Please wait a minute...
90Life Research  2019, Vol. 2 Issue (1): 22-30    DOI: 10.12032/life2019-0125-005
The polygenic risk in schizophrenia: assessing GWASs and evaluating Clozapine, ECT and other treatment modalities
Shiruli Dash*()
International Medical School, Tianjin Medical University, Tianjin, China.
Download: HTML     PDF(4657KB)
Export: BibTeX | EndNote (RIS)      


Research shows that the mortality rate among people with schizophrenia is up to four times higher than that in the general population. The subsequent high comorbidities and societal cost of schizophrenia necessitate finding better, more effective treatments and strategies for prevention. One of the current obstacles are the complicated gene etiologies that are involved in the pathophysiology of schizophrenia. So far, an increasing number of clinical and experimental studies show links between schizophrenia treatment and genetic conditions. Here, we analyze the literature on schizophrenia genetics, with a particular focus on the brain, the mind and environmental insults. An overlap of schizophrenia with other psychotic disorders has also been taken into account with an attempt to find a parallel relationship between genetics and treatment. Finally, we summarize all the present-day treatment options for schizophrenia like clozapine and electroconvulsive therapy and also take into consideration the relatively unexplored role of traditional Chinese medicine.

Key wordsschizophrenia      traditional Chinese medicine      schizophrenia treatment      schizophrenia genetic     
Received: 15 January 2019      Published: 20 January 2019
Corresponding Authors: Dash Shiruli     E-mail:
Cite this article:

Shiruli Dash. The polygenic risk in schizophrenia: assessing GWASs and evaluating Clozapine, ECT and other treatment modalities. 90Life Research, 2019, 2(1): 22-30.


URL:     OR

 Photo by Yuris Alhumaydy
 Photo by Dmytro Tolokonov
 Photo by H Heyerlein
 Photo by Josh Riemer
 Photo by Jared Rice
 Many studies have shown that meditation can cure many mental illnesses by purifying the mind.
[1]   . Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci.Nature. 2014; 511(7510):421-427.
doi: 10.1038/nature13595
[2]   . Escudero I, Johnstone M.Genetics of schizophrenia.Curr Psychiatry Rep. 2014; 16(11):502.
doi: 10.1007/s11920-014-0502-8
[3]   . Brent BK, Rosso IM, Thermenos HW, et al.Alterations of lateral temporal cortical gray matter and facial memory as vulnerability indicators for schizophrenia: An MRI study in youth at familial high-risk for schizophrenia.Schizophr Res. 2015; 170(1):123-129.
[4]   . Dima D, Breen G.Polygenic risk scores in imaging genetics: Usefulness and applications.J Psychopharmacol. 2015; 29(8):867-871.
doi: 10.1177/0269881115584470
[5]   . Harrison PJ.Recent genetic findings in schizophrenia and their therapeutic relevance.J Psychopharmacol. 2015; 29(2):85-96.
doi: 10.1177/0269881114553647
[6]   . Ruderfer DM, Charney AW, Readhead B, et al.Polygenic overlap between schizophrenia risk and antipsychotic response: a genomic medicine approach.Lancet Psychiat. 2016; 3(4):350-357.
doi: 10.1016/S2215-0366(15)00553-2
[7]   . Sekar A, Bialas AR, de Rivera H, et al. Schizophrenia risk from complex variation of complement component 4.Nature. 2016; 530(7589):177-183.
doi: 10.1038/nature16549
[8]   . Tansey KE, Rees E, Linden DE, et al.Common alleles contribute to schizophrenia in CNV carriers.Mol Psychiatr. 2015; 21(8):1085-1089.
[9]   . Ouimet CC, Miller PE, Hemmings HC, et al.DARPP-32, a dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein enriched in dopamine-innervated brain regions. III. Immunocytochemical localization.J Neurosci. 1984; 4(1):111-124.
doi: 10.1523/JNEUROSCI.04-01-00111.1984
[10]   . Germine L, Robinson EB, Smoller JW, et al.Association between polygenic risk for schizophrenia, neurocognition and social cognition across development.Transl Psychiat. 2016; 6(10):e924.
doi: 10.1038/tp.2016.147
[11]   . Devor A, Andreassen OA, Wang Y, et al.Genetic evidence for role of integration of fast and slow neurotransmission in schizophrenia.Mol Psychiatr. 2017; 22(6):792-801.
doi: 10.1038/mp.2017.33
[12]   . Sundararajan T, Manzardo AM, Butler MG.Functional analysis of schizophrenia genes using GeneAnalytics program and integrated databases.Gene. 2018; 641:25-34.
doi: 10.1016/j.gene.2017.10.035
[13]   . Lee SE, Kim JA, Chang S. nArgBP2-SAPAP-SHANK, the core postsynaptic triad associated with psychiatric disorders.Exp Mol Med. 2018; 50(4):2.
doi: 10.1038/s12276-017-0018-5
[14]   . Lee SE, Chang S. nArgBP2 as a hub molecule in the etiology of various neuropsychiatric disorders.Bmb Rep. 2016; 49(9):457-458.
doi: 10.5483/BMBRep.2016.49.9.138
[15]   . Andreassen OA, Djurovic S, Thompson WK, et al.Improved detection of common variants associated with schizophrenia by leveraging pleiotropy with cardiovascular-disease risk factors.Am J Hum Genet. 2013; 92(2):197-209.
doi: 10.1016/j.ajhg.2013.01.001
[16]   . Smeland OB, Frei O, Kauppi K, et al.Identification of Genetic Loci Jointly Influencing Schizophrenia Risk and the Cognitive Traits of Verbal-Numerical Reasoning, Reaction Time, and General Cognitive Function.JAMA Psychiatry. 2017; 74(10):1065-1075.
doi: 10.1001/jamapsychiatry.2017.1986
[17]   . Blokland G, Mesholam-Gately RI, Toulopoulou T, et al.Heritability of Neuropsychological Measures in Schizophrenia and Nonpsychiatric Populations: A Systematic Review and Meta-analysis. Schizophr Bull.2016; 43(4):788-800.
[18]   . Yang AC, Tsai SJ.New Targets for Schizophrenia Treatment beyond the Dopamine Hypothesis.Int J Mol Sci. 2017; 18(8):1689.
doi: 10.3390/ijms18081689
[19]   . Kim JH, Youn T, Choi JG, et al.Combination of Electroconvulsive Therapy and Clozapine in Treatment-Resistant Schizophrenia.Psychiat Invest. 2018; 15(8):829-835.
doi: 10.30773/pi.2018.05.15
[20]   . Muscatello MR, Bruno A, De Fazio P, et al.Augmentation strategies in partial responder and/or treatment-resistant schizophrenia patients treated with clozapine.Expert Opin Pharmaco. 2014; 15:2329-2345.
doi: 10.1517/14656566.2014.956082
[21]   . Arumugham SS, Thirthalli J, Andrade C.Efficacy and safety of combining clozapine with electrical or magnetic brain stimulation in treatment-refractory schizophrenia.Expert Rev Clin Phar. 2016; 9:1245-1252.
doi: 10.1080/17512433.2016.1200971
[22]   . Mondino M, Brunelin J, Palm U, et al.Transcranial Direct Current Stimulation for the Treatment of Refractory Symptoms of Schizophrenia. Current Evidence and Future Directions.Curr Pharm Design. 2015; 21:3373.
doi: 10.2174/1381612821666150619093648
[23]   . Fröhlich F, Burrello TN, Mellin JM, et al.Exploratory study of once-daily transcranial direct current stimulation (tDCS) as a treatment for auditory hallucinations in schizophrenia.Eur Psychiatry. 2016; 33:54-60.
doi: 10.1016/j.eurpsy.2015.11.005
[24]   . Seidman LJ, Rosso IM, Thermenos HW, et al.Medial temporal lobe default mode functioning and hippocampal structure as vulnerability indicators for schizophrenia: a MRI study of non-psychotic adolescent first-degree relatives.Schizophr Res. 2014; 159:426-434.
doi: 10.1016/j.schres.2014.09.011
[25]   . Ho NF, Holt DJ, Cheung M, et al.Progressive Decline in Hippocampal CA1 Volume in Individuals at Ultra-High-Risk for Psychosis Who Do Not Remit: Findings from the Longitudinal Youth at Risk Study.Neuropsychopharmacology. 2017; 42(6):1361-1370.
doi: 10.1038/npp.2017.5
[26]   . Ho NF, Iglesias JE, Sum MY, et al.Progression from selective to general involvement of hippocampal subfields in schizophrenia.Mol Psychiatr. 2016; 22(1):142-152.
[27]   . Mathew I, Gardin TM, Tandon N, et al.Medial Temporal Lobe Structures and Hippocampal Subfields in Psychotic Disorders: Findings From the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) Study.JAMA Psychiatry. 2014; 71(7):769-777.
doi: 10.1001/jamapsychiatry.2014.453
[28]   . Rathbone J, Zhang L, Zhang M, et al.Chinese herbal medicine for schizophrenia: Cochrane systematic review of randomised trials.Br J Psychiatry. 2007; 190(5):379-384.
doi: 10.1192/bjp.bp.106.026880
[1] C.P. Ong. Taijiquan's Enigma[J]. 90Life Research, 2019, 2(1): 31-44.
[2] Gómez Jensen Alberto Alejandro, Martínez Diana Elina, Wan Qing Guo. Efficacy of Qigong for the treatment of alopecia universalis:a clinical case report[J]. 90Life Research, 2019, 2(1): 8-13.