Genetic boundaries of the schizophrenia spectrum: evidence from the Finnish Adoptive Family Study of Schizophrenia

OBJECTIVE: Identification of the genetically related disorders in the putative schizophrenia spectrum is an unresolved problem. Data from the Finnish Adoptive Family Study of Schizophrenia, which was designed to disentangle genetic and environmental factors influencing risk for schizophrenia, were used to examine clinical phenotypes of schizophrenia spectrum disorders in adopted-away offspring of mothers with schizophrenia spectrum disorders. METHOD: Subjects were 190 adoptees at broadly defined genetic high risk who had biological mothers with schizophrenia spectrum disorders, including a subgroup of 137 adoptees at narrowly defined high risk whose mothers had DSM-III-R schizophrenia. These high-risk groups, followed to a median age of 44 years, were compared diagnostically with 192 low-risk adoptees whose biological mothers had either a non-schizophrenia-spectrum diagnosis or no lifetime psychiatric diagnosis. RESULTS: In adoptees whose mothers had schizophrenia, the mean lifetime, age-corrected morbid risk for narrowly defined schizophrenia was 5.34% (SE=1.97%), compared to 1.74% (SE=1.00%) for low-risk adoptees, a marginally nonsignificant difference. In adoptees whose mothers had schizophrenia spectrum disorders, the mean age-corrected morbid risk for a schizophrenia spectrum disorder was 22.46% (SE=3.56%), compared with 4.36% (SE=1.51%) for low-risk adoptees, a significant difference. Within the comprehensive array of schizophrenia spectrum disorders, schizotypal personality disorder was found significantly more often in high-risk than in low-risk adoptees. The frequency of the group of nonschizophrenic nonaffective psychoses collectively differentiated high-risk and low-risk adoptees, but the frequencies of the separate disorders within this category did not. The two groups were not differentiated by the prevalence of paranoid personality disorder and of affective disorders with psychotic features. CONCLUSIONS: In adopted-away offspring of mothers with schizophrenia spectrum disorders, the genetic liability for schizophrenia-related illness (with the rearing contributions of the biological mothers disentangled) is broadly dispersed. Genetically oriented studies of schizophrenia-related disorders and studies of genotype-environment interaction should consider not only narrowly defined, typical schizophrenia but also schizotypal and schizoid personality disorders and nonschizophrenic nonaffective psychoses.     

Coping and optimism in relation to dental health behaviour--a study among Finnish young adults

Our aim in this paper was to investigate active coping in relation to optimism, dental health behavior and self-reported dental health among 31-yr-old men and women born in Northern Finland in 1966. Connecting coping strategies and optimism with health behavior is an unexplored approach in dentistry, even though both coping strategies and optimism are known to be associated with many health outcomes. The data were based on a postal questionnaire, which was sent to the Northern Finland 1966 Birth Cohort at age 31 yr (n = 11 541). The number of replies was 8690, with a 75.3% response rate. Active coping was measured using the Ways of Coping Checklist and optimism using a revised Life Orientation Test. Prevalence proportion ratios were estimated by applying a log-binomial regression models. The results showed a correlation between active coping and optimism. Both active coping and optimism were related to different dental health behaviors. The effect of active coping on dental health behavior disappeared by adjusting for optimism, education and gender. The results support the previous findings that active coping acts as a mediator between optimism and health. Optimism was also related to self-reported dental health, which supports the comprehensiveness of optimism as a determinant for health.     

Postpartum bone mineral density in women treated for thromboprophylaxis with unfractionated heparin or LMW heparin

Venous thromboembolism remains an important cause of maternal mortality. In a randomised open study, 44 pregnant women with confirmed previous or current thromboembolism were randomised to receive either low-molecular-weight heparin, dalteparin (N = 21) once daily subcutaneously or unfractionated sodium heparin (UF heparin, N = 23) twice daily subcutaneously for thromboprophylaxis during pregnancy and puerperium. Bone mineral density (BMD) in the lumbosacral spine was measured with dual X-ray absorptiometry (DEXA) 1, 6, 16, 52 weeks and, if possible, 3 years after delivery. BMD values were also compared with those of healthy, delivered women (N = 19). Mean BMD of the lumbar spine was significantly lower in the unfractionated heparin group compared with the dalteparin and with the control groups (repeated measures ANOVA p = 0.02). BMD in the dalteparin group did not differ from BMD of healthy delivered women. Multiple logistic regression analysis revealed that therapy was the only independent factor influencing BMD at weeks 16 and 52. Therefore we recommend use of dalteparin instead of UF heparin for long-term thromboprophylaxis during and after pregnancy.     

Brain catecholamine metabolism in catechol-O-methyltransferase (COMT)-deficient mice

Catechol-O-methyltransferase (COMT) catalyses the O-methylation of compounds having a catechol structure and its main function involves the elimination of biologically active or toxic catechols and their metabolites. By means of homologous recombination in embryonic stem cells, a strain of mice has been produced in which the gene encoding the COMT enzyme is disrupted. We report here the levels of catecholamines and their metabolites in striatal extracellular fluid in these mice as well as in homogenates from different parts of the brain, under normal conditions and after acute levodopa administration. In immunoblotting studies, COMT-knockout mice had no COMT protein in brain or kidney tissues but the amounts of catecholamine synthesizing and other metabolizing enzyme proteins were normal. Under normal conditions, COMT deficiency does not appear to affect significantly brain dopamine and noradrenaline levels in spite of relevant changes in their metabolites. This finding is consistent with previous pharmacological studies with COMT inhibitors and confirms the pivotal role of synaptic reuptake processes and monoamine oxidase-dependent metabolism in terminating the actions of catecholamines at nerve terminals. In contrast, when COMT-deficient mice are challenged with l-dihydroxyphenylalanine, they show an extensive accumulation of 3,4-dihydroxyphenylacetic acid and dihydroxyphenylglycol and even dopamine, revealing an important role for COMT under such situations. Notably, in some cases these changes appear to be Comt gene dosage-dependent, brain-region specific and sexually dimorphic. Our results may have implications for improving the treatment of Parkinson's disease and for understanding the contribution of the natural variation in COMT activity to psychiatric phenotypes.     

Experimental Chlamydia pneumoniae infection in NIH/S mice: effect of reinoculation with chlamydial or cell preparation on culture,PCR and histological findings of lung tissue

The cellular components present in chlamydial preparations may contribute to the course of the experimental infection. NIH/S mice were inoculated and reinoculated intranasally with Chlamydia pneumoniae or a cellular preparation. The mock inoculation induced only mild histological changes in the lungs, which possibly induced partial protection against subsequent C. pneumoniae infection and, when given as reinoculation, possibly reactivated the culture-negative infection as culture-positive. In addition, serum antibodies against mouse heat shock protein 60 (Hsp60) were found in a few mice. In conclusion, the main immunopathogenic factors in a C. pneumoniae mouse model are chlamydial components. However, a cellular preparation may participate in an inflammatory reaction. Autoimmunity against Hsp60 may also play a role in the pathogenesis of C. pneumoniae infection.     

Individually fitted sports shoes for overuse injuries among newspaper carriers

OBJECTIVES: The aim of the study was to determine the effectiveness of new, individually fitted sports shoes against overuse injuries to the lower limb among newspaper carriers. METHODS: Patients (N = 176) with lower-limb overuse injuries were randomly assigned to use new, individually adjusted footwear with good shock absorbing properties (test group = 86) or the subjects' own, used footwear (control group = 90). The main outcome measurements were lower-limb pain intensity during walking, as rated on a visual analogue scale (0-100), number of painful days, subjective assessment of global improvement, foot fatigue, number of hyperkeratotic skin lesions and diagnosed overuse injuries, and costs of foot care as compared between the treatment groups. RESULTS: At the 6-month follow-up there was a difference in favor of the test group with respect to lower-limb pain intensity and number of painful days, when compared with the control group. At 1 year, 53% and 33% of the test and control groups, respectively, thought they were better than at the time of the baseline examination (number needed to treat being 5 between the test and control groups). The test subjects had less foot fatigue and fewer hyperkeratotic skin lesions. There was no difference in the number of diagnosed overuse injuries between the groups. During the year of follow-up, the all-inclusive mean costs of foot care were USD 70 and USD 158 in the test and control groups, respectively. CONCLUSIONS: Individually adjusted shock-absorbing shoes offer slight health benefits for lower-limb overuse injuries. Proper shoes may decrease the need to use health care resources.     

Magnetocardiographic indices of left ventricular hypertrophy

OBJECTIVE: We tested the hypothesis that multichannel magnetocardiographic (MCG) mapping can detect and quantify the degree of left ventricular hypertrophy (LVH). DESIGN: A cross-sectional study. SETTING: Helsinki University Central Hospital, a tertiary referral center. PARTICIPANTS: Forty-two patients with pressure overload induced LVH by gender-specific echocardiographic criteria (LVH group), and 12 healthy middle-aged controls. MAIN OUTCOME MEASURES: MCG QRS-T area integrals and QRS-T angle in magnetic field maps in relation to echocardiographic LVH as well as left ventricular (LV) mass and structure. Conventional 12-lead electrocardiographic (ECG) LVH indices (Sokolow-Lyon voltage, Cornell voltage, Cornell voltage duration product) were assessed for comparison. RESULTS: MCG QRS- and T-wave integrals provided complementary information of echocardiographic LV mass. Their combination, the QRS-T integral, and the QRS-T angle were increased in patients with LVH and, in those patients, correlated significantly with LV mass indexed to body surface area (r = 0.455;P = 0.002 and r= 0.379; P= 0.013, respectively). A QRS-T integral 16000 fT.s had identical sensitivity of 62% at 92% specificity as the gender-adjusted Cornell voltage duration product of 240 micro V.s for the detection of LVH. CONCLUSIONS: The MCG method can detect patients with LVH and also quantify the degree of LVH in patients with increased LV mass.