title: What clinical features precede the onset of bipolar disorder?
abstract: Despite a growing number of reports, there is still limited knowledge of the clinical features that precede the onset of bipolar disorder (BD). To explore this, we investigated baseline data from a prospectively evaluated longitudinal cohort of subjects aged 12-30 years to compare: first, lifetime rates of clinical features between a) subjects at increased genetic risk for developing BD ('AR'), b) participants from families without mental illness ('controls'), and c) those with established BD; and, second, prior clinical features that predict the later onset of affective disorders in these same three groups. This is the first study to report such comparisons between these three groups (though certainly not the first to compare AR and control samples). 118 AR participants with a parent or sibling with BD (including 102 with a BD parent), 110 controls, and 44 BD subjects were assessed using semi-structured interviews. AR subjects had significantly increased lifetime risks for depressive, anxiety and behavioural disorders compared to controls. Unlike prior reports, preceding anxiety and behavioural disorders were not found to increase risk for later onset of affective disorders in the AR sample, perhaps due to limited sample size. However, preceding behavioural disorders did predict later onset of affective disorders in the BD sample. The findings that i) AR subjects had higher rates of depressive, anxiety and behavioural disorders compared to controls, and ii) prior behavioural disorders increased the risk to later development of affective disorders in the BD group, suggest the possibility of therapeutic targeting for these disorders in those at high genetic risk for BD.
authors.affiliation: School of Psychiatry, University of New South Wales, Australia; Black Dog Institute, Prince of Wales Hospital, Australia.
authors.forename: Tania
authors.initials: T
authors.lastname: Perich
authors.affiliation: School of Psychiatry, University of New South Wales, Australia; Black Dog Institute, Prince of Wales Hospital, Australia.
authors.forename: Phoebe
authors.initials: P
authors.lastname: Lau
authors.affiliation: School of Psychiatry, University of New South Wales, Australia; Black Dog Institute, Prince of Wales Hospital, Australia.
authors.forename: Dusan
authors.initials: D
authors.lastname: Hadzi-Pavlovic
authors.affiliation: School of Psychiatry, University of New South Wales, Australia; Black Dog Institute, Prince of Wales Hospital, Australia.
authors.forename: Gloria
authors.initials: G
authors.lastname: Roberts
authors.affiliation: School of Psychiatry, University of New South Wales, Australia; Black Dog Institute, Prince of Wales Hospital, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Frankland
authors.affiliation: School of Psychiatry, University of New South Wales, Australia; Black Dog Institute, Prince of Wales Hospital, Australia.
authors.forename: Adam
authors.initials: A
authors.lastname: Wright
authors.affiliation: School of Psychiatry, University of New South Wales, Australia.
authors.forename: Melissa
authors.initials: M
authors.lastname: Green
authors.affiliation: School of Psychiatry, University of New South Wales, Australia; Black Dog Institute, Prince of Wales Hospital, Australia; Division of Mental Health Research, Queensland Institute of Medical Research, Australia; Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Breakspear
authors.affiliation: School of Psychiatry, University of New South Wales, Australia; Black Dog Institute, Prince of Wales Hospital, Australia.
authors.forename: Justine
authors.initials: J
authors.lastname: Corry
authors.affiliation: School of Psychiatry, University of New South Wales, Australia; Black Dog Institute, Prince of Wales Hospital, Australia.
authors.forename: Basia
authors.initials: B
authors.lastname: Radlinska
authors.affiliation: School of Psychiatry, University of New South Wales, Australia; Black Dog Institute, Prince of Wales Hospital, Australia.
authors.forename: Clare
authors.initials: C
authors.lastname: McCormack
authors.affiliation: School of Psychiatry, University of New South Wales, Australia; Black Dog Institute, Prince of Wales Hospital, Australia.
authors.forename: Cassandra
authors.initials: C
authors.lastname: Joslyn
authors.affiliation: School of Psychiatry, University of New South Wales, Australia; Prince of Wales Hospital, Randwick, New South Wales, Australia.
authors.forename: Florence
authors.initials: F
authors.lastname: Levy
authors.affiliation: School of Psychiatry, University of New South Wales, Australia; Neuroscience Research Australia, Randwick, New South Wales, Australia.
authors.forename: Rhoshel
authors.initials: R
authors.lastname: Lenroot
authors.affiliation: Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, USA.
authors.forename: John I
authors.initials: JI
authors.lastname: Nurnberger Jnr
authors.affiliation: School of Psychiatry, University of New South Wales, Australia; Black Dog Institute, Prince of Wales Hospital, Australia; Prince of Wales Hospital, Randwick, New South Wales, Australia. Electronic address: phil.mitchell@unsw.edu.au.
authors.forename: Philip B
authors.initials: PB
authors.lastname: Mitchell
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy*; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors; D055815:Young Adult
keywords: Adolescent; At risk; Bipolar disorder; Genetic; High risk; Psychopathology