Which of the following neurotransmitter systems is most consistently implicated in the pathophysiology of autism spectrum disorder based on current neurobiological research?

Explanation

## Neurobiological Basis of Autism Spectrum Disorder ### The Excitatory-Inhibitory (E-I) Imbalance Hypothesis **Key Point:** The most widely supported neurobiological model of ASD involves an imbalance between excitatory glutamatergic and inhibitory GABAergic neurotransmission, with a relative excess of excitation or deficit in inhibition. **High-Yield:** The E-I imbalance hypothesis is central to current understanding of ASD neurobiology and is frequently tested in NEET PG psychiatry. This model explains both the cognitive and behavioral features of ASD. ### Evidence Supporting Glutamatergic-GABAergic Imbalance | Feature | Finding | |---------|----------| | **GABA levels** | Reduced GABA synthesis and signaling in ASD brains | | **Glutamate levels** | Elevated glutamate in cerebrospinal fluid and brain regions | | **GABA receptors** | Abnormal GABA~A~ and GABA~B~ receptor expression | | **Genetic basis** | Mutations in genes encoding GABA and glutamate receptors (GRIN2B, SLC6A8) | | **Clinical correlate** | Sensory hypersensitivity and repetitive behaviors reflect excessive excitation | ### Clinical Pearl The E-I imbalance explains why individuals with ASD often show: - **Sensory hypersensitivity** (excessive excitation to stimuli) - **Restricted, repetitive behaviors** (attempt to regulate excitation) - **Difficulty with social processing** (overload of social stimuli) **Mnemonic:** **GABA-Glut Imbalance** — **G**ABA (inhibition) ↓, **Glut**amate (excitation) ↑ = **ASD** features.