Monika Szewczuk-Bogusławska

The Lifetime Prevalence of Anxiety Disorders Among Patients with Irritable Bowel Syndrome

BACKGROUND The prevalence of irritable bowel syndrome (IBS), the most common functional gastrointestinal disorder, ranges from 10% to 20% in the general population. It is estimated that from 40% to 90% of persons with a diagnosis of IBS suffer from mental disorders, mainly anxiety and depressive disorders. OBJECTIVES The aim of the study was to assess the lifetime prevalence of anxiety disorders in IBS patients and to compare it with the prevalence of these disorders in a control group of patients with gastroesophageal reflux disease (GERD). MATERIAL AND METHODS The study included 106 patients with IBS and 53 patients with GERD. IBS was diagnosed according to the Rome II criteria after a basic evaluation to exclude an organic disease. Anxiety disorders were diagnosed using the Composite International Diagnostic Interview (CIDI) in accordance with ICD-10 diagnostic criteria. RESULTS Anxiety disorders during the patients lifetime were diagnosed in 50 IBS patients (47%). Specific phobias occurred in 23.5% of them, social phobias in 10.4%, generalized anxiety disorder in 10.4%, panic disorder in 3.8% and agoraphobia in 8.5%. In the control group with GERD, anxiety disorders during the subjects lifetime were diagnosed in 30% of the group. The difference in the prevalence of anxiety disorders between patients with IBS and GERD was statistically significant (p<0.05). CONCLUSIONS The lifetime prevalence of anxiety disorders in IBS patients was higher than in the control group with GERD (47% vs. 30%). The prevalence rate of anxiety disorders in the control group with GERD was similar to the prevalence rate in the general population.

Profiling inflammatory signatures of schizophrenia: A cross-sectional and meta-analysis study

We aimed to profile a broad panel of inflammatory markers in patients with schizophrenia and healthy controls. Additionally, we performed a meta-analysis of chemokine alterations that have not been subjected to quantitative synthesis so far. We recruited 78 patients with schizophrenia and 78 healthy controls, and measured inflammatory markers using the Luminex technology. After adjustment for multiple testing, we found elevated levels of interleukin (IL)-1 receptor antagonist (IL-1RA), IL-6, IL-7, IL-8, IL-9, IL-10, IL-13, interferon-γ, eotaxin-1, granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein-1 (MCP-1), platelet-derived growth factor with two B subunits (PDGF-BB), macrophage inflammatory protein (MIP)-1α, MIP-1β, vascular endothelial growth factor A (VEGF-A) and RANTES in multiple-episode schizophrenia (MES) patients. These differences, except for the difference in eotaxin-1 levels, appeared to be significant after co-varying for the dosage of antipsychotics. There were no significant differences in the levels of immune markers between first-episode schizophrenia (FES) patients and controls. Our meta-analysis revealed elevated levels of MCP-1 in first-episode psychosis (FEP) patients and MES individuals. Other chemokine alterations (elevated levels of IL-8, eotaxin-1 and MIP-1β) were present only in MES patients. Our results indicate that dysregulation of immune response in schizophrenia develops with illness progression or appears as a long-term medication effect. Chemokine alterations are another example of aberrant immune response in schizophrenia patients. Elevated levels of MCP-1 might represent trait markers since these alterations were found in FEP and MES patients. Other chemokine alterations might be the markers of disease progression or might represent medication effects.

CTLA4 and CD28 Gene Polymorphisms with Respect to Affective Symptom Domain in Schizophrenia

Background: Accumulating evidence indicates that immune alterations in schizophrenia are due to genetic underpinnings. Here, we aimed at investigating whether polymorphisms in CTLA4 and CD28 genes, encoding molecules that regulate T-cell activity, influence schizophrenia symptomatology. Method: We recruited 120 schizophrenia patients and 380 healthy age- and sex-matched controls. We divided the patients into two groups: one with no co-occurrence between psychotic and affective symptoms and the second one with psychotic symptoms dominating in the clinical manifestation, although also with occasional affective disturbances in the course of illness. Results: Among the patients with co-occurring affective symptoms, there were significantly more CTLA4 c.49A>G[A] alleles (p = 0.018, odds ratio (OR) 2.03, 95% confidence interval (CI) 1.2-3.66) and more CTLA4 g.319C>T[T] alleles (p = 0.07, OR 1.93, 95% CI 0.94-4.13) in comparison to the second group. Additionally, we have shown that CD28 c.17 + 3T>C[C+] were more significantly overrepresented among patients with co-occurring psychotic and affective symptoms (p = 0.0003, OR 3.36, 95% CI 1.69-6.68) than in patients without co-occurence between these symptoms (p = 0.012, OR 1.88, 95% CI 1.15-3.10). Conclusion:CTLA4 and CD28 gene polymorphisms may not only act in immune deregulation observed in schizophrenia, but may also influence the course of the illness by modifying the susceptibility to the co-occurrence of psychotic and affective symptoms.

Mo2040 Association of Polymorphisms in 5-HT2A and 5-HT2C Receptors Genes With Depressive and Anxiety Disorders in Patients With Irritable Bowel Syndrome

BACKGROUND: Subgroups of patients with irritable bowel syndrome (IBS) may have low grade mucosal immune activity. Fecal calprotectin (f-calprotectin) levels are considered a marker for mucosal neutrophil inflammation and may be used as a biomarker for disease activity in inflammatory diseases. IBS patients are reported to have normal levels of calprotectin, but the levels may vary within the patient group, and it is not known whether this variation within or slightly above the normal range may reflect pathology or symptoms of the patients. AIM: To determine if levels of f-calprotectin may reflect the clinical and pathophysiological phenotype of IBS patients. METHODS: Analyses of f-calprotectin in stool samples of 98 IBS patients and 35 healthy controls were performed with Buhlmann ELISA (lower detection limit 10 ug/g). All IBS subjects completed the Bristol stool form (BSF) scale and the IBS symptom severity scale (IBS-SSS) questionnaire to assess gastrointestinal symptom severity. Patients also underwent a rectal barostat test with ballon distentions and colonic transit time measurement with ingestion of radiopaque rings. RESULTS: IBS patients had comparable levels of f-calprotectin to controls (17.5 (10-47.0) vs. 11(10-44.0) (median (2575%) percentiles) ug/g; p=0.21)). Among IBS patients, 13 subjects (13.2%) had f-calprotectin levels above the 90th percentile in the controls (98.8ug/g). There was no difference in IBS subgroup according to Rome III (IBS-C, IBS-D, IBS-M, IBS-U) in patients with high as compared to normal f-calprotectin. Also the disease duration was comparable in the two groups (9.5 (2-15) vs. 10 (5-15.3) years; p=0.46). There was no difference between IBS patients with high vs. normal levels of f-calprotectin regarding intensity or frequency of pain, bloating severity, bowel habit dissatisfaction, or daily life as estimated by IBS-SSS (Table 1). Also, total IBS-SSS score was comparable in the two groups (Table 1). The average stool form according to BSF (3.7 (2.9-4.4) vs. 4.1 (3.3-4.9); p=0.2) and stool frequency (1.5 (0.75-1.9) vs. 1.6 (1.2-2.3); p=0.29) were also similar in patients with high respective normal calprotectin levels. The pain threshold in rectal barostat test was comparable in IBS patients with high respective normal levels of f-calprotectin (24 (24-28) vs. 24 (20-32) mmHg; p=0.65). Moreover, oroanal transit time (OATT) was comparable in the two groups (1.5 (0.5-1.9) vs. 1.2(0.7-1.9) days; p=0.95) CONCLUSION: Fecal calprotectin within the normal range is not associated with the severity of IBS symptoms or key pathophysiological factors. Our data do not support that mucosal neutrophil inflammation is of major importance for symptom generation in IBS. Table 1. Symptom severity assessed by -IBS-SSS in IBS patients with high respective normal levels of fecal calprotectin.

Cytokine alterations and cognitive impairment in major depressive disorder: From putative mechanisms to novel treatment targets

Overwhelming evidence indicates the involvement of immune-inflammatory processes in the pathophysiology of major depressive disorder (MDD). Peripheral cytokine alterations serve as one of most consistently reported indices of subthreshold inflammatory state observed in MDD. Although cytokines cannot pass directly through the blood-brain barrier, a number of transport mechanisms have been reported. In addition, peripheral cytokines may impact central nervous system via downstream effectors of their biological activity. Animal model studies have provided evidence that cytokines might impact cognitive performance through direct and indirect effects on long-term potentiation, neurogenesis and synaptic plasticity. Therefore, it has been hypothesized that cytokine alterations might contribute to cognitive impairment that is widely observed in MDD and persists beyond episodes of acute relapse in the majority of patients. Although several studies have provided that peripheral cytokine alterations might be related to cognitive deficits in patients with MDD, the quality of evidence still leaves much to be desired due to methodological heterogeneity and limitations. In this article, we provide an overview of studies investigating the association between peripheral cytokine alterations and cognitive performance in MDD, discuss underlying mechanisms and neural substrates. Finally, we propose possible treatment targets related to cytokine alterations taking into account existing evidence for antidepressant efficacy of anti-inflammatory pharmacological treatment modalities.

Assessment of the frequency criterion for the diagnosis of non-suicidal self-injury disorder in female adolescents with conduct disorder

Recent studies suggest a higher threshold number of self-injuries during the past year than the one proposed in the DSM-5 criteria for non-suicidal self-injury disorder (NSSID). Therefore, we aimed to test a validity of the frequency criterion in girls with conduct disorder (CD) based on psychopathology and the level of functioning. Mixture modelling analysis revealed that the frequency of at least 8 self-harm behaviours in the previous year differentiated adolescents with CD. Thus, we divided adolescents into three subgroups: group 1: at least 8 self-harm acts; group 2: 1-7 self-harm behaviours and group 3: those who did not injure themselves during the last 12 months. Individuals from group 1 were significantly younger and had earlier age of self-harm onset. There were significant differences between groups 1 and 3 in terms of anxiety and depressive symptoms, self-esteem, aggression and the global functioning level. The group 1 scored significantly higher on depressive symptoms compared to the group 2. The group 2 scored significantly higher than the group 3 on the level of hostility. Our results provide further evidence supporting the need for modification of the NSSID frequency criterion.

Not all drugs are created equal: impaired future thinking in opiate, but not alcohol, users

Episodic future thinking refers to the ability to travel forward in time to pre-experience an event. Although future thinking has been intimately linked with self and identity, to our knowledge, no prior research has compared episodic future thinking in populations with different substance use disorders. This study investigates whether there are differences in episodic future thinking between these alcohol and opiate users. The study recruited participants who were on the opiate substitution program (n = 31) and individuals who had been diagnosed with alcohol dependence (n = 21) from the Royal Prince Alfred Hospital Drug and Health Services. Healthy controls (n = 23) were recruited via Royal Prince Alfred Hospital databases and the general community. Past and future thinking was measured using four cue words. After each cue word, participants rated their phenomenological experience (e.g. emotion, reliving experience). Results indicated that alcohol-dependent individuals performed significantly higher in episodic future thinking compared to opiate users. These findings indicate that not all substance use disorder groups share similar episodic thinking capabilities. Our results suggest that the self-projection component of rehabilitation programs may have to be tailored to the different episodic construction abilities found in substance use disorder groups.

Serotonin-Related Gene Variants in Patients with Irritable Bowel Syndrome and Depressive or Anxiety Disorders

Aim To assess the association of six polymorphisms in serotonin-related genes with depressive or anxiety disorders in patients with irritable bowel syndrome (IBS). Methods The lifetime prevalence of depressive and anxiety disorders was assessed in 95 IBS patients (85% women) using the Munich version of the Composite International Diagnostic Interview (CIDI). IBS was diagnosed according to the Rome III criteria. SCL6A4 HTTLPR polymorphism (rs4795541) was determined using PCR-based method. Single-nucleotide polymorphisms in HTR1A (rs6295), HTR2A (rs6313 and rs6311), HTR2C (rs6318), and TPH1 (rs1800532) were detected by minisequencing method. Results IBS patients with depressive disorders were characterized by higher frequency of 5-HTTLPR L allele in comparison to IBS patients with anxiety disorders. The lower frequency of 1438 A allele in HTR2A was found in IBS patients with depressive disorders in comparison to IBS patients without mental disorders. The lower G allele frequency in HTR2C rs6318 polymorphism among IBS patients with anxiety disorders was also observed. Conclusions Our results provide further evidence for the involvement of SLC6A4 rs4795541 and HTR2A rs6311 polymorphisms in the pathophysiology of depressive disorders in IBS patients. The new findings indicate that HTR2C rs6318 polymorphism may be associated with the susceptibility to anxiety disorders in IBS patients.

YPSP01-14 - CD28 gene polymorphism with respect to affective symptoms in schizophrenia

Introduction Schizophrenia is complex and clinically heterogeneous psychiatric disorder that has an evidenced genetic basis. Several reports indicate a possible role of the activation of the immune system in the pathogenesis of schizophrenia. CD28 is a molecule expressed on T-cells that provides the major co-stimulatory signal required for activation of immune response. For many years now, it has been strongly advocated that biological underpinnings of schizophrenia should be investigated with respect to subpopulations of subjects defined by homogenous symptomatology. Objectives To investigate the association of polymorphism of the CD28 gene (T17int3C) with respect to schizophrenia symptomatology. Material and methods 105 patients diagnosed with schizophrenia according to ICD-10 criteria and 380 controls were included in the study. The patients were diagnosed using the Operational Criteria for Psychotic Illness checklist (OPCRIT). Based on confirmatory factor analysis on OPCRIT items performed by Serretti et al. (2004), in our study we considered five factors of symptomatology (mania, positive symptoms, disorganization, depression and negative symptoms). Results There was significant difference in distribution of genotypes between patients with schizophrenia with co-occurring manic symptoms and without co-occurring manic symptoms (respectively CC and/or TC: 23% vs. 47%, TT: 77% vs. 53%, p=0,040). There was also difference in distribution of genotypes between patients with schizophrenia with co-occurring depressive symptoms and without cooccurring depressive symptoms (respectively CC and/or TC: 24% vs. 47%, TT: 76% vs. 53%, p=0,043). Conclusion We have shown that CD28 gene polymorphism might increase risk for affective (depressive and/or manic) symptom dimension in schizophrenic patients.