Marta Flis

Processing speed is associated with differences in IQ and cognitive profiles between patients with schizophrenia and their healthy siblings

Abstract Background: Processing speed turns out to be the central area of research on cognition in schizophrenia. So far the relationship between this dimension and the IQ level of patients and their healthy siblings has not been investigated. Aim: To investigate the differences in cognitive speed in patients with schizophrenia and their healthy siblings, and to determine whether cognitive speed as a covariate affects differences in IQ and cognitive profiles between groups. Methods: Forty-seven inpatients diagnosed with schizophrenia according to DSM-IV (SCH) and their 36 healthy siblings (HSB) were tested with cognitive speed tasks according to Bartzokis et al. method and Wechsler Intelligence Scale. Additional control for the possible impact of antipsychotic drugs and selected demographic variables on the cognitive performance was taken into account. Results: The siblings scored significantly higher in the cognitive speed task (p < 0.01) than patients, the WAIS-R cognitive test profiles were also significantly different in two ways: between groups, and between single test results in each of the assessed groups. The interaction effect: ANOVA, F(10, 770) = 2.798, p = 0.002. Similarly, the Performance and Full Scale IQs were significantly different, at p < 0.01. After controlling for cognitive speed, all significant differences no longer exist: e.g. Full Scale IQ, p = 0.459. Conclusions: Significant differences in cognitive speed between patients and their healthy siblings generate the differences in the cognitive profile assessed with Wechsler Intelligence Scale. Some problems of cognitive speed diagnosis and further research on the cognitive schizophrenia endophenotype were discussed.

Correlations of Kynurenic Acid, 3-Hydroxykynurenine, sIL-2R, IFN-α, and IL-4 with Clinical Symptoms During Acute Relapse of Schizophrenia

Several lines of evidence suggest that up-regulation of immune response and alterations of kynurenine pathway function are involved in pathogenesis of schizophrenia. Correlations among clinical status (using PANNS, SANS and SAPS scales) and blood levels of kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK) and levels of selected immunoactive molecules, soluble interleukin-2 receptor (sIL-2R), interferon-α (IFN-α) and IL-4 were analyzed in 51 chronic schizophrenia patients during acute relapse, after four weeks of therapy and at remission. KYNA levels were significantly lower in comparison with controls (N=45) throughout the study, whereas 3-HK did not differ from controls at admission and during therapy, but increased at remission. The KYNA/3-HK ratio and IL-4 levels, but not sIL-2R and IFN-α levels, were consistently decreased in schizophrenia patients at all analyzed time points. KYNA level and KYNA/3-HK ratio measured at admission correlated negatively with the duration of illness, whereas 3-HK level correlated negatively with the improvement of SANS score at discharge. sIL-2R level before treatment was positively linked with number of relapses. In the subgroup of patients with poor response to pharmacotherapy, treated with clozapine later on, initial KYNA level and the ratio KYNA/3-HK correlated negatively with number of relapses. Positive association of sIL-2R level with number of relapses was also evident in this subgroup. Furthermore, among these patients, starting IFN-α level was negatively linked with the improvement of total PANSS score at discharge. Presented here data support the concept of disturbed kynurenine pathway function in schizophrenia and suggest that assessment of KYNA and 3-HK levels during acute relapse might be useful in prediction of response to antipsychotic therapy. Deficit of peripheral KYNA and higher 3-HK levels could be associated with more severe symptoms of schizophrenia. Further studies with larger samples size are needed to validate our results.

New prospects for antipsychotic treatment - the role of the kynurenine pathway

The mechanism of action of antipsychotic drugs is mainly associated with changes in dopaminergic system. The application of antipsychotic agents simultaneously produces changes in concentrations of metabolites (e.g. kynurenic acid - KYNA, 3-hydroxykynurenine - 3-OHKYN, kynurenine - KYN) of the kynurenine pathway, the pathway engaged in glutamatergic transmission. The increase in KYNA levels in certain areas of the central nervous system results in inhibition of glutamatergic transmission. Pharmacologically induced elevation of KYNA levels produces effects similar to those observed after administering ketamine or phencyclidine (the noncompetitive NMDA receptor antagonist), concerning increased activity of mesolimbic dopamine neurons, as well as reduction in dopamine release from the prefrontal cortex. Recent research results confirm the predictive value of changes in concentrations of kynurenine pathway metabolites for assessment of effectiveness of antipsychotic treatment. Significant relationships were found 1) in schizophrenia between the reduction of psychopathological symptoms and variations in 3-OHKYN levels as well as changes in KYNA/3-OHKYN and KYN/KYNA ratios, 2) in mania between varying tryptophan concentrations and the reduction in manic symptoms achieved with antipsychotic treatment. The research as well presented the possibilities of kynurenine pathway modifications, raising high hopes for their future application as target points for the action of novel antipsychotic agents.

Schizophrenia and anorexia nervosa – reciprocal relationships. A literature review

Although schizophrenia and anorexia nervosa are seemingly very distinct psychiatric disorders, their symptoms are connected by various types of relationships. The present article reviews the literature and recapitulates the views of various authors on the links between these two disorders. Symptoms of anorexia may 1) precede the onset of psychosis; 2) evolve in its active phase or more rarely manifest in remission; and, conversely, 3) psychotic symptoms may occur transiently in the course of anorexia nervosa. When anorexia precedes the manifestation of psychosis, symptoms of anorexia can be treated as a component of the prodromal phase of schizophrenia. Another possibility of co-existence of a psychosis (e.g., schizophrenia) with anorexia is when the eating disorder syndrome manifests at the same time as the full-blown psychotic syndrome. In such cases, when the symptoms of the two disorders occur simultaneously, it is often difficult to say whether the patient is suffering from schizophrenia, in the course of which anorexia has arisen secondary to psychotic symptoms or whether he/she is suffering from anorexia during which he/she has developed psychotic symptoms, usually thematically associated with eating. Studies published so far, mainly case reports, point to the complex nature of the interrelationships between schizophrenia and anorexia nervosa. Further research is needed to conclusively explain the relationships between psychotic disorders and anorexia nervosa, which would allow physicians to use more effective methods of treatment in this group of patients.

Review paper. Gluten-related disorders and schizophrenia - potential linking mechanisms, diagnostic and therapeutic challenge

Abstract More and more evidence confirms the theory that the intake of cereal products containing gluten may play an important role in the pathogenesis of many diseases. There are also premises indicating the relationship between the so-called gluten-related diseases and the development and course of mental disorders, including schizophrenia. The aim of this article is to review the literature on the potential relationship between the consumption of gluten and schizophrenia, considering the etiopathogenesis and the role of gluten-free diet in the treatment of schizophrenia. Methods: There were analysed available research papers in PubMed and Google Scholar with the key words: schizophrenia, gluten- related disorders, allergy to grain products, celiac disease, microbiota, immune system, exorphins and time span: 1960-2016 . Conclusions: Existing research results indicate a possible relationship between diet rich in grain products with high gluten content and the occurrence or exacerbation of schizophrenia symptoms. However, further studies are necessary to: 1) identify groups of patients for whom the consumption of cereal products (gluten) is associated with a particular risk of schizophrenia exacerbation, 2) determine the mechanisms relating the consumption of gluten with the mental state of schizophrenic patients, 3) get the possible benefits of implementing gluten-free diet in patients with schizophrenia.