Improving Therapeutic Interventions of Schizophrenia with Advances in Stem Cell Technology
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Although historic documents posit schizophrenia to the beginnings of mankind, its diagnosis remains poorly defined, currently relying on unspecific clinical symptoms; and controversies still maintain its origin under intense debate. This review aimed at quantitatively assessing the preferential forefronts of clinical trials towards the treatment of schizophrenia from inception till present, according to clinicaltrials.gov database registry. Towards that end study status and study phase classifications were used as criteria for progress in the field. Study groups by sex and age together with countries and organisms involved in the studies were used as indicators of the populations studied and as evidence of main promoter institutions, in both, pharmacological and drug-free protocols. The findings clearly show a decline of active clinical research with small synthetic compounds and limited numbers of novel initiatives, mostly based on drug-free alternatives with expected reduced secondary effects. A paucity of sex- and age-oriented designs is detected, and it is proposed that future clinical trials should set their basis on data obtained from patient-derived induced pluripotent stem cells, brain organoid systems and human brain circuitry platforms. Only individual precision medical approaches may turn effective for the treatment of this complex and highly incapacitating disease.
Abstract
Although historic documents posit schizophrenia to the beginnings of mankind, its diagnosis remains poorly defined, currently relying on unspecific clinical symptoms; and controversies still maintain its origin under intense debate. This review aimed at quantitatively assessing the preferential forefronts of clinical trials towards the treatment of schizophrenia from inception till present, according to clinicaltrials.gov database registry. Towards that end study status and study phase classifications were used as criteria for progress in the field. Study groups by sex and age together with countries and organisms involved in the studies were used as indicators of the populations studied and as evidence of main promoter institutions, in both, pharmacological and drug-free protocols. The findings clearly show a decline of active clinical research with small synthetic compounds and limited numbers of novel initiatives, mostly based on drug-free alternatives with expected reduced secondary effects. A paucity of sex- and age-oriented designs is detected, and it is proposed that future clinical trials should set their basis on data obtained from patient-derived induced pluripotent stem cells, brain organoid systems and human brain circuitry platforms. Only individual precision medical approaches may turn effective for the treatment of this complex and highly incapacitating disease.
참고문헌 (30)
- Cowen P, "Shorter oxford textbook of psychiatry" (2012), Oxford University Press
- The abandoned illness : a report by the Schizophrenia Commission, "Schizophrenia Commission", Rethink Mental Illness, ~ (2012)
- Cloutier M, "The economic burden of schizophrenia in the United States in 2013", J Clin Psychiatry, 77, pp.764~771 (2016)
- Owen MJ, "Schizophrenia", Lancet, 388, pp.86~97 (2016)
- Carter CJ, "Schizophrenia susceptibility genes directly implicated in the life cycles of pathogens : cytomegalovirus, influenza, herpes simplex, rubella, and Toxoplasma gondii", Schizophr Bull, 35, pp.1163~1182 (2009)
- Murray RM, "Different dopaminergic abnormalities underlie cannabis dependence and cannabis-induced psychosis", Biol Psychiatry, 75, pp.430~431 (2014)
- Yang AC, "New targets for schizophrenia treatment beyond the dopamine hypothesis", Int J Mol Sci, 18, pp.1689~ (2017)
- Lin CH, "Early identification and intervention of schizophrenia : insight from hypotheses of glutamate dysfunction and oxidative stress", Front Psychiatry, 10, pp.93~ (2019)
- Rodrigues-Amorim D, "Cytokines dysregulation in schizophrenia : a systematic review of psychoneuroimmune relationship", Schizophr Res, 197, pp.19~33 (2018)
- Fernandes BS, "C-reactive protein is increased in schizophrenia but is not altered by antipsychotics : meta-analysis and implications", Mol Psychiatry, 21, pp.554~564 (2016)
- Bertolote J, "Early intervention and recovery for young people with early psychosis : consensus statement", Br J Psychiatry Suppl, 48, pp.s116~s119 (2005)
- Keating D, "Pharmacological guidelines for schizophrenia : a systematic review and comparison of recommendations for the first episode", BMJ Open, 7, pp.e013881~ (2017)
- "2019exceptional surveillance of psychosis and schizophrenia in adults: prevention and management (NICE guideline CG178)" (2019)[URL]
- "ClinicalTrials.gov"[URL]
- Kennedy L, "Cognitive behavioral therapy compared with non-specialized therapy for alleviating the effect of auditory hallucinations in people with reoccurring schizophrenia : a systematic review and meta-analysis", Community Ment Health J, 53, pp.127~133 (2017)
- Chengappa KNR, "Adjunctive use of a standardized extract of Withania somnifera(Ashwagandha)to treat symptom exacerbation in schizophrenia : a randomized, double-blind, placebo-controlled study", J Clin Psychiatry, 79, pp.17m11826~ (2018)
- Wynn JK, "The effects of curcumin on brain-derived neurotrophic factor and cognition in schizophrenia : a randomized controlled study", Schizophr Res, 195, pp.572~573 (2018)
- Lane HY, "Add-on treatment of benzoate for schizophrenia : a randomized, double-blind, placebo-controlled trial of D-amino acid oxidase inhibitor", JAMA Psychiatry, 70, pp.1267~1275 (2013)
- Lin CH, "Sodium benzoate, a D-amino acid oxidase inhibitor, added to clozapine for the treatment of schizophrenia : a randomized, double-blind, placebo-controlled trial", Biol Psychiatry, 84, pp.422~432 (2018)
- Lin CY, "Adjunctive sarcosine plus benzoate improved cognitive function in chronic schizophrenia patients with constant clinical symptoms : a randomised, double-blind, placebo-controlled trial", World J Biol Psychiatry, 18, pp.357~368 (2017)
- Kraepelin E, "Psychiatrie: ein lehrbuch für studirende und aerzte" (1896), J.A. Barth
- Reveley AM, "Cerebral ventricular size in twins discordant for schizophrenia", Lancet, 1, pp.540~541 (1982)
- Goff DC, "Biomarkers for drug development in early psychosis : current issues and promising directions", Eur Neuropsychopharmacol, 26, pp.923~937 (2016)
- Maslej MM, "Individual differences in response to antidepressants: a meta-analysis of placebo-controlled randomized clinical trials", JAMA Psychiatry, pp.e194815~ (2020)
- Rajasekaran A, "Mitochondrial dysfunction in schizophrenia : pathways, mechanisms and implications", Neurosci Biobehav Rev, 48, pp.10~21 (2015)
- Föcking M, "Epigenetic factors in schizophrenia : mechanisms and experimental approaches", Mol Neuropsychiatry, 5, pp.6~12 (2019)
- Cannon TD, "Progressive reduction in cortical thickness as psychosis develops : a multisite longitudinal neuroimaging study of youth at elevated clinical risk", Biol Psychiatry, 77, pp.147~157 (2015)
- Ormel PR, "Microglia innately develop within cerebral organoids", Nat Commun, 9, pp.4167~ (2018)
- Tamminga CA, "The hippocampal formation in schizophrenia", Am J Psychiatry, 167, pp.1178~1193 (2010)
- Walton NM, "Detection of an immature dentate gyrus feature in human schizophrenia", bipolar patients, 2012, pp.2, e135~