title: Biological indicators of illness risk in offspring of bipolar parents: targeting the hypothalamic-pituitary-adrenal axis and immune system.
abstract: OBJECTIVE
  The study aims to provide a selective review of the literature pertaining to the hypothalamic-pituitary-adrenal (HPA) axis and immune abnormalities as informative biological indicators of vulnerability in bipolar disorder (BD).
  
  
  METHODS
  We summarize key findings relating to HPA axis and immunological abnormalities in bipolar patients and their high-risk offspring. Findings derive from a review of selected original papers published in the literature, and supplemented by papers identified through bibliography review. Neurobiological findings are discussed in the context of emergent BD in those at genetic risk and synthesized into a neurodevelopmental model of illness onset and progression.
  
  
  RESULTS
  BD is associated with a number of genetic and possibly epigenetic abnormalities associated with neurotransmitter, hormonal and immunologically mediated neurobiological pathways. Data from clinical and high-risk studies implicate HPA axis and immune system abnormalities, which may represent inherited vulnerabilities important for the transition to illness onset. Post-mortem and clinical studies implicate intracellular signal transduction processes and disturbance in energy metabolism associated with established BD. Specifically, long-standing maladaptive alterations such as changes in neuronal systems may be mediated through changes in intracellular signalling pathways, oxidative stress, cellular energy metabolism and apoptosis associated with substantial burden of illness.
  
  
  CONCLUSIONS
  Prospective longitudinal studies of endophenotypes and biomarkers such as HPA axis and immune abnormalities in high-risk offspring will be helpful to understand genetically mediated biological pathways associated with illness onset and progression. A clinical staging model describing emergent illness in those at genetic risk should facilitate this line of investigation.
authors.affiliation: Departments of Psychiatry, Dalhousie University, Halifax, Nova Scotia. anne.duffy@dal.ca
authors.forename: Anne
authors.initials: A
authors.lastname: Duffy
authors.forename: Ute
authors.initials: U
authors.lastname: Lewitzka
authors.forename: Sarah
authors.initials: S
authors.lastname: Doucette
authors.forename: Ana
authors.initials: A
authors.lastname: Andreazza
authors.forename: Paul
authors.initials: P
authors.lastname: Grof
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001714:Bipolar Disorder; D016241:Child of Impaired Parents; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D007107:Immune System / Q000378:metabolism*; D008954:Models, Biological; D010290:Parents / Q000523:psychology*; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D012307:Risk Factors; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D015415:Biomarkers