcriptomic profiling, we identified potential expression biomarkers of treatment outcomes for UD and BD. We also proved that the Ras-GEF pathway associated with long-term memory, female stress response, and treatment response modulation in animal studies impacts treatment efficacy in patients with BD. Further studies focused on the outlined genes may help provide predictive markers of treatment outcomes in UD and BD.

Correlation of metabolic parameters, neurotrophin-3, and neurotrophin-4 serum levels in women with schizophrenia and first-onset depression.

BACKGROUND: Neurotrophin-3 (NTF3) and neurotrophin-4 (NTF4) play a crucial role in the neurodevelopment, differentiation, survival, and protection of neurons in different brain regions. Schizophrenia and depression are highly associated with metabolic abnormalities. Longitudinal and cross-sectional comparisons of NTF3 and NTF4 levels, as well as clinical and metabolic parameters, were studied in schizophrenia, first-episode depression, and control groups. MATERIALS AND METHODS: Serum NTF3 and NTF4 levels, body mass index (BMI), fasting serum glucose and lipid profile: cholesterol, triglyceride, high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) were measured at baseline and week 8 in 133 women: 55 patients with schizophrenia (19 with first-episode and 36 chronic), 30 patients with a first-episode depression and 48 healthy controls. The severity of the symptoms was evaluated with the Positive and Negative Syndrome Scale, 17-item Hamilton Depression Rating Scale and the Beck Depression Inventory. RESULTS: Longitudinal and cross-sectional comparisons did not detect any differences in the serum levels of NTF3 and NTF4 between studied groups. NTF3 and NTF4 levels were strongly correlated. Correlation of NTF3 and HDL-C levels at baseline was observed. Significant changes in cholesterol and fasting serum glucose levels in first-episode depression patients during 8 weeks of treatment were detected. Significant differences in BMI and LDL-C levels between schizophrenia and first-episode depression patients were discovered. CONCLUSIONS: To our knowledge, this is the first research which correlates NTF3 and NTF4 with metabolic parameters. Our study does not support the theory that the peripheral levels of NTF3 and NTF4 are disturbed in schizophrenia or first-episode depression.

Genes involved in stress response influence lithium efficacy in bipolar patients.

OBJECTIVES: In mood disorders, chronic stimulation with stress results in aberrant regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Lithium was shown to influence HPA axis function. The underlying genetic background as well as environmental context may influence the stress response, and therefore lithium efficacy. The aim of the present study was to analyze if genetic variants located in genes involved in HPA axis regulation affect the response to long-term lithium treatment in bipolar patients. METHODS: We included 93 patients with bipolar disorder (32 males and 61 females), aged 31-80 years. The patients had been treated with lithium carbonate for at least 5 years. The magnitude of the lithium response was assessed using the Alda scale. Genotyping was performed for 28 polymorphisms in the genes encoding the following proteins involved in HPA axis regulation: corticotropin-releasing hormone receptor 1 (CRHR1), arginine vasopressin receptor 1B (AVPR1b), FK506 binding protein (FKBP) 5, FKBP4, BCL2-associated athanogene 1 (BAG1), stress induced phosphoprotein 1 (STIP1), glucocorticoid-induced transcript 1 (GLCC1), dual specificity phosphatase 1 (DUSP1) serine and arginine rich splicing factor (SRSF) 3, SRSF9, SRSF5, and acid phosphatase 1 (ACP1). Linkage disequilibrium and haplotype analysis were then performed, followed by statistical analysis (Statistica v.12; Stasoft, Krakow, Poland). RESULTS: We found a correlation between stressful life events at first episode and worse response to lithium (P=.019). In single marker analysis, we observed a significant association between three FKBP5 polymorphisms (rs1360780, rs7748266 and rs9296158), one ACP1 variant (rs300774) and one glucocorticoid-induced transcript 1 gene (GLCC1) variant (rs37972) and the degree of lithium response. Five out of seven FKBP5 polymorphisms showed strong linkage with one haplotype demonstrating an association with lithium efficacy (P=.008). No relationship was found between the other analyzed polymorphisms and lithium response. CONCLUSION: The response to lithium may depend on the variants of genes regulating the HPA axis and stressful life events in bipolar patients.

Brain-derived neurotrophic factor (BDNF) serum level in women with first-episode depression, correlation with clinical and metabolic parameters.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) influences neuron differentiation during development, as well as the synaptic plasticity and neuron survival in adulthood. BDNF has been implicated in the pathogenesis of psychiatric disorders and its serum level is a potential biomarker for depression. The aim of this study was to examine serum levels of BDNF in first-episode depression and its correlation with clinical and metabolic parameters. MATERIALS AND METHODS: The study was performed on a group of 60 women: 30 diagnosed with a first-episode of depression and 30 healthy controls. 17-Item Hamilton Depression Rating Scale (HDRS-17) was used to assess the severity of depression. Patients were randomly chosen for treatment with sertraline or venlafaxine. BDNF serum levels and metabolic parameters: fasting serum glucose, cholesterol, triglyceride (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C) were measured at baseline and week 8 of treatment. RESULTS: There were no differences between BDNF level in depressed patients compared with the healthy controls. Lack of differences in medication effect of sertraline or venlafaxine on HDRS-17 scores during 8 weeks of treatment was observed. Correlation of BDNF at baseline and fasting serum glucose at baseline and week 8 was detected. CONCLUSIONS: Correlations of BDNF serum levels with metabolic parameters were observed.

Impact of CYP2E1, GSTA1 and GSTP1 gene variants on serum alpha glutathione S-transferase level in patients undergoing anaesthesia.

BACKGROUND: The serum glutathione S-transferase alpha (α-GST) concentration has been used as a marker of hepatic condition. After sevoflurane anaesthesia a mild impairment of hepatocellular integrity was observed. Genetic polymorphisms in CYP2E1, GSTA1 and GSTP1 genes, affecting enzymes activity, may possibly influence the hepatotoxic effect of sevoflurane. The aim of this study was to assess the influence of genetic polymorphism of CYP2E1, GSTA1 and GSTP1 genes on serum α-GST level in 86 unrelated patients representing ASA physical status I-II, undergoing laryngological surgery under general anaesthesia with sevoflurane. METHODS: The serum samples from three perioperative time points were analyzed using ELISA. Genetic variants were detected by pyrosequencing and sequencing. Finally, the statistical associations between serum α-GST concentration and analyzed alleles of CYP2E1, GSTP1 and GSTA1 genes were estimated. RESULTS: The allele GSTA1*B (-567G, -69T, -52A) frequency was 0.43, whereas the alleles c.313G and c.341T of GSTP1 were identified with frequencies of 0.28 and 0.1 respectively. The -1053T allele of the CYP2E1 gene was observed with 0.01 frequency. We found serum α-GST concentrations in homozygous changes c.313A>G and c.341C>T of the GSTP1 gene significantly higher at the end of anaesthesia as compared with the levels at pre-anaesthetic and 24 h post-anaesthetic time points. Moreover, GSTA1 wild type genotype was associated with increased α-GST concentration at 24 h after the end of anaesthesia. CONCLUSIONS: GSTP1 gene polymorphism has an impact on the perioperative serum α-GST concentration in patients undergoing sevoflurane anaesthesia. A similar association, although not statistically significant exists between GSTA1 gene variants and perioperative serum α-GST level.

Can Psychological, Social and Demographical Factors Predict Clinical Characteristics Symptomatology of Bipolar Affective Disorder and Schizophrenia?

Schizophrenia (SCH) is a complex, psychiatric disorder affecting 1 % of population. Its clinical phenotype is heterogeneous with delusions, hallucinations, depression, disorganized behaviour and negative symptoms. Bipolar affective disorder (BD) refers to periodic changes in mood and activity from depression to mania. It affects 0.5-1.5 % of population. Two types of disorder (type I and type II) are distinguished by severity of mania episodes. In our analysis, we aimed to check if clinical and demographical characteristics of the sample are predictors of symptom dimensions occurrence in BD and SCH cases. We included total sample of 443 bipolar and 439 schizophrenia patients. Diagnosis was based on DSM-IV criteria using Structured Clinical Interview for DSM-IV. We applied regression models to analyse associations between clinical and demographical traits from OPCRIT and symptom dimensions. We used previously computed dimensions of schizophrenia and bipolar affective disorder as quantitative traits for regression models. Male gender seemed protective factor for depression dimension in schizophrenia and bipolar disorder sample. Presence of definite psychosocial stressor prior disease seemed risk factor for depressive and suicidal domain in BD and SCH. OPCRIT items describing premorbid functioning seemed related with depression, positive and disorganised dimensions in schizophrenia and psychotic in BD. We proved clinical and demographical characteristics of the sample are predictors of symptom dimensions of schizophrenia and bipolar disorder. We also saw relation between clinical dimensions and course of disorder and impairment during disorder.

[Factors connected with efficacy of single ketamine infusion in bipolar depression]. / Czynniki skutecznosci jednorazowego wlewu ketaminy w depresji w przebiegu choroby afektywnej dwubiegunowej.

AIM: The aim of this study was to evaluate the efficacy of single ketamine infusion and clinical and biochemical factors connected with such efficacy, in patients with bipolar depression, which had not improved on antidepressant treatment. METHODS: The study included 42 patients (32 women, 10 men), aged 22-67 years, with bipolar depression. They received > or = 1 mood-stabilizing medications of first and/or second generation. After discontinuation of antidepressants (> or = 7 days), intravenous infusion of ketamine (0.5 mg/kg body weight) was performed. The assessment of depression by the 17-item Hamilton Depression Rating Scale was made before, and after 1, 3, 7 and 14 days following administration of ketamine. The assumed criterion for clinical improvement was the reduction of > or = 50% score on the Hamilton scale after 7 days. In a subgroup of 20 patients, prior to administration of ketamine, serum concentrations of homocysteine, vitamin B12, folic acid, neurotrophins and inflammatory proteins were measured. RESULTS: In the whole group, the severity of depression on the Hamilton scale decreased significantly 24 hours after administration of ketamine from 22.6 +/- 5.1 to 15.6 +/- 7.4 points. After 7 days it was 13 +/- 7 and after 14 days - 11.8 +/- 7.8 points. Patients showing clinical improvement (n = 22) had significantly higher frequency of alcohol addiction and family history of alcoholism. Biochemical tests in the subset of 20 patients demonstrated that those with clinical improvement (n = 10) had higher serum concentrations of vitamin B12 and receptor-1 Vascular Endothelial Growth Factor before administration of ketamine. Ketamine infusion was well tolerated. CONCLUSIONS: The results confirm a rapid antidepressant effect of ketamine infusion maintaining for 2 weeks, in a considerable proportion of patients with bipolar depression, and good clinical tolerance of such procedure. Also, some clinical and biochemical factors associated with ketamine efficacy were shown.

Alterations in Neurotrophins in Alcohol-Addicted Patients during Alcohol Withdrawal.

BACKGROUND: Alcohol use disorder (AUD) is related to mental and somatic disorders that result in alcohol withdrawal syndrome (AWS), with 30% of AWS cases leading to life-threatening delirium tremens (DTs). Currently, studies do not support using any one biomarker in DTs. Neurotrophins affect neuromodulation, playing a role in the pathogenesis of AUD, AWS, and DTs. METHODS: This review aims to summarize experimental and clinical data related to neurotrophins and S100B in neuroplasticity, as well as neurodegeneration in the context of AUD, AWS, and DTs. This work used publications that were selected based on the protocol consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. RESULTS: The BDNF level could be a good candidate biomarker for relapse susceptibility, as it is significantly reduced during consumption and gradually increases during abstinence. GDNF influences AUD through its integral role in the function of dopaminergic neurons and ablates the return to alcohol-drinking behavior. NGF protects neurons from ethanol-induced cytotoxic damage and affects recovery from cognitive deficits after brain damage. The NT-3 level is decreased after alcohol exposure and is involved in compensatory mechanisms for cognitive decline in AUD. NT-4 affects oxidative stress, which is associated with chronic alcohol consumption. S100B is used as a biomarker of brain damage, with elevated levels in serum in AUD, and can protect 5-HT neurons from the damage caused by alcohol. CONCLUSIONS: BDNF, GDNF, NT-3, NT-4, NGF, and S100B may be valuable markers for withdrawal syndrome. In particular, the most relevant is their association with the development of delirium complications. However, there are few data concerning some neurotrophins in AWS and DTs, suggesting the need for further research.

Transcriptome profiling as a biological marker for bipolar disorder sub-phenotypes.

PURPOSE: Bipolar affective disorder (BP) causes major functional impairment and reduced quality of life not only for patients, but also for many close relatives. We aimed to investigate mRNA levels in BP patients to find differentially expressed genes linked to specific clinical course variants; assuming that several gene expression alterations might indicate vulnerability pathways for specific course and severity of the disease. MATERIALS: We searched for up- and down-regulated genes comparing patients with diagnosis of BP type I (BPI) vs type II (BPII), history of suicide attempts, psychotic symptoms, predominance of manic/hypomanic episodes, and history of numerous episodes and comorbidity of substance use disorders or anxiety disorders. RNA was extracted from peripheral blood mononuclear cells and analyzed with use of microarray slides. RESULTS: Differentially expressed genes (DEGs) were found in all disease characteristics compared. The lowest number of DEGs were revealed when comparing BPI and BPII patients (18 genes), and the highest number when comparing patients with and without psychotic symptoms (3223 genes). Down-regulated genes identified here with the use of the DAVID database were among others linked to cell migration, defense response, and inflammatory response. CONCLUSIONS: The most specific transcriptome profile was revealed in BP with psychotic symptoms. Differentially expressed genes in this variant include, among others, genes involved in inflammatory and immune processes. It might suggest the overlap of biological background between BP with a history of psychotic features and schizophrenia.

Hyperhomocysteinemia in bipolar depression: clinical and biochemical correlates.

BACKGROUND: Depression may be associated with elevated homocysteine (HCY) levels. Procedures aiming at its decrease, i.e. supplementation with folic acid or vitamin B12, have antidepressant effect. Both depression and elevated HCY can increase cardiovascular risk. In this study, clinical and biochemical factors, including markers of endothelial function, in relation to hyperhomocysteinemia, in patients with bipolar depression during acute episode were studied. METHOD: One hundred and twelve patients (24 male, 88 female), aged 20-78 (mean 51 ± 14 years), with depressive episode in the course of bipolar mood disorder have been included. The assays were made of serum concentrations of HCY, vitamin B12, folic acid as well as markers of endothelial function such as E-selectin and intracellular adhesion molecule-1 (ICAM-1). RESULTS: Hyperhomocysteinemia (>15 mM) was found in 50 patients (45%), significantly more frequently in male (67%) than in female subjects (39%). Female patients with hyperhomocysteinemia were significantly older than the remaining ones. A significant inverse correlation between HCY level and concentration of folic acid and vitamin B12 as well as with E-selectin and ICAM-1 was observed. CONCLUSION: The results point to a significant prevalence of hyperhomocysteinemia in bipolar depressed patients during an acute episode. They also corroborate the correlation between increased concentration of HCY and lower level of vitamin B12 and folic acid. An unexpected finding of negative correlation of HCY level with markers of endothelial functions in such patients is discussed in view of current concepts of the role of HCY in various conditions.

Serum neurotrophin concentrations in polish adolescent girls with anorexia nervosa.

OBJECTIVES: Several lines of evidence suggest that brain-derived neurotrophic factor (BDNF) plays an important role in weight regulation and eating behaviors as well as in the activity-dependent neuroplasticity underlying learning and memory behaviors involving the hippocampus. In anorexia nervosa (AN) patients, abnormal serum BDNF concentrations, cognitive impairments and specific personality traits have been traditionally observed. This study explores the levels of four serum neurotrophins [BDNF, neurotrophin 3 (NTF3), neurotrophin 4 (NTF4) and glial cell line-derived neurotrophic factor (GDNF)] with respect to their use as potential biomarkers for AN. This study also investigates any associations that might exist between serum neurotrophin levels and neurocognitive impairment or personality traits. METHODS: Serum neurotrophin concentrations were measured in 60 AN patients (AN group) and 45 healthy controls (HC group). We correlated the serum levels of the four neurotrophins BDNF, NTF3, NTF4 and GDNF and the clinical type of anorexia. We also analyzed the relationship between serum neurotrophin levels and the Beck Depression Inventory, body mass index, executive functions by the Wisconsin Card Sorting test (WCST) and personality dimensions by the Temperament and Character Inventory (TCI) test. RESULTS: Serum NTF4 concentrations were significantly lower when comparing all AN patients (34.7 ± 72.5 pg/ml) or restriction type AN patients (29.1 ± 62.5 pg/ml) with the HC group (58.4 ± 135.8 pg/ml; p = 0.004 and p = 0.005, respectively). A significant correlation (p < 0.005) between BDNF serum levels and patient personality dimensions as measured by the TCI test was observed. Furthermore, significant correlations were observed between NTF4 and GDNF serum levels and executive function as measured by the WCST. CONCLUSIONS: These data suggest that NTF4 might serve as a biomarker for AN. Furthermore, BDNF and GDNF serum levels appear to be associated with personality traits and executive function.

Single ketamine infusion in bipolar depression resistant to antidepressants: are neurotrophins involved?

OBJECTIVES: We investigated serum brain-derived neurotrophin factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NTF3), neurotrophin-4 (NTF4) and the glial-derived neurotrophic factor (GDNF), in relation to ketamine efficacy, in bipolar depressed patients resistant to treatment with antidepressants. METHODS: Twenty-five patients (4 male, 21 female), aged 27-67 years, with bipolar depression, receiving mood-stabilizing medications, were studied. Antidepressants were discontinued for at least 7 days before single intravenous ketamine infusion (0.5 mg/kg body weight). Response to ketamine was defined as ≥ 50% reduction on 17-item Hamilton Depression Rating Scale (HDRS) after 1 week, and remission as HDRS score ≤ 7. Serum BDNF, NGF, NTF3, NTF4 and GDNF levels were estimated by enzyme-linked immunosorbent assay. RESULTS: There were 13 ketamine responders and 12 non-responders. The remission was obtained in eight and 12 patients after seven and 14 days, respectively. At baseline, there were no differences between responders and non-responders in any of the neurotrophins. Serum BDNF was significantly reduced after 7 days in non-responders. Serum NGF, NT3, NT4 and GDNF did not significantly change. CONCLUSIONS: The results confirm an antidepressant effect of ketamine infusion as an add-on to mood-stabilizing drugs in bipolar depression resistant to antidepressant treatment. They may also suggest a possible involvement of BDNF in this effect.

[No association of glucocorticoid receptor gene polymorphism (rs6190) with unipolar and bipolar disorder]. / Brak zwiazku polimorfizmu (rs6190) genu receptora glikokortykoidowego z choroba afektywna jedno- i dwubiegunowa.

AIM: Functional polymorphism ER22/23EK glucocorticoid receptor leads to reduction of its resistance and to increase in its sensitivity to the glucocorticoid that regulate the functioning of the axis hypothalamus - pituitary - adrenal glands. Disturbances in the regulation of this axis are observed in patients with psychiatric disorders. The aim of this study was to demonstrate the association ER22/23EK polymorphism with bipolar disorder and major depressive disorders. METHODS: In the study 144 patients with unipolar disorders and 479 patients with bipolar disorder were included. Patients were diagnosed by two psychiatrists on the basis of medical records and interview based on SCID criteria (Structured Clinical Interview for DSM Disorders). The control group comprised 595 healthy subjects. As the research material peripheral blood was used, from which DNA was obtained. Genotyping was performed using PCR - RFLP method. RESULTS: No association of ER22/23EK polymorphism with unipolar disorder or with bipolar disorder was found. GA genotype was not observed in any of the subjects. CONCLUSION: ER22/23EK functional polymorphism of the glucocorticoid receptor gene is not associated with unipolar and bipolar disorder.

Diet and physical activity and metabolic disorders in patients with schizophrenia and bipolar affective disorder in the Polish population.

Introduction: There are numerous reports of a higher prevalence of metabolic disorders in patients with schizophrenia and bipolar disorder (BD), yet its connections to diet and physical activity remain not fully explained. This article aimed to evaluate diet, physical activity and selected biochemical and anthropometric parameters associated with metabolism in patients with schizophrenia and BD and to analyse the relationships between these variables in the subjects. Materials and Methods: A total of 126 adults participated in the study: 47 patients with schizophrenia, 54 patients with BD and 25 patients in mental illness remission (reference group). Data were collected on the underlying illness and concomitant illnesses, and the severity of symptoms of the current episode was assessed using the following scales: PANSS, MADRS and YMRS. An assessment of the subjects' diet (KomPAN questionnaire) and their physical activity (International Physical Activity Questionnaire) was carried out. Anthropometric and blood pressure measurements were taken and BMI and WHR were calculated. Serum concentrations of fasting glucose, TSH, total cholesterol, LDL and HDL fractions, triglycerides and leptin, ghrelin and resistin were determined. For statistical analysis, the significance level was set at 0.05. For multiple comparisons one way ANOVA or Kruskal Wallis were used with post hoc Tukey and Dunn tests, respectively. To determine correlation of variables, Pearson's linear correlation coefficient or Spearman's rank correlation coefficient were used. Results: A total of 50.8% of the subjects had at least one metabolic disorder-most commonly excessive body weight (66.7%) and abdominal obesity (64.3%). Patients did not differ significantly in terms of physical activity, but they did differ in mean time spent sitting-with this being significantly longer for all groups than in the general population. The subjects differed in diet: patients with BD consumed less unhealthy foods than patients with schizophrenia. The highest correlations between physical activity, diet and variables defining metabolic disorders were found in patients with BD. Only in patients with schizophrenia were there significant correlations between the course of the disease and physical activity. Discussion: The results suggest the existence of associations between diet, physical activity, and metabolic disorders in both BD and schizophrenia patients. They also suggest a tendency among those patients to spend long periods of time sitting.

Peripheral S100B Protein Levels in Five Major Psychiatric Disorders: A Systematic Review.

Five major psychiatric disorders: schizophrenia, major depressive disorder, bipolar disorder, autistic spectrum disorder, and attention-deficit/hyperactivity disorder, show a shared genetic background and probably share common pathobiological mechanisms. S100B is a calcium-binding protein widely studied in psychiatric disorders as a potential biomarker. Our systematic review aimed to compare studies on peripheral S100B levels in five major psychiatric disorders with shared genetic backgrounds to reveal whether S100B alterations are disease-specific. EMBASE, Web of Science, and PubMed databases were searched for relevant studies published until the end of July 2023. This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols (PRISMA) guidelines. Overall, 1215 publications were identified, of which 111 full-text articles were included in the systematic review. Study designs are very heterogeneous, performed mostly on small groups of participants at different stages of the disease (first-episode or chronic, drug-free or medicated, in the exacerbation of symptoms or in remission), and various clinical variables are analyzed. Published results are inconsistent; most reported elevated S100B levels across disorders included in the review. Alterations in S100B peripheral levels do not seem to be disease-specific.

Plasma biomarkers in adolescents with schizophrenia-spectrum disorder.

AIM: Schizophrenia onset in the developmental age has a strong neurodevelopmental burden and is associated with a poorer prognosis. The approach to diagnosis is still based on symptomatic description without objective validation. In this study, we aimed to compare the peripheral blood levels of hypothesized biomarker proteins: brain-derived neurotrophic factor (BDNF), proBDNF, p75 neurotrophin receptor (p75NTR ) and S100B between early-onset schizophrenia-spectrum adolescents (n = 45) and healthy controls (n = 34). METHODS: Clinical assessment of the participants encompassed symptomatic description with the use of structured interviews and executive function objective measurement. Plasma levels of BDNF protein were significantly lower in schizophrenia patients than in controls both at admission (p = .003) and 6-8 weeks follow-up (p = .007). RESULTS: We observed significant correlations between BDNF, proBDNF and p75NTR levels and positive and negative symptoms scale (PANSS) scores, p75NTR and S100B levels and suicidal parameters, as well as a correlation of BDNF plasma level with the risky decision-making style in Iowa Gambling Task (IGT). CONCLUSIONS: The results indicate a potential value of studied proteins as a biomarker in the diagnosis and monitoring of the disease's course.

Clinical assessment of impulsiveness and defence mechanisms in young patients with mood disorders in a two-year prospective study.

AIM: There have been limited prospective investigations of early clinical markers involved in mood regulation and diagnosis change in young patients. This study aimed to evaluate the changes in impulsivity and defence mechanisms in patients with major depressive disorder (MDD) and bipolar disorder (BD) with acute symptoms and remission compared to healthy controls (HC), and possible psychological predictors of diagnosis conversion. METHODS: Seventy-nine young MDD or BD patients and 40 HC were enrolled in a two-year prospective study. A comprehensive clinical interview focused on clinical and psychological evaluation during follow-up visits. The severity of depressive symptoms was evaluated using the Hamilton Depression Rating Scale (HDRS-17), whilst the Young Mania Rating Scale (YMRS) was used for hypo/manic symptoms during each control visit. All patients completed the Defence Style Questionnaire (DSQ-40) and Barratt Impulsiveness Scale (BIS-11). RESULTS: Patients used more immature defences, and had significantly higher total impulsivity scores than controls. BD patients had elevated motor and non-planning impulsivity compared with HC and MDD subjects. Total and non-planning impulsiveness remained elevated in euthymia in BD and MDD compared to HC. There were no statistically significant differences in total defence styles and impulsiveness scores at baseline vs. euthymia in MDD or BD patients groups. Significantly higher dissociation scores at baseline discriminated depressive patients who convert to BD in their diagnosis. CONCLUSIONS: Patients with acute mood symptoms used more frequent immature defences and had significantly higher total impulsivity scores than healthy persons. A lack of differences in total defence styles and impulsiveness between patients with acute symptoms and after reaching euthymia in both MDD and BD groups indicates that they are independent of disease status. Dissociation defence mechanisms may be an early diagnostic indicator of BD.

Changes in Adipokine, Resitin, and BDNF Concentrations in Treatment-Resistant Depression after Electroconvulsive Therapy.

OBJECTIVES: One of the current challenges in psychiatry is the search for answers on how to effectively manage drug-resistant depression. The occurrence of drug resistance in patients is an indication for the use of electroconvulsive therapy (ECT). This method is highly effective and usually results in relatively quick health improvement. Despite the knowledge of how ECT works, not all of the biological pathways activated during its use have been identified. Hence, based on the neuroinflammatory hypothesis of depression, we investigated the concentration of two opposite-acting adipokines (anti-inflammatory adiponectin and proinflammatory resistin) and BDNF in antidepressant-resistant patients undergoing ECT. METHODS: The study group comprised 52 patients hospitalized due to episodes of depression in the course of unipolar and bipolar affective disorder. The serum concentration of adipokines and BDNF was determined before and after the therapeutic intervention using an ELISA method. In the analyses, we also included comparisons considering the type of depression, sex, and achieving remission. RESULTS: Adiponectin, resistin, and BDNF concentrations change after ECT treatment. These changes are correlated with an improvement in the severity of depressive symptoms and are more or less pronounced depending on the type of depression. CONCLUSIONS: Although not all observed changes reach statistical significance, adipokines in particular remain exciting candidates for biomarkers in assessing the course of the disease and response to ECT treatment.

Dimensions of the Hamilton Depression Rating Scale Correlate with Impulsivity and Personality Traits among Youth Patients with Depression.

The heterogeneity of symptoms in young patients with major depression disorder makes it difficult to properly identify and diagnose. Therefore, the appropriate evaluation of mood symptoms is important in early intervention. The aim of this study was to (a) establish dimensions of the Hamilton Depression Rating Scale (HDRS-17) in adolescents and young adults and (b) perform correlations between the identified dimensions and psychological variables (impulsivity, personality traits). This study enrolled 52 young patients with major depression disorder (MDD). The severity of the depressive symptoms was established using the HDRS-17. The factor structure of the scale was studied using the principal component analysis (PCA) with varimax rotation. The patients completed the self-reported Barratt Impulsiveness Scale (BIS-11) and Temperament and Character Inventory (TCI). The three dimensions of the HDRS-17 identified as core in adolescent and young patients with MDD were (1) psychic depression/motor retardation, (2) disturbed thinking, and (3) sleep disturbances/anxiety. In our study, dimension 1 correlated with reward dependence and cooperativeness; dimension 2 correlated with non-planning impulsivity, harm avoidance, and self-directedness; and dimension 3 correlated with reward dependence. Conclusions: Our study supports the previous findings, which indicate that a certain set of clinical features (including the HDRS-17 dimensions, not only total score) may represent a vulnerability pattern that characterizes patients with depression.