Table 2.
Selected studies investigating major depressive disorder using iPSCs from patients.
| iPSC Model (s) | Observation (s) | Implication (s) | References |
|---|---|---|---|
| The iPSCs from SSRI-remitters and differentiated to serotonergic neurons | The SSRI-non-remitters patient-derived neurons displayed 5-HT-induced hyperactivity via upregulated 5-HT2A and 5-HT7 receptors | The SSRI-resistant patients represent a subset of MDD patients with differential responses to 5-HT | Vadodaria et al., 2019 [57] |
| The iPSCs from SSRI-remitters and SSRI-non-remitters differentiated to serotonergic neurons | Altered morphological phenotypes associated with SSRI-non-remission downstream of PCDHA6 and PCDHA8 genes | The differences in serotonergic neuron morphology may contribute to SSRI-non-remission in MDD patients | Vadodaria et al. [58] |
| The MDD BP-responders’ and- non-responders’ LCLs, reprogrammed to iPSCs, and differentiated to mature prefrontal cortex neurons | Following BP treatment, cortical neurons of BP-responders, compared with vehicle treatment, had significant differences, including enhanced colocalization of synaptic markers and spine morphology | The enhanced colocalization of synaptic markers observed in BP-responders’ derived cells could be indicative of enhanced connectivity following effective antidepressant treatment. The synaptic changes could be used as a biomarker for BP effects in vitro | Avior et al., 2021 [59] |
| The iPSC-derived dopaminergic neurons | Ketamine elicits structural plasticity in iPSCs-derived DA neurons by recruitment of AMPA, mTOR and BDNF signaling | The transient exposure to ketamine dose-dependently promotes structural plasticity as determined by enhanced dendritic outgrowth and increased soma size | Cavalleri et al., 2018 [60] |
| The iPSCs from healthy donors differentiated to dopaminergic neurons | Exposure to the ketamine metabolite HNK for 6 h produces AMPA receptor-mediated and mTOR-mediated dendrite outgrowth when measured 3 days after exposure | The prolonged antidepressant. Effect after a single infusion of ketamine is based on the triggering of long-lasting neuroplasticity |
Collo et al., 2018 [61] |
SSRI: selective serotonin reuptake inhibitor; BP: bupropion; LCLs: lymphoblastoid cell lines; AMPA: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; BDNF: brain-derived neurotrophic factor; mTOR: mammalian target of rapamycin; DA: dopaminergic; HNK: (2R,6R)-hydroxynorketamine.