Pathophysiology
Clinical meaning
Neurotransmitter systems modulate every aspect of brain function, and their imbalance underlies major neurological and psychiatric disorders. Dopamine pathways: (1) Nigrostriatal โ substantia nigra to striatum; degeneration causes Parkinson disease (bradykinesia, rigidity, tremor); (2) Mesolimbic โ VTA to nucleus accumbens; hyperactivity associated with psychosis and addiction; (3) Mesocortical โ VTA to prefrontal cortex; hypoactivity contributes to negative symptoms of schizophrenia and executive dysfunction; (4) Tuberoinfundibular โ hypothalamus to pituitary; dopamine tonically inhibits prolactin release (antipsychotic blockade causes hyperprolactinemia). Serotonin (5-HT) is synthesized from tryptophan in raphe nuclei and modulates mood, appetite, sleep, and pain perception; deficiency is implicated in depression, anxiety, and OCD (basis for SSRI therapy). Serotonin excess causes serotonin syndrome (hyperthermia, clonus, agitation โ potentially fatal). GABA is the primary inhibitory neurotransmitter; reduced GABAergic transmission lowers seizure threshold (anticonvulsants like valproate and benzodiazepines enhance GABA); GABAergic medications (benzodiazepines, barbiturates, alcohol) produce sedation, anxiolysis, and respiratory depression. Glutamate is the primary excitatory neurotransmitter; excess glutamate causes excitotoxicity (calcium influx through NMDA receptors โ mitochondrial damage โ cell death) in stroke, TBI, and status epilepticus. This excitotoxic cascade is the...