{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:14:33Z","timestamp":1788480873483,"version":"build-2803163510"},"reference-count":45,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Psychiatry"],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:sec id=\"ab-yoi250032-4\"><jats:title>Importance<\/jats:title><jats:p>The etiologic interrelationship of 4 rare\/controversial psychotic disorders (delusional disorder [DD], acute psychoses [AP], psychosis not otherwise specified [PNOS], and schizoaffective disorder [SAD]) is poorly understood.<\/jats:p><\/jats:sec><jats:sec id=\"ab-yoi250032-5\"><jats:title>Objective<\/jats:title><jats:p>To assess levels of the family genetic risk score (FGRS) for schizophrenia (SZ), bipolar disorder (BD), and major depression (MD) in individuals with DD, AP, PNOS, and SAD, thereby clarifying their genetic relationships.<\/jats:p><\/jats:sec><jats:sec id=\"ab-yoi250032-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This cohort study included all individuals born in Sweden between 1950 and 2000 to Swedish-born parents followed up until 2018 with diagnoses of MD, BD, SZ, SAD, AP, PNOS, and DD, based on diagnosis codes from national registries.<\/jats:p><\/jats:sec><jats:sec id=\"ab-yoi250032-7\"><jats:title>Exposures<\/jats:title><jats:p>FGRS for SZ, BD, and MD calculated from first- through fifth-degree relatives, controlling for cohabitation.<\/jats:p><\/jats:sec><jats:sec id=\"ab-yoi250032-8\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>Diagnoses of DD, AP, PNOS, and SAD<\/jats:p><\/jats:sec><jats:sec id=\"ab-yoi250032-9\"><jats:title>Results<\/jats:title><jats:p>In the cohort, 667\u202f012 individuals had MD (420\u202f142 females [63%] and 246\u202f870 males [37.0%]), 58\u202f385 had BD (36\u202f344 females [62%] and 22\u202f041 males [38%]), 17\u202f465 had SZ (6330 females [36%] and 11\u202f135 males [64%]), 7597 had SAD (4125 females [54%] and 3472 males [46%]), 16\u202f315 had AP (7907 females [49%] and 8408 males [51%]), 27\u202f127 had PNOS (12\u202f277 females [45%] and 14\u202f850 males [55%]), and 11\u202f560 had DD (5060 females [44%] and 6500 males [56%]). On \u201cgenetic maps\u201d of SZ FGRS, BD FGRS, and MD FGRS, DD stood alone with approximately half the genetic risk for SZ compared with SZ cases and similar levels of BD and MD risk. SAD was also distinct as the only disorder with quite high genetic risks for both SZ and BD and was clearly separable from psychotic BD. AP and PNOS had similar genetic profiles with levels of SZ FGRS similar to DD but higher levels of genetic risk for BD and MD. Subdividing psychoses by outcome produced minimal effects on the DD genetic profile, moderate effects on AP and PNOS, and large effects on SAD, with good social outcomes associated with decreased SZ FGRS and increased BD FGRS.<\/jats:p><\/jats:sec><jats:sec id=\"ab-yoi250032-10\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>In a Swedish population, none of the 4 disorders appeared, from a genetic perspective, to be subtypes of SZ, BD, or MD. Further genetics research on the syndromes of DD, AP, PNOS, and SAD have much to teach about the relationship between dimensions of genetic risks and the clinical presentation and course of psychotic illness.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamapsychiatry.2025.1289","type":"journal-article","created":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T15:00:46Z","timestamp":1752073246000},"page":"926","source":"Crossref","is-referenced-by-count":4,"title":["Profiles of Genetic Risks for Psychotic Disorders"],"prefix":"10.1001","volume":"82","author":[{"given":"Kenneth S.","family":"Kendler","sequence":"first","affiliation":[{"name":"Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond"},{"name":"Department of Psychiatry, Virginia Commonwealth University, Richmond"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Ohlsson","sequence":"additional","affiliation":[{"name":"Center for Primary Health Care Research, Department of Clinical Sciences, Lund University, Malm\u00f6, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Sundquist","sequence":"additional","affiliation":[{"name":"Center for Primary Health Care Research, Department of Clinical Sciences, Lund University, Malm\u00f6, Sweden"},{"name":"University Clinic Primary Care Sk\u00e5ne, Region Sk\u00e5ne, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Sundquist","sequence":"additional","affiliation":[{"name":"Center for Primary Health Care Research, Department of Clinical Sciences, Lund University, Malm\u00f6, Sweden"},{"name":"University Clinic Primary Care Sk\u00e5ne, Region Sk\u00e5ne, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"key":"yoi250032r1","first-page":"368","article-title":"Uber Monomanie als primare Form der Seelenstorung.","volume":"21","author":"Snell","year":"1865","journal-title":"Allgemeine Zeitschrift fur Psychiatrie"},{"issue":"2","key":"yoi250032r2","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1007\/BF02089723","article-title":"Ueber eine specielle Form der prim\u00e4ren Verr\u00fccktheit.","volume":"1","author":"Sander","year":"1868","journal-title":"Eur Arch Psychiatry Clin Neurosci"},{"issue":"4","key":"yoi250032r3","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1093\/schbul\/sbaa039","article-title":"Tracing the roots of dementia praecox: the emergence of verr\u00fccktheit as a primary delusional-hallucinatory psychosis in German psychiatry from 1860 to 1880.","volume":"46","author":"Kendler","year":"2020","journal-title":"Schizophr Bull"},{"issue":"12","key":"yoi250032r4","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1001\/jamapsychiatry.2018.2377","article-title":"The development of Kraepelin\u2019s mature diagnostic concepts of paranoia (die verr\u00fccktheit) and paranoid dementia praecox (dementia paranoides): a close reading of his textbooks from 1887 to 1899.","volume":"75","author":"Kendler","year":"2018","journal-title":"JAMA Psychiatry"},{"key":"yoi250032r5","first-page":"129","article-title":"Du d\u00e9lire de pers\u00e9cutions.","volume":"28","author":"Las\u00e8gue","year":"1852","journal-title":"Archives G\u00e9n\u00e9rales de M\u00e9decine"},{"issue":"5","key":"yoi250032r6","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1093\/schbul\/sbad086","article-title":"Tracing the roots of dementia praecox: Charles Las\u00e8gue and his 1852 essay \u201cDu d\u00e9lire de pers\u00e9cutions\u201d (On persecutory delusions).","volume":"49","author":"Kendler","year":"2023","journal-title":"Schizophr Bull"},{"issue":"4","key":"yoi250032r8","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1093\/schbul\/sbad156","article-title":"The Development of Non-affective Psychotic Syndromes in the 19th Century: LeGrand du Saulle and His 1871 Monograph \u201cLe Delire De Persecutions\u201d (Persecutory Delusions).","volume":"50","author":"Kendler","year":"2024","journal-title":"Schizophr Bull"},{"issue":"6","key":"yoi250032r9","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/S0010-440X(97)90001-8","article-title":"Delusional disorder (paranoia).","volume":"18","author":"Winokur","year":"1977","journal-title":"Compr Psychiatry"},{"issue":"6","key":"yoi250032r10","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1001\/archpsyc.1980.01780190097012","article-title":"The nosologic validity of paranoia (simple delusional disorder): a review.","volume":"37","author":"Kendler","year":"1980","journal-title":"Arch Gen Psychiatry"},{"issue":"1","key":"yoi250032r14","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1176\/ajp.90.1.97","article-title":"The acute schizoaffective psychoses.","volume":"90","author":"Kasanin","year":"1933","journal-title":"Am J Psychiatry"},{"issue":"1","key":"yoi250032r15","doi-asserted-by":"publisher","first-page":"47","DOI":"10.3109\/10401239109147967","article-title":"Schizoaffective disorder: a review.","volume":"31","author":"Miller","year":"2019","journal-title":"Ann Clin Psychiatry"},{"issue":"6","key":"yoi250032r16","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.2147\/NDT.S4120","article-title":"Is schizoaffective disorder a distinct categorical diagnosis? a critical review of the literature.","volume":"4","author":"Abrams","year":"2008","journal-title":"Neuropsychiatr Dis Treat"},{"issue":"3","key":"yoi250032r17","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.jad.2007.07.009","article-title":"Does schizoaffective disorder really exist? a systematic review of the studies that compared schizoaffective disorder with schizophrenia or mood disorders.","volume":"106","author":"Cheniaux","year":"2008","journal-title":"J Affect Disord"},{"issue":"7","key":"yoi250032r18","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1001\/jamapsychiatry.2021.0336","article-title":"Family genetic risk scores and the genetic architecture of major affective and psychotic disorders in a Swedish national sample.","volume":"78","author":"Kendler","year":"2021","journal-title":"JAMA Psychiatry"},{"issue":"6","key":"yoi250032r19","doi-asserted-by":"publisher","first-page":"2389","DOI":"10.1017\/S0033291721004268","article-title":"Impact of comorbidity on family genetic risk profiles for psychiatric and substance use disorders: a descriptive analysis.","volume":"53","author":"Kendler","year":"2023","journal-title":"Psychol Med"},{"issue":"1","key":"yoi250032r20","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1038\/s41398-021-01454-z","article-title":"The patterns of family genetic risk scores for eleven major psychiatric and substance use disorders in a Swedish national sample.","volume":"11","author":"Kendler","year":"2021","journal-title":"Transl Psychiatry"},{"issue":"3","key":"yoi250032r21","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1001\/jamapsychiatry.2022.4676","article-title":"Relationship of family genetic risk score with diagnostic trajectory in a Swedish national sample of incident cases of major depression, bipolar disorder, other nonaffective psychosis, and schizophrenia.","volume":"80","author":"Kendler","year":"2023","journal-title":"JAMA Psychiatry"},{"issue":"8","key":"yoi250032r22","doi-asserted-by":"publisher","first-page":"3448","DOI":"10.1017\/S0033291721005535","article-title":"Differences in genetic risk score profiles for drug use disorder, major depression, and ADHD as a function of sex, age at onset, recurrence, mode of ascertainment, and treatment.","volume":"53","author":"Kendler","year":"2023","journal-title":"Psychol Med"},{"issue":"11","key":"yoi250032r23","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1176\/appi.ajp.2011.11010048","article-title":"Diagnostic shifts during the decade following first admission for psychosis.","volume":"168","author":"Bromet","year":"2011","journal-title":"Am J Psychiatry"},{"key":"yoi250032r24","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.schres.2023.01.007","article-title":"Schizophrenia or schizoaffective disorder? a 50-year assessment of diagnostic stability based on a national case registry.","volume":"252","author":"Florentin","year":"2023","journal-title":"Schizophr Res"},{"issue":"9","key":"yoi250032r25","doi-asserted-by":"publisher","first-page":"2733","DOI":"10.1038\/s41380-024-02516-6","article-title":"Genetic contribution to disease-course severity and progression in the SUPER-Finland study, a cohort of 10,403 individuals with psychotic disorders.","volume":"29","author":"K\u00e4mpe","year":"2024","journal-title":"Mol Psychiatry"},{"issue":"5","key":"yoi250032r26","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1176\/ajp.152.5.755","article-title":"Examining the validity of DSM-III-R schizoaffective disorder and its putative subtypes in the Roscommon Family Study.","volume":"152","author":"Kendler","year":"1995","journal-title":"Am J Psychiatry"},{"issue":"1","key":"yoi250032r27","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/S0010-440X(68)80027-6","article-title":"Family history studies. 3. Schizoaffective disorder, clinical and genetic factors including a one to two year follow-up.","volume":"9","author":"Clayton","year":"1968","journal-title":"Compr Psychiatry"},{"issue":"5","key":"yoi250032r28","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1176\/ajp.148.5.612","article-title":"A family study of DSM-III-R schizoaffective disorder, depressive type, compared with schizophrenia and psychotic and nonpsychotic major depression.","volume":"148","author":"Maj","year":"1991","journal-title":"Am J Psychiatry"},{"issue":"11","key":"yoi250032r29","doi-asserted-by":"publisher","first-page":"2494","DOI":"10.1016\/j.ajhg.2024.09.009","article-title":"Genetic liability estimated from large-scale family data improves genetic prediction, risk score profiling, and gene mapping for major depression.","volume":"111","author":"Dybdahl Krebs","year":"2024","journal-title":"Am J Hum Genet"},{"issue":"9","key":"yoi250032r32","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1001\/archpsyc.1981.01780340037004","article-title":"An independent analysis of the Copenhagen sample of the Danish adoption study of schizophrenia. III. The relationship between paranoid psychosis (delusional disorder) and the schizophrenia spectrum disorders.","volume":"38","author":"Kendler","year":"1981","journal-title":"Arch Gen Psychiatry"},{"issue":"6","key":"yoi250032r33","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1111\/j.1600-0447.1995.tb09796.x","article-title":"Schizophreniform disorder, delusional disorder and psychotic disorder not otherwise specified: clinical features, outcome and familial psychopathology.","volume":"91","author":"Kendler","year":"1995","journal-title":"Acta Psychiatr Scand"},{"issue":"6","key":"yoi250032r35","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1007\/s001270050152","article-title":"Family study of acute and transient psychotic disorders: comparison with schizophrenia.","volume":"34","author":"Das","year":"1999","journal-title":"Soc Psychiatry Psychiatr Epidemiol"},{"key":"yoi250032r36","first-page":"1","article-title":"Reactive psychoses, a clinical and genetic investigation.","volume":"259","author":"McCabe","year":"1975","journal-title":"Acta Psychiatr Scand Suppl"},{"issue":"3","key":"yoi250032r37","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1007\/s11920-003-0041-1","article-title":"Outcome of schizophreniform disorder.","volume":"5","author":"Benazzi","year":"2003","journal-title":"Curr Psychiatry Rep"},{"issue":"4","key":"yoi250032r38","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1001\/archpsyc.1988.01800280038006","article-title":"A controlled family study of chronic psychoses: schizophrenia and schizoaffective disorder.","volume":"45","author":"Gershon","year":"1988","journal-title":"Arch Gen Psychiatry"},{"issue":"4","key":"yoi250032r39","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1001\/archpsyc.1988.01800280033005","article-title":"The heritability of schizophrenia and schizoaffective disorder: a family study.","volume":"45","author":"Coryell","year":"1988","journal-title":"Arch Gen Psychiatry"},{"issue":"3","key":"yoi250032r40","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1093\/schbul\/sbu016","article-title":"Genetic relationships between schizophrenia, bipolar disorder, and schizoaffective disorder.","volume":"40","author":"Cardno","year":"2014","journal-title":"Schizophr Bull"},{"issue":"10","key":"yoi250032r41","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1017\/S0033291706008385","article-title":"Recurrence risks for schizophrenia in a Swedish national cohort.","volume":"36","author":"Lichtenstein","year":"2006","journal-title":"Psychol Med"},{"issue":"6","key":"yoi250032r42","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1111\/j.1600-0447.2011.01747.x","article-title":"Validity of bipolar disorder hospital discharge diagnoses: file review and multiple register linkage in Sweden.","volume":"124","author":"Sellgren","year":"2011","journal-title":"Acta Psychiatr Scand"},{"issue":"6","key":"yoi250032r43","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1080\/08039480500360906","article-title":"Evaluation of diagnostic procedures in Swedish patients with schizophrenia and related psychoses.","volume":"59","author":"Ekholm","year":"2005","journal-title":"Nord J Psychiatry"},{"issue":"11","key":"yoi250032r44","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1176\/appi.ajp.2018.17111251","article-title":"The genetic epidemiology of treated major depression in Sweden.","volume":"175","author":"Kendler","year":"2018","journal-title":"Am J Psychiatry"},{"issue":"1","key":"yoi250032r45","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1186\/s12888-017-1381-4","article-title":"Common adult psychiatric disorders in Swedish primary care where most mental health patients are treated.","volume":"17","author":"Sundquist","year":"2017","journal-title":"BMC Psychiatry"},{"key":"yoi250032r7","volume-title":"Le D\u00e9lire des Pers\u00e9cution","author":"Legrand du Saulle","year":"1871"},{"key":"yoi250032r11","volume-title":"Psychogenic Psychoses","author":"Wimmer","year":"2003"},{"key":"yoi250032r12","volume-title":"The Schizophreniform States","author":"Langfeldt","year":"1939"},{"key":"yoi250032r13","volume-title":"Paranoid and Paranoiac Psychoses","author":"Retterstol","year":"1966"},{"key":"yoi250032r31","year":"2012"},{"key":"yoi250032r34","volume-title":"Die Primare Verrucktheit (Primary paranoia)","author":"Kolle","year":"1931"},{"key":"yoi250032r30","doi-asserted-by":"crossref","unstructured":"Dybdahl Krebs? M, Appadurai? V, Georgii Hellberg? KL, . The relationship between genotype- and phenotype-based estimates of genetic liability to human psychiatric disorders, in practice and in theory.? medRxiv. 2023:epub.","DOI":"10.1101\/2023.06.19.23291606"}],"container-title":["JAMA Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamapsychiatry\/articlepdf\/2836263\/jamapsychiatry_kendler_2025_oi_250032_1755883037.7784.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T15:00:55Z","timestamp":1756911655000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamapsychiatry\/fullarticle\/2836263"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,1]]},"references-count":45,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamapsychiatry.2025.1289","relation":{},"ISSN":["2168-622X"],"issn-type":[{"value":"2168-622X","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9,1]]}}}