Clinical Manifestations Of Schizophrenia Research Articles

Correlation between the features of cognitive activity and clinical manifestations of schizophrenia in patients who have committed socially dangerous acts

The commission of socially dangerous acts always sparks a public outcry, and special attention and close interest are noted when the perpetrator suffers from a mental disorder. As far as the mental disorders diagnosed in this group of individuals are concerned, schizophrenia ranks among the first, and the research of its complex clinical picture is a promising direction for studying the features of delinquent behavior. The relevance of the study lies in the investigation of the nature of cognitive activity and its relationship with the clinical manifestations of schizophrenia. The purpose of the work was to analyze cognitive activity in schizophrenia patients who committed socially dangerous acts and identify their relationship with clinical manifestations of schizophrenia. The study was performed on 22 examinees of the department of inpatient forensic psychiatric examination for persons in custody who committed socially dangerous acts against the health and life of an individual, and 26 patients who were being treated in a general psychiatric department. According to the criteria of ICD-10, all subjects were diagnosed with paranoid schizophrenia at the stage of inpatient remission. In all participants of the experiment, the clinical picture of schizophrenia using the Positive and Negative Syndrome Scale (PANSS) was assessed, and the analysis of cognitive activity by means of the method of discrimination of properties of concepts was carried out. It has been established that the clinical manifestations of schizophrenia are characterized by diversity, persistence, and independence from committed aggressive delicts, and the cognitive activity of such patients is characterized by pronounced subjectivity and moderate realism, which makes their behavior peculiar, rigid to external influence, and extremely persistent in relation to their own goals.

Relationship between blood-based inflammatory indices and clinical score of schizophrenia patients: A cross-sectional study

Schizophrenia is a severe mental disorder that may involve inflammation. Inflammatory indices, such as the neutrophil to lymphocyte ratio (NLR), the monocyte to lymphocyte ratio (MLR), the platelet to lymphocyte ratio (PLR), and the systemic inflammation index (SII), are simple and inexpensive measures of inflammation that have been associated with various diseases. However, few studies have compared these indices and their relationships with clinical symptoms in schizophrenia. We conducted a cross-sectional study of 121 schizophrenia patients (101 males, 20 females). We measured the blood-based inflammatory indices (NLR, MLR, PLR, and SII) and assessed the clinical symptoms of schizophrenia using the Positive and Negative Syndrome Scale (PANSS). Statistical analyses were performed to examine the correlations and effects of the inflammatory indices on PANSS scores. We found that NLR, MLR, PLR, and SII were positively correlated with PANSS total score, PANSS positive score, PANSS negative score, and general psychopathology score (adjusted P < 0.02 for all correlations). Subgroup analysis showed that correlations between inflammatory indices and the clinical scores differed by gender. In males, all inflammatory indices were positively correlated with all clinical scores. On the other hand, in females, only NLR and SII were positively correlated with all clinical scores. After adjusting for confounders, we also found that NLR was a predictor of PANSS total score (β = 23, adjusted P < 0.02), PANSS positive score (β = 2.6, adjusted P = 0.03), PANSS negative score (β = 6.8, adjusted P < 0.02), and PANSS general psychopathology score (β = 13.6, adjusted P < 0.02), while SII was only a predictor for PANSS total score (β = −0.00003, adjusted P = 0.01) and general psychopathology scores (β = −0.00002, adjusted P < 0.02). These findings suggest that inflammation is involved in the pathophysiology and clinical manifestations of schizophrenia, and that blood-based inflammatory indices may serve as screening tools or indicators for the inflammatory status and severity of symptoms of schizophrenia patients.

Regulatory T cells mediate insomnia-related psychotic symptoms and cognitive impairment in chronic schizophrenia patients

Insomnia occurs frequently in schizophrenia patients and is often accompanied with severe psychotic symptoms and cognition impairment. Moreover, chronic insomnia is associated with immune alterations. This study explored the correlations between insomnia and clinical manifestations of schizophrenia and analyzed mediation effects of regulatory T cells (Tregs) on these correlations. In a total of 655 chronic schizophrenia patients, 70 persons (10.69%) had an ISI (Insomnia Severity Index) score >7 and were referred to as Insomnia group. Compared to non-Insomnia group, Insomnia group presented more severe psychotic symptoms (assessed by PANSS) and cognitive impairment (assessed by RBANS). The total effect of ISI on PANSS/RBANS total score was not significant due to the mediation effects by Tregs, in which Tregs strongly mediated the effect of ISI on PANSS total score in negative direction but mediated the effect of ISI on RBANS total score in positive direction. Pearson Correlation Coefficient revealed negative correlations between Tregs and PANSS total score or disorganization subscale of PANSS. Positive correlations existed between Tregs and RBANS total score, between Tregs and the subscales of attention, delayed memory, or language of RBANS. These mediation effects of Tregs on insomnia-related psychotic symptoms and cognitive impairment in chronic schizophrenia patients point to a potential therapeutic strategy of modulating Tregs for the patients.

Partial ablation of frontal cortical subplate leads to developmental abnormalities in KCC2 in the prefrontal cortex

During early brain development, the subplate relays thalamocortical afferents to the overlying cortex. Disconnection of thalamic inputs to the prefrontal cortex by lesions of the subplate of the developing prefrontal cortex at early neonatal periods result in adult-onset behavioral abnormalities reminiscent of positive, negative, and cognitive symptoms of schizophrenia. Delayed maturation of γ-amino butyric acid (GABA) function may contribute to certain abnormalities of the prefrontal cortex and clinical manifestations of schizophrenia. Lesions to the subplate have also been implicated in developmental abnormalities of GABA neurotransmission in somatosensory and visual cortices. Therefore, we sought to examine the effects of subplate lesions in the developing prefrontal cortex of rats on the expression of GABA markers [parvalbumin and glutamic acid decarboxylase (GAD67)] and proteins responsible for GABAergic synaptic maturation [potassium-chloride cotransporter (KCC2) and sodium‑potassium-chloride cotransporter (NKCC1)]. Lesioned and control rats were sacrificed between postnatal days (P) 5 and 90 and immunolabeled for parvalbumin, GAD67, KCC2, and NKCC1 in the prelimbic area of the prefrontal cortex. We found decreased immunoreactivity of KCC2 on neuronal cell membranes at P11 compared to control rats. However, the overall immunoreactivity of KCC2 and NKCC1 did not differ between lesion and control animals at all time points studied. Lesioned rats also showed decreased expression of parvalbumin, but not GAD67. Our results indicate that mechanisms underlying trafficking and membrane binding of KCC2 may contribute to altered GABA receptor function during development in schizophrenia.

Contribution of astrocytes to familial risk and clinical manifestation of schizophrenia.

Previous studies have implicated several brain cell types in schizophrenia (SCZ), but the genetic impact of astrocytes is unknown. Considering their high complexity in humans, astrocytes are likely key determinants of neurodevelopmental diseases, such as SCZ. Human induced pluripotent stem cell (hiPSC)‐derived astrocytes differentiated from five monozygotic twin pairs discordant for SCZ and five healthy subjects were studied for alterations related to high genetic risk and clinical manifestation of SCZ in astrocyte transcriptomics, neuron‐astrocyte co‐cultures, and in humanized mice. We found gene expression and signaling pathway alterations related to synaptic dysfunction, inflammation, and extracellular matrix components in SCZ astrocytes, and demyelination in SCZ astrocyte transplanted mice. While Ingenuity Pathway Analysis identified SCZ disease and synaptic transmission pathway changes in SCZ astrocytes, the most consistent findings were related to collagen and cell adhesion associated pathways. Neuronal responses to glutamate and GABA differed between astrocytes from control persons, affected twins, and their unaffected co‐twins and were normalized by clozapine treatment. SCZ astrocyte cell transplantation to the mouse forebrain caused gene expression changes in synaptic dysfunction and inflammation pathways of mouse brain cells and resulted in behavioral changes in cognitive and olfactory functions. Differentially expressed transcriptomes and signaling pathways related to synaptic functions, inflammation, and especially collagen and glycoprotein 6 pathways indicate abnormal extracellular matrix composition in the brain as one of the key characteristics in the etiology of SCZ.

Association of Cognitive Impairment With Anhedonia in Patients With Schizophrenia.

Anhedonia is considered as one of the five dimensions of negative symptoms and mainly refers to the reduction of the capacity of feeling pleasure. Increasing evidence suggests that anhedonia in schizophrenia may be partly explained by cognitive impairment. However, the associations between specific cognitive impairment and anhedonia are not fully investigated. The purpose of this study was to examine anticipatory anhedonia, consummatory anhedonia, and their cognitive associations in schizophrenia. A total number of 100 patients with schizophrenia and 67 healthy volunteers were recruited. The clinical symptoms of schizophrenia were assessed. Anticipatory pleasure, consummatory pleasure, and cognitive functions of each participant were measured. Multiple linear regression analysis was performed to investigate the influencing factors of anhedonia in schizophrenia. The results showed no significant differences in sex, age, education year, body mass index (BMI), and marital status between the schizophrenia group and healthy control group (all P > 0.05). Both anticipatory and consummatory pleasure in the schizophrenia group were significantly lower than those in the healthy control group (all P < 0.05). Immediate memory, visual spanning, language, attention, and delayed memory were significantly poorer in the schizophrenia group (all P < 0.05). The results showed that language deficit is an independent risk factor for anticipatory anhedonia (B' = 0.265, P = 0.008, 95% CI: 0.038-0.244), while delayed memory deficit is an independent risk factor for consummatory anhedonia (B' = 0.391, P < 0.001, 95% CI:0.085-0.237). To the best of our knowledge, this is the first study that reported the specific cognitive associations of anhedonia in schizophrenia. The findings have added new evidence on the influencing factors of anhedonia and provided clues for the associations between clinical manifestations of schizophrenia.

Preliminary evidence that oxytocin does not improve mentalizing in women with schizophrenia

IntroductionMentalizing, the ability to infer other people's intentions and emotions, is commonly impaired in schizophrenia and may represent an endophenotype. The hypothalamic neuropeptide oxytocin has been shown to improve mentalizing in men with schizophrenia, but its effects in women remain unclear. Given sex differences in the clinical manifestations of schizophrenia and oxytocin system function, this is an important gap to address. MethodsWe tested the effects of a single-dose oxytocin challenge (40 IU) on mentalizing task performance among 26 women with schizophrenia and 38 healthy control women using a randomized, placebo-controlled, double-blind, crossover design. We aimed to replicate our prior study of oxytocin effects on mentalizing in men with schizophrenia, using the same oxytocin administration procedures and performance-based assessments. We used mixed-effects models and equivalence testing as well as Bayesian hierarchical models to examine oxytocin effects. ResultsIn contrast to our previous finding in a male sample, oxytocin did not improve mentalizing in this sample of women with schizophrenia. Exploratory analyses showed that higher anti-dopaminergic medication dosage was associated with a decreased response to oxytocin, consistent with previous findings in men. ConclusionThese findings provide preliminary evidence that exogenous oxytocin administration may have sex-specific effects on mentalizing in schizophrenia. Inclusion of women in future clinical studies with larger samples is critical, as oxytocin effects observed in men may not extend to women with the disorder.

The metacognitive functioning of patients with paranoid schizophrenia through the prism of emotional intelligence: a connection with cognitive deficit, clinical manifestations, social functioning and quality of life

Metacognitive functioning is the basis of the individual’s ideas about his ability to build relationships with other people and manage own’s social behavior. Deterioration of metacognitive functioning in schizophrenia patients, presumably due to neurocognitive deficiency and other manifestations of the disease, probably contributes to disruptions of social functioning and quality of life. The aim of this study was to assess the metacognitive functioning (MF) of patients with paranoid schizophrenia, operationalized as a cognitive ability to understand their own and other people’s emotions, and to explore the connection between social functioning (SF) and quality of life (QOL), as well as to establish logical relationships between MF with clinical indicators and socio-demographic characteristics of patients. In a sample of 300 patients with paranoid schizophrenia (age from 18 to 50 years, disease duration of at least 5 years, a total PANSS score of less than 120), MF was assessed using the Lyusin emotional intelligence test (EmIn) and the subjective assessment of interpersonal relationships (SOMO) test. Cognitive deficit was verified using a standardized battery of a Brief Assessment of Cognition in Schizophrenia (BACS). The indicators obtained using the quality of life questionnaire for schizophrenia patients (QOL-SM) and the social functioning scale (PSP) were used to create an integrated indicator that comprehensively assesses SF and QOL of schizophrenia patients (Factor B). Reliable associations of this factor with indicators obtained using the Emin method (p&lt;0.05), SOMO (p&lt;0.001), the PSP scale, the QOL-SM questionnaire, the BACS and PANSS scales, and also with a number of clinical-dynamic and socio-demographic characteristics were established. Significant relationships between the parameters of MF, SF and QOL were obtained, and logical relationships between MF, neurocognitive deficiency and other clinical manifestations of schizophrenia were established.

Gene expression meta-analysis reveals the down-regulation of three GABA receptor subunits in the superior temporal gyrus of patients with schizophrenia

One of the main theories accounting for the underlying pathophysiology of schizophrenia posits alterations in GABAergic neurotransmission. While previous gene expression studies of postmortem brain samples typically report the down-regulation of GABA related genes in schizophrenia, the results are often inconsistent and not uniform across studies.We performed a systematic gene expression analysis of 22 GABA related genes in postmortem superior temporal gyrus (STG) samples of 19 elderly subjects with schizophrenia (mean age: 77) and 14 matched controls from the Icahn school of Medicine at Mount Sinai (MSSM) cohort. To test the validity and robustness of the resulting differentially expressed genes, we then conducted a meta-analysis of the MSSM and an independent dataset from the Stanley Consortium of 14 STG samples of relatively young subjects with schizophrenia (mean age: 44) and 15 matched controls.For the first time, the findings showed the down-regulation of three GABA-receptor subunits of type A, GABRA1, GABRA2 and GABRB3, in the STG samples of subjects with schizophrenia, in both the elderly and the relatively young patients.These findings, as well as previous results, lend weight to the notion of a common upstream pathology that alters GABAergic neurotransmission in schizophrenia. GABRA1, GABRA2 and GABRB3 down-regulation may contribute to the pathophysiology and clinical manifestations of schizophrenia through altered oscillation synchronization in the STG.

Dopaminergic control of ADAMTS2 expression through cAMP/CREB and ERK: molecular effects of antipsychotics

A better understanding of the molecular mechanisms that participate in the development and clinical manifestations of schizophrenia can lead to improve our ability to diagnose and treat this disease. Previous data strongly associated the levels of deregulated ADAMTS2 expression in peripheral blood mononuclear cells (PBMCs) from patients at first episode of psychosis (up) as well as in clinical responders to treatment with antipsychotic drugs (down). In this current work, we performed an independent validation of such data and studied the mechanisms implicated in the control of ADAMTS2 gene expression. Using a new cohort of drug-naïve schizophrenia patients with clinical follow-up, we confirmed that the expression of ADAMTS2 was highly upregulated in PBMCs at the onset (drug-naïve patients) and downregulated, in clinical responders, after treatment with antipsychotics. Mechanistically, ADAMTS2 expression was activated by dopaminergic signalling (D1-class receptors) and downstream by cAMP/CREB and mitogen-activated protein kinase (MAPK)/ERK signalling. Incubation with antipsychotic drugs and selective PKA and MEK inhibitors abrogated D1-mediated activation of ADAMTS2 in neuronal-like cells. Thus, D1 receptors signalling towards CREB activation might participate in the onset and clinical responses to therapy in schizophrenia patients, by controlling ADAMTS2 expression and activity. The unbiased investigation of molecular mechanisms triggered by antipsychotic drugs may provide a new landscape of novel targets potentially associated with clinical efficacy.

M98 - EVENT-RELATED P300 AMPLITUDE AS AN ENDOPHENOTYPE OF SCHIZOPHRENIA: ASSOCIATION WITH GENOME WIDE SIGNIFICANT INDEX SINGLE NUCLEOTIDE POLYMORPHISMS

Background Reduced amplitude of the event related P300 potential is a prominent finding in schizophrenia patients and a promising endophenotype for genetic research. As yet, little is known on common genetic risk factors for P300 amplitude reduction and the clinical manifestation of schizophrenia. Recently, the Psychiatric Genomics Consortium (PGC2) identified 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance. We used data from 269 normal subjects with both electrophysiological and genotype data to explore the possible relevance of these schizophrenia index SNPs on the P300 amplitude. Methods The sample comprised 269 unrelated healthy volunteers of German descent from the general population of Munich, Germany. Subjects with neuropsychiatric disorders were excluded. Evoked potentials were recorded using an auditory oddball paradigm with 80% non-target stimuli (540 tones, 500 Hz) and 20% target stimuli (135 tones, 1000 Hz) presented binaurally through headphones in a pseudo randomized order. The P300 amplitude was detected semiautomatically as the most positive value in the timeframe 250–500ms post-stimulus with a visual control afterwards at the electrode position Fz. The sample was genotyped on different platforms following established quality control and imputation protocols. After excluding two SNPs with insufficient quality of imputation, 126 genome-wide significant schizophrenia index SNPs from PGC2 could be evaluated for association with P300 amplitude by linear regression. Results There were 12 associations significant on the p=0.05 level (chr5_140143664_I, rs6002655, rs12887734, rs11191419, rs75059851, rs7907645, rs7432375, rs12421382, rs36068923, rs6065094, chr10_104957618_I, rs6670165). None of the associations survived Bonferroni correction for 126 comparisons. When employing the exact binomial test the number of significant associations observed exceeded chance expectation (p=0,024). Only one half of the associations showed effects in the expected direction (lower P300 amplitude associated with schizophrenia risk allele or amplitude associated with protective allele). Discussion Although we found an overrepresentation of significant associations of schizophrenia index SNPs with event related P300 amplitudes we were unable to establish the connection for any specific locus with sufficient statistical power. The pattern of observed effects was not supportive of a specific role of PGC2 schizophrenia risk alleles in P300 amplitude in normal subjects.

T187. ALTERED DNA METHYLATION OF THE OXYTOCIN RECEPTOR GENE IS ASSOCIATED WITH SUSCEPTIBILITY TO PSYCHOSIS AND ANHEDONIA-ASOCIALITY IN FEMALES: EPIGENETIC EVIDENCE IN RECENT-ONSET SCHIZOPHRENIA AND ULTRA-HIGH RISK FOR PSYCHOSIS

BackgroundOxytocin is one of the key hormones involved in human social and emotional processing. In this regard, abnormal functioning of the oxytocin system has been suggested to influence on the clinical manifestation of schizophrenia, especially negative symptoms. The aim of the present study was to investigate epigenetic modification of the oxytocin receptor gene (OXTR) and its association with negative symptoms in individuals with recent-onset schizophrenia (SCZ) and at ultra-high risk (UHR) for psychosis.MethodsSixty-four SCZ patients (< 5 years of duration of illness; 25 men, 39 women), 46 UHR individuals (27 men, 19 women), and 98 healthy controls (HCs; 46 men, 52 women) participated in the present study. DNA methylation was quantified from peripheral blood using pyrosequencing at CpG sites in OXTR intron 1 (hg19, chr3: 8,810,729–8,810,845) and exon 3 (hg19, chr3: 8,809,281–8,809,534). The severity of negative symptoms in clinical groups was measured using the Scale for the Assessment of Negative Symptoms (SANS) and Scale for the Assessment of Positive Symptoms (SAPS).ResultsA multivariate analysis of covariance revealed significant differences in OXTR methylation between groups (F = 16.00, p < 0.001) and gender (F = 2.84, p = 0.025). Compared to HCs, both UHR and SCZ participants showed lower levels of OXTR intron 1 methylation, particularly at CpG site -934 upstream of the OXTR start codon (HCs = 47.3 ± 4.1 [mean ± SD], UHR = 38.8 ± 4.8, SCZ = 40.2 ± 5.3; F = 73.74, p < 0.001). Besides, female participants showed higher OXTR intron 1 methylation at CpG site -934 than male participants (male = 42.3 ± 6.1, female = 44.1 ± 5.8, F = 9.08, p = 0.003). Multiple linear regression analysis with clinical symptoms demonstrated that the degree of DNA methylation at CpG site -934 was significantly associated with the SANS anhedonia-asociality subscale scores in the entire group of female UHR and SCZ participants (beta = -0.44, p = 0.001).DiscussionThe present study demonstrated decreased OXTR methylation in both UHR and SCZ individuals compared to HCs. Furthermore, the severity of anhedonia-asociality was significantly associated with the degree of OXTR methylation in female UHR and SCZ individuals. These findings suggest that epigenetic aberration of OXTR may confer susceptibility to schizophrenia spectrum psychosis and influence the early pathogenesis of schizophrenia prior to the onset of overt psychosis, particularly in females.

Second-to-fourth digit length ratio is associated with negative and affective symptoms in schizophrenia patients

BackgroundHigher levels of circulating oestrogens in women and testosterone in men have been shown to have a protective effect against the clinical manifestations of schizophrenia, mostly with respect to negative symptomatology. Certain studies suggest that they also have a protective effect against the neuropsychological impairment observed in the disease. We investigated whether greater prenatal exposure to estrogens in women and to testosterone in men, reflected by the 2D:4D ratio, was similarly associated with decreased negative symptomatology and improved neuropsychological functioning in patients. Method51 schizophrenia patients and 50 healthy participants were administered a neuropsychological battery. The 2D:4D ratio was measured in all participants. Positive, negative, and affective symptoms were assessed in patients. Regression analyses were conducted separately in male and female subgroups. ResultsNo associations with positive symptoms were revealed. In male patients, the 2D:4D ratio was positively associated with avolition and inversely associated with anxiety. In female patients, it was inversely associated with alogia, and tended to be positively associated with depression. No association between higher prenatal concentration of the relevant sex hormone and improved neuropsychological performance emerged in patients. ConclusionsHigher concentrations of prenatal testosterone in male patients, and prenatal oestrogens in female patients, are associated with a decrement in certain aspects of negative symptomatology. In addition, prenatal sex hormone concentration seems to be associated with predisposition to anxiety in male patients, and to depression in female patients.

Identification of the Niacin-Blunted Subgroup of Schizophrenia Patients from Mood Disorders and Healthy Individuals in Chinese Population.

Schizophrenia (SZ) is a devastating mental disease caused by complex genetic and environmental factors. The pathological process and clinical manifestation of SZ are heterogeneous among patients, which hampers precise diagnosis and treatment of the disease. Since no objective marker for SZ has been established today, to identify a subgroup of the patients with homogeneous biochemical traits will provide a new angle for both researchers and clinicians to understand and manage the disease. In this study, we employed the niacin skin-flushing test in Chinese population and confirmed a niacin-blunted subgroup of SZ patients distinguishable from mood disorders (MD) and normal individuals. This subgroup accounted for 30.67% of the total SZ patients with a specificity of 88.37% in male subjects and 83.75% in female subjects. We support the notion that bluntness in niacin skin test might reflect abnormalities in membrane fatty acid composition, which could be induced by increased PLA2 enzyme activity, in vivo oxidative stress or lipid metabolism imbalance in SZ. Further studies are encouraged to clarify the molecular origins of niacin-bluntness in SZ, which would provide extra clues for etiological research in schizophrenia and for new targeted treatment.

Genetic aspects of schizophrenia

Schizophrenia is a disease with a complex non-Mendelian inheritance mechanism in most cases involving the combined action of a large number of genes. Identifying of genomic variations associated with schizophrenia endophenotypes has a great potential. This review describes genetic markers of the disease, current methods of their analysis, including genome-wide association study (GWAS). Certain genes with mutations that increase the risk of schizophrenia are described. Functional polymorphisms with phenotypic expression, which are significantly associated with clinical manifestation of schizophrenia, can serve as useful genetic markers. The authors highlight that currently there are no certain susceptibility genes. Further global research and search for markers in different population groups are needed.

Telomere length in subjects with schizophrenia, their unaffected siblings and healthy controls: Evidence of accelerated aging

Schizophrenia (SZ) is associated with broad burden. The clinical manifestations of SZ are related to pathophysiological alterations similar to what is seen in normal aging. Our aim was to evaluate the differences in telomere length (TL), a biomarker of cellular aging, in subjects with SZ (n=36), unaffected siblings (SB, n=36) and healthy controls (HC, n=47). SZ had shorter TL compared to HC, but no difference was found in SB comparing to SZ. These findings indicate that a pathological accelerated aging profile could be present in the course of SZ and further studies are needed to confirm TL as potential endophenotype, especially in at risk populations.

Temporal perception deficits in schizophrenia: integration is the problem, not deployment of attentions

Patients with schizophrenia are known to have impairments in sensory processing. In order to understand the specific temporal perception deficits of schizophrenia, we investigated and determined to what extent impairments in temporal integration can be dissociated from attention deployment using Attentional Blink (AB). Our findings showed that there was no evident deficit in the deployment of attention in patients with schizophrenia. However, patients showed an increased temporal integration deficit within a hundred-millisecond timescale. The degree of such integration dysfunction was correlated with the clinical manifestations of schizophrenia. There was no difference between individuals with/without schizotypal personality disorder in temporal integration. Differently from previous studies using the AB, we did not find a significant impairment in deployment of attention in schizophrenia. Instead, we used both theoretical and empirical approaches to show that previous findings (using the suppression ratio to correct for the baseline difference) produced a systematic exaggeration of the attention deficits. Instead, we modulated the perceptual difficulty of the task to bring the baseline levels of target detection between the groups into closer alignment. We found that the integration dysfunction rather than deployment of attention is clinically relevant, and thus should be an additional focus of research in schizophrenia.

Gender Dysphoria as a Clinical Manifestation of Schizophrenia – Case Series

Comorbidity of schizophrenia and transsexualism is still controversial. Some authors exclude diagnosis of transsexualism in patients with psychosis others report this coexistence as very rare. Delusions of sex change have been described by some authors in about 20-25% of schizophrenic patients. Patient's “pseudotranssexual” beliefs are usually bizarre and do not cause diagnostic doubts. In some cases complaints of gender dysphoria are predominant and psychotic symptoms can be underestimated or even unnoticed before sex reassignment procedure. Presentation of various clinical manifestation of gender dysphoria in patients with schizophrenia. Three clinical cases are described. Two patients have developed “pseudotranssexual” beliefs during course of psychosis. The first of them is an example of gender identity disorders related to psychotic process. The second patient presented complex psychopathology of schizophrenia and somatic symptoms which can hinder the diagnosis. The third patient has been diagnosed as a transsexual woman after diagnosis of severe schizophrenia and has undergone sex reassignment. Next she was hospitalized several times because relapses of psychosis but also because of alcohol withdrawal. Currently this patient has symptoms of dementia and a few severe somatic diagnoses. The experiences of practitioners indicate that coincidence of schizophrenia and gender identity disorder is possible. Nevertheless, the consequence of misdiagnosis and sex reassignment can be serious and unconvertible. That is why the diagnosis of transsexualism in patients with psychosis should not be made hastily. It needs time, careful observation, examination and cooperation of psychiatrist and sexologist.

Serum levels of BDNF, folate and homocysteine: In relation to hippocampal volume and psychopathology in drug naïve, first episode schizophrenia

ObjectiveThe present study was to examine serum levels of brain-derived neurotrophic factor (BDNF), folate, homocysteine (Hcy), and their relationships with hippocampal volume and psychopathology in drug naïve, first episode schizophrenia. MethodDrug naïve, first episode schizophrenia patients and healthy controls were enrolled in the study. Serum levels of BDNF, folate and Hcy were measured using enzyme-linked immunosorbent assay (ELISA), electrochemiluminescence immunoassay (ECLIA), and enzymatic cycling method respectively. Hippocampus was parcellated and bilateral hippocampal volumes were measured using FreeSurfer. ResultsForty-six patients with drug naïve, first episode schizophrenia (SZ group) and 30 healthy controls (control group) were enrolled. The SZ group had significantly lower serum levels of BDNF and folate, and significantly higher serum levels of Hcy compared with the control group (p=0.013, p<0.001, p=0.003 respectively). There were no significant differences in hippocampal volumes between the two groups (ps>0.2). Within the SZ group, there were significant positive relationships between serum levels of BDNF and both left and right hippocampal volumes (r=0.327, p=0.026; r=0.338, p=0.022 respectively). In contrast, such relationships did not exist in the control group. Within the SZ group, there were significant negative relationships between serum levels of folate and PANSS-total scores and PANSS-negative symptom scores (r=0.319, p=0.031; r=0.321, p=0.030 respectively); and there was a positive relationship between serum levels of Hcy and PANSS-total scores (r=0.312, p=0.035). Controlling for potential confounding variables resulted in similar findings. ConclusionsDrug naïve, first episode schizophrenia presents decreased serum levels of BDNF, folate and increased serum levels of Hcy, which may play an important role in the neurodevelopmental process and clinical manifestation of schizophrenia.

DNA-methylation gene network dysregulation in peripheral blood lymphocytes of schizophrenia patients

The epigenetic dysregulation of the brain genome associated with the clinical manifestations of schizophrenia (SZ) includes altered DNA promoter methylation of several candidate genes. We and others have reported that two enzymes that belong to the DNA-methylation/demethylation network pathways—DNMT1 (DNA-methyltransferase) and ten-eleven translocator-1(TET1) methylcytosine deoxygenase are abnormally increased in corticolimbic structures of SZ postmortem brain. The objective of this study was to investigate whether the expression of these components of the DNA-methylation–demethylation pathways known to be altered in the brain of SZ patients are also altered in peripheral blood lymphocytes (PBL). The data show that increases in DNMT1 and TET1 and in glucocorticoid receptor (GCortR) and brain derived neurotrophic factor (BDNF) mRNAs in PBL of SZ patients are comparable to those reported in the brain of SZ patients.The finding that the expressions of DNMT1 and TET1 are increased and SZ candidate genes such as BDNF and GCortR are altered in the same direction in both the brain and PBL together with recent studies showing highly correlated patterns of DNA methylation across the brain and blood, support the hypothesis that a common epigenetic dysregulation may be operative in the brain and peripheral tissues of SZ patients.