Table 1.

Summary of preclinical and clinical Nrxn1/NRXN1 deletion studies characterising behavioural and brain phenotypes.

	iPSC Model	Murine Model	Human
Clinical/behavioural phenotype	N/A	Male and female mice: ↑ Repetitive self -grooming behaviors (Etherton et al., 2009) ↓ Communication complexity in early development (ultrasonic vocalization and restricted repertoire of calls; Armstrong et al., 2020) ↓ Social memory (Dachtler et al., 2015) ↓ Sensorimotor gating (Etherton et al., 2009) ↓ Reward processing (Alabi et al., 2020) Male mice only: ↑ Responsiveness to novelty (Laarakker et al., 2012) ↑ Aggression and anxiety (Grayton et al., 2013) ↓ Social behaviour (Grayton et al., 2013) Male and female rats: ↑ Nurturing behaviour (Kight et al., 2021) ↓ Ultrasonic vocalization in early development (Kight et al., 2021) ↓ Prosocial helping (Kight et al., 2021) ↓ Learning (Kight et al., 2021) ↓ Reward processing (Esclassan et al., 2015) Male rats only: ↓ Social play (Kight et al., 2021) ↑ Locomotor activity and object exploration (Kight et al., 2021)	Clinical diagnosis most reported: Autism, intellectual disability and speech and language delay (Lowther et al., 2017; Al Shehhi et al., 2019; Castronovo et al., 2020) Other conditions: ADHD, schizophrenia, anxiety, Tourette syndrome, obsessive compulsive disorder (Béna et al., 2013; Dabell et al., 2013; Al Shehhi et al., 2019; Castronovo et al., 2020) Some reports of motor delay and hypotonia (Al Shehhi et al., 2019) ↑ Autism traits (Chawner et al., 2019) ↓ Social functioning(Chawner et al., 2019) ↑ Hyperactivity (Chawner et al., 2019) ↑ Sleep disturbances in some (Chawner et al., 2023)
Brain phenotype	↑ Calcium signalling in autism (Avazzadeh et al., 2019) ↑ Neuronal excitability in autism (Avazzadeh et al., 2021) ↓ Neuronal activity in schizophrenia (Pak et al., 2015) Upregulation of interacellular CASK protein in schizophrenia (Pak et al., 2015, 2021)	Mice: ↓ Hippocampal excitatory synaptic strength and no change in inhibitory synaptic transmission (Etherton et al., 2009) No change in synaptic transmission in cortical neurons (Pak et al., 2015) ↓ Glutamate release and synaptic strength from dorsal prefrontal cortex to dorsal medial striatum (Davatolhagh and Fuccillo, 2021) ↓ Excitatory transmission from dorsal medial prefrontal cortex to basal amygdala (Asede et al., 2020) PET analogue: Medial prefrontal cortex hypometabolism and dorsal raphé nucleus hypermetabolism (Hughes et al., 2022) Rats: ↑ Spontaneous gamma band oscillatory power and coherence in cortico-triatal and thalamocortical circuits (Janz et al., 2022) ↓ Auditory-evoked oscillations and evoked-potentials (Janz et al., 2022) DTI and NODDI: ↓white matter integrity in the left capsule and right neocortex, and no difference in neurite density (Barnett et al., 2020)	Epilepsy (Møller et al., 2013) MRI: ↑ temporal horns of lateral ventricles in common SNP (Alliey-Rodriguez et al., 2019) No MRI studies in CNV carriers