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Review

Cortico-limbic connectivity as a possible biomarker for bipolar disorder: where are we now?

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Pages 159-172 | Received 20 Sep 2018, Accepted 19 Dec 2018, Published online: 01 Jan 2019

References

  • APA. Diagnostic and statistical manual of mental disorders: DSM-IV. Washington, DC: APA; 2000. (4th, text revision ed.).
  • Murray CJ, Lopez AD. Evidence-based health policy–lessons from the global burden of disease study. Science. 1996;274(5288):740–743.
  • Wittchen HU. The burden of mood disorders. Science. 2012 Oct 5;338(6103):15.
  • Hirschfeld R, Lewis L, Vornik LA. Perceptions and impact of bipolar disorder: how far have we really come? Results of the national depressive and manic-depressive association 2000 survey of individuals with bipolar disorder. J Clin Psychiatry. 2003;64(2):161–74..
  • Strakowski SM, Adler CM, Almeida J, et al. The functional neuroanatomy of bipolar disorder: a consensus model. Bipolar Disord. 2012 Jun;14(4):313–325.
  • Frey BN, Andreazza AC, Houenou J, et al. Biomarkers in bipolar disorder: a positional paper from the international society for bipolar disorders biomarkers task force. Aust N Z J Psychiatry. 2013 Apr;47(4):321–332.
  • Friston KJ. Functional and effective connectivity: a review. Brain Connect. 2011;1(1):13–36.
  • Koch MA, Norris DG, Hund-Georgiadis M. An investigation of functional and anatomical connectivity using magnetic resonance imaging. Neuroimage. 2002 May;16(1):241–250.
  • Fingelkurts AA, Kahkonen S. Functional connectivity in the brain–is it an elusive concept?. Neurosci Biobehav Rev. 2005 Jan;28(8):827–836.
  • Vai B, Bollettini I, Benedetti F. Corticolimbic connectivity as a possible biomarker for bipolar disorder. Expert Rev Neurother. 2014 Jun;14(6):631–650.
  • Cerullo MA, Fleck DE, Eliassen JC, et al. A longitudinal functional connectivity analysis of the amygdala in bipolar I disorder across mood states. Bipolar Disord. 2012 Mar;14(2):175–184.
  • Townsend JD, Torrisi SJ, Lieberman MD, et al. Frontal-amygdala connectivity alterations during emotion downregulation in bipolar I disorder. Biol Psychiatry. 2013 Jan 15;73(2):127–135.
  • Versace A, Thompson WK, Zhou D, et al. Abnormal left and right amygdala-orbitofrontal cortical functional connectivity to emotional faces: state versus trait vulnerability markers of depression in bipolar disorder. Biol Psychiatry. 2010 Mar 1;67(5):422–431.
  • Radaelli D, Sferrazza Papa G, Vai B, et al. Fronto-limbic disconnection in bipolar disorder. Eur Psychiatry. 2014;30(1):82–8.
  • Pompei F, Dima D, Rubia K, et al. Dissociable functional connectivity changes during the Stroop task relating to risk, resilience and disease expression in bipolar disorder. Neuroimage. 2011 Jul 15;57(2):576–582.
  • Ladouceur CD, Farchione T, Diwadkar V, et al. Differential patterns of abnormal activity and connectivity in the amygdala-prefrontal circuitry in bipolar-I and bipolar-NOS youth. J Am Acad Child Adolesc Psychiatry. 2011 Dec;50(12):1275–89 e2.
  • Benedetti F, Yeh PH, Bellani M, et al. Disruption of white matter integrity in bipolar depression as a possible structural marker of illness. Biol Psychiatry. 2011 Feb 15;69(4):309–317.
  • Benedetti F, Absinta M, Rocca MA, et al. Tract-specific white matter structural disruption in patients with bipolar disorder. Bipolar Disord. 2011 Jun;13(4):414–424.
  • Chaddock CA, Barker GJ, Marshall N, et al. White matter microstructural impairments and genetic liability to familial bipolar I disorder. Br J Psychiatry. 2009 Jun;194(6):527–534.
  • Frazier JA, Breeze JL, Papadimitriou G, et al. White matter abnormalities in children with and at risk for bipolar disorder. Bipolar Disord. 2007 Dec;9(8):799–809.
  • Adler CM, Adams J, DelBello MP, et al. Evidence of white matter pathology in bipolar disorder adolescents experiencing their first episode of mania: a diffusion tensor imaging study. Am J Psychiatry. 2006 Feb;163(2):322–324.
  • Tighe SK, Reading SA, Rivkin P, et al. Total white matter hyperintensity volume in bipolar disorder patients and their healthy relatives. Bipolar Disord. 2012 Dec;14(8):888–893.
  • Sprooten E, Fleming KM, Thomson PA, et al. White matter integrity as an intermediate phenotype: exploratory genome-wide association analysis in individuals at high risk of bipolar disorder. Psychiat Res. 2013 Apr 30;206(2–3):223–231.
  • Drevets WC, Price JL, Furey ML. Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression. Brain Struct Funct. 2008 Sep;213(1–2):93–118.
  • Chen G, Henter ID, Manji HK. Translational research in bipolar disorder: emerging insights from genetically based models. Mol Psychiatry. 2010 Sep;15(9):883–895.
  • Meyer-Lindenberg A, Weinberger DR. Intermediate phenotypes and genetic mechanisms of psychiatric disorders. Nat Rev Neurosci. 2006 Oct;7(10):818–827.
  • Insel TR, Cuthbert BN. Brain disorders? Precisely. Science. 2015;348(6234):499–500.
  • Assaf Y, Pasternak O. Diffusion tensor imaging (DTI)-based white matter mapping in brain research: a review. J Mol Neurosci. 2008;34(1):51–61.
  • Xekardaki A, Giannakopoulos P, Haller S. White matter changes in bipolar disorder, alzheimer disease, and mild cognitive impairment: new insights from DTI. J Aging Res. 2011;2011:286564.
  • Song SK, Yoshino J, Le TQ, et al. Demyelination increases radial diffusivity in corpus callosum of mouse brain. Neuroimage. 2005 May 15;26(1):132–140.
  • Sun SW, Liang HF, Trinkaus K, et al. Noninvasive detection of cuprizone induced axonal damage and demyelination in the mouse corpus callosum. Magn Reson Med. 2006 Feb;55(2):302–308.
  • Song SK, Sun SW, Ramsbottom MJ, et al. Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water. Neuroimage. 2002 Nov;17(3):1429–1436.
  • Song SK, Sun SW, Ju WK, et al. Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia. Neuroimage. 2003 Nov;20(3):1714–1722.
  • Pierpaoli C, Jezzard P, Basser PJ, et al. Diffusion tensor MR imaging of the human brain. Radiology. 1996 Dec;201(3):637–648.
  • Sen PN, Basser PJ. A model for diffusion in white matter in the brain. Biophys J. 2005 Nov;89(5):2927–2938.
  • Concha L, Gross DW, Wheatley BM, et al. Diffusion tensor imaging of time-dependent axonal and myelin degradation after corpus callosotomy in epilepsy patients. Neuroimage. 2006 Sep;32(3):1090–1099.
  • Emsell L, Leemans A, Langan C, et al. Limbic and callosal white matter changes in euthymic bipolar I disorder: an advanced diffusion magnetic resonance imaging tractography study. Biol Psychiatry. 2013 Jan 15;73(2):194–201.
  • Leow A, Ajilore O, Zhan L, et al. Impaired inter-hemispheric integration in bipolar disorder revealed with brain network analyses. Biol Psychiatry. 2013 Jan 15;73(2):183–193.
  • Bollettini I, Poletti S, Locatelli C, et al. Disruption of white matter integrity marks poor antidepressant response in bipolar disorder. J Affect Disord. 2015 Mar;15(174):233–240.
  • Kurumaji A, Itasaka M, Uezato A, et al. A distinctive abnormality of diffusion tensor imaging parameters in the fornix of patients with bipolar II disorder. Psychiat Res Neuroim. 2017 Aug;30(266):66–72.
  • Cyprien F, de Champfleur NM, Deverdun J, et al. Corpus callosum integrity is affected by mood disorders and also by the suicide attempt history: A diffusion tensor imaging study. J Affect Disord. 2016 Jul;19(206):115–124.
  • Pezzoli S, Emsell L, Yip SW, et al. Meta-analysis of regional white matter volume in bipolar disorder with replication in an independent sample using coordinates, T-maps, and individual MRI data. Neurosci Biobehav Rev. 2018;84:162–170.
  • Nortje G, Stein DJ, Radua J, et al. Systematic review and voxel-based meta-analysis of diffusion tensor imaging studies in bipolar disorder. J Affect Disord. 2013 Sep 5;150(2):192–200.
  • Vederine FE, Wessa M, Leboyer M, et al. A meta-analysis of whole-brain diffusion tensor imaging studies in bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2011 Dec 1;35(8):1820–1826.
  • Wessa M, Houenou J, Leboyer M, et al. Microstructural white matter changes in euthymic bipolar patients: a whole-brain diffusion tensor imaging study. Bipolar Disord. 2009 Aug;11(5):504–514.
  • Versace A, Almeida JR, Hassel S, et al. Elevated left and reduced right orbitomedial prefrontal fractional anisotropy in adults with bipolar disorder revealed by tract-based spatial statistics. Arch Gen Psychiatry. 2008 Sep;65(9):1041–1052.
  • Haarman BCM, Rf R-VDL, Burger H, et al. Diffusion tensor imaging in euthymic bipolar disorder - A tract-based spatial statistics study. J Affect Disord. 2016;203:281–291.
  • Matsuo K, Nielsen N, Nicoletti MA, et al. Anterior genu corpus callosum and impulsivity in suicidal patients with bipolar disorder. Neurosci Lett. 2010 Jan 18;469(1):75–80.
  • Poletti S, Bollettini I, Mazza E, et al. Cognitive performances associate with measures of white matter integrity in bipolar disorder. J Affect Disord. 2015;174:342–352.
  • Oertel-Knochel V, Reinke B, Alves G, et al. Frontal white matter alterations are associated with executive cognitive function in euthymic bipolar patients. J Affect Disord. 2014;155:223–233.
  • Benedetti F, Melloni EMT, Dallaspezia S, et al. Night sleep influences white matter microstructure in bipolar depression. J Affect Disord. 2017 Aug;15(218):380–387.
  • Bollettini I, Poletti S, Locatelli C, et al. Disruption of white matter integrity marks poor antidepressant response in bipolar disorder. J Affect Disord. 2015;174:233–240.
  • Hoeft F, Barnea-Goraly N, Haas BW, et al. More is not always better: increased fractional anisotropy of superior longitudinal fasciculus associated with poor visuospatial abilities in Williams syndrome. J Neurosci. 2007 Oct 31;27(44):11960–11965.
  • Benedetti F, Bollettini I, Barberi I, et al. Lithium and GSK3-beta promoter gene variants influence white matter microstructure in bipolar disorder. Neuropsychopharmacology. 2013 Jan;38(2):313–327.
  • Ongur D, Bechtholt AJ, Carlezon WA, et al. Glial abnormalities in mood disorders. Harv Rev Psychiatry. 2014 Nov-Dec;22(6):334–337.
  • Sporns O, Tononi G, Kotter R. The human connectome: A structural description of the human brain. PLoS Comput Biol. 2005 Sep;1(4):e42.
  • Bullmore ET, Bassett DS. Brain graphs: graphical models of the human brain connectome. Annu Rev Clin Psychol. 2011;7:113–140.
  • Sporns O. The non-random brain: efficiency, economy, and complex dynamics. Front Comput Neurosci. 2011;5:5.
  • Gadelkarim JJ, Ajilore O, Schonfeld D, et al. Investigating brain community structure abnormalities in bipolar disorder using path length associated community estimation. Hum Brain Mapp. 2014 May;35(5):2253–2264.
  • Forde NJ, O’Donoghue S, Scanlon C, et al. Structural brain network analysis in families multiply affected with bipolar I disorder. Psychiat Res. 2015 Oct 30;234(1):44–51.
  • Collin G, van Den Heuvel MP, Abramovic L, et al. Brain network analysis reveals affected connectome structure in bipolar I disorder. Hum Brain Mapp. 2016 Jan;37(1):122–134.
  • Wang Y, Deng F, Jia Y, et al. Disrupted rich club organization and structural brain connectome in unmedicated bipolar disorder. Psychol Med. 2018;8:1–9.
  • Peters A. The effects of normal aging on myelinated nerve fibers in monkey central nervous system. Front Neuroanat. 2009;3:11.
  • Adler CM, DelBello MP, Strakowski SM. Brain network dysfunction in bipolar disorder. CNS Spectr. 2006 Apr;11(4):312–320. quiz 323–4.
  • Price JL, Drevets WC. Neurocircuitry of mood disorders. Neuropsychopharmacology. 2010 Jan;35(1):192–216.
  • Wang F, Kalmar JH, He Y, et al. Functional and structural connectivity between the perigenual anterior cingulate and amygdala in bipolar disorder. Biol Psychiatry. 2009 Sep 01;66(5):516–521.
  • Strakowski SM, Delbello MP, Adler CM. The functional neuroanatomy of bipolar disorder: a review of neuroimaging findings. Mol Psychiatry. 2005 Jan;10(1):105–116.
  • Phillips ML, Ladouceur CD, Drevets WC. A neural model of voluntary and automatic emotion regulation: implications for understanding the pathophysiology and neurodevelopment of bipolar disorder. Mol Psychiatry. 2008 Sep;13(9):829,833–57.
  • Phillips ML, Drevets WC, Rauch SL, et al. Neurobiology of emotion perception II: implications for major psychiatric disorders. Biol Psychiatry. 2003 Sep 1;54(5):515–528.
  • Cabeza R, Nyberg L. Imaging cognition II: an empirical review of 275 PET and fMRI studies. J Cogn Neurosci. 2000 Jan;12(1):1–47.
  • Fuster JM. The prefrontal cortex–an update: time is of the essence. Neuron. 2001 May;30(2):319–333.
  • Amaral DG, Price JL. Amygdalo-cortical projections in the monkey (Macaca fascicularis). J Comp Neurol. 1984 Dec 20;230(4):465–496.
  • LeDoux JE. Emotion circuits in the brain. Annu Rev Neurosci. 2000;23:155–184.
  • Townsend J, Altshuler LL. Emotion processing and regulation in bipolar disorder: a review. Bipolar Disord. 2012 Jun;14(4):326–339.
  • Chen CH, Suckling J, Lennox BR, et al. A quantitative meta-analysis of fMRI studies in bipolar disorder. Bipolar Disord. 2011 Feb;13(1):1–15.
  • Delvecchio G, Sugranyes G, Frangou S. Evidence of diagnostic specificity in the neural correlates of facial affect processing in bipolar disorder and schizophrenia: a meta-analysis of functional imaging studies. Psychol Med. 2013 Mar;43(3):553–569.
  • Fusar-Poli P, Howes O, Bechdolf A, et al. Mapping vulnerability to bipolar disorder: a systematic review and meta-analysis of neuroimaging studies. J Psychiatry Neurosci. 2012 May;37(3):170–184.
  • Chang K, Garrett A, Kelley R, et al. Anomalous prefrontal-limbic activation and connectivity in youth at high-risk for bipolar disorder. J Affect Disord. 2017;222:7–13.
  • Tseng W-L, Thomas LA, Harkins E, et al. Functional connectivity during masked and unmasked face emotion processing in bipolar disorder. Psychiat Res Neuroim. 2016;258:1–9.
  • Zhang L, Opmeer EM, van der Meer L, et al. Altered frontal‐amygdala effective connectivity during effortful emotion regulation in bipolar disorder. Bipolar Disord. 2018;20(4):349–58.
  • Caseras X, Murphy K, Lawrence NS, et al. Emotion regulation deficits in euthymic bipolar I versus bipolar II disorder: a functional and diffusion‐tensor imaging study. Bipolar Disord. 2015;17(5):461–470.
  • Vai B, Poletti S, Radaelli D, et al. Successful antidepressant chronotherapeutics enhance fronto-limbic neural responses and connectivity in bipolar depression. Psychiat Res Neuroim. 2015;233(2):243–253.
  • Zhang L, Vander Meer L, Opmeer EM, et al. Altered functional connectivity during self-and close other-reflection in patients with bipolar disorder with past psychosis and patients with schizophrenia. Neuropsychologia. 2016;93:97–105.
  • Alloy LB, Abramson LY, Walshaw PD, et al. Behavioral approach system and behavioral inhibition system sensitivities and bipolar spectrum disorders: prospective prediction of bipolar mood episodes. Bipolar Disord. 2008;10(2):310–322.
  • Meyer B, Johnson SL, Winters R. Responsiveness to threat and incentive in bipolar disorder: relations of the BIS/BAS scales with symptoms. J Psychopathol Behav Assess. 2001;23(3):133–143.
  • Alloy LB, Abramson LY, Walshaw PD, et al. Behavioral approach system (BAS) sensitivity and bipolar spectrum disorders: A retrospective and concurrent behavioral high-risk design. Motiv Emot. 2006;30(2):143–155.
  • Alloy LB, Abramson LY. The role of the behavioral approach system (BAS) in bipolar spectrum disorders. Curr Dir Psychol Sci. 2010;19(3):189–194.
  • Gruber J. A review and synthesis of positive emotion and reward disturbance in bipolar disorder. Clin Psychol Psychother. 2011;18(5):356–365.
  • Bermpohl F, Kahnt T, Dalanay U, et al. Altered representation of expected value in the orbitofrontal cortex in mania. Hum Brain Mapp. 2010;31(7):958–969.
  • Chase HW, Nusslock R, Almeida JR, et al. Dissociable patterns of abnormal frontal cortical activation during anticipation of an uncertain reward or loss in bipolar versus major depression. Bipolar Disord. 2013;15(8):839–854.
  • Nusslock R, Almeida JR, Forbes EE, et al. Waiting to win: elevated striatal and orbitofrontal cortical activity during reward anticipation in euthymic bipolar disorder adults. Bipolar Disord. 2012;14(3):249–260.
  • de Almeida JRC, Phillips ML. Distinguishing between unipolar depression and bipolar depression: current and future clinical and neuroimaging perspectives. Biol Psychiatry. 2013;73(2):111–118.
  • Phillips ML, Kupfer DJ. Bipolar disorder diagnosis: challenges and future directions. Lancet. 2013;381(9878):1663–1671.
  • Singh MK, Chang KD, Kelley RG, et al. Reward processing in adolescents with bipolar I disorder. J Am Acad Child Adolesc Psychiatry. 2013;52(1):68–83.
  • Manelis A, Ladouceur CD, Graur S, et al. Altered functioning of reward circuitry in youth offspring of parents with bipolar disorder. Psychol Med. 2016;46(1):197–208.
  • Singh MK, Kelley RG, Howe ME, et al. Reward processing in healthy offspring of parents with bipolar disorder. JAMA Psychiatry. 2014;71(10):1148–1156.
  • Dutra SJ, Man V, Kober H, et al. Disrupted cortico-limbic connectivity during reward processing in remitted bipolar I disorder. Bipolar Disord. 2017;19(8):661–675.
  • Lee MH, Hacker CD, Snyder AZ, et al. Clustering of resting state networks. PLoS One. 2012;7(7):40370.
  • Buckner RL. The serendipitous discovery of the brain’s default network. Neuroimage. 2012 Aug 15;62(2):1137–1145.
  • Anand A, Li Y, Wang Y, et al. Resting state corticolimbic connectivity abnormalities in unmedicated bipolar disorder and unipolar depression. Psychiat Res. 2009 Mar 31;171(3):189–198.
  • Chai XJ, Whitfield-Gabrieli S, Shinn AK, et al. Abnormal medial prefrontal cortex resting-state connectivity in bipolar disorder and schizophrenia. Neuropsychopharmacology. 2011 Sep;36(10):2009–2017.
  • Chepenik LG, Raffo M, Hampson M, et al. Functional connectivity between ventral prefrontal cortex and amygdala at low frequency in the resting state in bipolar disorder. Psychiat Res. 2010 Jun 30;182(3):207–210.
  • Anticevic A, Brumbaugh MS, Winkler AM, et al. Global prefrontal and fronto-amygdala dysconnectivity in bipolar I disorder with psychosis history. Biol Psychiatry. 2013 Mar 15;73(6):565–573.
  • Ongur D, Lundy M, Greenhouse I, et al. Default mode network abnormalities in bipolar disorder and schizophrenia. Psychiat Res. 2010 Jul 30;183(1):59–68.
  • Liu CH, Ma X, Li F, et al. Regional homogeneity within the default mode network in bipolar depression: a resting-state functional magnetic resonance imaging study. PLoS One. 2012;7(11):e48181.
  • Li M, Huang C, Deng W, et al. Contrasting and convergent patterns of amygdala connectivity in mania and depression: a resting-state study. J Affect Disord. 2015;173:53–58.
  • Lois G, Linke J, Wessa M. Altered functional connectivity between emotional and cognitive resting state networks in euthymic bipolar I disorder patients. PLoS One. 2014;9(10):e107829.
  • Chen L, Wang Y, Niu C, et al. Common and distinct abnormal frontal-limbic system structural and functional patterns in patients with major depression and bipolar disorder. NeuroImage Clin. 2018;20:42–50.
  • Ellard KK, Zimmerman JP, Kaur N, et al. Functional connectivity between anterior insula and key nodes of frontoparietal executive control and salience networks distinguish bipolar depression from unipolar depression and healthy control subjects. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018;3(5):473–484.
  • Roberts G, Lord A, Frankland A, et al. Functional dysconnection of the inferior frontal gyrus in young people with bipolar disorder or at genetic high risk. Biol Psychiatry. 2017;81(8):718–727.
  • Syan SK, Smith M, Frey BN, et al. Resting-state functional connectivity in individuals with bipolar disorder during clinical remission: a systematic review. J Psychiatry Neurosci. 2018 Aug;43(5):298–316.
  • Nguyen TT, Kovacevic S, Dev SI, et al. Dynamic functional connectivity in bipolar disorder is associated with executive function and processing speed: A preliminary study. Neuropsychology. 2017;31(1):73.
  • Vargas C, Lopez-Jaramillo C, Vieta E. A systematic literature review of resting state network–functional MRI in bipolar disorder. J Affect Disord. 2013 Sep 25;150(3):727–735.
  • Gong J, Chen G, Jia Y, et al. Disrupted functional connectivity within the default mode network and salience network in unmedicated bipolar II disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2019;88:11–18.
  • Magioncalda P, Martino M, Conio B, et al. Functional connectivity and neuronal variability of resting state activity in bipolar disorder—reduction and decoupling in anterior cortical midline structures. Hum Brain Mapp. 2015;36(2):666–682.
  • Doucet GE, Bassett DS, Yao N, et al. The role of intrinsic brain functional connectivity in vulnerability and resilience to bipolar disorder. Am J Psychiatry. 2017;174(12):1214–1222.
  • Goikolea JM, Dima D, Landín-Romero R, et al. Multimodal brain changes in first-episode mania: a voxel-based morphometry, functional magnetic resonance imaging, and connectivity study. Schizophrenia Bull. 2018.
  • Wang Y, Wang J, Jia Y, et al. Topologically convergent and divergent functional connectivity patterns in unmedicated unipolar depression and bipolar disorder. Transl Psychiatry. 2017;7(7):e1165.
  • Brady RO, Tandon N, Masters GA, et al. Differential brain network activity across mood states in bipolar disorder. J Affect Disord. 2017;207:367–376.
  • Brady RO, Margolis A, Masters GA, et al. Bipolar mood state reflected in cortico-amygdala resting state connectivity: A cohort and longitudinal study. J Affect Disord. 2017;217:205–209.
  • Wei S, Geng H, Jiang X, et al. Amygdala-prefrontal cortex resting-state functional connectivity varies with first depressive or manic episode in bipolar disorder. Neurosci Lett. 2017;641:51–55.
  • Seeberg I, Kjaerstad HL, Miskowiak KW. Neural and behavioral predictors of treatment efficacy on mood symptoms and cognition in mood disorders: a systematic review. Front Psychiatry. 2018;9:337.
  • Altinay M, Karne H, Anand A. Lithium monotherapy associated clinical improvement effects on amygdala-ventromedial prefrontal cortex resting state connectivity in bipolar disorder. J Affect Disord. 2018;225:4–12.
  • Barnett JH, Smoller JW. The genetics of bipolar disorder. Neuroscience. 2009 Nov 24;164(1):331–343.
  • McGuffin P, Rijsdijk F, Andrew M, et al. The heritability of bipolar affective disorder and the genetic relationship to unipolar depression. Arch Gen Psychiatry. 2003 May;60(5):497–502.
  • Bogdan R, Salmeron BJ, Carey CE, et al. Imaging genetics and genomics in psychiatry: a critical review of progress and potential. Biol Psychiatry. 2017;82(3):165–175.
  • Piguet C, Fodoulian L, Aubry JM, et al. Bipolar disorder: functional neuroimaging markers in relatives. Neurosci Biobehav Rev. 2015;57:284–296.
  • Pereira LP, Kohler CA, de Sousa RT, et al. The relationship between genetic risk variants with brain structure and function in bipolar disorder: A systematic review of genetic-neuroimaging studies. Neurosci Biobehav Rev. 2017;79:87–109.
  • Frangou S. Brain structural and functional correlates of resilience to bipolar disorder. Front Hum Neurosci. 2011 Dec;6(5):184.
  • Dima D, Roberts RE, Frangou S. Connectomic markers of disease expression, genetic risk and resilience in bipolar disorder. Transl Psychiatry. 2016 Jan;5(6):e706.
  • Benedetti F, Bollettini I, Poletti S, et al. White matter microstructure in bipolar disorder is influenced by the serotonin transporter gene polymorphism 5-HTTLPR. Genes Brain Behav. 2015 Mar;14(3):238–250.
  • Benedetti F, Bollettini I, Barberi I, et al. Lithium and GSK3-β promoter gene variants influence white matter microstructure in bipolar disorder. Neuropsychopharmacology. 2013;38(2):313.
  • Poletti S, Aggio V, Bollettini I, et al. SREBF-2 polymorphism influences white matter microstructure in bipolar disorder. Psychiat Res Neuroim. 2016;257:39–46.
  • Mazza E, Poletti S, Bollettini I, et al. Body mass index associates with white matter microstructure in bipolar depression. Bipolar Disord. 2017 Mar;19(2):116–127.
  • Poletti S, Bollettini I, Lorenzi C, et al. White matter microstructure in bipolar disorder is influenced by the interaction between a glutamate transporter EAAT1 gene variant and early stress. Mol Neurobiol. 2018;1–9. doi:10.1007/s12035-018-1117-6. [Epub ahead of print]
  • Benedetti F, Poletti S, Locatelli C, et al. A Homer 1 gene variant influences brain structure and function, lithium effects on white matter, and antidepressant response in bipolar disorder: a multimodal genetic imaging study. Prog Neuropsychopharmacol Biol Psychiatry. 2018;81:88–95.
  • Bollettini I, Melloni EMT, Aggio V, et al. Clock genes associate with white matter integrity in depressed bipolar patients. Chronobiol Int. 2017;34(2):212–224.
  • Ota M, Hori H, Sato N, et al. Effects of ankyrin 3 gene risk variants on brain structures in patients with bipolar disorder and healthy subjects. Psychiatry Clin Neurosci. 2016 Nov;70(11):498–506.
  • Lippard ETC, Jensen KP, Wang F, et al. Effects of ANK3 variation on gray and white matter in bipolar disorder. Mol Psychiatry. 2017 Sep;22(9):1345–1351.
  • Poletti S, Riberto M, Vai B, et al. A glutamate transporter EAAT1 gene variant influences amygdala functional connectivity in bipolar disorder. J Mol Neurosci. 2018;65(4):536–545.
  • Vai B, Riberto M, Ghiglino D, et al. A 5-HT1Areceptor promoter polymorphism influences fronto-limbic functional connectivity and depression severity in bipolar disorder. Psychiat Res Neuroim. 2017;270:1–7.
  • Vai B, Riberto M, Poletti S, et al. Catechol-O-methyltransferase val (108/158) met polymorphism affects fronto-limbic connectivity during emotional processing in bipolar disorder. Eur Psychiatry. 2017;41:53–59.
  • Ochsner KN, Ray RD, Cooper JC, et al. For better or for worse: neural systems supporting the cognitive down- and up-regulation of negative emotion. Neuroimage. 2004 Oct;23(2):483–499.
  • Urry HL, van Reekum CM, Johnstone T, et al. Amygdala and ventromedial prefrontal cortex are inversely coupled during regulation of negative affect and predict the diurnal pattern of cortisol secretion among older adults. J Neurosci. 2006 Apr 19;26(16):4415–4425.
  • Driscoll D, Tranel D, Anderson SW. The effects of voluntary regulation of positive and negative emotion on psychophysiological responsiveness. Int J Psychophysiol. 2009 Apr;72(1):61–66.
  • Ochsner KN, Bunge SA, Gross JJ, et al. Rethinking feelings: an FMRI study of the cognitive regulation of emotion. J Cogn Neurosci. 2002 Nov 15;14(8):1215–1229.
  • Kafantaris V, Kingsley P, Ardekani B, et al. Lower orbital frontal white matter integrity in adolescents with bipolar I disorder. J Am Acad Child Adolesc Psychiatry. 2009 Jan;48(1):79–86.
  • Barnea-Goraly N, Chang KD, Karchemskiy A, et al. Limbic and corpus callosum aberrations in adolescents with bipolar disorder: a tract-based spatial statistics analysis. Biol Psychiatry. 2009 Aug 1;66(3):238–244.
  • Wang F, Jackowski M, Kalmar JH, et al. Abnormal anterior cingulum integrity in bipolar disorder determined through diffusion tensor imaging. Br J Psychiatry. 2008 Aug;193(2):126–129.
  • Von Der Heide RJ, Skipper LM, Klobusicky E, et al. Dissecting the uncinate fasciculus: disorders, controversies and a hypothesis. Brain. 2013 Jun;136(Pt 6):1692–1707.
  • Weathers J, Lippard ETC, Spencer L, et al. Longitudinal diffusion tensor imaging study of adolescents and young adults with bipolar disorder. J Am Acad Child Adolesc Psychiatry. 2018 Feb;57(2):111–117.
  • 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 Aug;171(8):829–843.
  • Heilbronner SR, Haber SN. Frontal cortical and subcortical projections provide a basis for segmenting the cingulum bundle: implications for neuroimaging and psychiatric disorders. J Neurosci. 2014 Jul 23;34(30):10041–10054.
  • Bertocci MA, Bebko G, Versace A, et al. Predicting clinical outcome from reward circuitry function and white matter structure in behaviorally and emotionally dysregulated youth. Mol Psychiatry. 2016 Sep;21(9):1194–1201.
  • Kafantaris V, Spritzer L, Doshi V, et al. Changes in white matter microstructure predict lithium response in adolescents with bipolar disorder. Bipolar Disord. 2017 Nov;19(7):587–594.
  • Benedetti F, Poletti S, Radaelli D, et al. Lithium and GSK-3beta promoter gene variants influence cortical gray matter volumes in bipolar disorder. Psychopharmacology (Berl). 2015 Apr;232(7):1325–1336.
  • Wang F, Bobrow L, Liu J, et al. Corticolimbic functional connectivity in adolescents with bipolar disorder. PLoS One. 2012;7(11):50177.
  • Garrett AS, Reiss AL, Howe ME, et al. Abnormal amygdala and prefrontal cortex activation to facial expressions in pediatric bipolar disorder. J Am Acad Child Adolesc Psychiatry. 2012 Aug;51(8):821–831.
  • Singh MK, Kelley RG, Chang KD, et al. Intrinsic amygdala functional connectivity in youth with bipolar i disorder. J Am Acad Child Adolesc Psychiatry. 2015 Sep;54(9):763–770.
  • Hafeman D, Bebko G, Bertocci MA, 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 Jan;15(208):94–100.
  • Manelis A, Ladouceur CD, Graur S, et al. Altered amygdala-prefrontal response to facial emotion in offspring of parents with bipolar disorder. Brain. 2015 Sep;138(Pt 9):2777–2790.
  • Manelis A, Ladouceur CD, Graur S, et al. Altered functioning of reward circuitry in youth offspring of parents with bipolar disorder. Psychol Med. 2016 Jan;46(1):197–208.
  • Singh MK, Chang KD, Kelley RG, et al. Reward processing in adolescents with bipolar I disorder. J Am Acad Child Adolesc Psychiatry. 2013 Jan;52(1):68–83.
  • Meda SA, Gill A, Stevens MC, et al. Differences in resting-state functional magnetic resonance imaging functional network connectivity between schizophrenia and psychotic bipolar probands and their unaffected first-degree relatives. Biol Psychiatry. 2012 May 15;71(10):881–889.
  • Liu CH, Li F, Li SF, et al. Abnormal baseline brain activity in bipolar depression: a resting state functional magnetic resonance imaging study. Psychiat Res. 2012 Aug-Sep;203(2–3):175–179.
  • Chen L, Wang Y, Niu C, et al. Common and distinct abnormal frontal-limbic system structural and functional patterns in patients with major depression and bipolar disorder. Neuroimage Clin. 2018;20:42–50.
  • Kanske P, Schonfelder S, Forneck J, et al. Impaired regulation of emotion: neural correlates of reappraisal and distraction in bipolar disorder and unaffected relatives. Transl Psychiatry. 2015 Jan;20(5):e497.
  • Johnston JAY, Wang F, Liu J, et al. Multimodal neuroimaging of frontolimbic structure and function associated with suicide attempts in adolescents and young adults with bipolar disorder. Am J Psychiatry. 2017 Jul 1;174(7):667–675.
  • Baldessarini RJ, Tondo L, Baethge CJ, et al. Effects of treatment latency on response to maintenance treatment in manic-depressive disorders. Bipolar Disord. 2007 Jun;9(4):386–393.
  • Rive MM, Redlich R, Schmaal L, et al. Distinguishing medication-free subjects with unipolar disorder from subjects with bipolar disorder: state matters. Bipolar Disord. 2016 Nov;18(7):612–623.
  • Judd LL, Akiskal HS, Schettler PJ, et al. A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Arch Gen Psychiatry. 2003;60(3):261–269.
  • Cardoso de Almeida JR, Phillips ML. Distinguishing between unipolar depression and bipolar depression: current and future clinical and neuroimaging perspectives. Biol Psychiatry. 2013 Jan 15;73(2):111–118.
  • Wise T, Radua J, Nortje G, et al. Voxel-Based Meta-Analytical Evidence of Structural Disconnectivity in Major Depression and Bipolar Disorder. Biol Psychiatry. 2016 Feb 15;79(4):293–302.
  • Repple J, Meinert S, Grotegerd D, et al. A voxel-based diffusion tensor imaging study in unipolar and bipolar depression. Bipolar Disord. 2017 Feb;19(1):23–31.
  • Matsuoka K, Yasuno F, Kishimoto T, et al. Microstructural differences in the corpus callosum in patients with bipolar disorder and major depressive disorder. J Clin Psychiatry. 2017 Jan;78(1):99–104.
  • Versace A, Almeida JR, Quevedo K, et al. Right orbitofrontal corticolimbic and left corticocortical white matter connectivity differentiate bipolar and unipolar depression. Biol Psychiatry. 2010 Sep 15;68(6):560–567.
  • Marchand WR, Lee JN, Johnson S, et al. Differences in functional connectivity in major depression versus bipolar II depression. J Affect Disord. 2013 Sep 5;150(2):527–532.
  • Lingford-Hughes AKalk N. Clinical neuroanatomy. In: Wright P, Stern J, Phelan M, editors. Core Psychiatry, 3rd edition. Edinburgh: Saunders - Elsevier; 2012: p. 13–34. ISBN 978-0-7020-3397-1
  • Ambrosi E, Arciniegas DB, Madan A, et al. Insula and amygdala resting-state functional connectivity differentiate bipolar from unipolar depression. Acta Psychiatr Scand. 2017 Jul;136(1):129–139.
  • Goya-Maldonado R, Brodmann K, Keil M, et al. Differentiating unipolar and bipolar depression by alterations in large-scale brain networks. Hum Brain Mapp. 2016 Feb;37(2):808–818.
  • Li M, Das T, Deng W, et al. Clinical utility of a short resting-state MRI scan in differentiating bipolar from unipolar depression. Acta Psychiatr Scand. 2017 Sep;136(3):288–299.
  • Liu Y, Wu X, Zhang J, et al. Altered effective connectivity model in the default mode network between bipolar and unipolar depression based on resting-state fMRI. J Affect Disord. 2015 Aug;15(182):8–17.
  • Wang Y, Zhong S, Jia Y, et al. Interhemispheric resting state functional connectivity abnormalities in unipolar depression and bipolar depression. Bipolar Disord. 2015 Aug;17(5):486–495.
  • Han K-M, De Berardis D, Fornaro M, et al. Differentiating between bipolar and unipolar depression in functional and structural MRI studies. Prog Neuropsychopharmacol Biol Psychiatry. 2018. doi:10.1016/j.pnpbp.2018.03.022. [Epub ahead of print].
  • He H, Yu Q, Du Y, et al. Resting-state functional network connectivity in prefrontal regions differs between unmedicated patients with bipolar and major depressive disorders. J Affect Disord. 2016 Jan;15(190):483–493.
  • Wang Y, Wang J, Jia Y, et al. Topologically convergent and divergent functional connectivity patterns in unmedicated unipolar depression and bipolar disorder. Transl Psychiatry. 2017 Jul 4;7(7):e1165.
  • Pang Y, Chen H, Wang Y, et al. Transdiagnostic and diagnosis-specific dynamic functional connectivity anchored in the right anterior insula in major depressive disorder and bipolar depression. Prog Neuropsychopharmacol Biol Psychiatry. 2018 Jul;13(85):7–15.
  • Satterthwaite TD, Kable JW, Vandekar L, et al. Common and dissociable dysfunction of the reward system in bipolar and unipolar depression. Neuropsychopharmacology. 2015 Aug;40(9):2258–2268.
  • Manelis A, Almeida JR, Stiffler R, et al. Anticipation-related brain connectivity in bipolar and unipolar depression: a graph theory approach. Brain. 2016 Sep;139(Pt 9):2554–2566.
  • Lichtenstein P, Yip BH, Bjork C, et al. Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet. 2009 Jan 17;373(9659):234–239.
  • Cardno AG, Owen MJ. Genetic relationships between schizophrenia, bipolar disorder, and schizoaffective disorder. Schizophr Bull. 2014 May;40(3):504–515.
  • Cross-Disorder Group of the Psychiatric GenomicsConsortium. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat Genet. 2013 Sep;45(9):984–94.
  • Tamminga CA, Ivleva EI, Keshavan MS, et al. Clinical phenotypes of psychosis in the bipolar-schizophrenia network on intermediate phenotypes (B-SNIP). Am J Psychiatry. 2013 Nov 1;170(11):1263–1274.
  • O’Donoghue S, Holleran L, Cannon DM, et al. Anatomical dysconnectivity in bipolar disorder compared with schizophrenia: A selective review of structural network analyses using diffusion MRI. J Affect Disord. 2017;209:217–228.
  • Dong D, Wang Y, Chang X, et al. Shared abnormality of white matter integrity in schizophrenia and bipolar disorder: A comparative voxel-based meta-analysis. Schizophr Res. 2017;185:41–50.
  • Li J, Tang Y, Womer F, et al. Two patterns of anterior insular cortex functional connectivity in bipolar disorder and schizophrenia. World J Biol Psychiatry. 2017;23:1–9.
  • Skatun KC, Kaufmann T, Brandt CL, et al. Thalamo-cortical functional connectivity in schizophrenia and bipolar disorder. Brain Imaging Behav. 2018 Jun;12(3):640–652.
  • Rashid B, Damaraju E, Pearlson GD, et al. Dynamic connectivity states estimated from resting fMRI Identify differences among Schizophrenia, bipolar disorder, and healthy control subjects. Front Hum Neurosci. 2014;8:897.
  • Anticevic A, Savic A, Repovs G, et al. Ventral anterior cingulate connectivity distinguished nonpsychotic bipolar illness from psychotic bipolar disorder and schizophrenia. Schizophr Bull. 2015 Jan;41(1):133–143.
  • Wu G, Wang Y, Mwansisya TE, et al. Effective connectivity of the posterior cingulate and medial prefrontal cortices relates to working memory impairment in schizophrenic and bipolar patients. Schizophr Res. 2014 Sep;158(1–3):85–90.
  • Vandevelde A, Leroux E, Delcroix N, et al. Fronto-subcortical functional connectivity in patients with schizophrenia and bipolar disorder during a verbal fluency task. World J Biol Psychiatry. 2017 Aug 8:1–9.
  • Mukherjee P, Sabharwal A, Kotov R, et al. Disconnection between amygdala and medial prefrontal cortex in psychotic disorders. Schizophr Bull. 2016 Jul;42(4):1056–1067.
  • Colombo RR, Schaufelberger MS, Santos LC, et al. Voxelwise evaluation of white matter volumes in first-episode psychosis. Psychiat Res. 2012 Jun 30;202(3):198–205.
  • Lu LH, Zhou XJ, Keedy SK, et al. White matter microstructure in untreated first episode bipolar disorder with psychosis: comparison with schizophrenia. Bipolar Disord. 2011 Nov-Dec;13(7–8):604–613.
  • Akiskal HS, Judd LL, Gillin JC, et al. Subthreshold depressions: clinical and polysomnographic validation of dysthymic, residual and masked forms. J Affect Disord. 1997 Aug;45(1–2):53–63.
  • Das P, Calhoun V, Malhi GS. Bipolar and borderline patients display differential patterns of functional connectivity among resting state networks. Neuroimage. 2014 Sep;98:73–81.
  • Orru G, Pettersson-Yeo W, Marquand AF, et al. Using support vector machine to identify imaging biomarkers of neurological and psychiatric disease: a critical review. Neurosci Biobehav Rev. 2012 Apr;36(4):1140–1152.
  • Librenza-Garcia D, Kotzian BJ, Yang J, et al. The impact of machine learning techniques in the study of bipolar disorder: A systematic review. Neurosci Biobehav Rev. 2017;80:538–554.
  • Schnack HG, Nieuwenhuis M, van Haren NE, et al. Can structural MRI aid in clinical classification? A machine learning study in two independent samples of patients with schizophrenia, bipolar disorder and healthy subjects. Neuroimage. 2014 1;Jan(84):299–306.
  • Redlich R, Almeida JJ, Grotegerd D, et al. Brain morphometric biomarkers distinguishing unipolar and bipolar depression. A voxel-based morphometry-pattern classification approach. JAMA Psychiatry. 2014 Nov;71(11):1222–1230.
  • Fung G, Deng Y, Zhao Q, et al. Distinguishing bipolar and major depressive disorders by brain structural morphometry: a pilot study. BMC Psychiatry. 2015 Nov;21(15):298.
  • Grotegerd D, Suslow T, Bauer J, et al. Discriminating unipolar and bipolar depression by means of fMRI and pattern classification: a pilot study. Eur Arch Psychiatry Clin Neurosci. 2013 Mar;263(2):119–131.
  • Grotegerd D, Stuhrmann A, Kugel H, et al. Amygdala excitability to subliminally presented emotional faces distinguishes unipolar and bipolar depression: an fMRI and pattern classification study. Hum Brain Mapp. 2014 Jul;35(7):2995–3007.
  • Mourao-Miranda J, Almeida JR, Hassel S, et al. Pattern recognition analyses of brain activation elicited by happy and neutral faces in unipolar and bipolar depression. Bipolar Disord. 2012 Jun;14(4):451–460.
  • Costafreda SG, Fu CH, Picchioni M, et al. Pattern of neural responses to verbal fluency shows diagnostic specificity for schizophrenia and bipolar disorder. BMC Psychiatry. 2011 Jan;28(11):18.
  • Frangou S, Dima D, Jogia J. Towards person-centered neuroimaging markers for resilience and vulnerability in bipolar disorder. Neuroimage. 2017 Jan 15;145(Pt B):230–237.
  • Roberts G, Lord A, Frankland A, et al. Functional dysconnection of the inferior frontal gyrus in young people with bipolar disorder or at genetic high risk. Biol Psychiatry. 2017 Apr 15;81(8):718–727.
  • Jie NF, Zhu MH, Ma XY, et al. Discriminating bipolar disorder from major depression based on SVM-FoBa: efficient feature selection with multimodal brain imaging data. IEEE Trans Auton Ment Dev. 2015 Dec;7(4):320–331.
  • Anticevic A, Cole MW, Repovs G, et al. Characterizing thalamo-cortical disturbances in schizophrenia and bipolar illness. Cereb Cortex. 2014 Dec;24(12):3116–3130.
  • Besga A, Termenon M, Grana M, et al. Discovering Alzheimer’s disease and bipolar disorder white matter effects building computer aided diagnostic systems on brain diffusion tensor imaging features. Neurosci Lett. 2012 Jun 27;520(1):71–76.
  • Librenza-Garcia D, Kotzian BJ, Yang J, et al. The impact of machine learning techniques in the study of bipolar disorder: a systematic review. Neurosci Biobehav Rev. 2017;80:538–554.
  • Bzdok D, Meyer-Lindenberg A. Machine learning for precision psychiatry: opportunities and challenges. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018 Mar;3; (3):223–230.
  • Fletcher PC, Grafton ST. Repeat after me: replication in clinical neuroimaging is critical. Neuroimage Clin. 2013;2:247–248.
  • Borgwardt S, Fusar-Poli P. White matter pathology–an endophenotype for bipolar disorder?. BMC Psychiatry. 2012;12:138.
  • Gitlin MJ, Swendsen J, Heller TL, et al. Relapse and impairment in bipolar disorder. Am J Psychiatry. 1995 Nov;152(11):1635–1640.
  • Schaffer A, Isometsa ET, Tondo L, et al. Epidemiology, neurobiology and pharmacological interventions related to suicide deaths and suicide attempts in bipolar disorder: part I of a report of the international society for bipolar disorders task force on suicide in bipolar disorder. Aust N Z J Psychiatry. 2015 Sep;49(9):785–802.

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