Hostname: page-component-8448b6f56d-qsmjn Total loading time: 0 Render date: 2024-04-23T23:22:01.961Z Has data issue: false hasContentIssue false
  • English
  • Français

Behavioral and emotional dysregulation trajectories marked by prefrontal–amygdala function in symptomatic youth

Published online by Cambridge University Press:  27 January 2014

M. A. Bertocci ,
G. Bebko ,
T. Olino ,
J. Fournier ,
A. K. Hinze ,
L. Bonar ,
J. R. C. Almeida ,
S. B. Perlman ,
A. Versace  and
M. Travis
...Show all authors
M. A. Bertocci*
Affiliation:
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA
G. Bebko
Affiliation:
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA
T. Olino
Affiliation:
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA
J. Fournier
Affiliation:
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA
A. K. Hinze
Affiliation:
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA
L. Bonar
Affiliation:
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA
J. R. C. Almeida
Affiliation:
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA Alpert Medical School, Brown University, Providence, RI, USA
S. B. Perlman
Affiliation:
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA
A. Versace
Affiliation:
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA
M. Travis
Affiliation:
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA
M. K. Gill
Affiliation:
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA
C. Demeter
Affiliation:
University Hospitals Case Medical Center/Case Western Reserve University, Cleveland, OH, USA
V. A. Diwadkar
Affiliation:
Department of Psychiatry and Behavioral Neuroscience, Wayne State University, Detroit, MI, USA
R. White
Affiliation:
Department of Psychiatry and Behavioral Neuroscience, Wayne State University, Detroit, MI, USA
C. Schirda
Affiliation:
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA
J. L. Sunshine
Affiliation:
University Hospitals Case Medical Center/Case Western Reserve University, Cleveland, OH, USA
L. E. Arnold
Affiliation:
Department of Psychiatry, Ohio State University, Columbus, OH, USA
S. K. Holland
Affiliation:
Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA
R. A. Kowatch
Affiliation:
The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA
B. Birmaher
Affiliation:
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA
D. Axelson
Affiliation:
Department of Psychiatry, Ohio State University, Columbus, OH, USA
E. A. Youngstrom
Affiliation:
Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
R. L. Findling
Affiliation:
University Hospitals Case Medical Center/Case Western Reserve University, Cleveland, OH, USA Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA
S. M. Horwitz
Affiliation:
Department of Child Psychiatry, New York University School of Medicine, New York, NY, USA
M. A. Fristad
Affiliation:
Department of Psychiatry, Ohio State University, Columbus, OH, USA
M. L. Phillips
Affiliation:
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA
*
*Address for correspondence: M. A. Bertocci, Ph.D., Department of Psychiatry, University of Pittsburgh School of Medicine, 3811 O'Hara Street, Loeffler Building, Room 203, Pittsburgh, PA 15213, USA. (Email: bertoccima@upmc.edu)
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Neuroimaging measures of behavioral and emotional dysregulation can yield biomarkers denoting developmental trajectories of psychiatric pathology in youth. We aimed to identify functional abnormalities in emotion regulation (ER) neural circuitry associated with different behavioral and emotional dysregulation trajectories using latent class growth analysis (LCGA) and neuroimaging.

Method

A total of 61 youth (9–17 years) from the Longitudinal Assessment of Manic Symptoms study, and 24 healthy control youth, completed an emotional face n-back ER task during scanning. LCGA was performed on 12 biannual reports completed over 5 years of the Parent General Behavior Inventory 10-Item Mania Scale (PGBI-10M), a parental report of the child's difficulty regulating positive mood and energy.

Results

There were two latent classes of PGBI-10M trajectories: high and decreasing (HighD; n = 22) and low and decreasing (LowD; n = 39) course of behavioral and emotional dysregulation over the 12 time points. Task performance was >89% in all youth, but more accurate in healthy controls and LowD versus HighD (p < 0.001). During ER, LowD had greater activity than HighD and healthy controls in the dorsolateral prefrontal cortex, a key ER region, and greater functional connectivity than HighD between the amygdala and ventrolateral prefrontal cortex (p's < 0.001, corrected).

Conclusions

Patterns of function in lateral prefrontal cortical–amygdala circuitry in youth denote the severity of the developmental trajectory of behavioral and emotional dysregulation over time, and may be biological targets to guide differential treatment and novel treatment development for different levels of behavioral and emotional dysregulation in youth.

Keywords

Behavioral and emotional dysregulationemotion regulationemotional n-backfunctional magnetic resonance imaginglatent class growth analysisyouth
Type
Original Articles
Information
Psychological Medicine , Volume 44 , Issue 12 , September 2014 , pp. 2603 - 2615
Copyright
Copyright © Cambridge University Press 2014 

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

Axelson, DA, Birmaher, B, Brent, DA, Wassick, S, Hoover, C, Bridge, J, Ryan, ND (2003). A preliminary study of the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children mania rating scale for children and adolescents. Journal of Child and Adolescent Psychopharmacology 13, 463–470.Google Scholar
Bebko, G, Bertocci, MA, Fournier, JC, Hinze, AK, Bonar, L, Almeida, JR, Perlman, SB, Versace, A, Schirda, C, Travis, M, Gill, MK, Demeter, C, Diwadkar, VA, Ciuffetelli, G, Rodriguez, E, Olino, T, Forbes, E, Sunshine, JL, Holland, SK, Kowatch, RA, Birmaher, B, Axelson, D, Horwitz, SM, Arnold, LE, Fristad, MA, Youngstrom, EA, Findling, RL, Phillips, ML (2013). 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. Published online 27 November 2013 . doi:10.1001/jamapsychiatry.2013.2870.Google Scholar
Birmaher, B, Brent, DA, Chiappetta, L, Bridge, J, Monga, S, Baugher, M (1999). Psychometric properties of the Screen for Child Anxiety Related Emotional Disorders (SCARED): a replication study. Journal of the American Academy of Child and Adolescent Psychiatry 38, 1230–1236.CrossRefGoogle ScholarPubMed
Brotman, M, Schmajuk, M, Rich, B, Dickstein, D, Guyer, A, Costello, E, Egger, H, Angold, A, Pine, D, Leibenluft, E (2006). Prevalence, clinical correlates, and longitudinal course of severe mood dysregulation in children. Biological Psychiatry 60, 991–997.Google Scholar
Charney, DS, Babich, KS (2002). Foundation for the NIMH strategic plan for mood disorders research. Biological Psychiatry 52, 455–456.CrossRefGoogle ScholarPubMed
Cusi, A, Nazarov, A, Holshausen, K, Macqueen, G, McKinnon, M (2012). Systematic review of the neural basis of social cognition in patients with mood disorders. Journal of Psychiatry Neuroscience 37, 154–169.Google Scholar
Desmond, J, Glover, G (2002). Estimating sample size in functional MRI (fMRI) neuroimaging studies: statistical power analyses. Journal of Neuroscience Methods 118, 115–128.Google Scholar
Eklund, A, Andersson, M, Josephson, C, Johannesson, M, Knutsson, H (2012). Does parametric fMRI analysis with SPM yield valid results? An empirical study of 1484 rest datasets. NeuroImage 61, 565–578.CrossRefGoogle ScholarPubMed
Findling, RL, Jo, B, Frazier, TW, Youngstrom, EA, Demeter, CA, Fristad, MA, Birmaher, B, Kowatch, RA, Arnold, E, Axelson, DA, Ryan, N, Hauser, JC, Brace, DJ, Marsh, LE, Gill, MK, Depew, J, Rowles, BM, Horwitz, SM (2013). The 24-month course of manic symptoms in children. Bipolar Disorders 15, 669–679.Google Scholar
Findling, RL, Youngstrom, EA, Fristad, M, Birmaher, B, Kowatch, R, Arnold, LE, Frazier, TW, Axelson, DA, Ryan, ND, Demeter, C, Gill, MK, Fields, B, Depew, J, Kennedy, S, Marsh, L, Rowles, B, Horwitz, SM (2010). Characteristics of children with elevated symptoms of mania: the Longitudinal Assessment of Manic Symptoms (LAMS) study. Journal of Clinical Psychiatry 71, 1664–1672.Google Scholar
Frazier, TW, Youngstrom, EA, Horwitz, SM, Demeter, C, Fristad, M, Arnold, LE, Birmaher, B, Kowatch, R, Axelson, DA, Ryan, ND, Gill, MK, Findling, RL (2011). Relationship of persistent manic symptoms to the diagnosis of pediatric bipolar spectrum disorders. Journal of Clinical Psychiatry 72, 846–853.Google Scholar
Friedman, L, Glover, G (2006). Report on a multicenter fMRI quality assurance protocol. Journal of Magnetic Resonance Imaging 23, 827–839.Google Scholar
Friedman, L, Glover, G; fBIRN Consortium (2006). Reducing interscanner variability of activation in a multicenter fMRI study: controlling for signal-to-fluctuation-noise-ratio (SFNR) differences. NeuroImage 33, 471–481.CrossRefGoogle Scholar
Gee, D, Karlsgodt, K, van Erp, T, Bearden, C, Lieberman, M, Belger, A, Perkins, D, Olvet, D, Cornblatt, B, Constable, T, Woods, S, Addington, J, Cadenhead, K, McGlashan, T, Seidman, L, Tsuang, M, Walker, E, Cannon, T (2012). Altered age-related trajectories of amygdala–prefrontal circuitry in adolescents at clinical high risk for psychosis: a preliminary study. Schizophrenia Research 134, 1–9.CrossRefGoogle ScholarPubMed
Halari, R, Simic, M, Pariante, C, Papadopoulos, A, Cleare, A, Brammer, M, Fombonne, E, Rubia, K (2009). Reduced activation in lateral prefrontal cortex and anterior cingulate during attention and cognitive control functions in medication-naive adolescents with depression compared to controls. Journal of Child Psychology and Psychiatry 50, 307–316.Google Scholar
Hasler, G, Drevets, WC, Gould, TD, Gottesman, II, Manji, HK (2006). Toward constructing an endophenotype strategy for bipolar disorders. Biological Psychiatry 60, 93–105.Google Scholar
Haxby, J, Ungerleider, L, Horwitz, B, Rapoport, S, Grady, C (1995). Hemispheric differences in neural systems for face working memory: a PET-rCBF study. Human Brain Mapping 3, 68–82.Google Scholar
Horwitz, SM, Demeter, C, Pagano, M, Youngstrom, EA, Fristad, M, Arnold, LE, Birmaher, B, Gill, MK, Axelson, DA, Kowatch, R, Frazier, T, Findling, RL (2010). Longitudinal Assessment of Manic Symptoms (LAMS) study: background, design, and initial screening results. Journal of Clinical Psychiatry 71, 1511–1517.Google Scholar
Hulvershorn, L, Cullen, K, Anand, A (2011). Toward dysfunctional connectivity: a review of neuroimaging findings in pediatric major depressive disorder. Brain Imaging Behavior 5, 307–328.CrossRefGoogle ScholarPubMed
Insel, T, Cuthbert, B, Garvey, M, Heinssen, R, Pine, D, Quinn, K, Sanislow, C, Wang, P (2010). Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. American Journal of Psychiatry 167, 748–751.Google Scholar
Kaufman, J, Birmaher, B, Brent, DA, Rao, U, Flynn, C, Moreci, P, Williamson, D, Ryan, ND (1997). Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. Journal of the American Academy of Child and Adolescent Psychiatry 36, 980–988.CrossRefGoogle ScholarPubMed
Ladouceur, C, Silk, JS, Dahl, RE, Ostapenko, L, Kronhaus, DM, Phillips, ML (2009 a). Fearful faces influence attentional control processes in anxious youth and adults. Emotion 9, 855–864.Google Scholar
Ladouceur, CD, Farchione, T, Diwadkar, V, Pruitt, P, Radwan, J, Axelson, D, Birmaher, B, Phillips, ML (2011). Differential patterns of abnormal activity and connectivity in the amygdala–prefrontal circuitry in bipolar-I and bipolar-NOS youth. Journal of the American Academy of Child and Adolescent Psychiatry 50, 1275–1289.CrossRefGoogle ScholarPubMed
Ladouceur, CD, Silk, JS, Dahl, RE, Ostapenko, L, Kronhaus, D, Phillips, ML (2009 b). Fearful faces influence attentional control processes in anxious youth and adults. Emotion 9, 855–864.Google Scholar
Lewinsohn, P, Klein, D, Seeley, J (2000). Bipolar disorder during adolescence and young adulthood in a community sample. Bipolar Disorders 2, 281–293.CrossRefGoogle Scholar
Magnotta, V, Friedman, L (2006). Measurement of signal-to-noise and contrast-to-noise in the fBIRN multicenter imaging study. Journal of Digital Imaging 19, 140–147.CrossRefGoogle ScholarPubMed
Maldjian, JA, Laurienti, PJ, Kraft, RA, Burdette, JH (2003). An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. Neuroimage 19, 1233–1239.Google Scholar
Morgan, J, Olino, TM, McMakin, D, Ryan, ND, Forbes, EE (2013). Neural response to reward as a predictor of increases in depressive symptoms in adolescence. Neurobiological Disorders 52, 66–74.Google Scholar
Muthén, LK, Muthén, BO (1998–2011). Mplus User's Guide, sixth edn. Muthén & Muthén: Los Angeles, CA.Google Scholar
Nylund, KL, Asparouhov, T, Muthén, BO (2007). Deciding on the number of classes in latent class analysis and growth mixture modeling: a Monte Carlo simulation study. Structural Equation Modeling 14, 535–569.CrossRefGoogle Scholar
Ochsner, KN, Gross, JJ (2005). The cognitive control of emotion. Trends in Cognitive Sciences 9, 242–249.Google Scholar
Passarotti, A, Ellis, J, Wegbreit, E, Stevens, M, Pavuluri, M (2012). Reduced functional connectivity of prefrontal regions and amygdala within affect and working memory networks in pediatric bipolar disorder. Brain Connectivity 2, 320–334.Google Scholar
Passarotti, A, Sweeney, J, Pavuluri, M (2010 a). Emotion processing influences working memory circuits in pediatric bipolar disorder and attention-deficit/hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry 49, 1064–1080.CrossRefGoogle ScholarPubMed
Passarotti, A, Sweeney, J, Pavuluri, M (2010 b). Neural correlates of response inhibition in pediatric bipolar disorder and attention deficit hyperactivity disorder. Psychiatry Research: Neuroimaging 181, 36–43.CrossRefGoogle ScholarPubMed
Pavuluri, M, O'Connor, M, Harral, E, Sweeney, J (2008). An fMRI study of the interface between affective and cognitive neural circuitry in pediatric bipolar disorder. Psychiatry Research: Neuroimaging 162, 244–255.Google Scholar
Perlman, G, Simmons, A, Wu, J, Hahn, K, Tapert, S, Max, J, Paulus, M, Brown, G, Frank, G, Campbell-Sills, L, Yang, T (2012). Amygdala response and functional connectivity during emotion regulation: a study of 14 depressed adolescents. Journal of Affective Disorders 139, 75–84.Google Scholar
Phillips, M, Ladouceur, C, Drevets, W (2008). A neural model of voluntary and automatic emotion regulation: implications for understanding the pathophysiology and neurodevelopment of bipolar disorder. Molecular Psychiatry 13, 833–857.Google Scholar
Phillips, ML, Frank, E (2006). Redefining bipolar disorder: toward DSM5. American Journal of Psychiatry 163, 1135–1136.Google Scholar
Rich, B, Carver, F, Holroyd, T, Rosen, H, Mendoza, J, Cornwell, B, Fox, N, Pine, D, Coppola, R, Leibenluft, E (2011). Different neural pathways to negative affect in youth with pediatric bipolar disorder and severe mood dysregulation. Journal of Psychiatry Research 45, 1283–1294.Google Scholar
Rich, B, Fromm, S, Berghorst, L, Dickstein, D, Brotman, M, Pine, D, Leibenluft, E (2008). Neural connectivity in children with bipolar disorder: impairment in the face emotion processing circuit. Journal of Child Psychology and Psychiatry 49, 88–96.CrossRefGoogle ScholarPubMed
Rygula, R, Walker, S, Clarke, H, Robbins, T, Roberts, A (2010). Differential contributions of the primate ventrolateral prefrontal and orbitofrontal cortex to serial reversal learning. Journal of Neuroscience 30, 14552–14559.CrossRefGoogle ScholarPubMed
Segall, J, Turner, J, van Erp, T, White, T, Bockholt, H, Gollub, R, Ho, B, Magnotta, V, Jung, R, McCarley, R, Schulz, S, Lauriello, J, Clark, V, Voyvodic, J, Diaz, M, Calhoun, V (2009). Voxel-based morphometric multisite collaborative study on schizophrenia. Schizophrenia Bulletin 35, 82–95.CrossRefGoogle Scholar
Stringaris, A, Goodman, R (2009). Mood lability and psychopathology in youth. Psychological Medicine 39, 1237–1245.CrossRefGoogle ScholarPubMed
Youngstrom, EA, Frazier, T, Demeter, C, Calabrese, J, Findling, RL (2008). Developing a 10-item mania scale from the Parent General Behavior Inventory for children and adolescents. Journal of Clinical Psychiatry 69, 831–839.CrossRefGoogle ScholarPubMed
Youngstrom, EA, Meyers, O, Demeter, C, Youngstrom, J, Morello, L, Piiparinen, R, Feeny, N, Calabrese, J, Findling, RL (2005). Comparing diagnostic checklists for pediatric bipolar disorder in academic and community mental health settings. Bipolar Disorders 7, 507–517.Google Scholar
Supplementary material: File

Bertocci Supplementary Material

Supplementary Material

Download Bertocci Supplementary Material(File)
File 62.4 KB