Schizophrenia—An Overview

JAMA Psychiatry, Journal Year: 2019, Volume and Issue: 77(2), P. 201 - 201

Published: Oct. 30, 2019

Importance

Schizophrenia is a common, severe mental illness that most clinicians will encounter regularly during their practice. This report provides an overview of the clinical characteristics, epidemiology, genetics, neuroscience, and psychopharmacology schizophrenia to provide basis understand disorder its treatment. educational review integrated with case highlight how recent research findings can inform understanding.

Observations

The first theme considered role early-life environmental genetic risk factors in altering neurodevelopmental trajectories predispose individual leading development prodromal symptoms. second cortical excitatory-inhibitory imbalance cognitive negative symptoms disorder. third considers psychosocial stressors, psychological factors, subcortical dopamine dysfunction onset positive final mechanisms underlying treatment for common adverse effects

Conclusions Relevance

has complex presentation multifactorial cause. Nevertheless, advances neuroscience have identified roles key circuits, particularly involving frontal, temporal, mesostriatal brain regions, positive, negative, Current pharmacological treatments operate using same mechanism, blockade D₂receptor, which contribute effects. However, circuit discussed herein identify novel potential targets may be particular benefit symptom domains not well served by existing medications.

Language: Английский

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Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis

The Lancet Psychiatry, Journal Year: 2019, Volume and Issue: 7(1), P. 64 - 77

Published: Dec. 18, 2019

Antipsychotic treatment is associated with metabolic disturbance. However, the degree to which alterations occur in different antipsychotics unclear. Predictors of dysregulation are poorly understood and association between change psychopathology uncertain. We aimed compare rank on basis their side-effects, identify physiological demographic predictors antipsychotic-induced dysregulation, investigate relationship psychotic symptoms parameters antipsychotic treatment.

Language: Английский

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Evidence-based guidelines for the pharmacological treatment of schizophrenia: Updated recommendations from the British Association for Psychopharmacology

Journal of Psychopharmacology, Journal Year: 2019, Volume and Issue: 34(1), P. 3 - 78

Published: Dec. 12, 2019

These updated guidelines from the British Association for Psychopharmacology replace original version published in 2011. They address scope and targets of pharmacological treatment schizophrenia. A consensus meeting was held 2017, involving experts schizophrenia its treatment. were asked to review key areas consider strength evidence on risk-benefit balance interventions clinical implications, with an emphasis meta-analyses, systematic reviews randomised controlled trials where available, plus updates current practice. The cover management across various stages illness, including first-episode, relapse prevention, illness that has proved refractory standard It is hoped practice recommendations presented will support decision making practitioners, serve as a source information patients carers, inform quality improvement.

Language: Английский

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Dopamine and glutamate in schizophrenia: biology, symptoms and treatment

World Psychiatry, Journal Year: 2020, Volume and Issue: 19(1), P. 15 - 33

Published: Jan. 10, 2020

Glutamate and dopamine systems play distinct roles in terms of neuronal signalling, yet both have been proposed to contribute significantly the pathophysiology schizophrenia. In this paper we assess research that has implicated aetiology disorder. We examine evidence from post‐mortem, preclinical, pharmacological vivo neuroimaging studies. Pharmacological preclinical studies implicate systems, imaging system consistently identified elevated striatal synthesis release capacity Imaging glutamate other aspects on produced less consistent findings, potentially due methodological limitations heterogeneity Converging indicates genetic environmental risk factors for schizophrenia underlie disruption glutamatergic dopaminergic function. However, while influences may directly dysfunction, few variants system, indicating aberrant signalling is likely be predominantly factors. discuss neural circuits through which two interact, how their cause psychotic symptoms. also mechanisms existing treatments operate, recent highlighted opportunities development novel therapies. Finally, consider outstanding questions field, including what remains unknown regarding nature function schizophrenia, needs achieved make progress developing new treatments.

Language: Английский

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Cognitive impairment in schizophrenia: aetiology, pathophysiology, and treatment

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(5), P. 1902 - 1918

Published: Jan. 23, 2023

Abstract Cognitive deficits are a core feature of schizophrenia, account for much the impaired functioning associated with disorder and not responsive to existing treatments. In this review, we first describe clinical presentation natural history these deficits. We then consider aetiological factors, highlighting how range similar genetic environmental factors both cognitive function schizophrenia. review pathophysiological mechanisms thought underlie symptoms, including role dopamine, cholinergic signalling balance between GABAergic interneurons glutamatergic pyramidal cells. Finally, management impairments candidate novel

Language: Английский

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Treatment resistance in psychiatry: state of the art and new directions

Molecular Psychiatry, Journal Year: 2021, Volume and Issue: 27(1), P. 58 - 72

Published: July 13, 2021

Treatment resistance affects 20-60% of patients with psychiatric disorders; and is associated increased healthcare burden costs up to ten-fold higher relative in general. Whilst there has been a recent increase the proportion research focussing on treatment (R2 = 0.71, p < 0.0001), absolute terms this less than 1% total output grossly out its prevalence impact. Here, we provide an overview resistance, considering conceptualisation, assessment, epidemiology, impact, common neurobiological models. We also review new treatments development future directions. identify 23 consensus guidelines definition, covering schizophrenia, major depressive disorder, bipolar affective obsessive compulsive disorder (OCD). This shows three core components but identifies heterogeneity lack criteria for number disorders, including panic post-traumatic stress substance dependence. reporting check-list aid comparisons across studies. consider concept pseudo-resistance, linked poor adherence or other factors, algorithm clinical assessment resistance. nine drugs non-pharmacological approaches being developed OCD. Key outstanding issues include absence criteria, understanding neurobiology, under-investment, treatments. make recommendations address these issues, harmonisation definitions, into mechanisms novel interventions enable targeted personalised therapeutic approaches.

Language: Английский

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A Non–D2-Receptor-Binding Drug for the Treatment of Schizophrenia

New England Journal of Medicine, Journal Year: 2020, Volume and Issue: 382(16), P. 1497 - 1506

Published: April 15, 2020

An oral compound, SEP-363856, that does not act on dopamine D2 receptors but has agonist activity at trace amine–associated receptor 1 (TAAR1) and 5-hydroxytryptamine type 1A (5-HT1A) receptors, may represent a new class of psychotropic agent for the treatment psychosis in schizophrenia.

Language: Английский

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A neuroimaging biomarker for striatal dysfunction in schizophrenia

Nature Medicine, Journal Year: 2020, Volume and Issue: 26(4), P. 558 - 565

Published: March 23, 2020

Language: Английский

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Synaptic density marker SV2A is reduced in schizophrenia patients and unaffected by antipsychotics in rats

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Jan. 14, 2020

Synaptic dysfunction is hypothesised to play a key role in schizophrenia pathogenesis, but this has not been tested directly vivo. Here, we investigated synaptic vesicle glycoprotein 2A (SV2A) levels and their relationship symptoms structural brain measures using [11C]UCB-J positron emission tomography 18 patients with controls. We found significant group group-by-region interaction effects on volume of distribution (VT). VT was significantly lower the frontal anterior cingulate cortices large effect sizes (Cohen's d = 0.8-0.9), there no difference hippocampus. also antipsychotic drug administration SV2A Sprague-Dawley rats western blotting, [3H]UCB-J autoradiography immunostaining confocal microscopy, finding any measure. These findings indicate that are terminal protein vivo exposure unlikely account for them.

Language: Английский

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The clinical significance of duration of untreated psychosis: an umbrella review and random‐effects meta‐analysis

World Psychiatry, Journal Year: 2021, Volume and Issue: 20(1), P. 75 - 95

Published: Jan. 12, 2021

The idea that a longer duration of untreated psychosis (DUP) leads to poorer outcomes has contributed extensive changes in mental health ser-vices worldwide and attracted considerable research interest over the past 30 years. However, strength evidence underlying this notion is unclear. To address issue, we conducted an umbrella review available meta-analyses performed random-effects meta-analysis primary studies. MEDLINE, Web Science, PsycINFO EMBASE were searched from inception September 3, 2020 identify relevant studies including patients with schizophrenia spectrum disorders, first-episode psychosis, or affective non-affective psychosis. Thirteen included, corresponding 129 individual total sample size 25,657 patients. We detected potential violations statistical assumptions some these meta-analyses. therefore new association between DUP each outcome was graded according standardized classification into convincing, highly suggestive, weak, non-significant. At first presentation, there suggestive for relationship more severe negative symptoms (beta=-0.07, p=3.6×10-5 ) higher chance previous self-harm (odds ratio, OR=1.89, p=1.1×10-5 ). follow-up, positive (beta=-0.16, p=4.5×10-8 ), (beta=-0.11, p=3.5×10-10 lower remission (OR=2.16, p=3.0×10-10 overall functioning p=2.2×10-6 global psychopathology p=4.7×10-6 Results unchanged when analysis restricted prospective These effect sizes are clinically meaningful, four weeks predicting >20% at follow-up relative one week. conclude important prognostic factor presentation predicts course illness. discuss conceptual issues methodological limitations current evidence, provide recommendations future research.

Language: Английский

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