68 research outputs found
Schizophrenia as a systemic disorder : studies of peripheral and central biological functions
No full textPsychiatric disturbances with an onset in adulthood may show subtle signs in childhood and school age. This is particularly applicable to patients with schizophrenia. A plasma membrane disturbance has been proposed as a common denominator responsible for both the central nervous system abnormalities and the changes in peripheral organs in patients with schizophrenia. The aim of the present thesis was to investigate central (neuropsychological, neurological and psychomotor) and peripheral (neuromuscular, tyrosine transport across the cell membrane) functions in schizophrenia with tyrosine kinetics as an indicator of membrane function. Another aim was to study possible familial transmission(s) of central and peripheral biological changes by investigating the occurrences of such abnormalities in unaffected first-degree relatives to the patients.Patients with schizophrenia (n = 39) their first degree- relatives (n = 44) and healthy controls (n = 55) were investigated according to the below listed studies.I. Clinical neurological investigation of neurological signs were performed. Psychomotor functions were investigated using the finger tapping, Purdue pegboard and pronation-supination tests, hand grasp strength, and gait.II. Histopathological examination of the skeletal muscle fibre was performed. The electrophysiological properties of the motor unit was studied in patients with schizophrenia and controls using the macro electromyographical (EMG) technique.III. Investigation of the muscle fibre histology and electrophysiology was performed as in study II in unaffected first-degree relatives to patients with schizophrenia.IV. Tyrosine transport (Km and Vmax) across the cell membrane was investigated in vitro using cultivated fibroblasts from patient with schizophrenia and healthy controls.V. Cognitive functions in patients with schizophrenia, their first-degree relatives and controls were assessed using an extensive battery of neuropsychological tests.Patients with schizophrenia exhibited neurological abnormalities and aberrant psychomotor performance to a significantly greater extent than healthy controls. Neuromuscular changes were found significantly more often in patients with schizophrenia and their unaffected first-degree relatives compared to controls. The most frequent histopathological finding in patients was muscle fibre atrophies, affecting both type I and type II fibres. Increased amplitude and area of the motor unit action potentials were found in the macro EMG recordings from patients and relatives but not in that from controls. The patients exhibited aberrant tyrosine transport kinetics with significantly lower Vmax (indicating lower tyrosine transport) and Km (indicating higher affinity) compared to controls. Finally, the patients performed significantly worse than their first-degree relatives and the controls in most of the neuropsychological tests and this significantly correlated with a lower level of functioning.Biological and clinical changes have been demonstrated deriving both from the central nervous system and peripheral organs indicating that schizophrenia is a systemic disease. Furthermore, the type of macro EMG findings and tyrosine transport aberrations indicate a membrane dysfunction. These results entail a different perspective on the ethiology of schizophrenia.List of scientific papersI. Flyckt L, Sydow O, Bjerkenstedt L, Edman G, Rydin E, Wiesel FA (1999). "Neurological signs and psychomotor performance in patients with schizophrenia, their relatives and healthy controls" Psychiatry Res 86(2): 113-29 https://pubmed.ncbi.nlm.nih.gov/10397414II. Flyckt L, Borg J, Borg K, Ansved T, Edman G, Bjerkenstedt L, Wiesel FA (2000). "Muscle biopsy, macro EMG, and clinical characteristics in patients with schizophrenia" Biol Psychiatry 47(11): 991-9 https://pubmed.ncbi.nlm.nih.gov/10838067III. Flyckt L, Wiesel FA, Borg J, Edman G, Ansved T, Sydow O, Borg K (2000). "Neuromuscular and psychomotor abnormalities in patients with schizophrenia and their first-degree relatives" J Psychiatr Res 34(4-5): 355-64 https://pubmed.ncbi.nlm.nih.gov/11104850IV. Flyckt L, Venizelos N, Edman G, Bjerkenstedt L, Hagenfeldt L, Wiesel FA (2000). "Aberrant tyrosine transport across the cell membrane in patients with schizophrenia." (Submitted)V. Eriksson A, Nyman H, Flyckt L, Edman G, Bjerkenstedt L, Wiesel FA (2000). "Neuropsychological function in patients with schiziphrenia, their relatives, and normals." (Submitted)</p
The impact of the GLOSSY2 and GLOSSY2-LIKE BAHD-proteins in affecting the product profile of the maize fatty acid elongase
No full textThe maize glossy2 and glossy2-like genes are homologs, which encode proteins that belong to the BAHD family of acyltransferases. In planta genetic studies have demonstrated that these genes may be involved in the elongation of very long chain fatty acids (VLCFAs) that are precursors of the cuticular wax fraction of the plant cuticle. VLCFAs are synthesized by a fatty acyl-CoA elongase complex (FAE) that consists of four component enzymes. Previously, we functionally identified the maize FAE component enzymes by their ability to complement haploid Saccharomyces cerevisiae strains that carry lethal deletion alleles for each FAE component enzyme. In this study we used these complemented haploid strains and wild-type diploid strains to evaluate whether the co-expression of either GLOSSY2 or GLOSSY2-LIKE with individual maize FAE component enzymes affects the VLCFA product-profile of the FAE system. Wild-type diploid strains produced VLCFAs of up to 28-carbon chain length. Co-expression of GLOSSY2 or GLOSSY2-LIKE with a combination of maize 3-ketoacyl-CoA synthases stimulated the synthesis of longer VLCFAs, up to 30-carbon chain lengths. However, such results could not be recapitulated when these co-expression experiments were conducted in the yeast haploid mutant strains that lacked individual components of the endogenous FAE system. Specifically, lethal yeast mutant strains that are genetically complemented by the expression of maize FAE-component enzymes produce VLCFAs that range between 20- and 26-carbon chain lengths. However, expressing either GLOSSY2 or GLOSSY2-LIKE in these complemented strains does not enable the synthesis of longer chain VLCFAs. These results indicate that the apparent stimulatory role of GLOSSY2 or GLOSSY2-LIKE to enable the synthesis of longer chain VLCFAs in diploid yeast cells may be associated with mixing plant enzyme components with the endogenous FAE complex.This article is published as Alexander LE, Winkelman D, Stenback KE, Lane M, Campbell KR, Trost E, Flyckt K, Schelling MA, Rizhsky L, Yandeau-Nelson MD and Nikolau BJ (2024) The impact of the GLOSSY2 and GLOSSY2-LIKE BAHD-proteins in affecting the product profile of the maize fatty acid elongase. Front. Plant Sci. 15:1403779. doi: 10.3389/fpls.2024.1403779. © 2024 Alexander, Winkelman, Stenback, Lane, Campbell, Trost, Flyckt, Schelling, Rizhsky, Yandeau-Nelson and Nikolau. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms
Burden of informal care giving to patients with psychoses: A descriptive and methodological study
No full textBackground: There is a lack of studies of the size of burden associated with informal care giving in psychosis. Aims: To evaluate the objective and subjective burden of informal care giving to patients with psychoses, and to compare a diary and recall method for assessments of objective burden. Method: Patients and their informal caregivers were recruited from nine Swedish psychiatric outpatient centres. Subjective burden was assessed at inclusion using the CarerQoL and COPE index scales. The objective burden (time and money spent) was assessed by the caregivers daily using diaries over four weeks and by recall at the end of weeks 1 and 2. Results: One-hundred and seven patients (53% females; mean age 43 ± 11) and 118 informal caregivers (67%; 58 ± 15 years) were recruited. Informal caregivers spent 22.5 hours/week and about 14% of their gross income on care-related activities. The time spent was underestimated by two to 20 hours when assessed by recall than by daily diary records. The most prominent aspects of the subjective burden were mental problems. Conclusion: Despite a substantial amount of time and money spent on care giving, the informal caregivers perceived the mental aspects of burden as the most troublesome. The informal caregiver burden is considerable and should be taken into account when evaluating effects of health care provided to patients with psychoses. </jats:sec
Predicting 5-year outcome in first-episode psychosis: Construction of a prognostic rating scale
No full textObjective: The aim of this study was to construct a rating scale to predict long-term outcome on the basis of clinical and sociodemographic characteristics in patients with symptoms of psychosis who seek psychiatric help for the first time. Method: Patients (N = 153) experiencing their first episode of psychosis (DSM-IV schizophrenia, schizophreniform disorder, schizoaffective disorder, brief psychotic episode, delusional disorder, affective psychosis with mood-incongruent delusions, or psychotic disorder not otherwise specified or being actively psychotic) were consecutively recruited from 17 psychiatric clinics in Sweden from January 1996 through December 1997 (24 months). Baseline characteristics were assessed with an extensive battery of psychiatric rating scales; duration of untreated psychosis, premorbid characteristics, and cognitive functioning were also assessed. The relationship between baseline characteristics and the 5-year outcome was analyzed using a stepwise logistic regression model. Results: In the logistic regression analysis, 5 variables were found to have unique contributions in the prediction of outcome. In order of magnitude of the odds ratios, these variables were Global Assessment of Functioning (GAF) score during the year before first admission, education level, actual GAF score at first admission, gender, and social network. The sensitivity, i.e., correctly identified cases (poor outcome), was 0.84, and the specificity, i.e., the correctly identified non-cases (good outcome), was 0.77. Conclusion: To initiate adequate interventions, it is crucial to identify patients experiencing their first episode of psychosis who are likely to have an unfavorable long-term outcome. The predictive rating scale described here is a feasible tool for early detection of these patients
Aberrant tyrosine transport across the fibroblast membrane in patients with schizophrenia –indications of maternal inheritance
No full textVulnerability and Social Functioning in Schizophrenia [Elektronisk resurs]
No full textThis thesis offers a broad approach in elucidating biological risk factors, as well as psychological and social functioning in schizophrenia. The aims are as follows: (I) investigate the association between birth characteristics and schizophrenia, (II) study the association between levels of neurotransmitter neuropeptide Y (NPY) in cerebrospinal fluid (CSF), social function and longitudinal outcome in schizophrenia, (III) compare social functioning of patients with schizophrenia with their biological siblings and (IV) explore how siblings to patients with schizophrenia perceive the sibling relationship and their role.Paper I was a cohort analysis of 11,360 same-sexed twins in which obstetric records were used. Low birth weight and small head circumference were associated with later development of schizophrenia. To some extent the results persisted in the within-pair analyses conducted on 82 pairs discordant for schizophrenia.Fifty-six patients with schizophrenia were included in paper II. Levels of NPY in CSF correlated to social competence at index admission. For each standard deviation increase in baseline NPY, there was a concomitant increased risk of being unemployed, having moderate or severe symptoms or recent hospitalization at the 3-year follow-up.In paper III, social functioning was investigated using the Swedish version of the videotaped test Assessment of Interpersonal Problem Solving Skills (AIPSS) in 70 participants (25 patients with schizophrenia, 20 siblings and 25 randomly selected controls). The patients presented severe deficits in social functioning. The siblings expressed subtle impairments in nonverbal language but did not generally differ from the controls.To explore the siblings’ perspective on schizophrenia a qualitative study was conducted with interviews of 16 siblings in paper IV. A unifying major theme was an emotional sibling bond. Siblings developed several coping patterns, including avoidance, isolation, normalization, care giving and grieving. A third major theme consisted of the fear of inheriting schizophrenia.In conclusion, fetal growth, altered levels of NPY in CSF and subtle impairments in nonverbal social behavior might be important risk factors in schizophrenia. Patients with schizophrenia revealed extensive impaired social functioning, and from the siblings’ perspective, a brother or sister’s diagnosis of schizophrenia seems to have a profound psychological impact on the siblings.</p
Meta-analysis of cognitive performance in drug-naïve patients with schizophrenia
No full textAbstractCognitive deficits represent a significant characteristic of schizophrenia. However, a majority of the clinical studies have been conducted in antipsychotic drug treated patients. Thus, it remains unclear if significant cognitive impairments exist in the absence of medication. This is the first meta-analysis of cognitive findings in drug-naïve patients with schizophrenia. Cognitive data from 23 studies encompassing 1106 patients and 1385 controls published from 1992 to 2013 were included. Tests were to a large extent ordered in cognitive domains according to the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) battery. Analysis was performed with STATA using the random-effects model and heterogeneity as well as Egger's publication bias was assessed. Overall the results show that patients performed worse than healthy controls in all cognitive domains with medium to large effect sizes. Verbal memory, speed of processing and working memory were three of the domains with the greatest impairments. The pattern of results is in line with previous meta-analytic findings in antipsychotic treated patients. The present meta-analysis confirms the existence of significant cognitive impairments at the early stage of the illness in the absence of antipsychotic medication
Patient-Initiated Brief Admission for Individuals with Emotional Instability and Self-Harm : An Evaluation of Psychiatric Symptoms and Health-Related Quality of Life
No full textPatient-initiated brief admission (PIBA) was developed for patients with emotional instability and self-harm, to cope with crises. The hypothesis was that psychiatric symptoms would decrease, and health-related quality of life (HRQoL) increase, after 1-3 days at hospital. One hundred and thirteen patients were recruited from a psychiatric clinic in Stockholm during 2016-2020. At admission and discharge, the patients completed the Hospital Anxiety and Depression Scale (HADS) and the EuroQoL-5 Dimension Questionnaire (EQ-5D). The patients also evaluated PIBA as a crisis intervention. A significant decrease in symptoms of anxiety and depression was found. HRQoL increased significantly assessed with EQ-5D and 95.2% of the participants found PIBA to be a constructive intervention.</p
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