Basic sciences relevant to psychiatry: neuroanatomy, neurophysiology, neurochemistry, psychopharmacology, genetics
This domain tests whether you can turn neurobiology into a clinical decision: which pathway explains a side effect, which receptor explains a switch, which gene justifies a monitoring rule.
Core rules
- Four dopamine tracts: mesolimbic (positive symptoms), mesocortical (negative/cognitive symptoms, prefrontal D1 hypofunction), nigrostriatal (extrapyramidal symptoms), tuberoinfundibular (prolactin rise from loss of tonic D2 inhibition of lactotrophs).
- Tyrosine hydroxylase is the rate-limiting step in catecholamine synthesis; MAO and COMT degrade catecholamines.
- Serotonin: 5-HT2A antagonism improves sleep and lowers EPS; 5-HT2C antagonism drives weight gain (olanzapine, mirtazapine); 5-HT1A partial agonism (buspirone, aripiprazole, vilazodone).
- Glutamate: NMDA hypofunction (ketamine, phencyclidine) reproduces positive, negative and cognitive symptoms.
- HPA axis: CRH to ACTH to cortisol; dexamethasone non-suppression and hypercortisolemia are typical of psychotic depression.
- Heritability: schizophrenia about 80%, bipolar disorder 60-80%, major depression about 35%. GWAS signals include CACNA1C, TCF4, ZNF804A and the MHC region; 22q11.2 deletion is the strongest single genetic risk for schizophrenia.
- Pharmacogenetics: CYP2D6 poor metabolizers and risperidone, aripiprazole, venlafaxine, tamoxifen; CYP2C19 and escitalopram; HLA-B15:02 before carbamazepine in Han Chinese; HLA-A31:01 for carbamazepine hypersensitivity; HLA-B*57:01 for abacavir.
Worked example
A 30-year-old man on haloperidol 10 mg/day for three months develops gynecomastia and milky discharge with normal hepatic and thyroid tests. Tuberoinfundibular D2 blockade has removed tonic inhibition of prolactin release. The answer is not to add a drug but to reduce or switch the antipsychotic (or add low-dose aripiprazole) after excluding other causes.
Traps
Swapping mesolimbic and mesocortical roles; forgetting that 5-HT2A blockade is why second-generation drugs cause less EPS; attributing hyperprolactinemia to serotonin; mismatching HLA alleles and drugs, or calling the rate-limiting enzyme dopa decarboxylase.