Magdalena Kotlicka-Antczak

PORT (Programme of Recognition and Therapy): the first Polish recognition and treatment programme for patients with an at‐risk mental state

To present the activities of the first early intervention centre in Poland and the Programme of Recognition and Therapy (PORT) run by the centre.

A randomized controlled study of the efficacy of six-month supplementation with concentrated fish oil rich in omega-3 polyunsaturated fatty acids in first episode schizophrenia

Short-term clinical trials of omega-3 polyunsaturated fatty acids (n-3 PUFA) as add-on therapy in patients with schizophrenia revealed mixed results. The majority of these studies used an 8- to 12-week intervention based on ethyl-eicosapentaenoic acid. A randomized placebo-controlled trial was designed to compare the efficacy of 26-week intervention, composed of either 2.2 g/day of n-3 PUFA, or olive oil placebo, with regard to symptom severity in first-episode schizophrenia patients. Seventy-one patients (aged 16-35) were enrolled in the study and randomly assigned to the study arms. The primary outcome measure of the clinical evaluation was schizophrenia symptom severity change measured by the Positive and Negative Syndrome Scale (PANSS). Mixed models repeated measures analysis revealed significant differences between the study arms regarding total PANSS score change favouring n-3 PUFA (p = 0.016; effect size (ES) = 0.29). A fifty-percent improvement in symptom severity was achieved significantly more frequently in the n-3 PUFA group than in the placebo group (69.4 vs 40.0%; p = 0.017). N-3 PUFA intervention was also associated with an improvement in general psychopathology, measured by means of PANSS (p = 0.009; ES = 0.32), depressive symptoms (p = 0.006; ES = 0.34), the level of functioning (p = 0.01; ES = 0.31) and clinical global impression (p = 0.046; ES = 0.29). The findings suggest that 6-month intervention with n-3 PUFA may be a valuable add-on therapy able to decrease the intensity of symptoms and improve the level of functioning in first-episode schizophrenia patients.

Supplementation of antipsychotic treatment with sarcosine – GlyT1 inhibitor – causes changes of glutamatergic 1NMR spectroscopy parameters in the left hippocampus in patients with stable schizophrenia

Glutamatergic system, the main stimulating system of the brain, plays an important role in the pathogenesis of schizophrenia. Hippocampus, a structure crucial for memory and cognitive functions and rich in glutamatergic neurons, is a natural object of interest in studies on psychoses. Sarcosine, a glycine transporter (GlyT-1) inhibitor influences the function of NMDA receptor and glutamate-dependent transmission. The aim of the study was to assess the effects of sarcosine on metabolism parameters in the left hippocampus in patients with schizophrenia. Assessments were performed using proton nuclear magnetic resonance ((1)H NMR) spectroscopy (1.5T). Fifty patients diagnosed with schizophrenia (DSM-IV-TR), with dominant negative symptoms, in stable clinical condition and stable antipsychotics doses were treated either with sarcosine (n=25) or placebo (n=25). Spectroscopic parameters were evaluated within groups and between two groups before and after 6-month intervention. All patients were also assessed with the Positive and Negative Syndrome Scale (PANSS). In the sarcosine group, after 6-month treatment, we found significant decrease in hippocampal Glx/Cr (Glx-complex of glutamate, glutamine and GABA, Cr-creatine) and Glx/Cho (Cho-choline), while N-acetylaspartate (NAA), myo-inositol (mI), Cr and Cho parameters remained stable along the study and also did not differ significantly between both groups. This is the first study showing that a pharmacological intervention in schizophrenia, particularly augmentation of the antypsychotic treatment with sarcosine, may reverse the pathological increase in glutamatergic transmission in the hippocampus. The results confirm involvement of glutamatergic system in the pathogenesis of schizophrenia and demonstrate beneficial effects of GlyT-1 inhibitor on the metabolism in the hippocampus and symptoms of schizophrenia.

Obstetrical complications and Apgar score in subjects at risk of psychosis

The objective of the study was to identify associations between a history of obstetrical complications (OCs) and the future development of symptoms indicating risk of psychosis (At Risk Mental State - ARMS). The frequency of OCs was assessed in 66 ARMS subjects, 50 subjects with the first episode of schizophrenia (FES) and 50 healthy controls. Obstetrical data was obtained from medical documentation and evaluated with the Lewis and Murray Scale. Definite OCs, according to the Lewis and Murray Scale, occurred significantly more frequently in the ARMS group compared to the controls (χ(2) = 7.79, p = 0.005; OR = 4.20, 95% CI = 1.46-12.11), as well as in the FES subjects compared to the controls (χ(2) = 8.39, p = 0.004; OR = 4.64, 95% CI = 1.56-13.20). Apgar scores in the first (Apgar 1) and the fifth minute after birth (Apgar 5) were significantly lower in the FES subjects compared to the controls (for Apgar 1 score Z = 4.439, p < 0.0001; for Apgar 5 score Z = 5.250, p < 0.0001). The ARMS subjects demonstrated significantly lower Apgar 5 scores compared to the healthy controls (Z = 3.458, p = 0.0016). The results indicate that OCs and low Apgar 5 score should be considered important factors in identifying subjects at risk of developing psychosis.

Differences in omega-3 and omega-6 polyunsaturated fatty acid consumption in people at ultra-high risk of psychosis, first-episode schizophrenia, and in healthy controls

Supplementation with omega‐3 PUFA showed efficacy in reducing the risk of transition into psychosis in UHR individuals. It is uncertain whether dietary patterns can be partly responsible for n‐3 deficiencies observed in susceptible participants before the diagnosis of schizophrenia.

Telomere length in blood cells is related to the chronicity, severity, and recurrence rate of schizophrenia

Introduction Telomere shortening is strongly associated with higher mortality rates and has been shown in a number of age-related diseases, such as cardiovascular disorders, diabetes mellitus, Alzheimer’s disease, and psychiatric disorders. Oxidative stress is known to induce DNA breaks and genome instability. Telomeric DNA rich in guanosine is particularly sensitive to such oxidative damages. Psychosis is associated with a disequilibrium between free radical production and antioxidative defense. Although telomere attrition has been demonstrated in schizophrenia, no relationship has been reported between telomere length and severity of schizophrenia. Aim The aim of the present study was to identify differences in telomere length in peripheral blood cells between patients with chronic schizophrenia (C-SCZ) and early schizophrenia (E-SCZ) and to identify any relationship between telomere length and disease chronicity and severity. Methods Relative average telomere lengths were determined using qPCR assay in patients with E-SCZ (n=42) and C-SCZ (n=44) hospitalized due to schizophrenia exacerbation. E-SCZ was diagnosed when less than 2 years had passed since the beginning of psychotic symptoms. The severity of symptoms was assessed using appropriate scales. Results The severity of schizophrenia symptoms, as well as the number of psychotic episodes and hospital admissions, correlated significantly with telomere length in univariate analyses. Regression analysis revealed that a model incorporating study group (E-SCZ or C-ECZ), sex, and age, as well as the combined number of documented psychotic episodes and hospital admissions, can significantly predict the length of telomeres in patients with schizophrenia, with over 50% of variance in telomere length explained by the model (adjusted R2=0.512). Conclusion The results of the current study indicate that the recurrence of psychotic symptoms as well as their intensity and chronicity may be correlated with telomere attrition, which is well known to contribute to the development of premature senescence and age-related diseases.

Schizophrenia patients have higher-order language and extralinguistic impairments

INTRODUCTION The extralinguistic and paralinguistic aspects of the language refer to higher-order language functions such as lexical-semantic processes, prosody, indirect speech acts or discourse comprehension and production. Studies suggest that these processes are mediated by the Right Hemisphere (RH) and there is also some evidence of RH dysfunctions in schizophrenia. The aim of the paper is to investigate the extralinguistic and paralinguistic processing mediated by Right Hemisphere in schizophrenia patients using a validated and standardized battery of tests. METHODS Two groups of participants were examined: a schizophrenia sample (40 participants) and a control group (39 participants). Extralinguistic and paralinguistic processing was assessed in all subjects by the Polish version of the Right Hemisphere Language Battery (RHLB-PL), which measures comprehension of implicit information, naming, understanding humor, inappropriate remarks and comments, explanation and understanding of metaphors, understanding emotional and language prosody and discourse understanding. RESULTS Schizophrenia patients scored significantly lower than controls in subtests measuring comprehension of implicit information, interpretation of humor, explanation of metaphors, inappropriate remarks and comments, discernment of emotional and language prosody and comprehension of discourse. No differences were observed in naming, understanding metaphors or in processing visuo-spatial information. CONCLUSIONS Extralinguistic and paralinguistic dysfunctions appear to be present in schizophrenia patients and they suggest that RH processing may be disturbed in that group of patients. As the disturbances of higher-order language processes mediated by the RH may cause serious impairments in the social communication of patients, it is worth evaluating them during clinical examination.

Supplementation of Antipsychotic Treatment with the Amino Acid Sarcosine Influences Proton Magnetic Resonance Spectroscopy Parameters in Left Frontal White Matter in Patients with Schizophrenia

Dysfunction of the glutamatergic system, the main stimulating system in the brain, has a major role in pathogenesis of schizophrenia. The frontal white matter (WM) is partially composed of axons from glutamatergic pyramidal neurons and glia with glutamatergic receptors. The natural amino acid sarcosine, a component of a normal diet, inhibits the glycine type 1 transporter, increasing the glycine level. Thus, it modulates glutamatergic transmission through the glutamatergic ionotropic NMDA (N-methyl-d-aspartate) receptor, which requires glycine as a co-agonist. To evaluate the concentrations of brain metabolites (NAA, N-acetylaspartate; Glx, complex of glutamate, glutamine, and γ-aminobutyric acid (GABA); mI, myo-inositol; Cr, creatine; Cho, choline) in the left frontal WM, Proton Nuclear Magnetic Resonance (1H-NMR) spectroscopy was used. Twenty-five patients randomly chosen from a group of fifty with stable schizophrenia (DSM-IV-TR) and dominant negative symptoms, who were receiving antipsychotic therapy, were administered 2 g of sarcosine daily for six months. The remaining 25 patients received placebo. Assignment was double blinded. 1H-NMR spectroscopy (1.5 T) was performed twice: before and after the intervention. NAA, Glx and mI were evaluated as Cr and Cho ratios. All patients were also assessed twice with the Positive and Negative Syndrome Scale (PANSS). Results were compared between groups and in two time points in each group. The sarcosine group demonstrated a significant decrease in WM Glx/Cr and Glx/Cho ratios compared to controls after six months of therapy. In the experimental group, the final NAA/Cr ratio significantly increased and Glx/Cr ratio significantly decreased compared to baseline values. Improvement in the PANSS scores was significant only in the sarcosine group. In patients with schizophrenia, sarcosine augmentation can reverse the negative effect of glutamatergic system overstimulation, with a simultaneous beneficial increase of NAA/Cr ratio in the WM of the left frontal lobe. Our results further support the glutamatergic hypothesis of schizophrenia.

Adding Sarcosine to Antipsychotic Treatment in Patients with Stable Schizophrenia Changes the Concentrations of Neuronal and Glial Metabolites in the Left Dorsolateral Prefrontal Cortex.

The glutamatergic system is a key point in pathogenesis of schizophrenia. Sarcosine (N-methylglycine) is an exogenous amino acid that acts as a glycine transporter inhibitor. It modulates glutamatergic transmission by increasing glycine concentration around NMDA (N-methyl-d-aspartate) receptors. In patients with schizophrenia, the function of the glutamatergic system in the prefrontal cortex is impaired, which may promote negative and cognitive symptoms. Proton nuclear magnetic resonance (1H-NMR) spectroscopy is a non-invasive imaging method enabling the evaluation of brain metabolite concentration, which can be applied to assess pharmacologically induced changes. The aim of the study was to evaluate the influence of a six-month course of sarcosine therapy on the concentration of metabolites (NAA, N-acetylaspartate; Glx, complex of glutamate, glutamine and γ-aminobutyric acid (GABA); mI, myo-inositol; Cr, creatine; Cho, choline) in the left dorso-lateral prefrontal cortex (DLPFC) in patients with stable schizophrenia. Fifty patients with schizophrenia, treated with constant antipsychotics doses, in stable clinical condition were randomly assigned to administration of sarcosine (25 patients) or placebo (25 patients) for six months. Metabolite concentrations in DLPFC were assessed with 1.5 Tesla 1H-NMR spectroscopy. Clinical symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS). The first spectroscopy revealed no differences in metabolite concentrations between groups. After six months, NAA/Cho, mI/Cr and mI/Cho ratios in the left DLPFC were significantly higher in the sarcosine than the placebo group. In the sarcosine group, NAA/Cr, NAA/Cho, mI/Cr, mI/Cho ratios also significantly increased compared to baseline values. In the placebo group, only the NAA/Cr ratio increased. The addition of sarcosine to antipsychotic therapy for six months increased markers of neurons viability (NAA) and neurogilal activity (mI) with simultaneous improvement of clinical symptoms. Sarcosine, two grams administered daily, seems to be an effective adjuvant in the pharmacotherapy of schizophrenia.

Figural fluency and immediate visual memory in patients with at‐risk mental state for psychosis: empirical study

Although a number of cognitive functions have been assessed in the ultra‐high risk (UHR) population, only one study has reported on figural fluency. Visual memory was measured by different tests providing inconsistent results. The aim of the present study was to compare figural fluency and visual immediate memory performance in UHR patients and normal subjects.