Hostname: page-component-cd9895bd7-jkksz Total loading time: 0 Render date: 2024-12-26T18:30:09.891Z Has data issue: false hasContentIssue false
  • English
  • Français

Clinical predictors of conversion to bipolar disorder in a prospective longitudinal familial high-risk sample: focus on depressive features

Published online by Cambridge University Press:  07 November 2017

Andrew Frankland ,
Gloria Roberts ,
Ellen Holmes-Preston ,
Tania Perich ,
Florence Levy ,
Rhoshel Lenroot ,
Dusan Hadzi-Pavlovic ,
Michael Breakspear  and
Philip B. Mitchell
Andrew Frankland
Affiliation:
School of Psychiatry, University of New South Wales, Sydney, Australia Black Dog Institute, Sydney, Australia
Gloria Roberts
Affiliation:
School of Psychiatry, University of New South Wales, Sydney, Australia Black Dog Institute, Sydney, Australia
Ellen Holmes-Preston
Affiliation:
School of Psychiatry, University of New South Wales, Sydney, Australia Black Dog Institute, Sydney, Australia
Tania Perich
Affiliation:
School of Psychiatry, University of New South Wales, Sydney, Australia Black Dog Institute, Sydney, Australia Western Sydney University, Sydney, Australia
Florence Levy
Affiliation:
School of Psychiatry, University of New South Wales, Sydney, Australia Prince of Wales Hospital, Sydney, Australia
Rhoshel Lenroot
Affiliation:
School of Psychiatry, University of New South Wales, Sydney, Australia Neuroscience Research Australia, Sydney, Australia
Dusan Hadzi-Pavlovic
Affiliation:
School of Psychiatry, University of New South Wales, Sydney, Australia Black Dog Institute, Sydney, Australia
Michael Breakspear
Affiliation:
School of Psychiatry, University of New South Wales, Sydney, Australia QIMR Berghofer, Brisbane, Australia
Philip B. Mitchell*
Affiliation:
School of Psychiatry, University of New South Wales, Sydney, Australia Black Dog Institute, Sydney, Australia
*
Author for correspondence: Philip B. Mitchell, E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Identifying clinical features that predict conversion to bipolar disorder (BD) in those at high familial risk (HR) would assist in identifying a more focused population for early intervention.

Method

In total 287 participants aged 12–30 (163 HR with a first-degree relative with BD and 124 controls (CONs)) were followed annually for a median of 5 years. We used the baseline presence of DSM-IV depressive, anxiety, behavioural and substance use disorders, as well as a constellation of specific depressive symptoms (as identified by the Probabilistic Approach to Bipolar Depression) to predict the subsequent development of hypo/manic episodes.

Results

At baseline, HR participants were significantly more likely to report ⩾4 Probabilistic features (40.4%) when depressed than CONs (6.7%; p < .05). Nineteen HR subjects later developed either threshold (n = 8; 4.9%) or subthreshold (n = 11; 6.7%) hypo/mania. The presence of ⩾4 Probabilistic features was associated with a seven-fold increase in the risk of ‘conversion’ to threshold BD (hazard ratio = 6.9, p < .05) above and beyond the fourteen-fold increase in risk related to major depressive episodes (MDEs) per se (hazard ratio = 13.9, p < .05). Individual depressive features predicting conversion were psychomotor retardation and ⩾5 MDEs. Behavioural disorders only predicted conversion to subthreshold BD (hazard ratio = 5.23, p < .01), while anxiety and substance disorders did not predict either threshold or subthreshold hypo/mania.

Conclusions

This study suggests that specific depressive characteristics substantially increase the risk of young people at familial risk of BD going on to develop future hypo/manic episodes and may identify a more targeted HR population for the development of early intervention programs.

Keywords

Anxiety disorderbehavioural disorderbipolar disorderdepressionfamilialhigh risklongitudinalprobabilisticprospective
Type
Original Articles
Information
Psychological Medicine , Volume 48 , Issue 10 , July 2018 , pp. 1713 - 1721
Copyright
Copyright © Cambridge University Press 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Akiskal, HS, Walker, P, Puzantian, VR, King, D, Rosenthal, TL and Dranon, M (1983) Bipolar outcome in the course of depressive illness. Journal of Affective Disorders 5, 115–128.CrossRefGoogle ScholarPubMed
Angst, J, Sellaro, R, Stassen, HH and Gamma, A (2005) Diagnostic conversion from depression to bipolar disorders: results of a long-term prospective study of hospital admissions. Journal of Affective Disorders 84, 149–157.CrossRefGoogle ScholarPubMed
Axelson, D, Goldstein, B, Goldstein, T, Monk, K, Yu, H, Hickey, MB, Sakolsky, D, Diler, R, Hafeman, D, Merranko, J, Iyengar, S, Brent, D, Kupfer, D and Birmaher, B (2015) Diagnostic precursors to bipolar disorder in offspring of parents With bipolar disorder: a longitudinal study. American Journal of Psychiatry 172, 638–646.CrossRefGoogle ScholarPubMed
Birmaher, B, Axelson, D, Monk, K, Kalas, C, Goldstein, B, Hickey, MB, Obreja, M, Ehmann, M, Iyengar, S, Shamseddeen, W, Kupfer, D and Brent, D (2009) Lifetime psychiatric disorders in school-aged offspring of parents with bipolar disorder: the Pittsburgh Bipolar Offspring study. Archives of General Psychiatry 66, 287–296.CrossRefGoogle ScholarPubMed
Breakspear, M, Roberts, G, Green, MJ, Nguyen, VT, Frankland, A, Levy, F, Lenroot, R and Mitchell, PB (2015) Network dysfunction of emotional and cognitive processes in those at genetic risk of bipolar disorder. Brain: A Journal of Neurology 138, 3427–3439.CrossRefGoogle ScholarPubMed
Bukh, JD, Andersen, PK and Kessing, LV (2016) Rates and predictors of remission, recurrence and conversion to bipolar disorder after the first lifetime episode of depression – a prospective 5-year follow-up study. Psychological Medicine 46, 1151–1161.CrossRefGoogle ScholarPubMed
Chang, KD, Steiner, H and Ketter, TA (2000) Psychiatric phenomenology of child and adolescent bipolar offspring. Journal of the American Academy of Child & Adolescent Psychiatry 39, 453–460.CrossRefGoogle ScholarPubMed
Coryell, W, Endicott, J, Maser, JD, Keller, B, Leon, C and Akiskal, HS (1995) Long-term stability of polarity distinctions in the affective disorders. American Journal of Psychiatry 152, 385–390.CrossRefGoogle Scholar
Diler, RS, Goldstein, TR, Hafeman, D, Rooks, BT, Sakolsky, D, Goldstein, BI, Monk, K, Hickey, MB, Axelson, D, Iyengar, S and Birmaher, B (2017) Characteristics of depression among offspring at high and low familial risk of bipolar disorder. Bipolar Disorders 19, 344–352.CrossRefGoogle ScholarPubMed
Dudek, D, Siwek, M, Zielinska, D, Jaeschke, R and Rybakowski, J (2013) Diagnostic conversions from major depressive disorder into bipolar disorder in an outpatient setting: results of a retrospective chart review. Journal of Affective Disorders 144, 112–115.CrossRefGoogle Scholar
Duffy, A, Alda, M, Crawford, L, Milin, R and Grof, P (2007) The early manifestations of bipolar disorder: a longitudinal prospective study of the offspring of bipolar parents. Bipolar Disorders 9, 828–838.CrossRefGoogle ScholarPubMed
Duffy, A, Alda, M, Hajek, T, Sherry, SB and Grof, P (2010) Early stages in the development of bipolar disorder. Journal of Affective Disorders 121, 127–135.CrossRefGoogle ScholarPubMed
Duffy, A, Horrocks, J, Doucette, S, Keown-Stoneman, C, McCloskey, S and Grof, P (2014) The developmental trajectory of bipolar disorder. The British Journal of Psychiatry 204, 122–128.Google ScholarPubMed
Fiedorowicz, JG, Endicott, J, Leon, AC, Solomon, DA, Keller, MB and Coryell, WH (2011) Subthreshold hypomanic symptoms in progression from unipolar major depression to bipolar disorder. The American Journal of Psychiatry 168, 40–48.CrossRefGoogle ScholarPubMed
Forty, L, Smith, D, Jones, L, Jones, I, Caesar, S, Cooper, C, Fraser, C, Gordon-Smith, K, Hyde, S, Farmer, A, McGuffin, P and Craddock, N (2008) Clinical differences between bipolar and unipolar depression. British Journal of Psychiatry 192, 388–389.CrossRefGoogle ScholarPubMed
Frankland, A, Cerrillo, E, Hadzi-Pavlovic, D, Roberts, G, Wright, A, Loo, CK, Breakspear, M and Mitchell, PB (2015) Comparing the phenomenology of depressive episodes in bipolar I and II disorder and major depressive disorder within bipolar disorder pedigrees. The Journal of Clinical Psychiatry 76, 32–39.CrossRefGoogle ScholarPubMed
Geller, B, Zimerman, B, Williams, M, Bolhofner, K, Craney, J, DelBello, M and Soutullo, C (2001) Reliability of the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) mania and rapid cycling sections. Journal of the American Academy of Child & Adolescent Psychiatry 40, 450–455.CrossRefGoogle Scholar
Goldberg, JF, Harrow, M and Whiteside, JE (2001) Risk for bipolar illness in patients initially hospitalized for unipolar depression. American Journal of Psychiatry 158, 1265–1270.CrossRefGoogle ScholarPubMed
Grande, I, Berk, M, Birmaher, B and Vieta, E (2016) Bipolar disorder. The Lancet 387, 1561–1572.CrossRefGoogle ScholarPubMed
Hafeman, DM, Merranko, J, Axelson, D, Goldstein, BI, Goldstein, T, Monk, K, Hickey, MB, Sakolsky, D, Diler, R, Iyengar, S, Brent, D, Kupfer, D and Birmaher, B (2016) Toward the definition of a bipolar prodrome: dimensional predictors of bipolar spectrum disorders in At-Risk Youths. American Journal of Psychiatry, 173, 695–704.CrossRefGoogle ScholarPubMed
Hafeman, DM, Merranko, J, Goldstein, TR, Axelson, D, Goldstein, BI, Monk, K, Hickey, MB, Sakolsky, D, Diler, R, Iyengar, S, Brent, DA, Kupfer, DJ, Kattan, MW and Birmaher, B (2017) Assessment of a person-level risk calculator to predict New-onset bipolar spectrum disorder in youth at familial risk. JAMA Psychiatry 74, 841–847.CrossRefGoogle ScholarPubMed
Henin, A, Biederman, J, Mick, E, Hirshfeld-Becker, DR, Sachs, GS, Wu, Y, Yan, L, Ogutha, J and Nierenberg, AA (2007) Childhood antecedent disorders to bipolar disorder in adults: a controlled study. Journal of Affective Disorders 99, 51–57.CrossRefGoogle ScholarPubMed
Leckman, J, Sholomskas, D, Thompson, W, Belanger, A and Weissman, M (1982) Best estimate of lifetime psychiatric diagnosis: a methodological study. Archives of General Psychiatry 39, 879–883.CrossRefGoogle ScholarPubMed
Leonpacher, AK, Liebers, D, Pirooznia, M, Jancic, D, MacKinnon, DF, Mondimore, FM, Schweizer, B, Potash, JB, Zandi, PP and Goes, FS (2015) Distinguishing bipolar from unipolar depression: the importance of clinical symptoms and illness features. Psychological medicine 45, 2437–2446.CrossRefGoogle ScholarPubMed
Martin, DJ and Smith, DJ (2013) Is there a clinical prodrome of bipolar disorder? A review of the evidence. Expert Review of Neurotherapeutics 13, 89–98.CrossRefGoogle Scholar
Maxwell, M (1992) Family Interview for Genetic Studies (FIGS): A Manual for FIGS. Bethesda, MD: Clinical Neurogenetics Branch, Intramural Research Program, National Institute of Mental Health.Google Scholar
McCormack, C, Green, MJ, Rowland, JE, Roberts, G, Frankland, A, Hadzi-Pavlovic, D, Joslyn, C, Lau, P, Wright, A, Levy, F, Lenroot, RK and Mitchell, PB (2016) Neuropsychological and social cognitive function in young people at genetic risk of bipolar disorder. Psychological Medicine 46, 745–758.CrossRefGoogle ScholarPubMed
Mesman, E, Nolen, WA, Reichart, CG, Wals, M and Hillegers, MHJ (2013) The Dutch bipolar offspring study: 12-year follow-up. The American Journal of Psychiatry 170, 542–549.CrossRefGoogle Scholar
Mitchell, PB, Frankland, A, Hadzi-Pavlovic, D, Roberts, G, Corry, J, Wright, A, Loo, CK and Breakspear, M (2011) Comparison of depressive episodes in bipolar disorder and in major depressive disorder within bipolar disorder pedigrees. The British Journal of Psychiatry 199, 303–309.CrossRefGoogle ScholarPubMed
Mitchell, PB, Goodwin, GM, Johnson, GF and Hirschfeld, RM (2008) Diagnostic guidelines for bipolar depression: a probabilistic approach. Bipolar Disorders 10, 144–152.CrossRefGoogle ScholarPubMed
Nurnberger, JI, Blehar, MC, Kaufmann, CA, York-cooler, C, Simpson, SG, Harkavy-friedman, J, Severe, JB and Malaspina, D (1994) Diagnostic interview for genetic studies. Archives of General Psychiatry 51, 849–859.CrossRefGoogle ScholarPubMed
Nurnberger, JI, Mcinnis, M, Reich, W, Kastelic, E, Wilcox, HC, Glowinski, A, Mitchell, P, Fisher, C, Erpe, M, Gershon, ES, Berrettini, W, Laite, G, Schweitzer, R, Rhoadarmer, K, Coleman, VV, Cai, X, Azzouz, F, Liu, H, Kamali, M, Brucksch, C and Monahan, PO (2011) A high-risk study of bipolar disorder: childhood clinical phenotypes as precursors of major mood disorders. Archives of General Psychiatry 68, 1012–1020.CrossRefGoogle ScholarPubMed
Perich, T, Lau, P, Hadzi-Pavlovic, D, Roberts, G, Frankland, A, Wright, A, Green, M, Breakspear, M, Corry, J, Radlinska, B, McCormack, C, Joslyn, C, Levy, F, Lenroot, R, Nurnberger Jnr, JI and Mitchell, PB (2015) What clinical features precede the onset of bipolar disorder? Journal of Psychiatric Research 62, 71–77.CrossRefGoogle ScholarPubMed
Pfennig, A, Ritter, PS, Höfler, M, Lieb, R, Bauer, M, Wittchen, H-U and Beesdo-Baum, K (2015) Symptom characteristics of depressive episodes prior to the onset of mania or hypomania. Acta Psychiatrica Scandinavica 133, 196–204.CrossRefGoogle ScholarPubMed
Phillips, ML and Kupfer, DJ (2013) Bipolar disorder diagnosis: challenges and future directions. The Lancet 381, 1663–1671.CrossRefGoogle ScholarPubMed
Roberts, G, Green, MJ, Breakspear, M, McCormack, C, Frankland, A, Wright, A, Levy, F, Lenroot, R, Chan, HN and Mitchell, PB (2013) Reduced inferior frontal gyrus activation during response inhibition to emotional stimuli in youth at high risk of bipolar disorder. Biological Psychiatry 74, 55–61.CrossRefGoogle ScholarPubMed
Roberts, G, Lord, A, Frankland, A, Wright, A, Lau, P, Levy, F, Lenroot, RK, Mitchell, PB and Breakspear, M (2017) Functional dysconnection of the inferior frontal gyrus in young people with bipolar disorder or at genetic high risk. Biological Psychiatry 81, 718–727.CrossRefGoogle ScholarPubMed
Roberts, G, Perry, A, Lord, A, Frankland, A, Leung, V, Holmes-Preston, E, Levy, F, Lenroot, RK, Mitchell, PB and Breakspear, M (2016) Structural dysconnectivity of key cognitive and emotional hubs in young people at high genetic risk for bipolar disorder. Molecular Psychiatry. doi: 10.1038/mp.2016.216. [Epub ahead of print].Google ScholarPubMed
Strober, M (1982) Bipolar illness in adolescents with major depression. Archives of General Psychiatry 39, 549.CrossRefGoogle ScholarPubMed
Tondo, L, Visioli, C, Preti, A, and Baldessarini, RJ (2014) Bipolar disorders following initial depression: modeling predictive clinical factors. Journal of Affective Disorders 167, 44–49.CrossRefGoogle ScholarPubMed
Whalley, HC, Sussmann, JE, Romaniuk, L, Stewart, T, Kielty, S, Lawrie, SM, Hall, J and McIntosh, AM (2015) Dysfunction of emotional brain systems in individuals at high risk of mood disorder with depression and predictive features prior to illness. Psychological Medicine 45, 1207–1218.CrossRefGoogle ScholarPubMed
Wong, S, Dunn, L, Tang, W, Chan, W and Chong, S (2009) A case-control study of bipolar depression, compared with unipolar depression, in a regional hospital in Hong Kong. Canadian Journal of Psychiatry. Revue canadienne de psychiatrie 54, 452–459.Google Scholar
Xiang, YT, Zhang, L, Wang, G, Hu, C, Ungvari, GS, Dickerson, FB, Kilbourne, AM, Si, TM, Fang, YR, Lu, Z, Yang, HC, Lai, KY, Lee, EH, Hu, J, Chen, ZY, Huang, Y, Sun, J, Wang, XP, Li, HC, Zhang, JB and Chiu, HF (2013) Sociodemographic and clinical features of bipolar disorder patients misdiagnosed with major depressive disorder in China. Bipolar Disorders 15, 199–205.CrossRefGoogle ScholarPubMed