Specificity and Continuity of Schizophrenia and Bipolar Disorder: Relation to Biomarkers

Author(s): Yuji Yamada, Madoka Matsumoto, Kazuki Iijima, Tomiki Sumiyoshi*

Journal Name: Current Pharmaceutical Design

Volume 26 , Issue 2 , 2020

Become EABM
Become Reviewer

Abstract:

Schizophrenia and bipolar disorder overlap considerably in terms of symptoms, familial patterns, risk genes, outcome, and treatment response. This article provides an overview of the specificity and continuity of schizophrenia and mood disorders on the basis of biomarkers, such as genes, molecules, cells, circuits, physiology and clinical phenomenology. Overall, the discussions herein provided support for the view that schizophrenia, schizoaffective disorder and bipolar disorder are in the continuum of severity of impairment, with bipolar disorder closer to normality and schizophrenia at the most severe end. This approach is based on the concept that examining biomarkers in several modalities across these diseases from the dimensional perspective would be meaningful. These considerations are expected to help develop new treatments for unmet needs, such as cognitive dysfunction, in psychiatric conditions.

Keywords: Schizophrenia, bipolar disorder, psychosis, differential diagnosis, RDoC, spectrum, cognitive dysfunction.

[1]
Pearlson GD, Clementz BA, Sweeney JA, Keshavan MS, Tamminga CA. Does biology transcend the symptom-based boundaries of psychosis? Psychiatr Clin North Am 2016; 39(2): 165-74.
[http://dx.doi.org/10.1016/j.psc.2016.01.001] [PMID: 27216897]
[2]
Ebert A, Bär KJ. Emil kraepelin: a pioneer of scientific understanding of psychiatry and psychopharmacology. Indian J Psychiatry 2010; 52(2): 191-2.
[http://dx.doi.org/10.4103/0019-5545.64591] [PMID: 20838510]
[3]
Kasanin J. The acute schizoaffective psychoses. 1933. Am J Psychiatry 1994; 151(6)(Suppl.): 144-54.
[http://dx.doi.org/10.1176/ajp.151.6.144] [PMID: 8192190]
[4]
van Os J, Kapur S. Schizophrenia. Lancet 2009; 374(9690): 635-45.
[http://dx.doi.org/10.1016/S0140-6736(09)60995-8] [PMID: 19700006]
[5]
Insel TR, Cuthbert BN. Endophenotypes: bridging genomic complexity and disorder heterogeneity. Biol Psychiatry 2009; 66(11): 988-9.
[http://dx.doi.org/10.1016/j.biopsych.2009.10.008] [PMID: 19900610]
[6]
Insel T, Cuthbert B, Garvey M, et al. Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am J Psychiatry 2010; 167(7): 748-51.
[http://dx.doi.org/10.1176/appi.ajp.2010.09091379] [PMID: 20595427]
[7]
Clark LA, Cuthbert B, Lewis-Fernández R, Narrow WE, Reed GM. Three approaches to understanding and classifying mental disorder: ICD-11, DSM-5, and the national institute of mental health’s research domain criteria (RDoC). Psychol Sci Public Interest 2017; 18(2): 72-145.
[http://dx.doi.org/10.1177/1529100617727266] [PMID: 29211974]
[8]
Cardno AG, Owen MJ. Genetic relationships between schizophrenia, bipolar disorder, and schizoaffective disorder. Schizophr Bull 2014; 40(3): 504-15.
[http://dx.doi.org/10.1093/schbul/sbu016] [PMID: 24567502]
[9]
Kendler KS, Diehl SR. The genetics of schizophrenia: a current, genetic-epidemiologic perspective. Schizophr Bull 1993; 19(2): 261-85.
[http://dx.doi.org/10.1093/schbul/19.2.261] [PMID: 8322035]
[10]
Kendler KS, McGuire M, Gruenberg AM, O’Hare A, Spellman M, Walsh D. The roscommon family study. I. methods, diagnosis of probands, and risk of schizophrenia in relatives. Arch Gen Psychiatry 1993; 50(7): 527-40.
[http://dx.doi.org/10.1001/archpsyc.1993.01820190029004] [PMID: 8317947]
[11]
Lichtenstein P, Yip BH, Björk C, et al. Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet 2009; 373(9659): 234-9.
[http://dx.doi.org/10.1016/S0140-6736(09)60072-6] [PMID: 19150704]
[12]
Tsuang MT, Winokur G, Crowe RR. Morbidity risks of schizophrenia and affective disorders among first degree relatives of patients with schizophrenia, mania, depression and surgical conditions. Br J Psychiatry 1980; 137: 497-504.
[http://dx.doi.org/10.1192/bjp.137.6.497] [PMID: 7214104]
[13]
Maier W, Lichtermann D, Minges J, et al. Continuity and discontinuity of affective disorders and schizophrenia. Results of a controlled family study. Arch Gen Psychiatry 1993; 50(11): 871-83.
[http://dx.doi.org/10.1001/archpsyc.1993.01820230041004] [PMID: 8215813]
[14]
Bertelsen A, Gottesman II. Schizoaffective psychoses: genetical clues to classification. Am J Med Genet 1995; 60(1): 7-11.
[http://dx.doi.org/10.1002/ajmg.1320600103] [PMID: 7485238]
[15]
Cardno AG, Gottesman II. Twin studies of schizophrenia: from bow-and-arrow concordances to star wars Mx and functional genomics. Am J Med Genet 2000; 97(1): 12-7.
[http://dx.doi.org/10.1002/(SICI)1096-8628(200021)97:1<12:AID-AJMG3>3.0.CO;2-U] [PMID: 10813800]
[16]
Cardno AG, Marshall EJ, Coid B, et al. Heritability estimates for psychotic disorders: the maudsley twin psychosis series. Arch Gen Psychiatry 1999; 56(2): 162-8.
[http://dx.doi.org/10.1001/archpsyc.56.2.162] [PMID: 10025441]
[17]
Van Snellenberg JX, de Candia T. Meta-analytic evidence for familial coaggregation of schizophrenia and bipolar disorder. Arch Gen Psychiatry 2009; 66(7): 748-55.
[http://dx.doi.org/10.1001/archgenpsychiatry.2009.64] [PMID: 19581566]
[18]
Ripke S, O’Dushlaine C, Chambert K, et al. Multicenter genetic studies of schizophrenia consortium; psychosis endophenotypes international consortium; wellcome trust case control consortium 2. Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nat Genet 2013; 45(10): 1150-9.
[http://dx.doi.org/10.1038/ng.2742] [PMID: 23974872]
[19]
Psychiatric GWAS consortium bipolar disorder working group. Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nat Genet 2011; 43(10): 977-83.
[http://dx.doi.org/10.1038/ng.943] [PMID: 21926972]
[20]
Sullivan PF, Daly MJ, O’Donovan M. Genetic architectures of psychiatric disorders: the emerging picture and its implications. Nat Rev Genet 2012; 13(8): 537-51.
[http://dx.doi.org/10.1038/nrg3240] [PMID: 22777127]
[21]
Kraguljac NV, Reid M, White D, et al. Neurometabolites in schizophrenia and bipolar disorder - a systematic review and meta-analysis. Psychiatry Res 2012; 203(2-3): 111-25.
[http://dx.doi.org/10.1016/j.pscychresns.2012.02.003] [PMID: 22981426]
[22]
Keshavan MS, Stanley JA, Pettegrew JW. Magnetic resonance spectroscopy in schizophrenia: methodological issues and findings-part II. Biol Psychiatry 2000; 48(5): 369-80.
[http://dx.doi.org/10.1016/S0006-3223(00)00940-9] [PMID: 10978720]
[23]
Steen RG, Hamer RM, Lieberman JA. Measurement of brain metabolites by 1H magnetic resonance spectroscopy in patients with schizophrenia: a systematic review and meta-analysis. Neuropsychopharmacology 2005; 30(11): 1949-62.
[http://dx.doi.org/10.1038/sj.npp.1300850] [PMID: 16123764]
[24]
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(6): 969-95.
[http://dx.doi.org/10.1016/j.pnpbp.2006.03.012] [PMID: 16677749]
[25]
Sager TN, Topp S, Torup L, Hanson LG, Egestad B, Møller A. Evaluation of CA1 damage using single-voxel 1H-MRS and un-biased stereology: Can non-invasive measures of N-acetyl-asparate following global ischemia be used as a reliable measure of neuronal damage? Brain Res 2001; 892(1): 166-75.
[http://dx.doi.org/10.1016/S0006-8993(00)03274-1] [PMID: 11172761]
[26]
Deicken RF, Pegues MP, Anzalone S, Feiwell R, Soher B. Lower concentration of hippocampal N-acetylaspartate in familial bipolar I disorder. Am J Psychiatry 2003; 160(5): 873-82.
[http://dx.doi.org/10.1176/appi.ajp.160.5.873] [PMID: 12727690]
[27]
Ohrmann P, Siegmund A, Suslow T, et al. Evidence for glutamatergic neuronal dysfunction in the prefrontal cortex in chronic but not in first-episode patients with schizophrenia: a proton magnetic resonance spectroscopy study. Schizophr Res 2005; 73(2-3): 153-7.
[http://dx.doi.org/10.1016/j.schres.2004.08.021] [PMID: 15653258]
[28]
Frey BN, Stanley JA, Nery FG, et al. Abnormal cellular energy and phospholipid metabolism in the left dorsolateral prefrontal cortex of medication-free individuals with bipolar disorder: an in vivo 1H MRS study. Bipolar Disord 2007; 9(Suppl. 1): 119-27.
[http://dx.doi.org/10.1111/j.1399-5618.2007.00454.x] [PMID: 17543030]
[29]
Rüsch N, Tebartz van Elst L, Valerius G, et al. Neurochemical and structural correlates of executive dysfunction in schizophrenia. Schizophr Res 2008; 99(1-3): 155-63.
[http://dx.doi.org/10.1016/j.schres.2007.05.024] [PMID: 17616347]
[30]
Sharif-Barfeh Z, Beigoli S, Marouzi S, Sharif-Rad A, Asoodeh A, Chamani J. Multi-spectroscopic and HPLC studies of the interaction between estradiol and cyclophosphamide with human serum albumin: binary and ternary systems. J Solution Chem 2017; 46: 488-504.
[http://dx.doi.org/10.1007/s10953-017-0590-2]
[31]
Goldsmith DR, Rapaport MH, Miller BJ. A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression. Mol Psychiatry 2016; 21(12): 1696-709.
[http://dx.doi.org/10.1038/mp.2016.3] [PMID: 26903267]
[32]
Misiak B, Stańczykiewicz B, Kotowicz K, Rybakowski JK, Samochowiec J, Frydecka D. Cytokines and C-reactive protein alterations with respect to cognitive impairment in schizophrenia and bipolar disorder: a systematic review. Schizophr Res 2018; 192: 16-29.
[http://dx.doi.org/10.1016/j.schres.2017.04.015] [PMID: 28416092]
[33]
Gray LJ, Dean B, Kronsbein HC, Robinson PJ, Scarr E. Region and diagnosis-specific changes in synaptic proteins in schizophrenia and bipolar I disorder. Psychiatry Res 2010; 178(2): 374-80.
[http://dx.doi.org/10.1016/j.psychres.2008.07.012] [PMID: 20488553]
[34]
Ren X, Rizavi HS, Khan MA, Bhaumik R, Dwivedi Y, Pandey GN. Alteration of cyclic-AMP response element binding protein in the postmortem brain of subjects with bipolar disorder and schizophrenia. J Affect Disord 2014; 152-154: 326-33.
[http://dx.doi.org/10.1016/j.jad.2013.09.033] [PMID: 24148789]
[35]
Folsom TD, Thuras PD, Fatemi SH. Protein expression of targets of the FMRP regulon is altered in brains of subjects with schizophrenia and mood disorders. Schizophr Res 2015; 165(2-3): 201-11.
[http://dx.doi.org/10.1016/j.schres.2015.04.012] [PMID: 25956630]
[36]
Leber SL, Llenos IC, Miller CL, Dulay JR, Haybaeck J, Weis S. Homer1a protein expression in schizophrenia, bipolar disorder, and major depression. J Neural Transm (Vienna) 2017; 124(10): 1261-73.
[http://dx.doi.org/10.1007/s00702-017-1776-x] [PMID: 28815330]
[37]
Torrey EF, Barci BM, Webster MJ, Bartko JJ, Meador-Woodruff JH, Knable MB. Neurochemical markers for schizophrenia, bipolar disorder, and major depression in postmortem brains. Biol Psychiatry 2005; 57(3): 252-60.
[http://dx.doi.org/10.1016/j.biopsych.2004.10.019] [PMID: 15691526]
[38]
Novikova SI, He F, Cutrufello NJ, Lidow MS. Identification of protein biomarkers for schizophrenia and bipolar disorder in the postmortem prefrontal cortex using SELDI-TOF-MS ProteinChip profiling combined with MALDI-TOF-PSD-MS analysis. Neurobiol Dis 2006; 23(1): 61-76.
[http://dx.doi.org/10.1016/j.nbd.2006.02.002] [PMID: 16549361]
[39]
Arnone D, Cavanagh J, Gerber D, Lawrie SM, Ebmeier KP, McIntosh AM. Magnetic resonance imaging studies in bipolar disorder and schizophrenia: meta-analysis. Br J Psychiatry 2009; 195(3): 194-201.
[http://dx.doi.org/10.1192/bjp.bp.108.059717] [PMID: 19721106]
[40]
Ellison-Wright I, Bullmore E. Anatomy of bipolar disorder and schizophrenia: a meta-analysis. Schizophr Res 2010; 117(1): 1-12.
[http://dx.doi.org/10.1016/j.schres.2009.12.022] [PMID: 20071149]
[41]
Maggioni E, Bellani M, Altamura AC, Brambilla P. Neuroanatomical voxel-based profile of schizophrenia and bipolar disorder. Epidemiol Psychiatr Sci 2016; 25(4): 312-6.
[http://dx.doi.org/10.1017/S2045796016000275] [PMID: 27095442]
[42]
Nenadic I, Maitra R, Langbein K, et al. Brain structure in schizophrenia vs. psychotic bipolar I disorder: a VBM study. Schizophr Res 2015; 165(2-3): 212-9.
[http://dx.doi.org/10.1016/j.schres.2015.04.007] [PMID: 25935815]
[43]
Brambilla P, Perlini C, Rajagopalan P, et al. Schizophrenia severity, social functioning and hippocampal neuroanatomy: three-dimensional mapping study. Br J Psychiatry 2013; 202(1): 50-5.
[http://dx.doi.org/10.1192/bjp.bp.111.105700] [PMID: 23284150]
[44]
Altamura AC, Bertoldo A, Marotta G, et al. White matter metabolism differentiates schizophrenia and bipolar disorder: a preliminary PET study. Psychiatry Res 2013; 214(3): 410-4.
[http://dx.doi.org/10.1016/j.pscychresns.2013.08.011] [PMID: 24144506]
[45]
O’Donoghue S, Holleran L, Cannon DM, McDonald C. Anatomical dysconnectivity in bipolar disorder compared with schizophrenia: a selective review of structural network analyses using diffusion MRI. J Affect Disord 2017; 209: 217-28.
[http://dx.doi.org/10.1016/j.jad.2016.11.015] [PMID: 27930915]
[46]
Stephan KE, Friston KJ, Frith CD. Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring. Schizophr Bull 2009; 35(3): 509-27.
[http://dx.doi.org/10.1093/schbul/sbn176] [PMID: 19155345]
[47]
Ellison-Wright I, Bullmore E. Meta-analysis of diffusion tensor imaging studies in schizophrenia. Schizophr Res 2009; 108(1-3): 3-10.
[http://dx.doi.org/10.1016/j.schres.2008.11.021] [PMID: 19128945]
[48]
Nortje G, Stein DJ, Radua J, Mataix-Cols D, Horn N. Systematic review and voxel-based meta-analysis of diffusion tensor imaging studies in bipolar disorder. J Affect Disord 2013; 150(2): 192-200.
[http://dx.doi.org/10.1016/j.jad.2013.05.034] [PMID: 23810479]
[49]
Vederine FE, Wessa M, Leboyer M, Houenou J. A meta-analysis of whole-brain diffusion tensor imaging studies in bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35(8): 1820-6.
[http://dx.doi.org/10.1016/j.pnpbp.2011.05.009] [PMID: 21624424]
[50]
Baker JT, Holmes AJ, Masters GA, et al. Disruption of cortical association networks in schizophrenia and psychotic bipolar disorder. JAMA Psychiatry 2014; 71(2): 109-18.
[http://dx.doi.org/10.1001/jamapsychiatry.2013.3469] [PMID: 24306091]
[51]
Bullmore E. Functional network endophenotypes of psychotic disorders. Biol Psychiatry 2012; 71(10): 844-5.
[http://dx.doi.org/10.1016/j.biopsych.2012.03.019] [PMID: 22520728]
[52]
De Peri L, Crescini A, Deste G, Fusar-Poli P, Sacchetti E, Vita A. Brain structural abnormalities at the onset of schizophrenia and bipolar disorder: a meta-analysis of controlled magnetic resonance imaging studies. Curr Pharm Des 2012; 18(4): 486-94.
[http://dx.doi.org/10.2174/138161212799316253] [PMID: 22239579]
[53]
Skudlarski P, Schretlen DJ, Thaker GK, et al. Diffusion tensor imaging white matter endophenotypes in patients with schizophrenia or psychotic bipolar disorder and their relatives. Am J Psychiatry 2013; 170(8): 886-98.
[http://dx.doi.org/10.1176/appi.ajp.2013.12111448] [PMID: 23771210]
[54]
Grace AA, Gomes FV. The circuitry of dopamine system regulation and its disruption in schizophrenia: insights into treatment and prevention. Schizophr Bull 2019; 45(1): 148-57.
[http://dx.doi.org/10.1093/schbul/sbx199] [PMID: 29385549]
[55]
Chai XJ, Whitfield-Gabrieli S, Shinn AK, et al. Abnormal medial prefrontal cortex resting-state connectivity in bipolar disorder and schizophrenia. Neuropsychopharmacology 2011; 36(10): 2009-17.
[http://dx.doi.org/10.1038/npp.2011.88] [PMID: 21654735]
[56]
Ongür D, Price JL. The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. Cereb Cortex 2000; 10(3): 206-19.
[http://dx.doi.org/10.1093/cercor/10.3.206] [PMID: 10731217]
[57]
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; 13(9): 829-57.
[http://dx.doi.org/10.1038/mp.2008.82] [PMID: 18574483]
[58]
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; 67(5): 422-31.
[http://dx.doi.org/10.1016/j.biopsych.2009.11.025] [PMID: 20159144]
[59]
Gilbert SJ, Spengler S, Simons JS, et al. Functional specialization within rostral prefrontal cortex (area 10): a meta-analysis. J Cogn Neurosci 2006; 18(6): 932-48.
[http://dx.doi.org/10.1162/jocn.2006.18.6.932] [PMID: 16839301]
[60]
Vinogradov S, Luks TL, Schulman BJ, Simpson GV. Deficit in a neural correlate of reality monitoring in schizophrenia patients. Cereb Cortex 2008; 18(11): 2532-9.
[http://dx.doi.org/10.1093/cercor/bhn028] [PMID: 18321870]
[61]
Buckner RL, Andrews-Hanna JR, Schacter DL. The brain’s default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci 2008; 1124: 1-38.
[http://dx.doi.org/10.1196/annals.1440.011] [PMID: 18400922]
[62]
Du Y, Pearlson GD, Lin D, et al. Identifying dynamic functional connectivity biomarkers using GIG-ICA: Application to schizophrenia, schizoaffective disorder, and psychotic bipolar disorder. Hum Brain Mapp 2017; 38(5): 2683-708.
[http://dx.doi.org/10.1002/hbm.23553] [PMID: 28294459]
[63]
Ivleva EI, Bidesi AS, Keshavan MS, et al. Gray matter volume as an intermediate phenotype for psychosis: bipolar-schizophrenia network on intermediate phenotypes (B-SNIP). Am J Psychiatry 2013; 170(11): 1285-96.
[http://dx.doi.org/10.1176/appi.ajp.2013.13010126] [PMID: 24185241]
[64]
Argyelan M, Ikuta T, DeRosse P, et al. Resting-state fMRI connectivity impairment in schizophrenia and bipolar disorder. Schizophr Bull 2014; 40(1): 100-10.
[http://dx.doi.org/10.1093/schbul/sbt092] [PMID: 23851068]
[65]
Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry 1996; 153(3): 321-30.
[http://dx.doi.org/10.1176/ajp.153.3.321] [PMID: 8610818]
[66]
Daban C, Martinez-Aran A, Torrent C, et al. Specificity of cognitive deficits in bipolar disorder versus schizophrenia. A systematic review. Psychother Psychosom 2006; 75(2): 72-84.
[http://dx.doi.org/10.1159/000090891] [PMID: 16508342]
[67]
Bora E, Yucel M, Pantelis C. Cognitive endophenotypes of bipolar disorder: a meta-analysis of neuropsychological deficits in euthymic patients and their first-degree relatives. J Affect Disord 2009; 113(1-2): 1-20.
[http://dx.doi.org/10.1016/j.jad.2008.06.009] [PMID: 18684514]
[68]
Burdick KE, Goldberg JF, Harrow M. Neurocognitive dysfunction and psychosocial outcome in patients with bipolar I disorder at 15-year follow-up. Acta Psychiatr Scand 2010; 122(6): 499-506.
[http://dx.doi.org/10.1111/j.1600-0447.2010.01590.x] [PMID: 20637012]
[69]
Reichenberg A, Harvey PD, Bowie CR, et al. Neuropsychological function and dysfunction in schizophrenia and psychotic affective disorders. Schizophr Bull 2009; 35(5): 1022-9.
[http://dx.doi.org/10.1093/schbul/sbn044] [PMID: 18495643]
[70]
Hill SK, Ragland JD, Gur RC, Gur RE. Neuropsychological profiles delineate distinct profiles of schizophrenia, an interaction between memory and executive function, and uneven distribution of clinical subtypes. J Clin Exp Neuropsychol 2002; 24(6): 765-80.
[http://dx.doi.org/10.1076/jcen.24.6.765.8402] [PMID: 12424651]
[71]
Burdick KE, Goldberg TE, Cornblatt BA, et al. The MATRICS consensus cognitive battery in patients with bipolar I disorder. Neuropsychopharmacology 2011; 36(8): 1587-92.
[http://dx.doi.org/10.1038/npp.2011.36] [PMID: 21451499]
[72]
Burdick KE, Russo M, Frangou S, et al. Empirical evidence for discrete neurocognitive subgroups in bipolar disorder: clinical implications. Psychol Med 2014; 44(14): 3083-96.
[http://dx.doi.org/10.1017/S0033291714000439] [PMID: 25065409]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 26
ISSUE: 2
Year: 2020
Page: [191 - 200]
Pages: 10
DOI: 10.2174/1381612825666191216153508

Article Metrics

PDF: 33
HTML: 7
EPUB: 3
PRC: 1