Basic Sciences Relevant to Psychiatry
What to master
Build a working map of the dopamine pathways, because almost every psychopharmacology question resolves through them. The mesolimbic pathway (VTA to nucleus accumbens) mediates reward and positive symptoms; mesocortical (VTA to prefrontal cortex) mediates negative and cognitive symptoms; nigrostriatal (substantia nigra to striatum) explains extrapyramidal effects; tuberoinfundibular explains hyperprolactinaemia. Know receptor profiles cold: D2 blockade (antipsychotic efficacy, EPS, prolactin), 5-HT2A antagonism (reduces EPS), H1 (sedation, weight gain), M1 (anticholinergic effects, cognitive blunting), alpha-1 (orthostasis).
Neurophysiology questions favour sleep architecture (reduced REM latency in depression; REM suppression by SSRIs and alcohol withdrawal rebound), the HPA axis and dexamethasone suppression, and kindling models of bipolar disorder. Genetics rewards the distinction between heritability estimates and mode of transmission: schizophrenia and bipolar disorder are polygenic, ~80% heritable, with high concordance in monozygotes but far below 100%, so no Mendelian model fits.
Traps
- Confusing serotonin syndrome (clonus, hyperreflexia, mydriasis, onset hours) with NMS (rigidity, bradyreflexia, hours to days, raised CK).
- Assuming antipsychotics treat negative symptoms by D2 blockade; they largely do not.
- Forgetting that clozapine's agranulocytosis is idiosyncratic and requires mandatory monitoring, while its seizure risk is dose-related.
Rule of thumb
When a drug effect is puzzling, ask which receptor, in which pathway, in which direction - that triad answers most items.