Hostname: page-component-78c5997874-fbnjt Total loading time: 0 Render date: 2024-11-19T04:22:59.314Z Has data issue: false hasContentIssue false
  • English
  • Français

Bipolar Disorder: Emotional Dysregulation and Neuronal Vulnerability

Published online by Cambridge University Press:  07 November 2014

Dan J. Stein ,
Neil Horn ,
Rajkumar Ramesar  and
Jonathan Savitz
Get access Rights & Permissions [Opens in a new window]

Abstract

Bipolar disorder is clinically characterized by fluctuating affect, and neuropsychologically by impairment in executive functions. Such phenomena are consistent with the centrality of emotional dysregulation and impulsivity to bipolar disorder. They are also consistent with a key role for prefrontal-subcortical (striatal-thalamic) and associated limbic circuitry in its mediation. Furthermore, there is growing data on the cellular mechanisms contributing to neuronal vulnerability in this mediating circuitry.

Type
Pearls in Clinical Neuroscience
Information
CNS Spectrums , Volume 14 , Issue 3 , March 2009 , pp. 122 - 126
Copyright
Copyright © Cambridge University Press 2009

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

REFERENCES

1.Savitz, JB, Solms, M, Ramesar, RS. Neurocognitive function as an endophenotype for genetic studies of bipolar affective disorder. Neuromolecular Med. 2005;7:275–286.Google Scholar
2.Arts, B, Jabben, N, Krabbendam, L, van Os, J. Meta-analyses of cognitive functioning in euthymic bipolar patients and their first-degree relatives. Psychol Med. 2008;38:771–785.Google Scholar
3.Bora, E, Yucel, M, Pantelis, C. Cognitive endophenotypes of bipolar disorder: a metaanalysis of neuropsychological deficits in euthymic patients and their first-degree relatives. J Affect Disord. 2009;113:1–20.Google Scholar
4.Robinson, LJ, Thompson, JM, Gallagher, P, et al.A meta-analysis of cognitive deficits in euthymic patients with bipolar disorder. J Affect Disord. 2006;93:105–115.Google Scholar
5.Green, MJ, Cahill, CM, Malhi, GS. The cognitive and neurophysiological basis of emotion dysregulation in bipolar disorder. J Affect Disord. 2007;103:29–42.Google Scholar
6.Phillips, M, Ladouceur, C, Drevets, W. A neural model of voluntary and automatic emotion regulation: implications for understanding the pathophysiology and neurodevelopment of bipolar disorder. Mol Psychiatry. 2008;13:833–857.CrossRefGoogle ScholarPubMed
7.Moeller, FG, Barratt, ES, Dougherty, DM, Schmitz, JM, Swann, AC. Psychiatric aspects of impulsivity. Am J Psychiatry. 2001;158:1783–1793.Google Scholar
8.Najt, P, Perez, J, Sanches, M, Peluso, MA, Glahn, D, Soares, JC. Impulsivity and bipolar disorder. Eur Neuropsychopharmacol. 2007;17:313–320.Google Scholar
9.Strakowski, SM, DelBello, MP, Adler, CM. The functional neuroanatomy of bipolar disorder: a review of neuroimaging findings. Mol Psychiatry. 2005;10:105–116.Google Scholar
10.Lyoo, IK, Hwang, J, Sim, M, Dunn, BJ, Renshaw, PF. Advances in magnetic resonance imaging methods for the evaluation of bipolar disorder. CNS Spectr. 2006;11:269–280.Google Scholar
11.Savitz, J, Drevets, WC. Bipolar and major depressive disorder: neuroimaging the developmental-degenerative divide. Neurosci Biobehav Rev. In press.Google Scholar
12.Schloesser, RJ, Huang, J, Klein, PS, et al.Cellular plasticity cascades in the pathophysiology and treatment of bipolar disorder. Neuropsychopharmacology. 2007;33:110–133.Google Scholar
13.Kato, T. Molecular neurobiology of bipolar disorder: a disease of ‘mood-stabilizing neurons’? Trends Neurosci. 2008;31:495–503.Google Scholar
14.Hassel, S, Almeida, JRC, Kerr, N, et al.Elevated striatal and decreased dorsolateral prefrontal cortical activity in response to emotional stimuli in euthymic bipolar disorder: no associations with psychotropic medication load. Bipolar Disord. 2008;10:916–927.Google Scholar
15.Foland, LC, Altshuler, LL, Bookheimer, SY, Eisenberger, N, Townsend, J, Thompson, PM. Evidence for deficient modulation of amygdala response by prefrontal cortex in bipolar mania. Psychiatry Res. 2008;162:27–37.Google Scholar
16.Blumberg, HP, Leung, HC, Skudlarski, P, et al.A functional magnetic resonance imaging study of bipolar disorder: state- and trait-related dysfunction in ventral prefrontal cortices. Arch Gen Psychiatry. 2003;60:601–609.Google Scholar
17.McDonald, C, Zanelli, J, Rabe-Hesketh, S, et al.Meta-analysis of magnetic resonance imaging brain morphometry studies in bipolar disorder. Biol Psychiatry. 2004;56:411–417.Google Scholar
18.Kempton, MJ, Geddes, JR, Ettinger, U, et al.Meta-analysis, database, and metaregression of 98 structural imaging studies in bipolar disorder. Arch Gen Psychiatry. 2008;65:1017–1032.Google Scholar
19.Konarski, JZ, Mcintyre, RS, Kennedy, SH, et al.Volumetric neuroimaging investigations in mood disorders: bipolar disorder versus major depressive disorder. Bipolar Disord. 2008;10:1–37.Google Scholar
20.Hajek, T, Carrey, N, Alda, M. Neuroanatomical abnormalities as risk factors for bipolar disorder. Bipolar Disord. 2005;7:393–403.Google Scholar
21.Pfeifer, JC, Welge, J, Strakowski, SM, Adler, CM, DelBello, MP. Meta-analysis of amygdala volumes in children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry. 2008;47:1289–1298.Google Scholar
22.Rajkowska, G. Cell pathology in bipolar disorder. Bipolar Disord. 2002;4:105–116.Google Scholar
23.Yildiz-Yesiloglu, A, Ankerst, DP. Neurochemical alterations of the brain in bipolar disorder and their implications for pathophysiology: a systematic review of the in vivo proton magnetic resonance spectroscopy findings. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30:969–995.Google Scholar
24.Quiroz, JA, Gray, NA, Kato, T, et al.Mitochondrially mediated plasticity in the pathophysiology and treatment of bipolar disorder. Neuropsychopharmacology. 2008;33:2551–2565.Google Scholar
25.Ng, F, Berk, M, Dean, O, Bush, Al. Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. Int J Neuropsychopharmacol. 2008;11:851–876.CrossRefGoogle ScholarPubMed
26.Stork, C, Renshaw, PF. Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research. Mol Psychiatry. 2005;10:900–919.Google Scholar
27.Zarate, CA, Du, J, Quiroz, J, et al.Regulation of cellular plasticity cascades in the pathophysiology and treatment of mood disorders: role of the glutamatergic system. Ann N Y Acad Sci. 2003;1003:273–291.Google Scholar
28.Berk, M, Conus, P, Lucas, N, et al.Setting the stage: from prodrome to treatment resistance in bipolar disorder. Bipolar Disord. 2007;9:671–678.Google Scholar
29.Post, RM. Kindling and sensitization as models for affective episode recurrence, cyclicity, and tolerance phenomena. Neurosci Biobehav Rev. 2007;31:858–873.CrossRefGoogle ScholarPubMed
30.Kapczinski, F, Vieta, E, Andreazza, AC, et al.Allostatic load in bipolar disorder: Implications for pathophysiology and treatment. Neurosci Biobehav Rev. 2008;32:675–692.Google Scholar
31.Machado-Vieira, R, Kapczinski, F, Soares, JC. Perspectives for the development of animal models of bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28:209–224.Google Scholar
32.Geyer, MA. Developing translational animal models for symptoms of schizophrenia or bipolar mania. Neurotox Res. 2008;14:71–78.Google Scholar
33.Kato, T, Kubota, M, Kasahara, T. Animal models of bipolar disorder. Neurosci Biobehav Rev. 2007;31:832–842.Google Scholar
34.Elashoff, M, Higgs, BW, Yolken, RH, et al.Meta-analysis of 12 genomic studies in bipolar disorder. J Mol Neurosci. 2007;31:221–243.Google Scholar
35.Kato, T. Molecular genetics of bipolar disorder and depression. Psychiatry Clin Neurosci. 2007;61:3–19.Google Scholar
36.Serretti, A, Mandelli, L. The genetics of bipolar disorder: genome ‘hot regions,’ genes, new potential candidates and future directions. Mol Psychiatry. 2008;13:742–771.Google Scholar
37.Etain, B, Henry, C, Bellivier, F, et al.Beyond genetics: childhood affective trauma in bipolar disorder. Bipolar Disord. 2008;10:867–876.CrossRefGoogle ScholarPubMed
38.Alloy, LB, Abramson, LY, Urosevic, S, Walshaw, PD, Nusslock, R, Neeren, AM. The psychosocial context of bipolar disorder: environmental, cognitive, and developmental risk factors. Clin Psychol Rev. 2005;25:1043–1075.CrossRefGoogle ScholarPubMed
39.Post, RM, Leverich, GS. The role of psychosocial stress in the onset and progression of bipolar disorder and its comorbidities: the need for earlier and alternative modes of therapeutic intervention. Dev Psychopathol. 2006;18:1181–1211.CrossRefGoogle ScholarPubMed
40.Burton, PR, Clayton, DG, Cardon, LR, et al.Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007;447:661–678Google Scholar
41.Sklar, P, Smoller, JW, Fan, J, et al.Whole-genome association study of bipolar disorder. Mol Psychiatry. 2008;13:558–569.Google Scholar
42.Savitz, J, Van Der Merwe, L, Stein, DJ, et al.Genotype and childhood sexual trauma moderate neurocognitive performance: a possible role for brain-derived neurotrophic factor and apolipoprotein E variants. Biol Psychiatry. 2007;62:391–399.Google Scholar
43.Savitz, JB, Van Der Merwe, L, Stein, DJ, et al.Neuropsychological task performance in bipolar spectrum illness: genetics, alcohol abuse, medication and childhood trauma. Bipolar Disord. 2008;10:49–494.CrossRefGoogle ScholarPubMed
44.Savitz, JB, Ramesar, RS. Personality: is it a viable endophenotype for genetic studies of bipolar affective disorder? Bipolar Disord. 2006;8:322–337.Google Scholar
45.Balanza-Martinez, V, Rubio, C, Selva-Vera, G, et al.Neurocognitive endophenotypes (endophenocognitypes) from studies of relatives of bipolar disorder subjects: a systematic review. Neurosci Biobehav Rev. 2008;32:1426–1438.Google Scholar
46.McDonald, C, Bullmore, ET, Sham, PC, et al.Association of genetic risks for schizophrenia and bipolar disorder with specific and generic brain structural endophenotypes. Arch Gen Psychiatry. 2004;61:974–984.CrossRefGoogle ScholarPubMed
47.Frey, BN, Walss-Bass, C, Stanley, JA, et al.Brain-derived neurotrophic factor val66met polymorphism affects prefrontal energy metabolism in bipolar disorder. Neuroreport. 2007;18:1567–1570.Google Scholar
48.Chepenik, LG, Fredericks, C, Papademetris, X, et al.Effects of the brain-derived neurotrophic growth factor val66met variation on hippocampus morphology in bipolar disorder. Neuropsychopharmacology. 2008 Aug 13. [Epub ahead of print].Google Scholar
49.Shah, MP, Wang, F, Kalmar, JH, et al.Role of variation in the serotonin transporter protein gene (SLC6A4) in trait disturbances in the ventral anterior cingulate in bipolar disorder. Neuropsychopharmacology. 2008 Nov 26. [Epub ahead of print].Google Scholar
50.Gardner, R. Mechanisms in manic-depressive disorder: an evolutionary model. Arch Gen Psychiatry. 1982;39:1436–1441.Google Scholar
51.Brody, JF. Evolutionary recasting: ADHD, mania and its variants. J Affect Disord. 2001;65:197–215.Google Scholar
52.Keller, MC, Miller, G. Resolving the paradox of common, harmful, heritable mental disorders: which evolutionary genetic models work best? Behav Brain Sci. 2006;29:385–404.Google Scholar
53.Bowden, CL. Bipolar pathophysiology and development of improved treatments. Brain Res. 2008;1235:92–97.Google Scholar
54.Patten, SB, Paris, J. The bipolar spectrum—a bridge too far? Can J Psychiatry. 2008;53:762–768.Google Scholar
55.Ghaemi, SN, Bauer, M, Cassidy, F, et al.Diagnostic guidelines for bipolar disorder: a summary of the International society for bipolar disorders diagnostic guidelines task force report. Bipolar Disord. 2008;10:117–128.Google Scholar
56.Vieta, E, Phillips, ML. Deconstructing bipolar disorder: a critical review of its diagnostic validity and a proposal for DSM-V and ICD-11. Schizophr Bull. 2007;33:886–892.Google Scholar
57.Phillips, ML, Vieta, E. Identifying functional neuroimaging biomarkers of bipolar disorder: toward DSM-V. Schizophr Bull. 2007;33:893–904.Google Scholar
58.Fajutrao, L, Locklear, JC, Priaulx, J, et al.A systematic review on the epidemiology and socioeconomic burden of bipolar disorder in Europe. Value Health. 2008;11:A580–A581.Google Scholar
59.Hawton, K, Sutton, L, Haw, C, et al.Suicide and attempted suicide in bipolar disorder: a systematic review of risk factors. J Clin Psychiatry. 2005;66:693–704.Google Scholar
60.Allen, R, Smith, DJ. Screening for bipolar disorder: strengths and limitations of currently available instruments. Prim Care Community Psychiatr. 2008;13:47–51.Google Scholar
61.Picardi, A. Rating scales in bipolar disorder. Curr Opin Psychiatry. 2009;22:42–49.CrossRefGoogle ScholarPubMed
62.Tohen, M, Bowden, C, Calabrese, J, et al.The international society of bipolar disorders task force on the nomenclature of course and outcome in bipolar disorders. Bipolar Disord. 2008;10:1.Google Scholar
63.Kupfer, DJ. The increasing medical burden in bipolar disorder. JAMA. 2005;293:2528–2530.Google Scholar
64.Evans, DL, Charney, DS, Lewis, L, et al.Mood disorders in the medically ill: scientific review and recommendations. Biol Psychiatry. 2005;58:175–189.Google Scholar
65.Mcintyre, RS, Soczynska, JK, Beyer, JL, et al.Medical comorbidity in bipolar disorder: reprioritizing unmet needs. Curr Opin Psychiatry. 2007;20:406–416.Google Scholar
66.Leibenluft, E, Rich, BA. Pediatric bipolar disorder. Ann Rev Clin Psychol. 2008;4:163–187.CrossRefGoogle ScholarPubMed
67.Ghaemi, SN, Martin, A. Defining the boundaries of childhood bipolar disorder. Am J Psychiatry. 2007;164:185–188.Google Scholar
68.Fountoulakis, KN, Vieta, E, Sanchez-Moreno, J, et al.Treatment guidelines for bipolar disorder: a critical review. J Affect Disord. 2005;86:1–10.Google Scholar
69.Geddes, JR, Burgess, S, Hawton, K, et al.Long-term lithium therapy for bipolar disorder: systematic review and meta-analysis of randomized controlled trialls. Am J Psychiatry. 2004;161:217–222.Google Scholar
70.Kleindienst, N, Engel, RR, Greil, W. Which clinical factors predict response to prophylactic lithium? A systematic review for bipolar disorders. Bipolar Disord. 2005;7:404–417.Google Scholar
71.Severus, WE, Kleindienst, N, Seemuller, F, et al.What is the optimal serum lithium level in the long-term treatment of bipolar disorder: a review? Bipolar Disord. 2008;10:231237.Google Scholar
72.Derry, S, Moore, RA. Atypical antipsychotics in bipolar disorder: systematic review of randomised trials. BMC Psychiatry. 2007;7:40.Google Scholar
73.Smith, LA, Cornelius, V, Warnock, A, et al.Pharmacological interventions for acute bipolar mania: a systematic review of randomized placebo-controlled trials. Bipolar Disord. 2007;9:551–560.Google Scholar
74.Smith, LA, Cornelius, V, Warnock, A, et al.Effectiveness of mood stabilizers and antipsychotics in the maintenance phase of bipolar disorder: a systematic review of randomized controlled trials. Bipolar Disord. 2007;9:394–412.Google Scholar
75.Smith, LA, Cornelius, V, Warnock, A, et al.Acute bipolar mania: a systematic review and meta-analysis of co-therapy vs. monotherapy. Acta Psychiatr Scand. 2007;115:12–20.Google Scholar
76.Fountoulakis, KN, Vieta, E. Treatment of bipolar disorder: a systematic review of available data and clinical perspectives. Int J Neuropsychopharmacol. 2008;11:999–1029.Google Scholar
77.Ghaemi, SN, Pardo, TB, Hsu, DJ. Strategies for preventing the recurrence of bipolar disorder. J Clin Psychiatry. 2004;65:16–23.Google Scholar
78.Ghaemi, SN, Wingo, AP, Filkowski, MA, et al.Long-term antidepressant treatment in bipolar disorder: meta-analyses of benefits and risks. Acta Psychiatr Scand. 2008;118:347–356.Google Scholar
79.Andreescu, C, Mulsanta, BH, Emanuel, JE. Complementary and alternative medicine in the treatment of bipolar disorder: a review of the evidence. J Affect Disord. 2008;110:16–26.Google Scholar
80.Montgomery, P, Richardson, AJ. Omega-3 fatty acids for bipolar disorder. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD005169.Google Scholar
81.Mathew, SJ, Manji, HK, Charney, DS. Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008;33:2080–2092.Google Scholar
82.Stein, DJ. Emotional regulation: implications for the psychobiology of psychotherapy. CNS Spectr. 2008;13:195–198.Google Scholar
83.Miklowitz, DJ, Johnson, SL. The psychopathology and treatment of bipolar disorder. Ann Rev Clin Psychol. 2006;2:199–235.Google Scholar
84.Beynon, S, Soares-Weiser, K, Woolacott, N, et al.Psychosocial interventions for the prevention of relapse in bipolar disorder: systematic review of controlled trials. Br J Psychiatry. 2008;192:5–11.Google Scholar
85.Justo, LP, Soares, BGO, Calil, HM. Family interventions for bipolar disorder. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005167.Google Scholar
86.Rouget, BW, Aubry, JM. Efficacy of psychoeducational approaches on bipolar disorders: a review of the literature. J Affect Disord. 2007;98:11–27.Google Scholar
87.Morriss, RK, Faizal, MA, Jones, AP, et al.Interventions for helping people recognise early signs of recurrence in bipolar disorder. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD004854.Google Scholar
88.Sajatovic, M, Chen, PJ, Dines, P, et al.Psychoeducational approaches to medication adherence in patients with bipolar disorder. Disease Management & Health Outcomes. 2007;15:181–192.CrossRefGoogle Scholar
89.Gaudiano, BA, Weinstock, LA, Miller, IW. Improving treatment adherence in bipolar disorder—a review of current psychosocial treatment efficacy and recommendations for future treatment development. Behav Modif. 2008;32:267–301.Google Scholar
90.Berk, M, Hallam, K, Lucas, N, et al.Early intervention in bipolar disorders: opportunities and pitfalls. Med J Aust. 2007;187(7 suppl):S11–S14.Google Scholar