TABLE 1.

Pharmacological studies using iPSC derived neurons from subjects with schizophrenia.

Donors	Neuronal types	Differentiation time (days)	Relevant phenotypic changes	Effective pharmacological agents	Non-effective pharmacological agents	References
Schizophrenia patients from high risk families: one childhood onset schizophrenia; two affected siblings (one schizophrenia and one schizoaffective disorder); one adult schizophrenia patient	Glutamatergic (70%), GABAergic (30%), dopaminergic less than 10%	1–3 months	Reduced dendritic number, neuronal connectivity and dendritic spines. Lower expression of glutamate receptors subunits GRIK1, GRIN2A, GRM7. Defective Wnt (e.g., decreased WNT7A) and cAMP signaling (e.g., increased PDE4D, PDE7B)	Loxapine (10 μM) increases neuronal connectivity	Clozapine (5 μM) Olanzapine (1 μM) Risperidone (10 μM) Thioridazine (5 μM)	Brennand et al., 2011
Members of a DISK 1 mutation family: one schizophrenia patient, one patient with ajor depression and two unaffected subjects. Isogenic iPSc lines	Glutamatergic (90%), very few GABAergic and dopaminergic	Up to 6 weeks	Reduced synaptic vesicle protein SV2 density, reduced vesicle release (FM1-43) and spontaneous ESP. Increase expression of SYN2 SYN3, SYP, SYNPR, NRXN1, VAMP2. Increase expression of transcription factor MEF2C.	Rolipram, reverses synaptic deficit		Wen et al., 2014, 2017
Monozygotic twin patients with treatment resistant schizophrenia, one responder to clozapine and one non-responder	Tuj1 positive neurons	2 weeks following Ngn2 overexpression	Reduced homophilic cell adhesion molecules (e.g., CDH8, DSC) protocadherin genes.	Clozapine (1 μM), differential gene expression between responder and not responder to clinical treatment		Nakazawa et al., 2017
Nine patients with treatment resistant schizophrenia and nine healthy donors	GABAergic cortical interneurons	6–8 weeks	Reduced ND2 and ND4L NADH dehydrogenases (complex I) Decrease mitochondrial function (maximal respiration and reserve capacity) Increased oxidative stress	Acetyl-l-carnitine, significant increases maximal respiration and reserve capacity Ameliorate arborization deficits	Omega-3 fatty acids, coenzyme Q10, N-acetyl cysteine, α-tocopherol	Ni et al., 2019