Finnish adoptive family study: sample selection and adoptee DSM‐III‐R diagnoses

Tienari, Pekka; Wynne, Lyman C.; Moring, Juha; Läksy, Kristian; Nieminen, Pentti; Sorri, Anneli; Lahti, L.; Ke, Wahlberg; Naarala, Mikko; Kurki‐Suonio, K.; Saarento, O; Koistinen, P.; Tarvainen, T.; Hakko, Helinä; Miettunen, Jouko

doi:10.1034/j.1600-0447.2000.101006433.x

Cited by 91 publications

(94 citation statements)

References 10 publications

(17 reference statements)

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“…The original studies of Kety et al (1968; found evidence for spectrum disorders genetically related to schizophrenia in the adopted away offspring of schizophrenic mothers. The Finish Adoptive Family Study of schizophrenia (Tienari et al, 2000) reported a life time prevalence of schizophrenia of 6.7% in the adopted offspring of schizophrenic mothers compared to 2% in controls but more strikingly 17% of adoptees with a schizophrenic mother and 4% of control adoptees attracted a diagnosis of either schizophrenia or a broadly defined schizophrenia spectrum disorder. Spectrum disorders included schizoaffective disorder, delusional disorder, bipolar disorder, psychotic depression and the personality disorders categorised as schizotypal, paranoid and schizoid.…”

Section: Clinical Spectra Of Schizophrenia and Bipolar Disordermentioning

confidence: 96%

Clinical phenotypes associated with DISC1, a candidate gene for schizophrenia

Blackwood

Muir

2004

neurotox res

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Genetic factors play an important part in the development of schizophrenia and bipolar disorder, and linkage analyses in families have successfully identified several chromosomal regions containing candidate genes. A single large pedigree has been described in which schizophrenia and depression segregate with a balanced chromosomal translocation involving the long arm of chromosome 1 and the short arm of chromosome 11. The gene named DISC1, disrupted at the chromosome 1 breakpoint, is a novel candidate gene that may have a role in the pathogenesis of schizophrenia. The cellular location and function of the protein coded by DISC1 is currently being investigated. The phenotype associated with DISC1 in the t (1;11) translocation family includes schizophrenia, schizoaffective disorder, recurrent major depression and bipolar disorder. Hence this locus is one of several now reported apparently showing linkage to both schizophrenia and bipolar disorder. The study of intermediate phenotypes or "endophenotypes" may clarify the relations between phenotype and genotype. Auditory event related potentials are EEG based physiological measures widely studied in schizophrenia. In particular the cognitive evoked potential, the P300 response generated during an "odd-ball" two-tone discrimination task consistently shows reduced amplitude in schizophrenia compared to controls. In members of the family with the t (1;11) translocation, P300 amplitude was reduced in relatives who carried the translocation compared to relatives with a normal karyotype. Furthermore the amplitude reduction was independent of the presence or absence of symptoms because asymptomatic translocation carriers showed similar P300 amplitude reduction as was found in translocation carriers who were diagnosed with schizophrenia, bipolar disorder or unipolar depression. The results confirm that subjects with schizophrenia who carry the t (1;11) translocation have similar phenotype to unrelated subjects with schizophrenia and a normal karyotype. Furthermore P300 amplitude may be a useful intermediate phenotype detecting the neuropathology of schizophrenia in "at risk" individuals even in the absence of clinical symptoms.

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Section: Clinical Spectra Of Schizophrenia and Bipolar Disordermentioning

confidence: 96%

Clinical phenotypes associated with DISC1, a candidate gene for schizophrenia

Blackwood

Muir

2004

neurotox res

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“…Tienari et al (27) has recently demonstrated interactions between genetic and environmental factors in schizophrenia. We could not investigate both genetic and environmental factors because data on familiality are not available for the cohort.…”

Section: Discussionmentioning

confidence: 99%

Birth order and risk for schizophrenia: a 31‐year follow‐up of the Northern Finland 1966 Birth Cohort

Kemppainen¹,

Veijola²,

Jokelainen³

et al. 2001

Acta Psychiatr Scand

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Objective: The Northern Finland 1966 Birth Cohort was studied in order to investigate the association between birth order and schizophrenia. Method: Four categories of birth order status (®rst-born, last-born, only child and other status) were formed and linked to data on psychiatric morbidity. Effects were adjusted for wantedness of pregnancy, perinatal complications, maternal age at delivery, family type and number of siblings. Results: The risk for schizophrenia was elevated among male ®rst-borns (ratio 1.5; 95% CI 1.0±2.2) and female last-borns (ratio 1.3; 95% CI 0.9± 1.9). The risk was lower than expected among male last-borns (ratio 0.7; 95% CI 0.5±0.9) and females belonging to other status (ratio 0.6; 95% CI 0.3±0.9). Conclusion: These results suggest that speci®c birth order status is an independent risk factor for schizophrenia. Theoretical explanations may arise from biological factors unidenti®ed here and/or psychological stressors linked with these positions.

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“…12,13 However, the limits of this spectrum and its relationship to other psychoses, affective and nonaffective, and nonpsychotic affective disorders remain uncertain. [14][15][16] Finally, although it is clear that individual differences in liability to schizophrenia are substantially genetic, we have no clear idea what form this 'liability' actually takes. That is to say, we are not yet able to identify the endophenotypes that are intermediate between genetic predisposition and the clinical phenotype of schizophrenia.…”

Section: Defining the Phenotypementioning

confidence: 99%

The molecular genetics of schizophrenia: new findings promise new insights

2003

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The high heritability of schizophrenia has stimulated much work aimed at identifying susceptibility genes using positional genetics. However, difficulties in obtaining clear replicated linkages have led to the scepticism that such approaches would ever be successful. Fortunately, there are now signs of real progress. Several strong and well-established linkages have emerged. Three of the best-supported regions are 6p24-22, 1q21-22 and 13q32-34. In these cases, single studies achieved genome-wide significance at Po0.05 and suggestive positive findings have also been reported in other samples. The other promising regions include 8p21-22, 6q21-25, 22q11-12, 5q21-q33, 10p15-p11 and 1q42. The study of chromosomal abnormalities in schizophrenia has also added to the evidence for susceptibility loci at 22q11 and 1q42. Recently, evidence implicating individual genes within some of the linked regions has been reported and more importantly replicated. The weight of evidence now favours NRG1 and DTNBP1 as susceptibility loci, though work remains before we understand precisely how genetic variation at each locus confers susceptibility and protection. The evidence for catechol-O-methyl transferase, RGS4 and G72 is promising but not yet persuasive. While further replications remain the top priority, the respective contributions of each gene, relationships with aspects of the phenotype, the possibility of epistatic interactions between genes and functional interactions between the gene products will all need investigation. The ability of positional genetics to implicate novel genes and pathways will open up new vistas for neurobiological research, and all the signs are that it is now poised to deliver crucial insights into the nature of schizophrenia.

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Finnish adoptive family study: sample selection and adoptee DSM‐III‐R diagnoses

Abstract: The genetic liability to 'typical' DSM-III-R schizophrenia is decisively confirmed. Additionally, the liability also extends to a broad spectrum of other psychotic and non-psychotic disorders.

Cited by 91 publications

References 10 publications

Clinical phenotypes associated with DISC1, a candidate gene for schizophrenia

Clinical phenotypes associated with DISC1, a candidate gene for schizophrenia

Birth order and risk for schizophrenia: a 31‐year follow‐up of the Northern Finland 1966 Birth Cohort

The molecular genetics of schizophrenia: new findings promise new insights

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