Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Clinical, cortical thickness and neural activity predictors of future affective lability in youth at risk for bipolar disorder: initial discovery and independent sample replication

Molecular Psychiatry volume 24, pages 1856–1867 (2019)Cite this article

Subjects

Abstract

We aimed to identify markers of future affective lability in youth at bipolar disorder risk from the Pittsburgh Bipolar Offspring Study (BIOS) (n = 41, age = 14, SD = 2.30), and validate these predictors in an independent sample from the Longitudinal Assessment of Manic Symptoms study (LAMS) (n = 55, age = 13.7, SD = 1.9). We included factors of mixed/mania, irritability, and anxiety/depression (29 months post MRI scan) in regularized regression models. Clinical and demographic variables, along with neural activity during reward and emotion processing and gray matter structure in all cortical regions at baseline, were used to predict future affective lability factor scores, using regularized regression. Future affective lability factor scores were predicted in both samples by unique combinations of baseline neural structure, function, and clinical characteristics. Lower bilateral parietal cortical thickness, greater left ventrolateral prefrontal cortex thickness, lower right transverse temporal cortex thickness, greater self-reported depression, mania severity, and age at scan predicted greater future mixed/mania factor score. Lower bilateral parietal cortical thickness, greater right entorhinal cortical thickness, greater right fusiform gyral activity during emotional face processing, diagnosis of major depressive disorder, and greater self-reported depression severity predicted greater irritability factor score. Greater self-reported depression severity predicted greater anxiety/depression factor score. Elucidating unique clinical and neural predictors of future-specific affective lability factors is a step toward identifying objective markers of bipolar disorder risk, to provide neural targets to better guide and monitor early interventions in bipolar disorder at-risk youth.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Phillips ML, Swartz HA. A critical appraisal of neuroimaging studies of bipolar disorder: toward a new conceptualization of underlying neural circuitry and a road map for future research. Am J Psychiatry. 2014;171:829–43.

    Article  Google Scholar 

  2. Singh MK, Chang KD. Brain structural response in individuals at familial risk for bipolar disorder: a tale of two outcomes. Biol Psychiatry. 2013;73:109–10.

    Article  Google Scholar 

  3. Axelson D, Goldstein B, Goldstein T, Monk K, Yu H, Hickey MB, et al. Diagnostic precursors to bipolar disorder in offspring of parents with bipolar disorder: a longitudinal study. Am J Psychiatry. 2015;172:638–46. https://doi.org/10.1176/appi.ajp.2014.14010035

    Article  PubMed  PubMed Central  Google Scholar 

  4. Birmaher B, Goldstein BI, Axelson DA, Monk K, Hickey MB, Fan J, et al. Mood lability among offspring of parents with bipolar disorder and community controls. Bipolar Disord. 2013;15:253–63. https://doi.org/10.1111/bdi.12060

    Article  PubMed  PubMed Central  Google Scholar 

  5. Hafeman DM, Merranko J, Axelson D, Goldstein BI, Goldstein T, Monk K, et al. Toward the definition of a bipolar prodrome: dimensional predictors of bipolar spectrum disorders in at-risk youths. Am J Psychiatry. 2016;173:695–704. https://doi.org/10.1176/appi.ajp.2015.15040414

    Article  PubMed  PubMed Central  Google Scholar 

  6. Howes OD, Lim S, Theologos G, Yung AR, Goodwin GM, McGuire P. A comprehensive review and model of putative prodromal features of bipolar affective disorder. Psychol Med. 2010;41:1567–77. https://doi.org/10.1017/S0033291710001790

    Article  PubMed  PubMed Central  Google Scholar 

  7. Angst J, Gamma A, Endrass J. Risk factors for the bipolar and depression spectra. Acta Psychiatr Scand Suppl. 2003;108:15–9.

    Article  Google Scholar 

  8. Aas M, Pedersen G, Henry C, Bjella T, Bellivier F, Leboyer M, et al. Psychometric properties of the Affective Lability Scale (54 and 18-item version) in patients with bipolar disorder, first-degree relatives, and healthy controls. J Affect Disord. 2015;172:375–80. https://doi.org/10.1016/j.jad.2014.10.028

    Article  PubMed  Google Scholar 

  9. Henry C, Van den Bulke D, Bellivier F, Roy I, Swendsen J, M’Bailara K, et al. Affective lability and affect intensity as core dimensions of bipolar disorders during euthymic period. Psychiatry Res. 2008;159:1–6. https://doi.org/10.1016/j.psychres.2005.11.016

    Article  PubMed  Google Scholar 

  10. Weibel S, Micoulaud-Franchi J-A, Brandejsky L, Lopez R, Prada P, Nicastro R, Ardu S, Dayer A, Lançon C, Perroud N. Psychometric Properties and Factor Structure of the Short Form of the Affective Lability Scale in Adult Patients With ADHD. Journal of Attention Disorders. 2017;0:1087054717690808.

  11. Harvey PD, Greenberg BR, Serper MR. The Affective Lability Scales: development, reliability, and validity. J Clin Psychol. 1989;45:786–93.

    Article  CAS  Google Scholar 

  12. Stringaris A, Goodman R. Mood lability and psychopathology in youth. Psychol Med. 2008;39:1237–45. https://doi.org/10.1017/S0033291708004662

    Article  PubMed  Google Scholar 

  13. Leopold K, Ritter P, Correll CU, Marx C, Özgürdal S, Juckel G, et al. Risk constellations prior to the development of bipolar disorders: rationale of a new risk assessment tool. J Affect Disord. 2012;136:1000–10.

    Article  Google Scholar 

  14. Hafeman DM, Merranko J, Goldstein TR, et al. Assessment of a person-level risk calculator to predict new-onset bipolar spectrum disorder in youth at familial risk. JAMA Psychiatry. 2017;74:841–7. https://doi.org/10.1001/jamapsychiatry.2017.1763

    Article  PubMed  PubMed Central  Google Scholar 

  15. Fergus EL, Miller RB, Luckenbaugh DA, Leverich GS, Findling RL, Speer AM, et al. Is there progression from irritability/dyscontrol to major depressive and manic symptoms? A retrospective community survey of parents of bipolar children. J Affect Disord. 2003;77:71–78.

    Article  Google Scholar 

  16. Bertocci MA, Bebko G, Olino T, Fournier J, Hinze AK, Bonar L, et al. Behavioral and emotional dysregulation trajectories marked by prefrontal-amygdala function in symptomatic youth. Psychol Med. 2014;27:1–13.

    Google Scholar 

  17. Bertocci MA, Bebko GM, Mullin BC, Langenecker SA, Ladouceur CD, Almeida JRC, et al. Abnormal anterior cingulate cortical activity during emotional n-back task performance distinguishes bipolar from unipolar depressed females. Psychol Med. 2011;42:1417–28. https://doi.org/10.1017/s003329171100242x

    Article  PubMed  PubMed Central  Google Scholar 

  18. Hafeman D, Bebko G, Bertocci MA, Fournier JC, Chase HW, Bonar L, et al. Amygdala-prefrontal cortical functional connectivity during implicit emotion processing differentiates youth with bipolar spectrum from youth with externalizing disorders. J Affect Disord. 2017;208:94–100. https://doi.org/10.1016/j.jad.2016.09.064

    Article  PubMed  Google Scholar 

  19. Aminoff SR, Jensen J, Lagerberg TV, Hellvin T, Sundet K, Andreassen OA, et al. An association between affective lability and executive functioning in bipolar disorder. Psychiatry Res. 2012;198:58–61. https://doi.org/10.1016/j.psychres.2011.12.044

    Article  PubMed  Google Scholar 

  20. Lan MJ, Chhetry BT, Oquendo MA, Sublette ME, Sullivan G, Mann JJ, et al. Cortical thickness differences between bipolar depression and major depressive disorder. Bipolar Disord. 2014;16:378–88. https://doi.org/10.1111/bdi.12175

    Article  PubMed  PubMed Central  Google Scholar 

  21. Hajek T, Cullis J, Novak T, Kopecek M, Blagdon R, Propper L, et al. Brain structural signature of familial predisposition for bipolar disorder: replicable evidence for involvement of the right inferior frontal gyrus. Biol Psychiatry. 2013;73:144–52. https://doi.org/10.1016/j.biopsych.2012.06.015

    Article  PubMed  Google Scholar 

  22. Strakowski SM, DelBello MP, Sax KW, Zimmerman ME, Shear PK, Hawkins JM, et al. Brain magnetic resonance imaging of structural abnormalities in bipolar disorder. Arch Gen Psychiatry. 1999;56:254–60.

    Article  CAS  Google Scholar 

  23. Birmaher B, Axelson D, Goldstein B, Monk K, Kalas C, Obreja M, et al. Psychiatric disorders in preschool offspring of parents with bipolar disorder: the Pittsburgh Bipolar Offspring Study (BIOS). Am J Psychiatry. 2010;167:321–30. https://doi.org/10.1176/appi.ajp.2009.09070977

    Article  PubMed  PubMed Central  Google Scholar 

  24. Birmaher B, Axelson D, Monk K, Kalas C, Goldstein B, Hickey MB, et al. Lifetime psychiatric disorders in school-aged offspring of parents with bipolar disorder: the Pittsburgh Bipolar Offspring study. Arch Gen Psychiatry. 2009;66:287–96. https://doi.org/10.1001/archgenpsychiatry.2008.546

    Article  PubMed  PubMed Central  Google Scholar 

  25. Goldstein BI, Shamseddeen W, Axelson DA, Kalas C, Monk K, Brent DA, et al. Clinical, demographic, and familial correlates of bipolar spectrum disorders among offspring of parents with bipolar disorder. J Am Acad Child Adolesc Psychiatry. 2010;49:388–96.

    PubMed  PubMed Central  Google Scholar 

  26. Birmaher B, Axelson D, Monk K, Kalas C, Goldstein B, Hickey MB, et al. Lifetime psychiatric disorders in school-aged offspring of parents with bipolar disorder: the Pittsburgh Bipolar Offspring study. Arch Gen Psychiatry. 2009;66:287–96.

    Article  Google Scholar 

  27. Smoller JW, Finn CT. Family, twin, and adoption studies of bipolar disorder. Am J Med Genet Part C Semin Med Genet. 2003;123C:48–58. https://doi.org/10.1002/ajmg.c.20013

    Article  PubMed  Google Scholar 

  28. Bebko G, Bertocci MA, Fournier JC, Hinze AK, Bonar L, Almeida JR, et al. Parsing dimensional vs diagnostic category–related patterns of reward circuitry function in behaviorally and emotionally dysregulated youth in the longitudinal assessment of manic symptoms study. JAMA Psychiatry. 2014;71:71–80.

    Article  Google Scholar 

  29. Perlman SB, Fournier JC, Bebko G, Bertocci MA, Hinze AK, Bonar L, et al. Emotional face processing in pediatric bipolar disorder: evidence for functional impairments in the fusiform gyrus. J Am Acad Child Adolesc Psychiatry. 2013;52:1314–25.e3

    Article  Google Scholar 

  30. Gerson AC, Gerring JP, Freund L, Joshi PT, Capozzoli J, Brady K, et al. The Children’s Affective Lability Scale: a psychometric evaluation of reliability. Psychiatry Res. 1996;65:189–98. https://doi.org/10.1016/S0165-1781(96)02851-X

    Article  CAS  PubMed  Google Scholar 

  31. Birmaher B, Brent DA, Chiappetta L, Bridge J, Monga S, Baugher M. Psychometric properties of the Screen for Child Anxiety Related Emotional Disorders (SCARED): a replication study. J Am Acad Child Adolesc Psychiatry. 1999;38:1230–6. https://doi.org/10.1097/00004583-199910000-00011

    Article  CAS  PubMed  Google Scholar 

  32. Angold A, Costello EJ, Messer SC, Pickles A. Development of a short questionnaire for use in epidemiological studies of depression in children and adolescents. International Journal of Methods in Psychiatric Research. 1995;5:237–249.

  33. Kaufman J, Birmaher B, Brent DA, Rao U, Flynn C, Moreci P, et al. Schedule for Affective Disorders and Schizophrenia for School-age Children-present and Lifetime Version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry. 1997;36:980–8.

    Article  CAS  Google Scholar 

  34. Axelson DA, Birmaher B, Brent DA, Wassick S, Hoover C, Bridge J, et al. A preliminary study of the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children mania rating scale for children and adolescents. J Child Adolesc Psychopharmacol. 2003;13:463–70.

    Article  Google Scholar 

  35. Friedman JH, Hastie T, Tibshirani R. glmnet: lasso and elastic-net regularized generalized linear models, 2014. http://CRANR-projectorg/package=glmnetRpackageversion2.0.2..

  36. Tibshirani R. Regression shrinkage and selection via the lasso. J Roy Stat Soc Ser B (Methodol). 1996;58:267–88. https://doi.org/10.2307/2346178

    Article  Google Scholar 

  37. Friedman J, Hastie T, Tibshirani R. Regularization paths for generalized linear models via coordinate descent. J Stat Softw. 2010;33:1–22.

    Article  Google Scholar 

  38. Ferro A, Bonivento C, Delvecchio G, Bellani M, Perlini C, Dusi N, et al. Longitudinal investigation of the parietal lobe anatomy in bipolar disorder and its association with general functioning. Psychiatry Res: Neuroimaging. 2017;267:22–31. https://doi.org/10.1016/j.pscychresns.2017.06.010

    Article  PubMed  Google Scholar 

  39. Jaworska N, MacMaster FP, Gaxiola I, Cortese F, Goodyear B, Ramasubbu R. A preliminary study of the influence of age of onset and childhood trauma on cortical thickness in major depressive disorder. BioMed Res. Int. 2014;2014:410472.

    Article  Google Scholar 

  40. Hatton SN, Lagopoulos J, Hermens DF, Scott E, Hickie IB, Bennett MR. Cortical thinning in young psychosis and bipolar patients correlate with common neurocognitive deficits. Int J Bipolar Disord. 2013;1:3.

    Article  Google Scholar 

  41. Hanford LC, Sassi RB, Minuzzi L, Hall GB. Cortical thickness in symptomatic and asymptomatic bipolar offspring. Psychiatry Res. 2016;251:26–33. https://doi.org/10.1016/j.pscychresns.2016.04.007

    Article  Google Scholar 

  42. Peterson BS, Warner V, Bansal R, Zhu H, Hao X, Liu J, et al. Cortical thinning in persons at increased familial risk for major depression. Proc Natl Acad Sci USA. 2009;106:6273–8. https://doi.org/10.1073/pnas.0805311106

    Article  PubMed  Google Scholar 

  43. Hartwigsen G, Baumgaertner A, Price CJ, Koehnke M, Ulmer S, Siebner HR. Phonological decisions require both the left and right supramarginal gyri. Proc Natl Acad Sci. 2010;107:16494–9.

    Article  CAS  Google Scholar 

  44. Blakemore S-J, Choudhury S. Development of the adolescent brain: implications for executive function and social cognition. J Child Psychol Psychiatry. 2006;47:296–312. https://doi.org/10.1111/j.1469-7610.2006.01611.x

    Article  PubMed  Google Scholar 

  45. Bush GCingulate. Frontal, and parietal cortical dysfunction in attention-deficit/hyperactivity disorder. Biol Psychiatry. 2011;69:1160–7. https://doi.org/10.1016/j.biopsych.2011.01.022

    Article  PubMed  PubMed Central  Google Scholar 

  46. Maller JJ, Thaveenthiran P, Thomson RH, McQueen S, Fitzgerald PB. Volumetric, cortical thickness and white matter integrity alterations in bipolar disorder type I and II. J Affect Disord. 2014;169:118–27.

    Article  Google Scholar 

  47. Hanford LC, Nazarov A, Hall GB, Sassi RB. Cortical thickness in bipolar disorder: a systematic review. Bipolar Disord. 2016;18:4–18. https://doi.org/10.1111/bdi.12362

    Article  PubMed  Google Scholar 

  48. Papmeyer M, Giles S, Sussmann JE, Kielty S, Stewart T, Lawrie SM, et al. Cortical thickness in individuals at high familial risk of mood disorders as they develop major depressive disorder. Biol Psychiatry. 2015;78:58–66. https://doi.org/10.1016/j.biopsych.2014.10.018

    Article  PubMed  Google Scholar 

  49. Chase HW, Nusslock R, Almeida JR, Forbes EE, LaBarbara EJ, Phillips ML. Dissociable patterns of abnormal frontal cortical activation during anticipation of an uncertain reward or loss in bipolar versus major depression. Bipolar Disord. 2013;15:839–54. https://doi.org/10.1111/bdi.12132

    Article  PubMed  PubMed Central  Google Scholar 

  50. Nusslock R, Almeida JR, Forbes EE, Versace A, Frank E, Labarbara EJ, et al. Waiting to win: elevated striatal and orbitofrontal cortical activity during reward anticipation in euthymic bipolar disorder adults. Bipolar Disord. 2012;14:249–60. https://doi.org/10.1111/j.1399-5618.2012.01012.x

    Article  PubMed  Google Scholar 

  51. Phillips ML, Drevets WC, Rauch SL, Lane R. Neurobiology of emotion perception II: implications for major psychiatric disorders. Biol Psychiatry. 2003;54:515–28.

    Article  Google Scholar 

  52. Lauter JL, Herscovitch P, Formby C, Raichle ME. Tonotopic organization in human auditory cortex revealed by positron emission tomography. Hear Res. 1985;20:199–205.

    Article  CAS  Google Scholar 

  53. Wicker B, Perrett DI, Baron-Cohen S, Decety J. Being the target of another’s emotion: a PET study. Neuropsychologia. 2003;41:139–46.

    Article  Google Scholar 

  54. Howard MA, Volkov I, Mirsky R, Garell P, Noh M, Granner M, et al. Auditory cortex on the human posterior superior temporal gyrus. J Comp Neurol. 2000;416:79–92.

    Article  CAS  Google Scholar 

  55. Macdonald H, Rutter M, Howlin P, Rios P, Conteur AL, Evered C, et al. Recognition and expression of emotional cues by autistic and normal adults. J Child Psychol Psychiatry. 1989;30:865–77. https://doi.org/10.1111/j.1469-7610.1989.tb00288.x

    Article  CAS  PubMed  Google Scholar 

  56. Persad SM, Polivy J. Differences between depressed and nondepressed individuals in the recognition of and response to facial emotional cues. J Abnorm Psychol. 1993;102:358.

    Article  CAS  Google Scholar 

  57. Mandal MK, Pandey R, Prasad AB. Facial expressions of emotions and schizophrenia: a review. Schizophr Bull. 1998;24:399.

    Article  CAS  Google Scholar 

  58. McClure EB, Pope K, Hoberman AJ, Pine DS, Leibenluft E. Facial expression recognition in adolescents with mood and anxiety disorders. Am J Psychiatry. 2003;160:1172–4.

    Article  Google Scholar 

  59. McCarthy G, Puce A, Gore JC, Allison T. Face-specific processing in the human fusiform gyrus. J Cogn Neurosci. 1997;9:605–10.

    Article  CAS  Google Scholar 

  60. Haxby JV, Hoffman EA, Gobbini MI. Human neural systems for face recognition and social communication. Biol Psychiatry. 2002;51:59–67. https://doi.org/10.1016/S0006-3223(01)01330-0

    Article  PubMed  Google Scholar 

  61. Hoffman EA, Haxby JV. Distinct representations of eye gaze and identity in the distributed human neural system for face perception. Nat Neurosci. 2000;3:80.

    Article  CAS  Google Scholar 

  62. Karim HT, Perlman SB. Neurodevelopmental maturation as a function of irritable temperament. Hum Brain Mapp. 2017;38:5307–21. https://doi.org/10.1002/hbm.23742

    Article  PubMed  PubMed Central  Google Scholar 

  63. Eichenbaum H, Yonelinas AR, Ranganath C. The medial temporal lobe and recognition memory. Annu Rev Neurosci. 2007;30:123–52. https://doi.org/10.1146/annurev.neuro.30.051606.094328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Navarro Schröder T, Haak KV, Zaragoza Jimenez NI, Beckmann CF, Doeller CF. Functional topography of the human entorhinal cortex. eLife. 2015;4:e06738 https://doi.org/10.7554/eLife.06738

    Article  PubMed Central  Google Scholar 

  65. Schultz H, Sommer T, Peters J. The role of the human entorhinal cortex in a representational account of memory. Front Human Neurosci 2015;9 https://doi.org/10.3389/fnhum.2015.00628.

  66. Cavada C, Goldman‐Rakic PS. Posterior parietal cortex in rhesus monkey: I. Parcellation of areas based on distinctive limbic and sensory corticocortical connections. J Comp Neurol. 1989;287:393–421.

    Article  CAS  Google Scholar 

  67. Cavada C, Goldman‐Rakic PS. Posterior parietal cortex in rhesus monkey: II. Evidence for segregated corticocortical networks linking sensory and limbic areas with the frontal lobe. J Comp Neurol. 1989;287:422–45.

    Article  CAS  Google Scholar 

  68. Ludlow L, Klein K. Suppressor variables: the difference between ‘is’ versus ‘acting as’. J Stat Educ. 2014;22:1–28.

    Article  Google Scholar 

  69. Stringaris A, Cohen P, Pine DS, Leibenluft E. Adult outcomes of youth irritability: a 20-year prospective community-based study. Am J Psychiatry. 2009;166:1048–54. https://doi.org/10.1176/appi.ajp.2009.08121849

    Article  PubMed  PubMed Central  Google Scholar 

  70. Strakowski SM, Adler CM, Cerullo M, Eliassen JC, Lamy M, Fleck DE, et al. Magnetic resonance imaging brain activation in first-episode bipolar mania during a response inhibition task. Early Interv Psychiatry. 2008;2:225–33. https://doi.org/10.1111/j.1751-7893.2008.00082.x

    Article  PubMed  PubMed Central  Google Scholar 

  71. Singh MK, Chang KD, Mazaika P, Garrett A, Adleman N, Kelley R, et al. Neural correlates of response inhibition in pediatric bipolar disorder. J Child Adolesc Psychopharmacol. 2010;20:15–24. https://doi.org/10.1089/cap.2009.0004

    Article  PubMed  PubMed Central  Google Scholar 

  72. Sepede G, De Berardis D, Campanella D, Perrucci MG, Ferretti A, Salerno RM, et al. Neural correlates of negative emotion processing in bipolar disorder. Progress Neuro-Psychopharmacol Biol Psychiatry. 2015;60:1–10.

    Article  Google Scholar 

  73. Bertocci MA, Bebko G, Dwojak A, Iyengar S, Ladouceur CD, Fournier JC, et al. Longitudinal relationships among activity in attention redirection neural circuitry and symptom severity in youth. Biol Psychiatry Cogn Neurosci neuroimaging. 2017;2:336–45. https://doi.org/10.1016/j.bpsc.2016.06.009

    Article  PubMed  PubMed Central  Google Scholar 

  74. Koolschijn PC, van Haren N, Lensvelt‐Mulders G, Hulshoff PH, Kahn R. Brain volume abnormalities in major depressive disorder: a meta‐analysis of magnetic resonance imaging studies. Hum Brain Mapp. 2009;30:3719–35. https://doi.org/10.1002/hbm.20801

    Article  PubMed  Google Scholar 

  75. Peterson BS, Warner V, Bansal R, Zhu H, Hao X, Liu J, et al. Cortical thinning in persons at increased familial risk for major depression. Proc Natl Acad Sci USA. 2009;106:6273–8.

    Article  CAS  Google Scholar 

  76. Peterson BS, Weissman MM. A brain-based endophenotype for major depressive disorder. Annu Rev Med. 2011;62:461–74.

    Article  CAS  Google Scholar 

  77. Forbes E, Brown S, Kimak M, Ferrell R, Manuck S, Hariri A. Genetic variation in components of dopamine neurotransmission impacts ventral striatal reactivity associated with impulsivity. Mol Psychiatry. 2009;14:60.

    Article  CAS  Google Scholar 

Download references

Funding

BIOS is supported by the National Institute of Mental Health grant R01 MH060952-16 (Birmaher and Phillips, University of Pittsburgh). LAMS was supported by the National Institute of Mental Health grants: 2R01 MH73953-09A1 (Birmaher and Phillips, University of Pittsburgh), 2R01 MH73816-09A1 (Holland, Children’s Hospital Medical Center), 2R01 MH73967-09A1 (Findling, Case Western Reserve University), and 2R01 MH73801-09A1 (Fristad, Ohio State University), and the Pittsburgh Foundation (Phillips).

Author information

Author notes

  1. These authors contributed equally: Michele A. Bertocci, Lindsay Hanford.

Authors and Affiliations

  1. Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA

    Michele A. Bertocci, Lindsay Hanford, Anna Manelis, Mary Kay Gill, Kelly Monk, Amelia Versace, Lisa Bonar, Genna Bebko, Cecile D. Ladouceur, Susan B Perlman, Rasim Diler, Danella Hafeman, Michael J. Travis, Boris Birmaher & Mary L. Phillips

  2. Department of Statistics, University of Pittsburgh, Pittsburgh, PA, USA

    Satish Iyengar

  3. Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Eric A. Youngstrom

  4. Department of Child and Adolescent Psychiatry, New York University School of Medicine, New York, NY, USA

    Sarah M. Horwitz

  5. Department of Psychiatry, Ohio State University, Columbus, OH, USA

    L. Eugene Arnold & Mary. A. Fristad

  6. Nationwide Children’s Hospital Columbus Ohio, Columbus, OH, USA

    Robert Kowatch

  7. Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA

    Scott K. Holland

  8. Department of Psychiatry, Johns Hopkins University, Baltimore, MD, USA

    Robert L. Findling

Authors
  1. Michele A. Bertocci
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lindsay Hanford
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anna Manelis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Satish Iyengar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eric A. Youngstrom
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mary Kay Gill
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kelly Monk
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Amelia Versace
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lisa Bonar
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Genna Bebko
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Cecile D. Ladouceur
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Susan B Perlman
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Rasim Diler
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Sarah M. Horwitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. L. Eugene Arnold
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Danella Hafeman
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Michael J. Travis
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Robert Kowatch
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Scott K. Holland
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Mary. A. Fristad
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Robert L. Findling
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Boris Birmaher
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Mary L. Phillips
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michele A. Bertocci.

Ethics declarations

Conflict of interest

BB has or will receive royalties from for publications from Random House, Inc (New hope for children and teens with bipolar disorder) and Lippincott Williams & Wilkins (Treating Child and Adolescent Depression). He is employed by the University of Pittsburgh and the University of Pittsburgh Medical Center and receives research funding from NIMH. MLP is a consultant for Roche Pharmaceuticals. LEA has received research funding from Curemark, Forest, Lilly, Neuropharm, Novartis, Noven, Shire, Supernus, and YoungLiving (as well as NIH and Autism Speaks) and has consulted with or been on advisory boards for Arbor, Gowlings, Ironshore, Neuropharm, Novartis, Noven, Organon, Otsuka, Pfizer, Roche, Seaside Therapeutics, Sigma Tau, Shire, Tris Pharma, and Waypoint and received travel support from Noven. RLF receives or has received research support, acted as a consultant and/or served on a speaker’s bureau for Aevi, Akili, Alcobra, Amerex, American Academy of Child & Adolescent Psychiatry, American Psychiatric Press, Bracket, Epharma Solutions, Forest, Genentech, Guilford Press, Ironshore, Johns Hopkins University Press, KemPharm, Lundbeck, Merck, NIH, Neurim, Nuvelution, Otsuka, PCORI, Pfizer, Physicians Postgraduate Press, Purdue, Roche, Sage, Shire, Sunovion, Supernus Pharmaceuticals, Syneurx, Teva, Tris, TouchPoint, Validus, and WebMD. MAF receives royalties from Guilford Press, American Psychiatric Press, and CFPSI. RK is a consultant for Forest Pharmaceutical and the REACH Foundation. He is employed by the Ohio State Wexner Medical Center. EAY has consulted with Pearson, Western Psychological Services, Lundbeck and Otsuka about assessment, as well as having grant support from the NIH. All the remaining authors declare that they have no conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bertocci, M.A., Hanford, L., Manelis, A. et al. Clinical, cortical thickness and neural activity predictors of future affective lability in youth at risk for bipolar disorder: initial discovery and independent sample replication. Mol Psychiatry 24, 1856–1867 (2019). https://doi.org/10.1038/s41380-018-0273-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41380-018-0273-4

This article is cited by

Search

Advanced search

Quick links