title: Utilising molecular biological and histopathological techniques to study the dopaminergic system in patients with melancholia.
abstract: OBJECTIVE
  To describe the rationale for investigating the dopaminergic system in patients with melancholia by applying molecular biological (notably, in situ hybridisation) and histopathological techniques in postmortem brain tissue.
  
  
  METHODS
  Relevant advances in the functional neuroanatomy of frontostriatal circuits, as well as insights from clinical neuroimaging studies in primary and secondary depressive disorders, are presented. These are integrated with developments in the pharmacological and molecular characteristics of dopamine receptor subtypes and recognition of their selective anatomical distribution.
  
  
  RESULTS
  Converging data from the basic and clinical neurosciences suggest that the pathophysiology of depressive disorders characterised by psychomotor phenomena, such as melancholia, may involve dysregulation of dopaminergic mechanisms within complex frontostriatal circuits.
  
  
  CONCLUSIONS
  The key feature of in situ hybridisation is its capacity to test for variations in the functional components of designated biochemical systems within highly specific anatomical regions. We utilise this approach, in combination with relevant histopathological techniques, to test the structural and functional integrity of the dopaminergic system within key fronto-striatal circuits in patients who had exhibited psychomotor phenomena. The same approach can also be used to study the integrity of other relevant biochemical systems, such as the serotoninergic and noradrenergic systems, in patients with other mood disorders.
authors.affiliation: Academic Department of Psychiatry, St George Hospital and Community Services, Kogarah, New South Wales, Australia.
authors.forename: I
authors.initials: I
authors.lastname: Hickie
authors.forename: A
authors.initials: A
authors.lastname: Lloyd
authors.forename: G
authors.initials: G
authors.lastname: Dixon
authors.forename: G
authors.initials: G
authors.lastname: Halliday
authors.forename: D
authors.initials: D
authors.lastname: McRitchie
authors.forename: E
authors.initials: E
authors.lastname: Scott
authors.forename: P
authors.initials: P
authors.lastname: Mitchell
authors.forename: D
authors.initials: D
authors.lastname: Wakefield
mesh_terms: D001931:Brain Mapping; D003342:Corpus Striatum / Q000473:pathology / Q000503:physiopathology; D003866:Depressive Disorder / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005625:Frontal Lobe / Q000473:pathology / Q000503:physiopathology; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D017403:In Situ Hybridization; D008967:Molecular Biology; D011954:Receptors, Dopamine / Q000235:genetics* / Q000502:physiology; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology
chemical_list: D011954:Receptors, Dopamine