Hostname: page-component-78c5997874-94fs2 Total loading time: 0 Render date: 2024-11-19T10:39:43.956Z Has data issue: false hasContentIssue false
  • English
  • Français

Altered functioning of reward circuitry in youth offspring of parents with bipolar disorder

Published online by Cambridge University Press:  16 September 2015

A. Manelis ,
C. D. Ladouceur ,
S. Graur ,
K. Monk ,
L. K. Bonar ,
M. B. Hickey ,
A. C. Dwojak ,
D. Axelson ,
B. I. Goldstein  and
T. R. Goldstein
...Show all authors
A. Manelis*
Affiliation:
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA
C. D. Ladouceur
Affiliation:
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA
S. Graur
Affiliation:
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA
K. Monk
Affiliation:
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA
L. K. Bonar
Affiliation:
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA
M. B. Hickey
Affiliation:
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA
A. C. Dwojak
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, Nationwide Children's Hospital and The Ohio State College of Medicine, Columbus, OH, USA
B. I. Goldstein
Affiliation:
Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto, Faculty of Medicine, Toronto, Ontario, Canada
T. R. Goldstein
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
M. A. Bertocci
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
B. Birmaher
Affiliation:
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, 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: A. Manelis, Department of Psychiatry, Western Psychiatric Institute and Clinic, 121 Meyran Avenue, Loeffler Building, Room 205, Pittsburgh, PA 15213, USA. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Background.

Offspring of parents with bipolar disorder (BD) (BO) are at higher risk of BD than offspring of parents with non-BD psychopathology (NBO), although both groups are at higher risk than offspring of psychiatrically healthy parents (HC) for other affective and psychiatric disorders. Abnormal functioning in reward circuitry has been demonstrated previously in individuals with BD. We aimed to determine whether activation and functional connectivity in this circuitry during risky decision-making differentiated BO, NBO and HC.

Method.

BO (n = 29; mean age = 13.8 years; 14 female), NBO (n = 28; mean age = 13.9 years; 12 female) and HC (n = 23; mean age = 13.7 years; 11 female) were scanned while performing a number-guessing reward task. Of the participants, 11 BO and 12 NBO had current non-BD psychopathology; five BO and four NBO were taking psychotropic medications.

Results.

A 3 (group) × 2 (conditions: win-control/loss-control) analysis of variance revealed a main effect of group on right frontal pole activation: BO showed significantly greater activation than HC. There was a significant main effect of group on functional connectivity between the bilateral ventral striatum and the right ventrolateral prefrontal cortex (Z > 3.09, cluster-p < 0.05): BO showed significantly greater negative functional connectivity than other participants. These between-group differences remained after removing youth with psychiatric disorders and psychotropic medications from analyses.

Conclusions.

This is the first study to demonstrate that reward circuitry activation and functional connectivity distinguish BO from NBO and HC. The fact that the pattern of findings remained when comparing healthy BO v. healthy NBO v. HC suggests that these neuroimaging measures may represent trait-level neurobiological markers conferring either risk for, or protection against, BD in youth.

Keywords

Biological markersbipolar disorderdecision-makingfrontal polefunctional magnetic resonance imaging
Type
Original Articles
Information
Psychological Medicine , Volume 46 , Issue 1 , January 2016 , pp. 197 - 208
Copyright
Copyright © Cambridge University Press 2015 

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

Alloy, LB, Bender, RE, Whitehouse, WG, Wagner, CA, Liu, RT, Grant, DA, Jager-Hyman, S, Molz, A, Choi, JY, Harmon-Jones, E, Abramson, LY (2012). High Behavioral Approach System (BAS) sensitivity, reward responsiveness, and goal-striving predict first onset of bipolar spectrum disorders: a prospective behavioral high-risk design. Journal of Abnormal Psychology 121, 339–351.CrossRefGoogle ScholarPubMed
Altshuler, L, Bookheimer, S, Townsend, J, Proenza, MA, Sabb, F, Mintz, J, Cohen, MS (2008). Regional brain changes in bipolar I depression: a functional magnetic resonance imaging study. Bipolar Disorders 10, 708–717.CrossRefGoogle ScholarPubMed
Andersson, JLR, Jenkinson, M, Smith, S (2007). Non-linear registration aka spatial normalisation. Technical Report FMRIB Technical Report TR07JA2. FMRIB Centre: Oxford.Google Scholar
Angold, A, Prendergast, M, Cox, A, Harrington, R, Simonoff, E, Rutter, M (1995). The Child and Adolescent Psychiatric Assessment (CAPA). Psychological Medicine 25, 739–753.Google Scholar
Baxter, MG, Murray, EA (2002). The amygdala and reward. Nature Reviews Neuroscience 3, 563–573.Google Scholar
Bebko, G, Bertocci, MA, Fournier, JC, Hinze, AK, Bonar, L, Almeida, JRC, 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 (2014). 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 71, 71–80.CrossRefGoogle ScholarPubMed
Bermpohl, F, Kahnt, T, Dalanay, U, Hgele, C, Sajonz, B, Wegner, T, Stoy, M, Adli, M, Krger, S, Wrase, J, Strhle, A, Bauer, M, Heinz, A (2010). Altered representation of expected value in the orbitofrontal cortex in mania. Human Brain Mapping 31, 958–969.CrossRefGoogle ScholarPubMed
Birmaher, B, Axelson, D, Goldstein, B, Monk, K, Kalas, C, Obreja, M, Hickey, MB, Iyengar, S, Brent, D, Shamseddeen, W, Diler, R, Kupfer, D (2010). Psychiatric disorders in preschool offspring of parents with bipolar disorder: the Pittsburgh Bipolar Offspring Study (BIOS). American Journal of Psychiatry 167, 321–330.CrossRefGoogle ScholarPubMed
Birmaher, B, Axelson, D, Monk, K, Kalas, C, Goldstein, B, Hickey, MB, Obreja, M, Ehmann, M, Iyengar, S, Shamseddeen, W, Kupfer, D, 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
Birmaher, B, Khetarpal, S, Brent, D, Cully, M, Balach, L, Kaufman, J, Neer, SM (1997). The Screen for Child Anxiety Related Emotional Disorders (SCARED): scale construction and psychometric characteristics. Journal of the American Academy of Child and Adolescent Psychiatry 36, 545–553.CrossRefGoogle ScholarPubMed
Boorman, ED, Behrens, TEJ, Woolrich, MW, Rushworth, MFS (2009). How green is the grass on the other side? Frontopolar cortex and the evidence in favor of alternative courses of action. Neuron 62, 733–743.CrossRefGoogle Scholar
Burgess, PW, Gilbert, SJ, Dumontheil, I (2007). Function and localization within rostral prefrontal cortex (area 10). Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 362, 887–899.CrossRefGoogle ScholarPubMed
Burgund, ED, Kang, HC, Kelly, JE, Buckner, RL, Snyder, AZ, Petersen, SE, Schlaggar, BL (2002). The feasibility of a common stereotactic space for children and adults in fMRI studies of development. NeuroImage 17, 184–200.Google Scholar
Cardoso de Almeida, JR, Phillips, ML (2013). Distinguishing between unipolar depression and bipolar depression: current and future clinical and neuroimaging perspectives. Biological Psychiatry 73, 111–118.CrossRefGoogle ScholarPubMed
Caseras, X, Lawrence, NS, Murphy, K, Wise, RG, Phillips, ML (2013). Ventral striatum activity in response to reward: differences between bipolar I and II disorders. American Journal of Psychiatry 170, 533–541.CrossRefGoogle ScholarPubMed
Chase, HW, Nusslock, R, Almeida, JR, Forbes, EE, Labarbara, EJ, Phillips, ML (2013). Dissociable patterns of abnormal frontal cortical activation during anticipation of an uncertain reward or loss in bipolar versus major depression. Bipolar Disorders 15, 839–854.CrossRefGoogle ScholarPubMed
Cremers, HR, Veer, IM, Spinhoven, P, Rombouts, SARB, Roelofs, K (2014). Neural sensitivity to social reward and punishment anticipation in social anxiety disorder. Frontiers in Behavioral Neuroscience 8, 439.Google ScholarPubMed
Croxson, PL, Walton, ME, O'Reilly, JX, Behrens, TEJ, Rushworth, MFS (2009). Effort-based cost–benefit valuation and the human brain. Journal of Neuroscience 29, 4531–4541.CrossRefGoogle ScholarPubMed
Del Arco, A, Mora, F (2009). Neurotransmitters and prefrontal cortex–limbic system interactions: implications for plasticity and psychiatric disorders. Journal of Neural Transmission 116, 941–952.Google Scholar
Elman, I, Lowen, S, Frederick, BB, Chi, W, Becerra, L, Pitman, RK (2009). Functional neuroimaging of reward circuitry responsivity to monetary gains and losses in posttraumatic stress disorder. Biological Psychiatry 66, 1083–1090.CrossRefGoogle ScholarPubMed
Ernst, M, Dickstein, DP, Munson, S, Eshel, N, Pradella, A, Jazbec, S, Pine, DS, Leibenluft, E (2004). Reward-related processes in pediatric bipolar disorder: a pilot study. Journal of Affective Disorders 82 (Suppl. 1), S89–S101.CrossRefGoogle ScholarPubMed
Findling, RL, Youngstrom, EA, Fristad, MA, Birmaher, B, Kowatch, RA, Arnold, LE, Frazier, TW, Axelson, D, Ryan, N, Demeter, CA, Gill, MK, Fields, B, Depew, J, Kennedy, SM, Marsh, L, Rowles, BM, 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.CrossRefGoogle ScholarPubMed
First, M, Spitzer, R, Gibbon, M, Williams, J (2002). Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Non-patient Edition (SCID-I/NP). Biometrics Research, New York State Psychiatric Institute: New York.Google Scholar
FitzGerald, THB, Friston, KJ, Dolan, RJ (2012). Action-specific value signals in reward-related regions of the human brain. Journal of Neuroscience 32, 16417–16423a.CrossRefGoogle ScholarPubMed
Forbes, EE, Brown, SM, Kimak, M, Ferrell, RE, Manuck, SB, Hariri, AR (2009). Genetic variation in components of dopamine neurotransmission impacts ventral striatal reactivity associated with impulsivity. Molecular Psychiatry 14, 60–70.CrossRefGoogle ScholarPubMed
Friston, KJ, Buechel, C, Fink, GR, Morris, J, Rolls, E, Dolan, RJ (1997). Psychophysiological and modulatory interactions in neuroimaging. NeuroImage 6, 218–229.CrossRefGoogle ScholarPubMed
Gerson, AC, Gerring, JP, Freund, L, Joshi, PT, Capozzoli, J, Brady, K, Denckla, MB (1996). The Children's Affective Lability Scale: a psychometric evaluation of reliability. Psychiatry Research 65, 189–198.CrossRefGoogle Scholar
Goldstein, BI, Shamseddeen, W, Axelson, DA, Kalas, C, Monk, K, Brent, DA, Kupfer, DJ, Birmaher, B (2010). Clinical, demographic, and familial correlates of bipolar spectrum disorders among offspring of parents with bipolar disorder. Journal of the American Academy of Child and Adolescent Psychiatry 49, 388–396.Google Scholar
Gorrindo, T, Blair, RJ, Budhani, S, Dickstein, DP, Pine, DS, Leibenluft, E (2005). Deficits on a probabilistic response-reversal task in patients with pediatric bipolar disorder. American Journal of Psychiatry 162, 1975–1977.CrossRefGoogle ScholarPubMed
Greenberg, T, Chase, HW, Almeida, JR, Stiffler, R, Zevallos, CR, Aslam, HA, Deckersbach, T, Weyandt, S, Cooper, C, Toups, M, Carmody, T, Kurian, B, Peltier, S, Adams, P, McInnis, MG, Oquendo, MA, McGrath, PJ, Fava, M, Weissman, M, Parsey, R, Trivedi, MH, Phillips, ML (2015). Moderation of the relationship between reward expectancy and prediction error-related ventral striatal reactivity by anhedonia in unmedicated major depressive disorder: findings from the EMBARC study. American Journal of Psychiatry 172, 881–891.CrossRefGoogle ScholarPubMed
Guyer, AE, Choate, VR, Detloff, A, Benson, B, Nelson, EE, Perez-Edgar, K, Fox, NA, Pine, DS, Ernst, M (2012). Striatal functional alteration during incentive anticipation in pediatric anxiety disorders. American Journal of Psychiatry 169, 205–212.Google Scholar
Haber, SN, Knutson, B (2010). The reward circuit: linking primate anatomy and human imaging. Neuropsychopharmacology 35, 4–26.CrossRefGoogle ScholarPubMed
Hollingshead, AA (1975). Four Factor Index of Social Status. Yale University Department of Sociology: New Haven, CT.Google Scholar
Horwitz, SM, Demeter, CA, Pagano, ME, Youngstrom, EA, Fristad, MA, Arnold, LE, Birmaher, B, Gill, MK, Axelson, D, Kowatch, RA, Frazier, TW, Findling, RL (2010). Longitudinal Assessment of Manic Symptoms (LAMS) study: background, design, and initial screening results. Journal of Clinical Psychiatry 71, 1511–1517.CrossRefGoogle ScholarPubMed
Ibanez, A, Cetkovich, M, Petroni, A, Urquina, H, Baez, S, Gonzalez-Gadea, ML, Kamienkowski, JE, Torralva, T, Torrente, F, Strejilevich, S, Teitelbaum, J, Hurtado, E, Guex, R, Melloni, M, Lischinsky, A, Sigman, M, Manes, F (2012). The neural basis of decision-making and reward processing in adults with euthymic bipolar disorder or attention-deficit/hyperactivity disorder (ADHD). PLOS ONE 7, e37306.CrossRefGoogle ScholarPubMed
Jenkinson, M (2003). Fast, automated, N-dimensional phase-unwrapping algorithm. Magnetic Resonance in Medicine 49, 193–197.CrossRefGoogle ScholarPubMed
Jenkinson, M, Bannister, P, Brady, M, Smith, S (2002). Improved optimization for the robust and accurate linear registration and motion correction of brain images. NeuroImage 17, 825–841.CrossRefGoogle ScholarPubMed
Jenkinson, M, Smith, S (2001). A global optimisation method for robust affine registration of brain images. Medical Image Analysis 5, 143–156.CrossRefGoogle ScholarPubMed
Kang, HC, Burgund, ED, Lugar, HM, Petersen, SE, Schlaggar, BL (2003). Comparison of functional activation foci in children and adults using a common stereotactic space. NeuroImage 19, 16–28.CrossRefGoogle ScholarPubMed
Kaufman, J, Birmaher, B, Brent, D, Rao, U, Flynn, C, Moreci, P, Williamson, D, Ryan, N (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
Knutson, B, Adams, CM, Fong, GW, Hommer, D (2001). Anticipation of increasing monetary reward selectively recruits nucleus accumbens. Journal of Neuroscience 21, RC159.CrossRefGoogle ScholarPubMed
Koechlin, E, Hyafil, A (2007). Anterior prefrontal function and the limits of human decision-making. Science 318, 594–598.Google Scholar
Kumar, P, Waiter, G, Ahearn, T, Milders, M, Reid, I, Steele, JD (2008). Abnormal temporal difference reward-learning signals in major depression. Brain 131, 2084–2093.CrossRefGoogle ScholarPubMed
Kurniawan, IT, Seymour, B, Talmi, D, Yoshida, W, Chater, N, Dolan, RJ (2010). Choosing to make an effort: the role of striatum in signaling physical effort of a chosen action. Journal of Neurophysiology 104, 313–321.CrossRefGoogle ScholarPubMed
Mason, L, O'Sullivan, N, Blackburn, M, Bentall, R, El-Deredy, W (2012). I want it now! Neural correlates of hypersensitivity to immediate reward in hypomania. Biological Psychiatry 71, 530–537.Google Scholar
Nusslock, R, Almeida, JR, Forbes, EE, Versace, A, Frank, E, Labarbara, EJ, Klein, CR, Phillips, ML (2012). Waiting to win: elevated striatal and orbitofrontal cortical activity during reward anticipation in euthymic bipolar disorder adults. Bipolar Disorders 14, 249–260.CrossRefGoogle ScholarPubMed
O'Doherty, JP (2004). Reward representations and reward-related learning in the human brain: insights from neuroimaging. Current Opinion in Neurobiology 14, 769–776.Google Scholar
Oldfield, RC (1971). The assessment and analysis of handedness: the Edinburgh Inventory. Neuropsychologia 9, 97–113.Google Scholar
Olsavsky, AK, Brotman, MA, Rutenberg, JG, Muhrer, EJ, Deveney, CM, Fromm, SJ, Towbin, K, Pine, DS, Leibenluft, E (2012). Amygdala hyperactivation during face emotion processing in unaffected youth at risk for bipolar disorder. Journal of the American Academy of Child and Adolescent Psychiatry 51, 294–303.CrossRefGoogle ScholarPubMed
Pagnoni, G, Zink, CF, Montague, PR, Berns, GS (2002). Activity in human ventral striatum locked to errors of reward prediction. Nature Neuroscience 5, 97–98.CrossRefGoogle ScholarPubMed
Phillips, ML, Kupfer, DJ (2013). Bipolar disorder diagnosis: challenges and future directions. Lancet 381, 1663–1671.CrossRefGoogle ScholarPubMed
Phillips, ML, Swartz, HA (2014). A critical appraisal of neuroimaging studies of bipolar disorder: toward a new conceptualization of underlying neural circuitry and a road map for future research. American Journal of Psychiatry 171, 829–843.CrossRefGoogle Scholar
Ramnani, N, Owen, AM (2004). Anterior prefrontal cortex: insights into function from anatomy and neuroimaging. Nature Reviews Neuroscience 5, 184–194.Google Scholar
Rich, BA, Schmajuk, M, Perez-Edgar, KE, Pine, DS, Fox, NA, Leibenluft, E (2005). The impact of reward, punishment, and frustration on attention in pediatric bipolar disorder. Biological Psychiatry 58, 532–539.Google Scholar
Rushworth, MFS, Noonan, MP, Boorman, ED, Walton, ME, Behrens, TE (2011). Frontal cortex and reward-guided learning and decision-making. Neuron 70, 1054–1069.CrossRefGoogle ScholarPubMed
Russo, SJ, Nestler, EJ (2013). The brain reward circuitry in mood disorders. Nature Reviews Neuroscience 14, 609–625.Google Scholar
Schultz, W, Tremblay, L, Hollerman, JR (2000). Reward processing in primate orbitofrontal cortex and basal ganglia. Cerebral Cortex 10, 272–284.CrossRefGoogle ScholarPubMed
Singh, MK, Chang, KD, Kelley, RG, Cui, X, Sherdell, L, Howe, ME, Gotlib, IH, Reiss, AL (2013). Reward processing in adolescents with bipolar I disorder. Journal of the American Academy of Child and Adolescent Psychiatry 52, 68–83.Google Scholar
Singh, MK, Kelley, RG, Howe, ME, Reiss, AL, Gotlib, IH, Chang, KD (2014). Reward processing in healthy offspring of parents with bipolar disorder. JAMA Psychiatry 71, 1148–1156.CrossRefGoogle ScholarPubMed
Smith, SM (2002). Fast robust automated brain extraction. Human Brain Mapping 17, 143–155.Google Scholar
Tachibana, Y, Hikosaka, O (2012). The primate ventral pallidum encodes expected reward value and regulates motor action. Neuron 76, 826–837.CrossRefGoogle ScholarPubMed
Tanaka, SC, Doya, K, Okada, G, Ueda, K, Okamoto, Y, Yamawaki, S (2004). Prediction of immediate and future rewards differentially recruits cortico-basal ganglia loops. Nature Neuroscience 7, 887–893.CrossRefGoogle ScholarPubMed
Trost, S, Diekhof, EK, Zvonik, K, Lewandowski, M, Usher, J, Keil, M, Zilles, D, Falkai, P, Dechent, P, Gruber, O (2014). Disturbed anterior prefrontal control of the mesolimbic reward system and increased impulsivity in bipolar disorder. Neuropsychopharmacology 39, 1914–1923.CrossRefGoogle ScholarPubMed
Walton, ME, Behrens, TEJ, Noonan, MP, Rushworth, MFS (2011). Giving credit where credit is due: orbitofrontal cortex and valuation in an uncertain world. Annals of the New York Academy of Sciences 1239, 14–24.Google Scholar
Walton, ME, Kennerley, SW, Bannerman, DM, Phillips, PEM, Rushworth, MFS (2006). Weighing up the benefits of work: behavioral and neural analyses of effort-related decision making. Neural Networks 19, 1302–1314.Google Scholar
Wechsler, D (1999). Wechsler Abbreviated Scale of Intelligence. The Psychological Corporation: San Antonio, TX.Google Scholar
Worsley, K (2001). Statistical analysis of activation images. In Functional MRI: an Introduction to Methods (ed. Jezzard, P., Matthews, P. M. and Smith, S. M.), pp. 251–270. Oxford University Press: New York.Google Scholar
Yoshida, W, Ishii, S (2006). Resolution of uncertainty in prefrontal cortex. Neuron 50, 781–789.Google Scholar
Youngstrom, EA, Frazier, TW, Demeter, C, Calabrese, JR, 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.Google Scholar
Supplementary material: File

Manelis supplementary material

Tables S1-S2 and Figures S1-S2

Download Manelis supplementary material(File)
File 141.8 KB