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Symptoms
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Cognitive decline Learning and memory impairments Attention and perception change Impaired social cognition Impaired social judgement Language impairments Difficulty regulating emotions and behavior Depression Sleep disturbances Mood change: agitation, aggression, self-injurious behavior, impulsivity, hyperactivity, anxiety Personality change: irritability, suspiciousness, or apathy Social Isolation
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Impaired communication Impaired reciprocal social interaction Restricted, repetitive, and stereotyped patterns of behaviors or interest learning difficulties Difficulty regulating emotions and behavior Dysfunction of working memory, planning, inhibition Depression Inattention Aggression Aggression, self-injurious behavior, impulsivity, irritability, hyperactivity, anxiety Sleep disturbance Social isolation
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Mechanisms
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Increase of Aβ peptide production and tau protein phosphorylation Altered synaptic plasticity Myelination changes Decrease of the extracellular matrix perineuronal net (PNN) Impairment of long-term synaptic plasticity in the hippocampus Neuregulin-1 (NRG1) decrease Impairment of serotonergic neurons Different methylation of oxytocin gene PI3K/Akt/mTOR/Rho GTPase pathway ERK/MAPK
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Brain growth: neuronal migration Synaptic dysfunction E/I imbalance: GABA, NMDA/AMPA Abnormal 5-HT and dopamine neurotransmission Altered circuit connectivity PSD integrity: SHANK3, glutamate transmission Metabolic pathway: tryptophan metabolism, NADH, lactate/pyruvate ROS Neuroinflammation PI3K/Akt/mTOR, ERK/MAPK, calcium signaling Neuropeptide: decrease of vasopressin, oxytocin level
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Therapeutic candidates
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Growth factor (Neuregulin-1) SLV (5-HT6 receptor antagonist) DETQ (dopamine D1 receptor modulator) Oxytocin (social hormone) Antioxidant (N-acetyl cysteine) Neurotrophic factor (BDNF, NGF) Cannabidiol, nabilone, dronabinol, THC-Free CBD, IGC-AD1, JZP541 (cannabinoid) Psilocybin (5-HT1A,2A, 2C) Masupirdine (5-HT6) AVP-786, AXS-05, dextromethorphan (NMDARc antagonist) Dexmedetomidine (α2 adrenergic agonist)
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Oxytocin (social hormone) ML-004 (5HT1b agonist) Brexpiprazole, caripiprazine, risperidone, aripiprazole (dopamine) EM-113, Arbaclofen (NMDARc antagonist) GWP42006, CBDV, JZP541 (cannabinoid) LSD, Psilocybin (5-HT1A,2A,2C) AB-2004, SB-121(microbiome) tDCS, rTMS (electroceutical)
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Common symptoms for social deficits
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Impaired social cognition: difficulty recognizing social cues, facial expressions, and body language. Problem with social judgment: inappropriate or disinhibited behaviors. Language impairments. Struggle to regulate emotions and behaviors: outbursts, crying, or inappropriate laughter. Personality change: irritability, suspicion, or apathy.
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