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October 30, 2019

Schizophrenia—An Overview

Author Affiliations
  • 1Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, London, United Kingdom
  • 2Psychiatric Imaging Group, Medical Research Council, London Institute of Medical Sciences, Hammersmith Hospital, London, United Kingdom
  • 3Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom
JAMA Psychiatry. 2020;77(2):201-210. doi:10.1001/jamapsychiatry.2019.3360

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 of schizophrenia to provide a basis to understand the disorder and its treatment. This educational review is integrated with a clinical case to highlight how recent research findings can inform clinical understanding.

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

Conclusions and Relevance  Schizophrenia has a complex presentation with a multifactorial cause. Nevertheless, advances in neuroscience have identified roles for key circuits, particularly involving frontal, temporal, and mesostriatal brain regions, in the development of positive, negative, and cognitive symptoms. Current pharmacological treatments operate using the same mechanism, blockade of dopamine D2 receptor, which contribute to their adverse effects. However, the circuit mechanisms discussed herein identify novel potential treatment targets that may be of particular benefit in symptom domains not well served by existing medications.

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2 Comments for this article
Review of schizophrenia ignores results of genetic sequencing studies
David Curtis, MBBS FRCPsych MD PhD | UCL Genetics Institute, University College London
The review of the genetics of schizophrenia completely ignores the important findings which have emerged from next generation sequencing studies, which convincingly implicate sets of genes and at least one individual gene, SETD1A 1–4. These results have allowed the development of an animal model of schizophrenia 5 and provide further support for the use of NMDA receptor enhancers such as sarcosine in the treatment of schizophrenia 6. The results from next generation sequencing studies are more useful for understanding the biology of schizophrenia than the GWAS results and CNV findings which the review did refer to.

1. Genovese
G, Fromer M, Stahl EA, et al. Increased burden of ultra-rare protein-altering variants among 4,877 individuals with schizophrenia. Nat Neurosci. 2016;19(11):1433-1441. doi:10.1038/nn.4402
2. Singh T, Kurki MI, Curtis D, et al. Rare loss-of-function variants in SETD1A are associated with schizophrenia and developmental disorders. Nat Neurosci. 2016;19(4):571-577. doi:10.1038/nn.4267
3. Coelewij L, Curtis D. Mini-review: Update on the genetics of schizophrenia. Ann Hum Genet. 2018;82(5):239-243. doi:10.1111/ahg.12259
4. Curtis D, Coelewij L, Liu S-H, Humphrey J, Mott R. Weighted Burden Analysis of Exome-Sequenced Case-Control Sample Implicates Synaptic Genes in Schizophrenia Aetiology. Behav Genet. October 2018:203521. doi:10.1007/s10519-018-9893-3
5. Mukai J, Cannavo E, Sun Z, et al. Recapitulation and reversal of schizophrenia-related phenotypes in Setd1a-deficient mice. bioRxiv. January 2019:529701. doi:10.1101/529701
6. Curtis D. A possible role for sarcosine in the management of schizophrenia. Br J Psychiatry. 2019;215(6):697-698. doi:10.1192/bjp.2019.194
James Perkins, MD OD Phd | Black Bottom Incorporated (Research)
This article is much needed considering there is a need for direction considering all the changes that have come forth (DSMV, Epigenetics, MRI) and attacks on Psychiatry in the last two years.