First-episode Schizophrenia Psychosis Research Articles

Effects of socio-demographic characteristics, premorbid functioning, and insight on duration of untreated psychosis in first-episode schizophrenia or schizophreniform disorder in Northern Malawi.

AimLong duration of untreated psychosis (DUP) is prevalent and has been shown to be associated with poorer prognosis. Thus, knowledge of its determinants may help to target early interventions to reduce DUP on the needed population. Previous studies seeking to understand determinants of DUP have been inconclusive. Therefore, this study aimed to investigate the effects of socio‐demographic characteristics, premorbid functioning, and insight on DUP in patients with first‐episode schizophrenia or schizophreniform disorder.MethodsThis cross‐sectional study recruited 110 subjects (aged 18‐65) during a pilot early intervention service for psychosis in Northern Malawi, between June 2009 and September 2012. Short DUP was defined as ≤6 months, whereas long DUP was defined as >6 months. Unadjusted and adjusted analyses were performed to identify determinants of DUP.ResultsOf the 110 subjects, 99 (90%) had schizophrenia. Median DUP was 27.5 months, while mean (SD) DUP was 71.24 (92.32) months. In addition, at least 75% had long DUP, which was associated with lower level of education, poor insight, younger age at onset, and at least one parent deceased.ConclusionsLong DUP is prevalent in Northern Malawi. Thus, early interventions to reduce DUP are warranted in this population. Although having at least one parent deceased predicted long DUP in this study, this remains speculative because factors, such as timing of parents' death and grief reactions of the patients were not assessed. Therefore, further investigations incorporating these factors are needed to ascertain this result.

Differences by year of publication in duration of untreated psychosis in first episode schizophrenia: Meta-analysis and meta-regression analysis

Microinjections, lesions, viral-mediated gene transfer, or designer receptors exclusively activated by designer drugs (DREADDs) can identify brain signaling pathways and their pharmacology in research animals. Genetically modified animals are used for more precise assessment of neural circuits. However, only a few of the gene-based pathway modifications are available for use in outbred rat strains.Behaviorally characterized Sprague-Dawley rats undergo tract tracing through microinjection of fluorospheres, followed by laser capture microdissection (LCM) and qPCR for detecting mRNA of pathway-associated gene products. Correlations between mRNA expression and behavior identify specific involvement of pharmacologically relevant molecules within cells of interest. Here, we examined this methodology in an impulsive choice paradigm and targeted projections from the orbital and medial prefrontal cortex.In this proof of concept study, we demonstrate relationships between measures of impulsive choice with distinct neurotransmitter receptor expression in cell populations from four different signaling pathways.Combining behavior, tract tracing, LCM, and gene expression profiling provides more cellular selectivity than localized lesions and DREADDs, and greater pharmacological specificity than microinjections and viral-mediated gene transfer due to targeting identified neurons. Furthermore, the assessment of inter-individual pathways provides insight into the complex nature of underlying mechanisms involved in typical and atypical behavior.The novel combination of behavior, tract tracing, LCM, and single gene or potential whole genome transcriptome analysis allows for a more targeted understanding of the interconnection of neural circuitry with behavior, and holds promise to identify more specific drug targets that are relevant to behavioral phenotypes.

Comparison of brain N-acetylaspartate levels and serum brain-derived neurotrophic factor (BDNF) levels between patients with first-episode schizophrenia psychosis and healthy controls

Background N-acetylaspartate (NAA) levels and serum brain-derived neurotrophic factor (BDNF) levels in patients with first-episode schizophrenia psychosis and age- and sex-matched healthy control subjects were investigated. In addition, plasma levels of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were compared between the two groups. Method Eighteen patients (nine males, nine females; age range: 13–52 years) were enrolled in the study, and 18 volunteers (nine males, nine females; age range: 15–49 years) with no current or past psychiatric history were also studied by magnetic resonance spectroscopy (MRS) as sex- and age-matched controls. Results Levels of NAA/Cr in the left basal ganglia ( p = 0.0065) and parieto-occipital lobe ( p = 0.00498), but not in the frontal lobe, were significantly lower in patients with first-episode schizophrenia psychosis than in control subjects. No difference was observed between the serum BDNF levels of patients with first-episode schizophrenia psychosis and control subjects. In regard to the plasma levels of catecholamine metabolites, plasma MHPG, but not HVA, was significantly lower in the patients with first-episode psychosis than in control subjects. In addition, a significantly positive correlation was observed between the levels of NAA/Cr of the left basal ganglia and plasma MHPG in all subjects. Conclusion These results suggest that brain NAA levels in the left basal ganglia and plasma MHPG levels were significantly reduced at the first episode of schizophrenia psychosis, indicating that neurodegeneration via noradrenergic neurons might be associated with the initial progression of the disease.

Long delays in seeking treatment for schizophrenia

Sir—Beng-Choon Ho and Nancy Andreasen, in their March 24 commentary, offer a timely and balanced commentary on the lengthy and damaging duration of untreated psychosis in first-episode schizophrenia. We agree that the importance of shortening this time is self-evident. We also agree that the secondary preventive potential of this action is by no means self-evident but remains to be shown, especially for early intervention in the prodromal or preonset phase of schizophrenia. We do not differ with Ho and Andreasen on these points but take issue with one interpretation and one polarisation. The interpretation involves their classification of Linszen and colleagues’ 1998 study among studies in which no association between long duration of untreated psychois and poor outcome was noted. Linszen and colleagues showed the lack of association was probably secondary to an overall absence of variation in duration of untreated psychosis in their sample— ie, the probability of a false-negative association was high. The polarisation in Ho and Andreasen’s commentary involves separating workers in the field of early detection and intervention into optimists and the understandably cautious. As such workers, we regard ourselves as embodying both attributes—optimism because we are there and caution because we are there as researchers. Overall, we wish Ho and Andreasen had made a clear distinction in their commentary between practice and research, because appropriate caution about early intervention as a practice is too frequently applied inappropriately and destructively at research efforts trying to show whether or not early intervention has risks or benefits. Ho and Andreasen end by calling for scepticism about the feasibility of early intervention. Research as hypothesis testing is formalised doubting, or scepticism par excellence. They, in essence, call for research, but their failure to distinguish between practice and research undermines the message.

Duration of untreated psychosis in first episode schizophrenia

Presque 20 ans après celle du DSM-IV, la publication du DSM-5 est un événement majeur dans le champ de la psychiatrie. Chaque révision du texte du DSM vise à améliorer la fidélité et la validité des diagnostics psychiatriques et améliorer ainsi son utilité clinique. Le DSM-5 s’écarte sur de nombreux points des éditions précédentes, apportant plusieurs changements concernant la schizophrénie : un abandon des formes cliniques de la schizophrénie en faveur d’une évaluation dimensionnelle des signes et des symptômes, une relativisation de l’importance des symptômes de premier rang ainsi qu’une clarification de la définition des symptômes négatifs, une nouvelle spécification de l’évolution, une clarification du statut nosologique de la catatonie, et une définition plus précise du trouble schizo-affectif délimitant ses contours et le séparant de la schizophrénie et des troubles de l’humeur avec caractéristiques psychotiques. Tous les changements ayant concerné la schizophrénie dans le DSM-5 devraient principalement faciliter son évaluation clinique et sa prise en charge thérapeutique, et constitueraient un champ de recherche visant à mieux comprendre sa pathogenèse. Nous proposons de dresser dans ce travail un portrait des principaux changements introduits dans le DSM-5, traitant plus spécifiquement de la schizophrénie et leurs justifications.The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) was issued almost 20 years after the previous edition, and it was a major event in the field of psychiatry. This new edition of the DSM aimed to improve the reliability of psychiatric diagnoses, to improve its clinical utility, to address problems identified in DSM-IV, and to incorporate new knowledge and understanding accumulated since the earlier version. The aim of this paper is to describe and comment the changes made from DSM-IV to DSM-5 concerning schizophrenia.PubMed and Medline search, Scopus, journal and textbook articles have been accessed for the review of literature on DSM-5 changes related to schizophrenia.Several minor but important changes have been made to the schizophrenia diagnostic criteria in DSM-5. The special treatment of Schneiderian first-rank hallucinations was removed because these symptoms have not been found to be specific for schizophrenia. Likewise, the privileged status of bizarre delusions was removed. Classic subtypes of schizophrenia provide a poor description of the heterogeneity of schizophrenia and had limited diagnostic stability and little clinical utility. As a result, all these subtypes were removed. Dimensional assessment of symptoms was added. It can be used for treatment monitoring and planning and the prediction of course and outcome. This change allowed for more specific and individualized assessment of patients, and better understanding of heterogeneity of schizophrenia. Negative symptoms were clarified. Diminished emotional expression and avolition were considered as the two domains of negative symptoms because they better describe distinguishable aspects of negative symptoms. The DSM-5 has also provided a clearer separation between schizophrenia with mood symptoms and schizoaffective disorder. Schizoaffective disorder was explicitly reconceptualized as a longitudinal and not a cross-sectional diagnosis. The relationship of schizophrenia to catatonia was clarified. Catatonia is treated consistently across the DSM-5 manual as a specifier, and the same criteria to diagnose catatonia are utilized across the manual. A new category of “attenuated psychosis syndrome” was added to section 3 (Appendix) of DSM-5 to describe a condition with recent onset of psychotic symptoms in attenuated forms. Demonstrating adequate reliability of the proposed disorder diagnosis was not possible. Therefore, attenuated psychosis syndrome requires further study.The etio-pathophysiological nosology of schizophrenia has remained elusive. Changes proposed in the DSM treatment of schizophrenia are relatively modest and the core of the DSM-IV diagnostic criteria is retained. The provision of dimensional assessments with a simple rating scale appears promising and should encourage provision of measurement-based care. These changes should improve characterization of individuals with schizophrenia and facilitate clinical assessment and treatment. In addition, they constitute a research field to better elucidate its nature and understand its pathogenic mechanism.