Abstract
Present time nosology has its roots in Kraepelin’s demarcation of schizophrenia and bipolar disorder. However, accumulating evidence has shed light on several commonalities between the two disorders, and some authors have advocated for the consideration of a disease continuum. Here, we review previous genetic, biological and pharmacological findings that provide the basis for this conceptualization. There is a cross-disease heritability, and they share single-nucleotide polymorphisms in some common genes. EEG and imaging patterns have a number of similarities, namely reduced white matter integrity and abnormal connectivity. Dopamine, serotonin, GABA and glutamate systems have dysfunctional features, some of which are identical among the disorders. Finally, cellular calcium regulation and mitochondrial function are, also, impaired in the two.
Keywords: Bipolar, schizophrenia, continuum, genetics, neurobiology, pharmacology.
[http://dx.doi.org/10.1016/S0920-9964(02)00328-6] [PMID: 12165371]
[http://dx.doi.org/10.1016/0010-440X(86)90059-3] [PMID: 3536286]
[http://dx.doi.org/10.1016/S0920-9964(97)00112-6] [PMID: 9468346]
[http://dx.doi.org/10.1097/YCO.0b013e3281a305ab] [PMID: 17551352]
[http://dx.doi.org/10.1016/j.schres.2019.01.024] [PMID: 30711315]
[http://dx.doi.org/10.1159/000090891] [PMID: 16508342]
[http://dx.doi.org/10.1016/j.jpsychires.2013.07.008] [PMID: 23907000]
[http://dx.doi.org/10.1016/j.neubiorev.2015.12.002] [PMID: 26691725]
[http://dx.doi.org/10.2174/1568026620666200131095328] [PMID: 32003690]
[http://dx.doi.org/10.3389/fpsyt.2020.00682] [PMID: 32765320]
[http://dx.doi.org/10.1016/S0140-6736(09)60072-6] [PMID: 19150704]
[http://dx.doi.org/10.1001/archpsyc.56.2.162] [PMID: 10025441]
[http://dx.doi.org/10.1176/ajp.143.9.1098] [PMID: 3752293]
[http://dx.doi.org/10.1001/archpsyc.1993.01820190029004] [PMID: 8317947]
[http://dx.doi.org/10.1176/appi.ajp.159.4.539] [PMID: 11925290]
[http://dx.doi.org/10.1017/S0033291709990419] [PMID: 19607751]
[http://dx.doi.org/10.1001/archpsyc.60.12.1209] [PMID: 14662553]
[http://dx.doi.org/10.1001/archpsyc.62.8.841] [PMID: 16061761]
[http://dx.doi.org/10.1001/archgenpsychiatry.2009.64] [PMID: 19581566]
[http://dx.doi.org/10.1016/S0140-6736(12)62129-1] [PMID: 23453885]
[http://dx.doi.org/10.1001/archpsyc.60.12.1187] [PMID: 14662550]
[http://dx.doi.org/10.1016/j.psychres.2019.06.010] [PMID: 31207455]
[http://dx.doi.org/10.1038/nrg3240] [PMID: 22777127]
[http://dx.doi.org/10.1038/s41588-019-0397-8] [PMID: 31043756]
[http://dx.doi.org/10.1038/ng.2711] [PMID: 23933821]
[http://dx.doi.org/10.1038/ng.940] [PMID: 21926974]
[http://dx.doi.org/10.1038/s41380-019-0622-y] [PMID: 31801967]
[http://dx.doi.org/10.1016/j.cell.2004.09.011] [PMID: 15454078]
[http://dx.doi.org/10.1016/j.nlm.2003.10.003] [PMID: 14990230]
[http://dx.doi.org/10.1523/JNEUROSCI.1531-05.2005] [PMID: 16251435]
[http://dx.doi.org/10.1101/lm.773208] [PMID: 18174367]
[http://dx.doi.org/10.1001/archgenpsychiatry.2010.96] [PMID: 20819988]
[http://dx.doi.org/10.1016/j.jaac.2012.06.005] [PMID: 22840553]
[http://dx.doi.org/10.1093/schbul/sbq009] [PMID: 20176860]
[http://dx.doi.org/10.1038/sj.mp.4002103] [PMID: 17925794]
[http://dx.doi.org/10.1016/S0896-6273(00)00087-8] [PMID: 11086985]
[http://dx.doi.org/10.1038/npp.2008.112] [PMID: 18668031]
[http://dx.doi.org/10.1002/glia.20612] [PMID: 18080294]
[http://dx.doi.org/10.1038/sj.mp.4001889] [PMID: 16940976]
[http://dx.doi.org/10.1001/archpsyc.62.6.642] [PMID: 15939841]
[http://dx.doi.org/10.1016/j.biopsych.2008.03.025] [PMID: 18466881]
[http://dx.doi.org/10.1021/cn200062k] [PMID: 22116789]
[http://dx.doi.org/10.1086/321969] [PMID: 11443544]
[http://dx.doi.org/10.1093/hmg/9.9.1415] [PMID: 10814723]
[http://dx.doi.org/10.1038/sj.mp.4001667] [PMID: 15940305]
[http://dx.doi.org/10.1093/hmg/ddg341] [PMID: 14532331]
[http://dx.doi.org/10.1086/425586] [PMID: 15386212]
[http://dx.doi.org/10.1016/j.biopsych.2006.03.032] [PMID: 16814263]
[http://dx.doi.org/10.1038/mp.2008.22] [PMID: 18317464]
[http://dx.doi.org/10.1038/sj.mp.4001669] [PMID: 15838535]
[http://dx.doi.org/10.1038/tpj.2010.40] [PMID: 20531374]
[http://dx.doi.org/10.1073/pnas.0500515102] [PMID: 15939883]
[http://dx.doi.org/10.1038/nature08185] [PMID: 19571811]
[http://dx.doi.org/10.1038/ng.2742] [PMID: 23974872]
[http://dx.doi.org/10.1371/journal.pgen.1005544] [PMID: 26540268]
[http://dx.doi.org/10.1176/appi.ajp.2013.13010126] [PMID: 24185241]
[http://dx.doi.org/10.1016/j.pscychresns.2012.05.001] [PMID: 23177922]
[http://dx.doi.org/10.1371/journal.pone.0232826] [PMID: 32379845]
[http://dx.doi.org/10.2174/138161212799316253] [PMID: 22239579]
[http://dx.doi.org/10.1016/j.jad.2008.10.007] [PMID: 19019455]
[http://dx.doi.org/10.1016/j.nicl.2019.101854] [PMID: 31121524]
[http://dx.doi.org/10.1176/appi.ajp.2013.12111448] [PMID: 23771210]
[http://dx.doi.org/10.1016/j.biopsych.2008.07.026] [PMID: 18814861]
[http://dx.doi.org/10.1371/journal.pone.0178089] [PMID: 28658249]
[http://dx.doi.org/10.1038/s41598-018-32355-9] [PMID: 30237410]
[http://dx.doi.org/10.1111/j.1399-5618.2008.00646.x] [PMID: 19133962]
[http://dx.doi.org/10.1017/S0033291714001810] [PMID: 25089761]
[http://dx.doi.org/10.1016/S0140-6736(03)14289-4] [PMID: 13678875]
[http://dx.doi.org/10.1016/S0361-9230(01)00528-7] [PMID: 11576756]
[http://dx.doi.org/10.1023/A:1020981510759] [PMID: 12462417]
[http://dx.doi.org/10.1016/j.neubiorev.2019.01.005] [PMID: 30629976]
[http://dx.doi.org/10.1093/schbul/sbt092] [PMID: 23851068]
[http://dx.doi.org/10.1016/j.neuroimage.2015.07.054] [PMID: 26216278]
[http://dx.doi.org/10.1016/j.pscychresns.2010.04.008] [PMID: 20553873]
[http://dx.doi.org/10.1001/jamapsychiatry.2013.3469] [PMID: 24306091]
[http://dx.doi.org/10.1073/pnas.1313093111] [PMID: 24778245]
[http://dx.doi.org/10.3389/fnins.2013.00064] [PMID: 23658536]
[http://dx.doi.org/10.1176/jnp.23.2.jnp121] [PMID: 21677237]
[http://dx.doi.org/10.1111/j.1460-9568.2005.04176.x] [PMID: 16029213]
[http://dx.doi.org/10.1007/s00429-019-01945-2] [PMID: 31451898]
[http://dx.doi.org/10.1073/pnas.0905314106]
[http://dx.doi.org/10.1093/brain/awl004] [PMID: 16399806]
[http://dx.doi.org/10.1016/j.biopsych.2012.01.025] [PMID: 22401986]
[http://dx.doi.org/10.3390/diagnostics11010095] [PMID: 33435624]
[http://dx.doi.org/10.1016/j.jad.2013.01.051] [PMID: 23489402]
[http://dx.doi.org/10.1016/j.pscychresns.2015.06.004] [PMID: 26123450]
[http://dx.doi.org/10.1016/j.nicl.2014.08.015] [PMID: 25379425]
[http://dx.doi.org/10.3389/fnhum.2014.00897] [PMID: 25426048]
[http://dx.doi.org/10.1017/S0033291709991000] [PMID: 19732478]
[http://dx.doi.org/10.1002/hbm.20463] [PMID: 17894392]
[http://dx.doi.org/10.1192/bjp.bp.113.129254] [PMID: 24434074]
[http://dx.doi.org/10.1016/j.schres.2014.06.033] [PMID: 25043264]
[http://dx.doi.org/10.1016/j.pscychresns.2012.02.003] [PMID: 22981426]
[http://dx.doi.org/10.1016/j.eurpsy.2007.07.006] [PMID: 17904824]
[http://dx.doi.org/10.1111/j.1600-0447.2004.00376.x] [PMID: 15352925]
[http://dx.doi.org/10.1080/09540260902962131] [PMID: 20374147]
[http://dx.doi.org/10.1111/j.1469-8986.2011.01327.x] [PMID: 22176721]
[http://dx.doi.org/10.1093/schbul/sbt179] [PMID: 24562492]
[http://dx.doi.org/10.1016/j.biopsych.2012.03.034] [PMID: 22572033]
[http://dx.doi.org/10.1016/j.tins.2018.12.004] [PMID: 30621912]
[http://dx.doi.org/10.1038/s41398-017-0071-9] [PMID: 29382821]
[http://dx.doi.org/10.1001/archpsyc.1995.03950180057008] [PMID: 7771917]
[http://dx.doi.org/10.1097/00004647-199703000-00010] [PMID: 9119906]
[http://dx.doi.org/10.1176/appi.ajp.159.10.1718] [PMID: 12359678]
[http://dx.doi.org/10.1007/BF02253582] [PMID: 1531387]
[http://dx.doi.org/10.1038/mp.2017.16] [PMID: 28289283]
[http://dx.doi.org/10.1002/hup.480] [PMID: 12766934]
[http://dx.doi.org/10.1017/S0033291700009132] [PMID: 3726006]
[http://dx.doi.org/10.1097/00004714-198512000-00006] [PMID: 4066999]
[http://dx.doi.org/10.1176/ajp.138.12.1624] [PMID: 7304798]
[http://dx.doi.org/10.1016/0163-8343(91)90041-T] [PMID: 1743505]
[http://dx.doi.org/10.1177/014107688708000620] [PMID: 3625697]
[PMID: 19015628]
[http://dx.doi.org/10.1016/j.mehy.2013.03.013] [PMID: 23557849]
[http://dx.doi.org/10.1176/jnp.9.1.1] [PMID: 9017523]
[http://dx.doi.org/10.1111/j.1471-4159.2005.03485.x] [PMID: 16277612]
[http://dx.doi.org/10.1017/S1092852918001013] [PMID: 29954475]
[http://dx.doi.org/10.1080/14728214.2020.1773792] [PMID: 32449404]
[http://dx.doi.org/10.1176/appi.ajp.2016.15081035] [PMID: 27282362]
[http://dx.doi.org/10.1016/S0165-0327(00)00226-3] [PMID: 11532527]
[http://dx.doi.org/10.1192/bjp.bp.108.057919] [PMID: 20044660]
[http://dx.doi.org/10.1016/j.biopsych.2003.09.017] [PMID: 14744462]
[http://dx.doi.org/10.1016/j.encep.2016.02.006] [PMID: 27000268]
[http://dx.doi.org/10.1016/S0893-133X(99)00042-1] [PMID: 10481837]
[http://dx.doi.org/10.1007/s11064-009-0048-z] [PMID: 19701707]
[http://dx.doi.org/10.1001/archpsyc.57.11.1061] [PMID: 11074872]
[http://dx.doi.org/10.1073/pnas.0703806104] [PMID: 17553960]
[http://dx.doi.org/10.1001/archpsyc.61.7.649] [PMID: 15237077]
[http://dx.doi.org/10.1016/j.schres.2007.06.023] [PMID: 17698324]
[http://dx.doi.org/10.1002/syn.21973] [PMID: 28316115]
[http://dx.doi.org/10.1016/j.neuropharm.2013.04.014] [PMID: 23628345]
[http://dx.doi.org/10.1177/0269881114563634] [PMID: 25586400]
[http://dx.doi.org/10.1016/j.schres.2004.02.016] [PMID: 15474907]
[http://dx.doi.org/10.1111/j.1399-5618.2012.01033.x] [PMID: 22834460]
[http://dx.doi.org/10.1016/j.schres.2005.06.012] [PMID: 16023328]
[http://dx.doi.org/10.1016/j.brainres.2006.09.011] [PMID: 17113057]
[http://dx.doi.org/10.1001/archpsyc.61.3.300] [PMID: 14993118]
[http://dx.doi.org/10.1016/j.ijdevneu.2010.08.007] [PMID: 20833242]
[http://dx.doi.org/10.1007/s11064-008-9865-8] [PMID: 18979198]
[http://dx.doi.org/10.1159/000441252] [PMID: 26550561]
[http://dx.doi.org/10.1016/S0165-0173(03)00203-0] [PMID: 14499463]
[http://dx.doi.org/10.1007/s12035-012-8293-6] [PMID: 22763587]
[http://dx.doi.org/10.1038/nrm1150] [PMID: 12838338]
[http://dx.doi.org/10.1007/s40263-016-0380-1] [PMID: 27638546]
[http://dx.doi.org/10.3390/ijms18122679] [PMID: 29232923]
[http://dx.doi.org/10.1523/JNEUROSCI.5251-14.2015] [PMID: 26311765]
[http://dx.doi.org/10.1007/s40473-020-00206-5]
[http://dx.doi.org/10.1016/j.neubiorev.2019.12.011] [PMID: 31821833]
[http://dx.doi.org/10.1159/000504496] [PMID: 31722343]
[http://dx.doi.org/10.1016/j.jpsychires.2016.12.007] [PMID: 27988330]
[http://dx.doi.org/10.1126/sciadv.aau8317] [PMID: 30775438]
[http://dx.doi.org/10.1016/j.bbi.2016.12.010] [PMID: 28003152]
[http://dx.doi.org/10.1016/j.schres.2020.02.010] [PMID: 32336581]
[http://dx.doi.org/10.1016/j.schres.2018.05.017] [PMID: 29859859]
[http://dx.doi.org/10.1002/ctm2.146] [PMID: 32898322]
[http://dx.doi.org/10.3389/fpsyt.2020.00156] [PMID: 32226399]