Induced pluripotent stem cell-derived neuronal models in psychiatry: Mechanistic insights and translational horizons

Table 1 Summary of induced pluripotent stem cell-derived neuronal findings in psychiatry

Disorder	Primary model	Key reported phenotypes	Ref.
Schizophrenia	Forebrain/cortical neurons; NPC → neurons; 22q11.2DS neurons; single-cell RNA-seq	Neurite/synaptic and connectivity deficits; catecholamine-release abnormalities; WNT/progenitor dysregulation; 22q11.2DS shows mitochondrial and developmental transcriptomic defects; single-cell heterogeneity shifts	[15-22]
Bipolar disorder	Neurons (electrophysiology); NPCs; cortical spheroids	Hyperexcitability with lithium-linked rescue; functional subgrouping; NPC calcium-entry and differentiation changes; lithium effects in spheroids; mitochondrial/bioenergetic abnormalities	[23-28]
Autism spectrum disorder	Neurons (syndromic/idiopathic); CNV/risk-gene cohorts; neuron-astrocyte co-culture; MEA/patch; iPSCs (NO assay)	Synapse/network phenotypes; 16p11.2 dosage effects; CNTN5/EHMT2 network hyperactivity; convergent expression modules; astrocyte modulation; nitric-oxide signature in iPSCs	[29-38]
Major depressive disorder	Serotonergic/forebrain neurons; cortical neurons; NPC → neurons; GABA interneurons; dopaminergic neurons	SSRI-resistance phenotypes including serotonin-evoked hyperactivity; antidepressant-response signatures; bioenergetic/electrophysiology changes; HTR2C-linked interneuron activity with rescue; ketamine plasticity pathways	[1,39-45]
ADHD	NSCs/NPCs; telencephalon organoids; cortical neurons; dopaminergic neurons (PARK2 CNVs)	Progenitor proliferation deficits; early cortical organization changes in organoids; glutamatergic and calcium-network hypoactivity; stress-modulated bioenergetic deficits	[47-52]
Anorexia nervosa	Neuronal cultures	Limited evidence; transcriptomic dysregulation signals; major gap in functional phenotyping	[53]
OCD	iPSC line resources	Mostly line derivation/validation; limited neuronal phenotyping	[54]

NPC: Neural progenitor cell; RNA-seq: RNA sequencing; CNV: Copy number variation; MEA: Multielectrode array; iPSCs: Induced pluripotent stem cells; NO: Nitric oxide; GABA: Gamma-aminobutyric acid; ADHD: Attention-deficit/hyperactivity disorder; SSRI: Selective serotonin reuptake inhibitor; NSCs: Neural stem cells; OCD: Obsessive-compulsive disorder.