The aetiology of social deficits within mental health disorders:The role of the immune system and endogenous opioids

The American National Institute for Mental Health (NIMH) has put out a set of research goals that include a long-term plan to identify more reliable endogenous explanations for a wide variety of mental health disorders (Insel, 2013). In response to this, we have identified a major symptom that underlies multiple mental health disorders – social bonding dysfunction. We suggest that endogenous opioid abnormalities can lead to altered social bonding, which is a symptom of various mental health disorders, including depression, schizophrenia and ASD. This article first outlines how endogenous opioids play a role in social bonding. Then we show their association with the body’s inflammation immune function, and review recent literature linking inflammation to mental health ‘immunophenotypes’. We finish by explaining how these immunophenotypes may be caused by alterations in the endogenous opioid system. This is the first overview of the role of inflammation across multiple disorders where we provide a biochemical explanation for why immunophenotypes might exist across diagnoses. We propose a novel mechanism of how the immune system may be causing ‘sickness-type’ behaviours (fatigue, appetite change, social withdrawal and inhibited motivation) in those who have these immunophenotypes. We hope that this novel aetiology can be used as a basis for future research in mental health

Toward Precision Psychiatry: Statistical Platform for the Personalized Characterization of Natural Behaviors.

There is a critical need for new analytics to personalize behavioral data analysis across different fields, including kinesiology, sports science, and behavioral neuroscience. Specifically, to better translate and integrate basic research into patient care, we need to radically transform the methods by which we describe and interpret movement data. Here, we show that hidden in the "noise," smoothed out by averaging movement kinematics data, lies a wealth of information that selectively differentiates neurological and mental disorders such as Parkinson's disease, deafferentation, autism spectrum disorders, and schizophrenia from typically developing and typically aging controls. In this report, we quantify the continuous forward-and-back pointing movements of participants from a large heterogeneous cohort comprising typical and pathological cases. We empirically estimate the statistical parameters of the probability distributions for each individual in the cohort and report the parameter ranges for each clinical group after characterization of healthy developing and aging groups. We coin this newly proposed platform for individualized behavioral analyses "precision phenotyping" to distinguish it from the type of observational-behavioral phenotyping prevalent in clinical studies or from the "one-size-fits-all" model in basic movement science. We further propose the use of this platform as a unifying statistical framework to characterize brain disorders of known etiology in relation to idiopathic neurological disorders with similar phenotypic manifestations

Basic Science Considerations in Primary Total Hip Replacement Arthroplasty

Total Hip Replacement is one of the most common operations performed in the developed world today. An increasingly ageing population means that the numbers of people undergoing this operation is set to rise. There are a numerous number of prosthesis on the market and it is often difficult to choose between them. It is therefore necessary to have a good understanding of the basic scientific principles in Total Hip Replacement and the evidence base underpinning them. This paper reviews the relevant anatomical and biomechanical principles in THA. It goes on to elaborate on the structural properties of materials used in modern implants and looks at the evidence base for different types of fixation including cemented and uncemented components. Modern bearing surfaces are discussed in addition to the scientific basis of various surface engineering modifications in THA prostheses. The basic science considerations in component alignment and abductor tension are also discussed. A brief discussion on modular and custom designs of THR is also included. This article reviews basic science concepts and the rationale underpinning the use of the femoral and acetabular component in total hip replacement

Pain perception in schizophrenia: influence of neuropeptides, cognitive disorders, and negative symptoms

Małgorzata Urban-Kowalczyk,1 Justyna Pigońska,2 Janusz Śmigielski3 1Department of Affective and Psychotic Disorders, Medical University of Łódź, Łódź, Poland; 2Department of Neurology and Movement Disorders, Medical University of Łódź, Łódź, Poland; 3Department of Geriatrics, Healthy Ageing Research Centre (HARC), Medical University of Łódź, Łódź, Poland Objectives: The causes and nature of insensitivity to pain in schizophrenia remain unknown. The role of endorphins and the association of cognitive dysfunction and negative symptoms are postulated.Methods: In this study, 43 patients with schizophrenia, five first-degree relatives, and 34 healthy controls were examined. Participants’ plasma concentrations of substance P, β-endorphin, and calcitonin gene-related peptide (CGRP) were assessed. In patients, the Trail-Making Test, the Color Reading Interference Test (Stroop test), and the Positive and Negative Syndrome Scale Negative Syndrome subscale (PANSS N) test were performed. We also evaluated pain threshold using nociceptive reflex (RTIII) testing.Results: The mean β-endorphin concentration was about 20% higher in patients than in healthy controls (P<0.05). CGRP concentrations were significantly higher in patients than in controls (5.34 ng/mL versus 4.16 ng/mL; P<0.01). Subjects treated with antipsychotic polytherapy had higher concentrations of CGRP than did patients treated with second-generation antipsychotic monotherapy (5.92 ng/mL versus 5.02 ng/mL; P<0.05). There were no correlations between any biochemical parameters and Trail-Making Test, Stroop test, and PANSS N scores. There were no differences in RTIII among study groups. Strong negative correlation (P<0.001) was found between PANSS N scores and subjective pain threshold on the right lower limb.Conclusion: The insensitivity to pain in schizophrenia is a complex phenomenon that is probably not related to changes in nociceptive pathways. Increase in β-endorphin level may be related to this issue, but it is uncertain if such concentration ensures analgesic effect. It is unknown if patients with schizophrenia in fact experience less pain. Cognitive impairment and excess negative symptoms may strongly influence the patient’s expression of pain. Keywords: schizophrenia, endorphin, substance P, calcitonin gene-related peptide, working memory, negative symptom

Comparison of beta-endorphin and CGRP levels before and after treatment for severe schizophrenia

Małgorzata Urban-Kowalczyk,1 Janusz Śmigielski,2 Dominik Strzelecki1 1Department of Affective and Psychotic Disorders, 2Department of Geriatrics, Healthy Aging Research Centre (HARC), Medical University of Lodz, Lodz, Poland Objectives: Links between endorphins and dopaminergic transmission have not been fully explored in schizophrenia. Both endorphins excess and deficiency were postulated. CGRP is probably involved in dopaminergic transmission. The aim of this study was the evaluation of beta-endorphin (BE) and CGRP blood concentrations before and after treatment of severe schizophrenia. Methods: Seventy patients treated with various antipsychotics, with severe symptoms of schizophrenia (51 with positive symptoms, 19 with negative symptoms), 15 first-degree relatives, and 44 healthy controls were included in the study. BE and CGRP blood concentrations were measured during patients severe schizophrenia and in their stable mental state after treatment. The results were compared with relatives and controls. Results: BE and CGRP concentrations in patients with negative symptoms were higher than in relatives and in controls. BE levels in patients with positive symptoms were lower than in patients with negative symptoms (P<0.0000) and controls (P<0.0006). No significant changes in CGRP concentration were found in patient samples. CGRP levels in these samples were independent of treatment, but they were significantly higher than in relatives and controls. After the treatment, BE level decreased in patients with negative symptoms (P<0.0001) and increased in patients with positive symptoms (P<0.0000). No differences in BE concentration between patients in stable mental state, their relatives, and controls were found. Conclusion: Effective antipsychotic treatment results in “normalization” of BE level. Specific changes in BE concentration could be involved in dopaminergic transmission and related to some symptoms of schizophrenia. Keywords: schizophrenia, negative symptoms, neuroleptics, β-endorphin, CGR

Risk Reduction of a Terrorist Attack on a Critical Infrastructure Facility of LGOM Based on the Example of the Żelazny Most Tailings Storage Facility (OUOW Żelazny Most)

This paper identifies the threats and risks of a terrorist attack on a critical infrastructure facility based on the example of Żelazny Most Tailings Storage Facility (OUOW). The threat analysis primarily took into account the threats of deliberate human actions. Identification of potential threats concerning the infrastructure surrounding the facility was conducted based on information that is readily available on the Internet. The reasons why it may be a potential target were also justified. Numerical calculations of the stress–deformation scale of the initial state of the reservoir, based on the Biot model with the Kelvin–Voight rheological skeleton, were presented as a starting point for in-depth research on the scale of threats and risks to the reservoir. The presented numerical model can be a starting point for calculating the stability of a reservoir subjected to explosives. The facility constitutes a major element of Lubińsko-Głogowski Okręg Miedziowy (Lubin-Głogów Copper District). OUOW Żelazny Most is the biggest such facility in Europe and is utilized to collect tailing waist. When expanded in its southern quarter, the facility will be the biggest in the world

Odor perception and hedonics in chronic schizophrenia and in first episode psychosis

Małgorzata Urban-Kowalczyk,1 Dominik Strzelecki,1 Janusz Śmigielski,2 Magdalena Kotlicka–Antczak1 1Department of Affective and Psychotic Disorders, Medical University of Łódź, Łódź, Poland; 2State Higher Vocational School in Konin, Konin, Poland Background and purpose: The study evaluated olfactory performance and pleasantness rating of odors in patients with first episode psychosis (FEP) and chronic schizophrenia (SCH) with regard to the severity of psychopathological symptoms and plasma β-endorphin concentration.Patients and methods: Twenty patients with FEP, 27 with SCH and 29 healthy individuals, were recruited to the research . The University of Pennsylvania Smell Identification Test (UPSIT), subjective odor hedonic judgment and plasma levels of β-endorphin (BE) assay were performed in all participants. Results: Individuals with SCH revealed higher BE concentration than other study groups (P=0.000). All patients identified pleasant odors poorer than controls, however, SCH made more identification errors (P=0.000) than those with FEP. Moreover, participants with FEP rated pleasant odors as more pleasant than individuals with chronic schizophrenia and healthy controls (P=0.009). Nevertheless, higher β-endorphin level was related with lower scores in pleasant odor identification (Rs=–0.452; P=0.046) and more severe psychotic symptoms in FEP sample. Chronic schizophrenia patients did not demonstrate any relationship between symptom severity, odor identification performance and β-endorphin concentration. No relationship was found between BE concentration and hedonic judgment of the presented odors among all study groups. Chronically ill subjects identified odors significantly more poorly than those with first episode psychosis. Deficits in identifying pleasant odors might not be the only potential risk factor for undergoing chronic, recurrent schizophrenia. All patients subjectively overrated pleasant odors. Those with SCH and more severe negative symptoms made significantly more identification errors. Conclusion: The endogenous morphine system deregulation is observed in first episode psychosis as well as in chronic schizophrenia. In first episode schizophrenia higher beta-endorphin concentration is related to pleasant odor identification deficit. Keywords: olfaction, negative symptoms, endogenous opioids, schizophreni