Genetic factors are known to contribute to the etiology of bipolar illness, but the actual genetic mechanisms remain to be clarified.
Methods:
This paper reviews the research undertaken to establish the genetic basis of bipolar illness and to elucidate the nature of its genetic predisposition.
Results:
The presented findings suggest that bipolar affective disorder is a heterogeneous condition characterized by a complex relationship between the genetic susceptibility and the clinical presentation. Linkage studies have generated promising and replicated findings on chromosomes 18 and 21.
Conclusion:
In spite of the methodological difficulties inherent in the genetic study of psychiatric disorders, recent investigations have made important advances and promise to identify specific susceptibility genes.
StenstedtA.A study in manic depressive psychosis: Clinical, social and genetic investigations. Acta Psychiatr Scand Suppl1952;79:1–112.
2.
PerrisC.A study of bipolar (manic-depressive) and unipolar recurrent depressive psychoses, II: Childhood environment and precipitating factors. Acta Psychiatr Scand Suppl1966;194:1–189.
3.
AngstJ.On the etiology and nosology of endogenous depressive psychoses: A genetic, sociologic and clinical study. Monographien aus dem Gesamtgebiete der Neurologie und Psychiatrie1966;112:1–118.
4.
GoetzlUGreenRWhybrowPJacksonR.X linkage revisited: A further family study of manic-depressive illness. Arch Gen Psychiatry1974;31:665–72.
5.
HelzerJEWinokurG.A family interview study of male manic depressives. Arch Gen Psychiatry1974;31:73–7.
6.
GershonESMarkACohenNBelizonNBaronMKnobeKE. Transmitted factors in the morbid risk of affective disorders: A controlled study. J Psychiatr Res1975;12:283–99.
7.
VidebechT.A study of genetic factors, childhood bereavement, and premorbid personality traits in patients with anancastic endogenous depression. Acta Psychiatr Scand1975;52:178–222.
8.
JamesNMChapmanCJ. A genetic study of bipolar affective disorder. Br J Psychiatry1975;126:449–56.
9.
TsuangMTWinokurGCroweRR. Morbidity risks of schizophrenia and affective disorders among first degree relatives of patients with schizophrenia, mania, depression and surgical conditions. Br J Psychiatry1980;137:497–504.
10.
TaylorMAAbramsR.Reassessing the bipolar-unipolar dichotomy. J Affect Disord1980;2:195–217.
11.
GershonESHamovitJGuroffJJDibbleELeckmanJFSceeryW, and others. A family study of schizoaffective, bipolar I, bipolar II, unipolar, and normal control probands. Arch Gen Psychiatry1982;39:1157–67.
12.
RiceJReichTAndreasenNCEndicottJVan EerdeweghMFishmanR, and others. The familial transmission of bipolar illness. Arch Gen Psychiatry1987;44:441–7.
13.
WeissmanMMGershonESKiddKKPrusoffBALeckmanJFDibbleE, and others. Psychiatric disorders in the relatives of probands with affective disorders: The Yale University–National Institute of Mental Health Collaborative Study. Arch Gen Psychiatry1984;41:13–21.
McGuffinPKatzR.The genetics of depression and manic-depressive disorder. Br J Psychiatry1989;155:294–304.
16.
MendlewiczJRainerJD. Adoption study supporting genetic transmission in manic-depressive illness. Nature1977;268:327–9.
17.
CadoretRJ. Evidence for genetic inheritance of primary affective disorder in adoptees. Am J Psychiatry1978;135:463–6.
18.
WenderPHKetySSRosenthalDSchulsingerFOrtmannJLundeI.Psychiatric disorders in the biological and adoptive families of adopted individuals with affective disorders. Arch Gen Psychiatry1986;43:923–9.
19.
von KnorringALCloningerCRBohmanMSigvardssonS.An adoption study of depressive disorders and substance abuse. Arch Gen Psychiatry1983;40:943–50.
20.
SimpsonSGFolsteinSEMeyersDAMcMahonFJBruscoDMDePauloJRJr.Bipolar II: The most common bipolar phenotype?Am J Psychiatry1993;150:901–3.
21.
DePauloJRJrSimpsonSGGayleJOFolsteinSE. Bipolar II disorder in six sisters. J Affect Disord1990;19:259–64.
22.
HeunRMaierW.The distinction of bipolar II disorder from bipolar I and recurrent unipolar depression: Results of a controlled family study. Acta Psychiatr Scand1993;87:279–84.
23.
EndicottJNeeJAndreasenNClaytonPKellerMCoryellW.Bipolar II: Combine or keep separate?J Affect Disord1985;8:17–28.
24.
CoryellWEndicottJReichTAndreasenNKellerM.A family study of bipolar II disorder. Br J Psychiatry1984;145:49–54.
25.
RiceJPMcDonald-ScottPEndicottJCoryellWGroveWMKellerMB, and others. The stability of diagnosis with an application to bipolar II disorder. Psychiatry Res1986;19:285–96.
26.
NurnbergerJJrGuroffJJHamovitJBerrettiniWGershonE.A family study of rapid-cycling bipolar illness. J Affect Disord1988;15:87–91.
27.
CoryellWEndicottJKellerM.Rapidly cycling affective disorder: Demographics, diagnosis, family history, and course. Arch Gen Psychiatry1992;49:126–31.
28.
BlackerDLavoriPWFaraoneSVTsuangMT. Unipolar relatives in bipolar pedigrees: A search for indicators of underlying bipolarity. Am J Med Genet1993;48:192–9.
29.
CrowTJ. A continuum of psychosis, one human gene, and not much else—the case for homogeneity. Schizophr Res1995;17:135–45.
30.
WeissmanMMFinkMEndicottJTaylorMAKendlerKSWinokurG, and others. Discussion of debate: Is there a genetic Kraepelinian dichotomy for manic-depressive illness and schizophrenia? In: GershonESCloningerCR, editors. Genetic approaches to mental disorders. Washington (DC): American Psychiatric Press; 1994. p 193–202.
31.
KendlerKSMcGuireMGruenbergAMO'HareASpellmanMWalshD.The Roscommon family study. IV: Affective illness, anxiety disorders, and alcoholism in relatives. Arch Gen Psychiatry1993;50:952–60.
32.
GershonESDeLisiLEHamovitJNurnbergerJIJrMaxwellMESchreiberJ, and others. A controlled family study of chronic psychoses. Schizophrenia and schizoaffective disorder. Arch Gen Psychiatry1988;45:328–36.
33.
MaierWLichtermannDMingesJHeunRHallmayerJBenkertO.Schizoaffective disorder and affective disorders with mood-incongruent psychotic features: Keep separate or combine? evidence from a family study. Am J Psychiatry1992;149:1666–73.
34.
DunnerDLHenselBMFieveRR. Bipolar illness: Factors in drinking behaviour. Am J Psychiatry1979;136:583–5.
35.
MaierWLichtermannDMingesJDelmoCHeunR.The relationship between bipolar disorder and alcoholism: A controlled family study. Psychol Med1995;25:787–96.
36.
MaierWMerikangasK.Co-occurrence and cotransmission of affective disorders and alcoholism in families. Br J Psychiatry Suppl1996;30:93–100.
37.
WinokurGCoryellWAkiskalHSMaserJDKellerMBEndicottJ, and others. Alcoholism in manic-depressive (bipolar) illness: Familial illness, course of illness, and the primary-secondary distinction. Am J Psychiatry1995;152:365–72.
38.
ToddRDGellerBNeumanRFoxLWHickokJ.Increased prevalence of alcoholism in relatives of depressed and bipolar children. J Am Acad Child Adolesc Psychiatry1996;35:716–24.
39.
VaillantGERostonDMcHugoGJ. An intriguing association between ancestral mortality and male affective disorder. Arch Gen Psychiatry1992;49:709–15.
40.
AngstJFreyRLohmeyerBZerbin-RudinE.Bipolar manic-depressive psychoses: Results of a genetic investigation. Hum Genet1980;55:237–54.
41.
GrofPAldaMGrofEZvolskyPWalshM.Lithium response and genetics of affective disorders. J Affect Disord1994;32:85–95.
42.
ReichTClaytonPJWinokurG.Family history studies, V: The genetics of mania. Am J Psychiatry1969;125:1358–69.
43.
WinokurGTannaVL. Possible role of X-linked dominant factor in manic depressive disease. Diseases of the Nervous System1969;30:89–94.
44.
MendlewiczJFleissJLFieveRR. Evidence for X-linkage in the transmission of manic-depressive illness. JAMA1972;222:1624–7.
45.
GershonESBaronMLeckmanJF. Genetic models of the transmission of affective disorders. J Psychiatr Res1975;12:301–17.
46.
GershonESBunneyWEJrLeckmanJFEerdeweghMDeBaucheBA. The inheritance of affective disorders: A review of data and of hypotheses. Behav Genet1976;6:227–61.
47.
SmeraldiEPetroccioneAGasperiniMMacciardiFOrsiniA.The search for genetic homogeneity in affective disorders. J Affect Disord1984;7:99–107.
48.
PaulsDLBaileyJNCarterASAllenCREgelandJA. Complex segregation analyses of old order Amish families ascertained through bipolar I individuals. Am J Med Genet1995;60:290–7.
49.
SpenceMAFlodmanPLSadovnickADBailey-WilsonJEAmeliHRemickRA. Bipolar disorder: Evidence for a major locus. Am J Med Genet1995;60:370–6.
50.
AldaMGrofPGrofEZvolskyPWalshM.Mode of inheritance in families of patients with lithium-responsive affective disorders. Acta Psychiatr Scand1994;90:304–10.
51.
AldaMGrofECavazzoniPDuffyAMartinRBRavindranL, and others. Autosomal recessive inheritance in families of responders to lithium prophylaxis? J Affect Disord1997; Forthcoming.
52.
GoldinLRGershonESTargumSDSparkesRSMcGinnissM.Segregation and linkage analyses in families of patients with bipolar, unipolar, and schizoaffective mood disorders. Am J Hum Genet1983;35:274–87.
53.
TureckiGRouleauGAMariJJMorganK.A systematic evaluation of linkage studies in bipolar disorder. Acta Psychiatr Scand1996;93:317–26.
54.
KeremBRommensJMBuchananJAMarkiewiczDCoxTKChakravartiA, and others. Identification of the cystic fibrosis gene: Genetic analysis. Science1989;245:1073–80.
55.
St ClairD.Genetics of Alzheimer's disease: Some molecular understanding of a diverse phenotype. Br J Psychiatry1994;164:153–6.
56.
SchellenbergGD. Progress in Alzheimer's disease genetics. Curr Opin Neurol1995;8:262–7.
57.
AitmanTJToddJA. Molecular genetics of diabetes mellitus. Baillieres Clin Endocrinol Metab1995;9:631–56.
58.
PillayTSLangloisWJOlefskyJM. The genetics of non-insulin-dependent diabetes mellitus. Adv Genet1995;32:51–98.
59.
FishmanPMSuarezBHodgeSEReichT.A robust method for the detection of linkage in familial disease. Am J Hum Genet1978;30:308–21.
60.
RischN.Linkage strategies for genetically complex traits, II: The power of affected relative pairs. Am J Hum Genet1990;46:229–41.
61.
WeeksDELangeK.A multilocus extension of the affected-pedigree-member method of linkage analysis. Am J Hum Genet1992;50:859–68.
62.
MortonNE. Sequential tests for the detection of linkage. Am J Hum Genet1955;7:277–318.
63.
KruglyakLDalyMJReeve-DalyMPLanderES. Parametric and nonparametric linkage analysis: A unified multipoint approach. Am J Hum Genet1996; 58:1347–63.
64.
GershonESBunneyWEJr.The question of X-linkage in bipolar manic-depressive illness. J Psychiatr Res1977;13:99–117.
65.
GershonESMatthysseS.X-linkage: Ascertainment through doubly ill probands. J Psychiatr Res1977;13:161–8.
66.
HebebrandJ.A critical appraisal of X-linked bipolar illness. Evidence for the assumed mode of inheritance is lacking. Br J Psychiatry1992;160:7–11.
67.
SmeraldiENegriFMelicaAMScorza-SmeraldiRFabioGBonaraP, and others. HLA typing and affective disorders: A study in the Italian population. Neuropsychobiology1978;4:344–52.
68.
WeitkampLRStancerHCPersadEFloodCGuttormsenS.Depressive disorders and HLA: A gene on chromosome 6 that can affect behaviour. N Engl J Med1981;305: 1301–6.
69.
StancerHCWeitkampLRPersadEFloodCJornaTGuttormsenSA, and others. Confirmation of the relationship of HLA (chromosome 6) genes to depression and manic depression, II: The Ontario follow-up and analysis of 117 kindreds. Ann Hum Genet1988;52:279–98.
70.
GoldinLRClerget-DarpouxFGershonES. Relationship of HLA to major affective disorder not supported. Psychiatry Res1982;7:29–45.
71.
SuarezBKCroughanJ.Is the major histocompatibility complex linked to genes that increase susceptibility to affective disorder? a critical appraisal. Psychiatry Res1982;7:19–27.
72.
SimpsonSGFolsteinSEMeyersDADePauloJR. Assessment of lineality in bipolar I linkage studies. Am J Psychiatry1992;149:1660–5.
73.
DibCFaureSFizamesCSamsonDDrouotNVignalA, and others. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature1996;380:152–4.
74.
EgelandJAGerhardDSPaulsDLSussexJNKiddKKAllenCR, and others. Bipolar affective disorders linked to DNA markers on chromosome 11. Nature1987;325:783–7.
75.
BaronMRischNHamburgerRMandelBKushnerSNewmanM, and others. Genetic linkage between X-chromosome markers and bipolar affective illness. Nature1987;326:289–92.
76.
Detera-WadleighSDBerrettiniWHGoldinLRBoormanDAndersonSGershonES. Close linkage of c-Harvey-ras-1 and the insulin gene to affective disorder is ruled out in three North American pedigrees. Nature1987;325:806–8.
77.
BerrettiniWHGoldinLRGelernterJGejmanPVGershonESDetera-WadleighS.X-chromosome markers and manic-depressive illness: Rejection of linkage to Xq28 in nine bipolar pedigrees. Arch Gen Psychiatry1990;47:366–73.
78.
KelsoeJRGinnsEIEgelandJAGerhardDSGoldsteinAMBaleSJ, and others. Re-evaluation of the linkage relationship between chromosome 11p loci and the gene for bipolar affective disorder in the Old Order Amish. Nature1989;342:238–43.
79.
BaronMFreimerNFRischNLererBAlexanderJRStraubRE, and others. Diminished support for linkage between manic depressive illness and X-chromosome markers in three Israeli pedigrees. Nat Genet1993;3:49–55.
80.
BerrettiniWHFerraroTNGoldinLRWeeksDEDetera-WadleighSNurnbergerJIJr, and others. Chromosome 18 DNA markers and manic-depressive illness: Evidence for a susceptibility gene. Proc Natl Acad Sci U S A1994;91:5918–21.
81.
StineOCXuJKoskelaRMcMahonFJGschwendMFriddleC, and others. Evidence for linkage of bipolar disorder to chromosome 18 with a parent-of-origin effect. Am J Hum Genet1995;57:1384–94.
82.
XuJMcMahonFJStineOCMcInnisMGSimpsonSGDePauloJR, and others. A two-locus analysis of chromosome 18 loci and the expression of bipolar phenotype in paternal transmitted pedigrees [abstract]. Am J Hum Genet (Suppl) 1996;59:A243.
83.
FreimerNBReusVIEscamillaMAMcInnesLASpesnyMLeonP, and others. Genetic mapping using haplotype, association and linkage methods suggests a locus for severe bipolar disorder (BPI) at 18q22-q23. Nat Genet1996;12:436–41.
84.
McInnesLAEscamillaMAServiceSKReusVILeonPSilvaS, and others. A complete genome screen for genes predisposing to sever bipolar disorder in two Costa Rican pedigrees. Proc Natl Acad Sci U S A1996;93:13060–5.
85.
RischNBotsteinD.A manic depressive history. Nat Genet1996;12:351–3.
86.
BardenNPlanteMRochetteDGagneBBordeleauLLabergeC, and others. Genome-wide microsatellite marker linkage study of bipolar affective disorders in a very large pedigree derived from a homogeneous population in Quebec points to susceptibility locus on chromosome 12 [abstract]. Psychiatr Genet1996;6:145–6.
87.
PaulsDLOttJPaulSMAllenCRFannCSCarulliJP, and others. Linkage analyses of chromosome 18 markers do not identify a major susceptibility locus for bipolar affective disorder in the Old Order Amish. Am J Hum Genet1995;57:636–43.
88.
LabudaMCMaldonadoMMarshallDOttenKGerhardDS. Afollow-up report of a genome search for affective disorder predisposition loci in the Old Order Amish. Am J Hum Genet1996;59:1343–62.
89.
StraubRELehnerTLuoYLothJEShaoWSharpeL, and others. A possible vulnerability locus for bipolar affective disorder on chromosome 21q22.3. Nat Genet1994;8:291–6.
90.
GurlingHSmythCKalsiGMoloneyERifkinLO'NeillJ, and others. Linkage findings in bipolar disorder. Nat Genet1995;10:8–9.
91.
Detera-WadleighSDBadnerJAGoldinLRBerrettiniWHSandersARRollinsDY, and others. Affected-sib-pair analyses reveal support of prior evidence for a susceptibility locus for bipolar disorder, on 21q. Am J Hum Genet1996;58:1279–85.
92.
BlackwoodDHHeLMorrisSWMcLeanAWhittonCThomsonM, and others. A locus for bipolar affective disorder on chromosome 4p. Nat Genet1996;12:427–30.
93.
GinnsEIOttJEgelandJAAllenCRFannCSPaulsDL, and others. A genome-wide search for chromosomal loci linked to bipolar affective disorder in the Old Order Amish. Nat Genet1996;12:431–5.
94.
SuarezBKHampeCLVan EerdeweghP.Problems of replicating linkage claims in psychiatry. In: GershonESCloningerCR, editors. Genetic approaches to mental disorders. Washington (DC): American Psychiatric Press; 1994. p 23–46.
95.
KendlerKS. Discussion: Genetic analysis. In: GershonESCloningerCR, editors. Genetic approaches to mental disorders. Washington (DC): American Psychiatric Press; 1994. p 99–106.
96.
BenjaminJGershonES. Genetic discoveries in human behavior: Small effect genes loom large. Biol Psychiatry1996;40:313–6.
97.
GershonESGoldinLR. Replication of genetic linkage by follow-up of previously studied pedigrees. Am J Hum Genet1994;54:715–8.
98.
GreenbergDA. Linkage analysis of “necessary” disease loci versus “susceptibility” loci. Am J Hum Genet1993;52:135–43.
99.
RischNMerikangasK.The future of genetic studies of complex human diseases. Science1996;273:1516–7.
100.
BrewertonDAJosephJ.Bunim Memorial Lecture: HLA-B27 and the inheritance of susceptibility to rheumatic disease. Arthritis Rheum1976;19:656–68.
101.
LangdonNWelshKIvan DamMVaughanRWParkesD.Genetic markers in narcolepsy. Lancet1984;2:1178–80.
102.
StrittmatterWJSaundersAMSchmechelDPericak-VanceMEnghildJSalvesenGS, and others. Apolipoprotein E: High-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci U S A1993;90:1977–81.
103.
ChakrabortyRWeissKM. Admixture as a tool for finding linked genes and detecting that difference from allelic association between loci. Proc Natl Acad Sci U S A1988;85:9119–23.
104.
FalkCTRubinsteinP.Haplotype relative risks: An easy way to construct a proper control sample for risk calculations. Ann Hum Genet1987;51:227–33.
SpielmanRSMcGinnisREEwensWJ. Transmission test for linkage disequilibrium: The insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet1993;52:506–16.
107.
LavoriPWKellerMBRothSL. Affective disorders and ABO blood groups: New data and a reanalysis of the literature using the logistic transformation of proportions. J Psychiatr Res1984;18:119–29.
108.
GrofPAldaMGrofEFoxDCameronP.The challenge of predicting response to stabilising lithium treatment: The importance of patient selection. Br J Psychiatry Suppl1993;21:16–9.
109.
LeboyerMMalafosseABoularandSCampionDGheysenFSamolykD, and others. Tyrosine hydroxylase polymorphisms associated with manic-depressive illness [letter]. Lancet1990;335:1219.
110.
MalletJMeloniRLaurentC.Catecholamine metabolism and psychiatric or behavioral disorders. Curr Opin Genet Dev1994;4:419–26.
111.
ToddRDO'MalleyKL. Population frequencies of tyrosine hydroxylase restriction fragment length polymorphisms in bipolar affective disorder. Biol Psychiatry1989;25:626–30.
112.
KornerJFritzeJProppingP.RFLP alleles at the tyrosine hydroxylase locus: No association found to affective disorders. Psychiatry Res1990;32:275–80.
CavazzoniPAldaMTureckiGRouleauGGrofEMartinR, and others. Lithium-responsive affective disorders—no association with the tyrosine hydroxylase gene. Psychiatry Res1996;64:91–6.
115.
NothenMMErdmannJKornerJLanczikMFritzeJFimmersR, and others. Lack of association between dopamine D1 and D2 receptor genes and bipolar affective disorder. Am J Psychiatry1992;149:199–201.
116.
ParsianAChakravertySToddRD. Possible association between the dopamine D3 receptor gene and bipolar affective disorder. Am J Med Genet1995;60:234–7.
117.
YonedaHSakaiTIshidaTInayamaYNonomuraYKonoY, and others. An association between manic-depressive illness and a pseudoautosomal DNA marker. Am J Hum Genet1992;51:1172–3.
118.
ParsianAToddRD. Bipolar disorder and the pseudoautosomal region: An association study. Am J Med Genet1994;54:5–7.
119.
ErdmannJShimron-AbarbanellDCichonSAlbusMMaierWLichtermannD, and others. Systematic screening for mutations in the promoter and the coding region of the 5-HT1A gene. Am J Med Genet1995;60:393–9.
120.
GutierrezBArranzMFananasLVallesVGuillamatRvan OsJ, and others. 5HT2A receptor gene and bipolar affective disorder [letter]. Lancet1995;346:969.
121.
LimLCPowellJFMurrayRGillM.Monoamine oxidase A gene and bipolar affective disorder. Am J Hum Genet1994;54:1122–4.
122.
KawadaYHattoriMDaiXYNankoS.Possible association between monoamine oxidase A gene and bipolar affective disorder. Am J Hum Genet1995;56:335–6.
123.
NothenMMEggermannKAlbusMBorrmannMRietschelMKornerJ, and others. Association analysis of the monoamine oxidase A gene in bipolar affective disorder by using family-based internal controls. Am J Hum Genet1995;57:975–8.
124.
TureckiGAldaMGrofPGrofEMartinRCavazzoniPA, and others. No association between chromosome-18 markers and lithium responsive affective disorders. Psychiatry Res1996;63:17–23.
125.
KunugiHTatsumiMSakaiTHattoriMNankoS.Serotonin transporter gene polymorphism and affective disorder [letter]. Lancet1996;347:1340.
126.
CollierDAStoberGLiTHeilsACatalanoMDi BellaD, and others. Susceptibility to bipolar affective disorders and unipolar depression is influenced by allelic variation of functional serotonin transporter expression [abstract]. Psychiatr Genet1996;6:147.
127.
CraddockNReesMNortonNFeldmanEMcGuffinPOwenMJ. Association between bipolar disorder and the VNTR polymorphism in intron 2 of the human serotonin transporter gene (HSERT) [abstract]. Psychiatr Genet1996;6:147.
128.
OgilvieADBattersbySBubbVJFinkGHarmarAJGoodwinGM, and others. Polymorphism in serotonin transporter gene associated with susceptibility to major depression. Lancet1996;347:731–3.
129.
StoberGHeilsALeschKP. Serotonin transporter gene polymorphism and affective disorder. Lancet1996;347:1340–1.
130.
LeschKPGrossJFranzekEWolozinBLRiedererPMurphyDL. Primary structure of the serotonin transporter in unipolar depression and bipolar disorder. Biol Psychiatry1995;37:215–23.
131.
KelsoeJRRemickRASadovnickADKristbjarnarsonHFlodmanPSpenceMA, and others. Genetic linkage study of bipolar disorder and the serotonin transporter. Am J Med Genet1996;67:215–7.
132.
PenroseLS. The problem of anticipation in pedigrees of dystrophia myotonica. Annals of Eugenics1948;14:125–32.
133.
McInnisMG. Anticipation: An old idea in new genes. Am J Hum Genet1996; 59:973–9.
134.
McInnisMGMcMahonFJChaseGASimpsonSGRossCADePauloJRJr.Anticipation in bipolar affective disorder. Am J Hum Genet1993;53:385–90.
135.
NylanderPOEngstromCChotaiJWahlstromJAdolfssonR.Anticipation in Swedish families with bipolar affective disorder. J Med Genet1994;31:686–9.
136.
ChotaiJEngstromCEkholmBBergsonMLAdolfssonRNylanderPO. Anticipation in Swedish families with schizophrenia. Psychiatr Genet1995;5:181–6.
137.
BassettASHonerWG. Evidence for anticipation in schizophrenia. Am J Hum Genet1994;54:864–70.
138.
LindbladKNylanderPODe BruynASoureyDZanderCEngstromC, and others. Detection of expanded CAG repeats in bipolar affective disorder using the repeat expansion detection (RED) method. Neurobiology of Disease1995;2:55–62.
139.
O'DonovanMCGuyCCraddockNMurphyKCCardnoAGJonesLA, and others. Expanded CAG repeats in schizophrenia and bipolar disorder. Nat Genet1995;10:380–1.
140.
O'DonovanMCGuyCCraddockNBowenTMcKeonPMacedoA, and others. Confirmation of association between expanded CAG/CTG repeats and both schizophrenia and bipolar disorder. Psychol Med1996;26:1145–53.
141.
McMahonFJStineOCMeyersDASimpsonSGDePauloJR. Patterns of maternal transmission in bipolar affective disorder. Am J Hum Genet1995;56:1277–86.
142.
RischN.Linkage strategies for genetically complex traits, I: Multilocus models. Am J Hum Genet1990;46:222–8.
143.
StollALTohenMBaldessariniRJ. Increasing frequency of the diagnosis of obsessive-compulsive disorder. Am J Psychiatry1992;149:638–40.
144.
StollALTohenMBaldessariniRJGoodwinDCSteinSKatzS, and others. Shifts in diagnostic frequencies of schizophrenia and major affective disorders at six North American psychiatric hospitals, 1972–1988. Am J Psychiatry1993;150:1668–73.
PekkaninenPPartonenTSuvisaariJBredbackaPEMuhonenLSeppalaJ, and others. Search for predisposing loci to severe bipolar disorder in the isolated subpopulations of Finland [abstract]. Am J Hum Genet Suppl1996;59:A386.
147.
StroberMMorrellWBurroughsJLampertCDanforthHFreemanR.A family study of bipolar I disorder in adolescence. Early onset of symptoms linked to increased familial loading and lithium resistance. J Affect Disord1988; 15:255–68.
148.
StroberM.Relevance of early age-of-onset in genetic studies of bipolar affective disorder. J Am Acad Child Adolesc Psychiatry1992;31:606–10.
149.
KutcherSMartonP.Affective disorders in first-degree relatives of adolescent onset bipolars, unipolars, and normal controls. J Am Acad Child Adolesc Psychiatry1991;30:75–8.
150.
el-MallakhRSLiR.Is the Na(+)-K(+)-ATPase the link between phosphoinositide metabolism and bipolar disorder?J Neuropsychiatry Clin Neurosci1993;5:361–8.
151.
ManjiHKPotterWZLenoxRH. Signal transduction pathways. Molecular targets for lithium's actions. Arch Gen Psychiatry1995;52:531–43.
152.
GrofEGrofPBrownGMDownieS.Lithium effects on neuroendocrine function. Prog Neuropsychopharmacol Biol Psychiatry1984;8:541–6.
153.
MendlewiczJFieveRRStalloneF.Relationship between the effectiveness of lithium therapy and family history. Am J Psychiatry1973;130:1011–3.
154.
ZvolskyPVinarovaEDostalTSoucekK.Family history of manic-depressive and endogenous depressive patients and clinical effect of treatment with lithium. Activitas Nervosa Superior1974;16:194–5.
155.
SmeraldiEPetroccioneAGasperiniMMacciardiFOrsiniAKiddKK. Outcomes on lithium treatment as a tool for genetic studies in affective disorders. J Affect Disord1984;6:139–51.
