Confirmation Bias in the Course of Instructed Reinforcement Learning in Schizophrenia-Spectrum Disorders.

A large body of research attributes learning deficits in schizophrenia (SZ) to the systems involved in value representation (prefrontal cortex, PFC) and reinforcement learning (basal ganglia, BG) as well as to the compromised connectivity of these regions. In this study, we employed learning tasks hypothesized to probe the function and interaction of the PFC and BG in patients with SZ-spectrum disorders in comparison to healthy control (HC) subjects. In the Instructed Probabilistic Selection task (IPST), participants received false instruction about one of the stimuli used in the course of probabilistic learning which creates confirmation bias, whereby the instructed stimulus is overvalued in comparison to its real experienced value. The IPST was administered to 102 patients with SZ and 120 HC subjects. We have shown that SZ patients and HC subjects were equally influenced by false instruction in reinforcement learning (RL) probabilistic task (IPST) (p-value = 0.441); however, HC subjects had significantly higher learning rates associated with the process of overcoming cognitive bias in comparison to SZ patients (p-value = 0.018). The behavioral results of our study could be hypothesized to provide further evidence for impairments in the SZ-BG circuitry; however, this should be verified by neurofunctional imaging studies.

The Role of Dopaminergic Genes in Probabilistic Reinforcement Learning in Schizophrenia Spectrum Disorders.

Schizophrenia spectrum disorders (SZ) are characterized by impairments in probabilistic reinforcement learning (RL), which is associated with dopaminergic circuitry encompassing the prefrontal cortex and basal ganglia. However, there are no studies examining dopaminergic genes with respect to probabilistic RL in SZ. Thus, the aim of our study was to examine the impact of dopaminergic genes on performance assessed by the Probabilistic Selection Task (PST) in patients with SZ in comparison to healthy control (HC) subjects. In our study, we included 138 SZ patients and 188 HC participants. Genetic analysis was performed with respect to the following genetic polymorphisms: rs4680 in COMT, rs907094 in DARP-32, rs2734839, rs936461, rs1800497, and rs6277 in DRD2, rs747302 and rs1800955 in DRD4 and rs28363170 and rs2975226 in DAT1 genes. The probabilistic RL task was completed by 59 SZ patients and 95 HC subjects. SZ patients performed significantly worse in acquiring reinforcement contingencies during the task in comparison to HCs. We found no significant association between genetic polymorphisms and RL among SZ patients; however, among HC participants with respect to the DAT1 rs28363170 polymorphism, individuals with 10-allele repeat genotypes performed better in comparison to 9-allele repeat carriers. The present study indicates the relevance of the DAT1 rs28363170 polymorphism in RL in HC participants.

A pro-inflammatory phenotype is associated with behavioural traits in children with Prader-Willi syndrome.

Several lines of evidence indicate that immune-inflammatory alterations are widely observed in various mental disorders. Genetic syndromes with high risk of psychiatric disorders may constitute a model for studies investigating this phenomenon. One of such genetically determined neurodevelopmental disorders is the Prader-Willi syndrome (PWS). Therefore, we aimed to profile a broad panel of immune-inflammatory markers in patients with PWS, taking into account co-morbid psychopathology. Participants were 20 children with PWS, and 20 healthy children matched for age, sex and body mass index. Behavioural symptoms and co-occurring psychopathological symptoms were assessed using the Child Behaviour Checklist (CBCL). We found significantly elevated levels of interleukin (IL)-1ß and IL-13 in patients with PWS. There were significant positive correlations between the levels of IL-1ß and scores of the following externalizing and internalizing CBCL domains: withdrawn/depressed, social problems, thought problems, attention problems, delinquent and aggressive behaviour in PWS children. Moreover, higher levels of IL-13 were associated with more severe psychopathology in terms of social and attention problems as well as delinquent and aggressive behaviour. Our findings imply that subclinical inflammation, observed as elevated IL-1ß and IL-13 levels, appears only in PWS patients and is correlated to several psychopathological symptoms.

Metabolic Parameters in Patients with Prader-Willi Syndrome and DiGeorge Syndrome with Respect to Psychopathological Manifestation.

PURPOSE: The purpose of our study was to compare the metabolic parameters in two genetic syndromes with a proven high risk of developing psychiatric comorbidities. These comorbidities, especially mood and psychotic disorders, may be associated with a risk of obesity, type 2 diabetes and other components of metabolic syndrome regardless of antipsychotic treatment. PATIENTS AND METHODS: Two groups of children diagnosed with Prader - Willi syndrome (PWS) (n = 20) and DiGeorge syndrome (DGS) (n = 18), aged 7-18 years, were enrolled. Behavioral symptoms and co-occurring psychopathological symptoms were assessed using the Child Behavior Checklist (CBCL). The levels of following biochemical parameters were measured: glucose, insulin, high-sensitivity C-reactive protein, total cholesterol, low- and high-density lipoproteins (LDL and HDL), triglycerides and non-HDL cholesterol. Additionally, the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was calculated. RESULTS: There were significantly higher levels of insulin and non-HDL in patients with PWS compared to those with DGS. The scores of four CBCL subscales (social problems, thought problems, delinquent behavior and aggressive behavior) were significantly higher in PWS patients. Higher scores of the CBCL-thought problems were associated with significantly higher levels of insulin as well as HOMA-IR. CONCLUSION: Patients with PWS seem to be more prone to develop subclinical metabolic dysregulation, in terms of elevated non-HDL levels and insulin levels, compared to DGS patients. Altered insulin sensitivity, present in both groups, even though it is not a specific risk factor, might be related to thought problems associated with psychosis.

Toward a unified theory of childhood trauma and psychosis: A comprehensive review of epidemiological, clinical, neuropsychological and biological findings.

There is a growing body of research focused on the relationship between childhood trauma and the risk of developing psychosis. Numerous studies, including many large-scale population-based studies, controlling for possible mediating variables, provide persuasive evidence of a dose-response association and are indicative of a causal relationship. Existing evidence supports the specificity model, showing differential associations between particular adversities and clinical symptoms, with cumulative adversity causing less favorable clinical and functional outcomes in psychotic patients. To date, several psychological and biological models have been proposed to search for underlying developmental trajectories leading to the onset of psychosis, influencing psychopathological manifestation and negative functional outcomes due to a history of childhood trauma. In this article, we provide a unified review on the relationship between childhood trauma and psychosis by integrating results of epidemiological, clinical, neuropsychological and biological studies. The question whether psychosis with a positive history of childhood trauma should be considered as a new psychotic phenotype, requiring specific therapeutic interventions, warrants further investigation.

Urogenital tract disorders in children suspected of being sexually abused.

INTRODUCTION: Child sexual abuse (CSA) is generally defined as child exploitation that leads to achievement of sexual satisfaction. According to data from European countries, sexual abuse of children affects 10-40% of girls and 5-20% of boys. MATERIAL AND METHODS: The Medline, and Web of Science databases were searched with no date limitation on May 2015 using the terms 'child abuse' in conjunction with 'urinary tract', 'urologist', 'urological dysfunction', 'urologic symptoms', 'LUTS' or 'urinary infection'. RESULTS: Awareness of the CSA problem among paediatricians and urologists is very important, because they are often the only physicians who are able to recognize the problem. CSA diagnosis is possible only through the proper collection of a medical history and a thorough physical examination. Urologists have to remember that children exposed to sexual abuse rarely exhibit abnormal genital findings. In fact, absence of genital findings is the rule rather than the exception. In most cases, the final diagnosis of sexual abuse is based on the child's history and behavior, along with the onset and exacerbation of urologic symptoms. CONCLUSIONS: In this article, we present a review of studies and literature concerning urinary symptoms in sexually abused children to clarify the problem for a broad group of urologists. We present common symptoms and premises that can point to the right diagnosis and basic guidelines of proceeding after suspicion of abuse.

From Prader-Willi syndrome to psychosis: translating parent-of-origin effects into schizophrenia research.

Prader-Willi syndrome (PWS) is a relatively rare disorder that originates from paternally inherited deletions and maternal disomy (mUPD) within the 15q11-q13 region or alterations in the PWS imprinting center. Evidence is accumulating that mUPD underlies high prevalence of psychosis among PWS patients. Several genes involved in differentiation and survival of neurons as well as neurotransmission known to act in the development of PWS have been also implicated in schizophrenia. In this article, we provide an overview of genetic and epigenetic underpinnings of psychosis in PWS indicating overlapping points in the molecular background of PWS and schizophrenia. Simultaneously, we highlight the need for studies investigating genetic and epigenetic makeup of the 15q11-q13 in schizophrenia indicating promising candidate genes.

Refining and integrating schizophrenia pathophysiology - relevance of the allostatic load concept.

Adaptation to stress leads to the activation of several biological systems that maintain homeostasis and enable effective coping with challenges. These adaptive processes have been designated as 'allostasis'. However, overactivation or aberrant performance of allostatic mechanisms due to chronic stress exposure may exert systemic deleterious effects. This condition has been called 'allostatic load' (AL). The AL concept is a useful framework allowing to understand the mulitisystem physiological dysregulation due to cumulative stressful demands over the lifespan. In the recent years, the AL paradigm has emerged as a novel concept explaining the morbidity and mortality with respect to several mental disorders. In this article, we suggest that AL provides a useful framework to describe schizophrenia - its etiology, course, outcome and comorbidities. Schizophrenia is a severe mental illness that is characterized by multidimensional psychopathology including positive and negative symptoms, affective symptoms and cognitive impairment with several known risk factors and accompanying pathophysiological correlates. However, there is a great need to refine and integrate the plethora of findings reported from various research perspectives. We propose that AL is a meaningful concept integrating findings on pathophysiological underpinnings, factors influencing course of the disorder and the development of co-occurring physical health impairments as well as substance use disorders in schizophrenia. Furthermore, there is an urgent necessity to investigate AL and its correlates in schizophrenia as no studies in this field have been performed so far.