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.

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.

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.

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.

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.

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.

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.

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.

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.

Interleukin-8 and tumor necrosis factor-alpha in youth with mood disorders-A longitudinal study.

Bipolar disorder (BD) is one of the most disabling psychiatric illnesses. Over half of BD patients experienced early onset of the disease, and in most cases, it begins with a depressed mood episode. Up to 50% of adolescents initially diagnosed with major depressive disorder (MDD) convert to bipolar spectrum disorder. Diagnostic tools or biomarkers to facilitate the prediction of diagnosis conversion from MDD to BD are still lacking. Our study aimed to find biomarkers of diagnosis conversion in young patients with mood disorders. We performed a 2-year follow-up study on 69 adolescent patients diagnosed with MDD or BD. The control group consisted of 31 healthy youths. We monitored diagnosis change from MDD to BD. Impulsiveness was assessed using Barratt Impulsiveness Scale (BIS-11) and defense mechanisms using Defense Style Questionnaire (DSQ-40). According to the immunological hypothesis of mood disorders, we investigated baseline cytokines levels either in depressive or hypomanic/manic episodes. We correlated interleukin 8 (IL-8) and Tumor Necrosis Factor-alpha (TNF-alpha) levels with clinical factors. We detected higher IL-8 and TNF-alpha in patients in hypomanic/manic compared to depressed episodes. We found correlations of cytokine levels with immature defense style. We did not discover predictors of diagnosis conversion from MDD to BD.

Disembodied Language in Early-Onset Schizophrenia.

A recent view on schizophrenia phenomenology underlines the impaired relations between the mind and the body. An aberrant feeling of ipseity may be the real source of suffering of the patients from psychosis and impacts general symptomatology. The disturbed connection between thinking processes and environmental stimuli may lead to language disembodiment. In the study, we aimed to experimentally test the presence of disembodied language and investigate its association with symptoms of psychosis in adolescents diagnosed with early-onset schizophrenia spectrum disorders. Assessment of language embodiment was conducted using the Zabór Verbal Task (ZVT) with concurrent linguistic and clinical assessment using the Thought, Language, and Communication Scale (TLCS) and Positive and Negative Symptoms Scale (PANSS). The study group of patients (n = 31) aged 11-18 years, with the diagnosis of schizophrenia spectrum according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) and the International Classification of Diseases (ICD-10) criteria, was compared with a sex- and age-matched healthy control sample (n = 31). Patients with psychosis made more errors in ZVT than healthy controls (p = 0.01) and this parameter did not improve after 6-8 weeks of standard treatment (p = 0.55). A higher number of errors in ZVT were associated with the presence of auditory hallucinations (odds ratio [OR] 1.14; 95% CI 1.02-1.26). ZVT errors coincided with perception disorders, alternatively to the TLCS scores where we observed association with abnormal beliefs. The results of these preliminary studies indicate the value of the phenomenological approach in the diagnosis of schizophrenia spectrum and suggest a potential involvement of language disembodiment in symptomatology.

The Effect of Physical Activity on Neurotrophin Concentrations and Cognitive Control in Patients With a Depressive Episode.

Background: Cognitive deficits occur in most patients with affective disorders. The role of neurotrophic factors (e.g., BDNF) as modulators of brain plasticity affecting neurocognitive abilities has been emphasized. Neurotrophin concentrations may change under the influence of various interventions, including physical activity. Selected studies have shown that cognitive function may also be affected by exercise. Aim: The aim of the study was to determine whether physical activity changes the concentration of neurotrophins and their receptors in patients with an episode of depression. It was also examined how one session of aerobic exercise affects cognitive control. Methods: The study included 41 participants. The subjects were asked to exercise on a cycloergometer for 40 min with individually selected exercise loads (70% VO2max). Before and shortly after the exercise blood samples were acquired to perform blood assays (proBDNF, BDNF, TrkB, NGFR). The participants also performed a Stroop test twice-before the exercise and 10 min after its cessation. Results: The single bout of physical exercise did not cause any significant changes in the concentration of neurotrophic factors. The SCWT results: both the mean reading time (29.3 s vs. 47.8 s) and the color naming time (36.7 s vs. 50.7 s) increased. The patients made more mistakes after physical exercise, both in part A (0.2 vs. 1.5) and B (0.6 vs. 1.5). The so-called interference effect decreased-the difference between naming and reading times was smaller after exercise (6.2 s vs. 2.4 s). No significant correlations were found between the concentrations of the studied neurotrophic factors and the Stroop test results. Conclusions: The results did not confirm changes in neurotrophin concentration under the influence of a single session of physical activity. The shortening of the interference time after exercise may be caused by practice effects. A significant limitation of the study is the use of the Stroop test twice in short intervals.

ProBDNF as an Indicator of Improvement among Women with Depressive Episodes.

Depression is a chronic psychiatric disorder with a heavy socioeconomic burden. Studies on biomarkers are needed to comprehend the pathophysiology of depression and to improve treatment outcomes. Research points to the importance of imbalance between mature brain-derived neurotrophic factor (BDNF) and its precursor, pro-brain-derived neurotrophic factor (proBDNF), in the pathophysiology of mood disorders and the potential neurodegenerative role of calcium-binding protein B (S100B). Our objective was to compare BDNF, proBDNF, and S100B serum levels before and after the treatment of acute depressive episodes and to assess their correlation with the severity of symptoms and history of stress. We also aimed to investigate the differences in BDNF, proBDNF, and S100B levels between depression in the course of bipolar disorder (BD) and major depressive disorder (MDD). We recruited 31 female patients diagnosed with BD or MDD who were hospitalized due to current depressive episodes. The patients had their serum BDNF, proBDNF, and S100B levels evaluated using the ELISA method upon admission and after the symptoms improved, at discharge. We found that proBDNF levels decreased significantly with the treatment (p = 0.0478), while BDNF and S100B levels were not altered significantly. No differences in biochemical parameters between MDD and BD subjects were observed. Consequently, we concluded that a decrease in serum proBDNF levels could be considered a biomarker of recovery from depressive episodes.

Temperament and character dimensions as psychological markers of mood disorders in Polish adolescents and young adults-A prospective study.

BACKGROUND: An increasing incidence of mood disorders in adolescents and young adults is being observed. The assessment of personality traits seems to be an interesting tool in identifying early markers of major depression (MD) or bipolar disorder (BD) as well as predictors of the course of the disease. The aim of this study was to compare the personality profiles in young patients with MD and BD in acute and remitted mood states. METHODS: Seventy-nine adolescents and young adults with mood disorder diagnoses (MD or BD) were included in the study. The participants were assessed based on structured diagnostic interviews and completed the Temperament and Character Inventory (TCI). The clinical evaluation was conducted during the acute episodes and after reaching the stabilized mood in the course of follow-up visits in a 2-year study observation. RESULTS: At baseline, MD patients had higher scores on the harm avoidance (HA) with more pronounced anticipatory worry and fatigability subscale than BD patients. Conversely, BD patients reached higher scores in the total self-directedness (SD) character dimension and its sub-dimensions. MD patients with acute depressive symptoms had higher scores in the HA dimension and its subscale: anticipatory worry, shyness, and fatigability compared with their euthymic states. No significant differences in TCI dimensions between baseline and euthymia in the BD subgroup were found, and no differences between euthymic MD and BD patients. CONCLUSIONS: Higher ST and SD sub-dimensions may constitute a personality profile specific to BD, while high HA seems to be related to major depression in both acute and remitted states in young patients.

Studies on candidate genes for lithium prophylaxis performed at the Poznan University of Medical Sciences. / Badania genów kandydujacych profilaktyki litem przeprowadzone na Uniwersytecie Medycznym w Poznaniu.

Lithium is a drug of choice as a mood-stabilizer for the maintenance treatment of bipolar disorder. The prophylactic efficacy of lithium can be determined by genetic factors, partially related to a predisposition to bipolar disorder. In the field of psychiatric genetics, the first decade of the 21st century was dominated by the "candidate gene" research. In this paper, the studies on candidate genes connected with lithium prophylaxis performed at the Poznan University of Medical Sciences in 2005-2018 are presented. During this time, the polymorphisms of multiple genes have been investigated, many of which are also connected with a predisposition to bipolar illness. The associations with lithium prophylactic efficacy were found for the polymorphisms in 5HTT, ACP1, ARNTL, BDNF, COMT, DRD1, FKBP5, FYN, GLCC, NR3C1, and TIM, genes, but not those in 5HT2A, 5HT2C, DRD2, DRD3, DRD4, GRIN2B, GSK-3ß, MMP-9, and NTRK2 genes. The polymorphism of the GSK-3ß gene was found to be associated with the kidney side-effects occurring during lithium therapy. Possible roles for these genes in both the mechanism of lithium prophylactic activity and pathogenesis of bipolar mood disorder were discussed.

Genetic association study reveals impact of interleukin 10 polymorphisms on cognitive functions in schizophrenia.

AIM: Cognitive deficits are the core factors impacting quality of life among patients diagnosed with schizophrenia. Effective method of treatment for this domain of symptoms remains lacking. Recent evidence suggests the link between impaired cognition and aberrant inflammatory response. Severity of symptoms might be linked to individual genetic predispositions and single-nucleotide polymorphisms (SNPs) in genes encoding interleukins and their receptors. Current genetic association studies include anti-inflammatory interleukins, such as IL10. Functional polymorphisms of IL10 (rs1800871, rs18008729) have been indicated to affect information processing in schizophrenia. MATERIALS AND METHODS: In this study, we analyzed the potential impact of 27 functional SNPs in 8 cytokine genes on cognitive parameters measured by Wisconsin card-sorting test (WCST) in schizophrenia group (n = 150) and healthy controls (n = 152). RESULTS: We found significant associations of two functional polymorphisms of IL10 (rs1800871, rs1800872) and WCST results. Allele A carriers in rs1800871 performed significantly better in Percent of Conceptual Level Responses (CLR%). Allele A carriers in rs1800871 and allele T carriers in rs1800872 obtained better results in Completed Categories (CC). The impact of illness duration was observed, with better performance of recent-onset patients. CONCLUSIONS: Results of this study indicate that genetic variants of inflammatory response are associated with cognitive deficits in schizophrenia. The role of cytokines in schizophrenia need to be investigated in the aspect of pro-/anti-inflammatory imbalance. Altered inflammatory response promote chronic mild inflammation in the brain and aberrant synaptic plasticity.

Elevated Epidermal Growth Factor (EGF) as Candidate Biomarker of Mood Disorders-Longitudinal Study in Adolescent and Young Adult Patients.

Bipolar disorder (BD) is a chronic mental disorder that affects more than 1% of the population worldwide. Over 65% of patients experience early onset of the disease. Most cases of juvenile bipolar disorder begin with a depressed mood episode, and up to 50% of youth initially diagnosed with major depression go onto developing a BD. Our study aimed to find biomarkers of diagnosis conversion in young patients with mood disorders. We performed a two-year follow-up study on 79 adolescent patients diagnosed with MDD or BD, with a detailed clinical assessment at five visits. We monitored diagnosis change from MDD to BD. The control group consisted of 31 healthy youths. According to the neurodevelopmental and neuroimmunological hypotheses of mood disorders, we analyzed serum levels of brain-derived neurotrophic factor (BDNF), proBDNF, epidermal growth factor (EGF), migration inhibitory factor (MIF), stem cell factor (SCF), and correlations with clinical factors. We detected a significant disease-dependent increase in EGF level in MDD and BP patients at baseline exacerbation of depressive or hypomanic/manic episodes as well as in euthymic state compared to healthy controls. No potential biological predictors of disease conversion were found. Replication studies on a larger cohort of patients are needed.

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.

Impulsivity as a Risk Factor for Suicide in Bipolar Disorder.

The accurate assessment of suicide risk in psychiatric, especially affective disorder diagnosed patients, remains a crucial clinical need. In this study, we applied temperament and character inventory (TCI), Barratt impulsiveness scale 11 (BIS-11), PEBL simple reaction time (SRT) test, continuous performance task (CPT), and Iowa gambling task (IGT) to seek for variables linked with attempted suicide in bipolar affective disorder group (n = 60; attempters n = 17). The main findings were: strong correlations between self-report tool scores and objective parameters in CPT; the difference between attempters and non-attempters was found in the number of correctly responded trials in IGT; only one parameter differed between attempters and non-attempters in BPI diagnosis; and no significant differences between suicide attempters and non-attempters in TCI, BIS-11, and SRT were found. These justify the conclusion that impulsivity itself is not a strong predictor, and used as a single variable might not be sufficient to indicate the high suicide risk group among bipolar patients.

Longitudinal assessment of S100B serum levels and clinical factors in youth patients with mood disorders.

Mood disorders have been discussed as being in relation to glial pathology. S100B is a calcium-binding protein, and a marker of glial dysfunctions. Although alterations in the S100B expression may play a role in various central nervous system diseases, there are no studies on the potential role of S100B in mood disorders in adolescents and young adults . In a prospective two-year follow-up study, peripheral levels of S100B were investigated in 79 adolescent/young adult patients (aged 14-24 years), diagnosed with mood disorders and compared with 31 healthy control subjects. A comprehensive clinical interview was conducted which focused on clinical symptoms and diagnosis change. The diagnosis was established and verified at each control visit. Serum S100B concentrations were determined. We detected: lower S100B levels in medicated patients, compared with those who were drug-free, and healthy controls; higher S100B levels in a depressed group with a family history of affective disorder; correlations between age and medication status; sex-dependent differences in S100B levels; and lack a of correlation between the severity of depressive or hypo/manic symptoms. The results of our study indicate that S100B might be a trait-dependent rather than a state-dependent marker. Due to the lack of such studies in the youth population, further research should be performed. A relatively small sample size, a lack of exact age-matched control group, a high drop-out rate.