Bipolar disorder (BPD) and schizophrenia (SCZ) have at least a partially convergent aetiology and thus may share genetic susceptibility loci. Multiple lines of evidence emphasize the role of disrupted-in-schizophrenia-1 (DISC1) gene in psychotic disorders such as SCZ. We monitored the association of allelic variants of translin-associated factor X (TSNAX)/DISC1 gene cluster using 13 single-nucleotide polymorphisms (SNPs) in 723 members of 179 Finnish BPD families. Consistent with an earlier finding in Finnish SCZ families, the haplotype T-A of rs751229 and rs3738401 at the 5' end of DISC1 was over-transmitted to males with psychotic disorder (P = 0.008; for an extended haplotype P = 0.0007 with both genders). Haplotypes at the 3' end of DISC1 associated with bipolar spectrum disorder (P = 0.0002 for an under-transmitted haplotype T-T of rs821616 and rs1411771, for an extended haplotype P = 0.0001), as did a two-SNP risk haplotype at the 5' end of TSNAX (P = 0.007). The risk haplotype for psychotic disorder also associated to perseverations (P = 0.035; for rs751229 alone P = 0.0012), and a protective haplotype G-T-G with rs1655285 in addition to auditory attention (P = 0.0059). The 3' end variants associated with several cognitive traits, with the most robust signal for rs821616 and verbal fluency and rs980989 and psychomotor processing speed (P = 0.011 for both). These results support involvement of DISC1 in the genetic aetiology of BPD and suggest that its distinct variants contribute to variation in the dimensional features of psychotic and bipolar spectrum disorders. Finding of alternative associating haplotypes in the same set of BPD families gives evidence for allelic heterogeneity within DISC1, eventually leading to heterogeneity in the clinical outcome as well.

Impaired psychomotor performance speed and executive function may represent endophenotypes of BPD, reflecting possible underlying vulnerability to the disorder. Verbal memory impairments appear to be more related to the fully developed disorder.

o t a r i andM. A n t i l a * Butter fat was subjected to interesterification reactions catalysed by Pseudomomfluorcscens lipase in media of variable water content. The reaction products were analysed by gas chromatography on an immobilised phenylmethylsilicone capillary column. Triacylglycerol compositions were determined by normalisation, and free fatty acid and mono-and diacylglycerol compositions and contents by internal standardisation. In general, the triacylglycerol compositions of interesterification products were similar to each other and distinctly different from those of untreated butter fat. The compositions of triacylglycerols of the reaction products were similar to the composition calculated according to random distribution, except for the higher proportions of saturated triacylglycerols with 36 and 42-50 acyl carbons and monoene triacylglycerols with 38 acyl carbons in the reaction products. Enzymatic deacylation of reaction products showed the fatty acyl groups to be nearly randomly distributed among the three positions of glycerol. The contents of the hydrolysis products (MAGs, DAGs and FFAs) depended on the water content of the reaction medium. Fat Sci. Technul. 91. Jahrgang Nr. i ISX!) Fat %I. Techno]. 91. Jahrgang Nr. 7 1989

Background: Despite increasing evidence of cognitive dysfunctions in bipolar I disorder, there is no specific neuropsychological profile of the disorder. Sampling and Method: The aim of the present study was to investigate the effect of processing speed on other cognitive functions in a population-based sample of 32 familial bipolar I disorder patients, their 40 unaffected first-degree relatives and 55 controls. A neuropsychological test battery was administered to all participants, and the effect of processing speed on other cognitive functions was analyzed with the digit symbol subtest of the Wechsler Adult Intelligence Scale-Revised both in within- and between-group comparisons. Results: After adjusting for the effect of processing speed, only small differences were detected in short-delay cued recall and in long-delay memory between patients and controls, as well as between patients and relatives. Relatives scored better than controls only in verbal ability. Processing speed had a significant effect on nearly all scores, differing by group when patients, relatives and controls were examined separately, the effect being most extensive in patients. Conclusions: These results support the view that impaired processing speed in particular contributes to a range of cognitive dysfunctions in bipolar disorder. However, it may not be specific to bipolar I disorder and can possibly be considered a shared endophenotype with other mental disorders.

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Bipolar disorder is highly heritable. Cognitive dysfunctions often observed in bipolar patients and their unaffected relatives implicate that these impairments may be associated with genetic predisposition to bipolar disorder and thus fulfill the criteria of a valid endophenotype for the disorder. However, the most fundamental criterion, their heritability, has not been directly studied in any bipolar population. This population-based study estimated the heritability of cognitive functions in bipolar disorder. A comprehensive neuropsychological test battery and the Structured Clinical Interview for DSM-IV were administered to a population-based sample of 110 individuals from 52 families with bipolar disorder. Heritability of cognitive functions as assessed with neuropsychological test scores were estimated using the Solar package. Significant additive heritabilities were found in verbal ability, executive functioning, and psychomotor processing speed. Genetic contribution was low to verbal learning functions. High heritability, in executive functioning and psychomotor processing speed suggest that these may be valid endophenotypic traits for genetic studies of bipolar disorder.

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