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J Lönnqvist

Publications and source records attributed to J Lönnqvist.

At least 19 recordsLinked to original sources
PubMed2006

Incorporating serotypes into family based association studies using the MFG test.

Family based association tests are widely used to detect genetic effects. The focus of this paper is the maternal-fetal genotype (MFG) incompatibility test, a family based association test which can be used to detect genetic effects that contribute to disease, including alleles in the child that increase disease risk, maternal alleles that increase disease risk in the child, and maternal-fetal genotype incompatibilities. Consideration of incomplete data resulting from using serotypes could expand the power of the MFG test for detecting genetic effects. Serotypes may be all that are available in certain families, or preferred because of convenience or low cost, and thus a modification of the MFG test will allow optimal use of such data. The modified MFG likelihood can accommodate the incomplete data that result from using serotypes rather than the corresponding codominant genotypes. The modified MFG test was evaluated with serotypes and genotypes from families with members affected with schizophrenia. In addition, simulation studies were performed. Results of the data analyses and simulation studies showed that serotypes can be used to augment genotypes within a sample, to increase power to detect effects when the candidate gene produces serotypes.

Blood Group Incompatibility↗
PubMed2005

A haplotype within the DISC1 gene is associated with visual memory functions in families with a high density of schizophrenia.

We have previously reported evidence of linkage and association between markers on 1q42 and schizophrenia in a study sample of 498 multiply affected Finnish nuclear families, leading to the recent identification of four significantly associated haplotypes that specifically implicate the Translin-Associated Factor X (TRAX) and Disrupted in Schizophrenia 1 and 2 (DISC1 and DISC2) genes in the genetic etiology of schizophrenia. Previously, the DISC genes were found to be disrupted by a balanced translocation (1;11)(q42.1;q14.3) that cosegregated with schizophrenia and related disorders in a large Scottish pedigree. Interestingly, we also reported earlier suggestive linkage between endophenotypic quantitative traits of visual and verbal memory and microsatellite markers in close proximity to TRAX/DISC, on 1q41. Here, we tested if the identified allelic haplotypes of TRAX/DISC would be associated with visual and/or verbal memory function impairments that are known to aggregate with schizophrenia in families. One haplotype of DISC1, HEP3, displayed association with poorer performance on tests assessing short-term visual memory and attention. Analysis of affected and unaffected offspring separately revealed that both samples contribute to the observed association to visual working memory. These results provide genetic support to the view that the DISC1 gene contributes to sensitivity to schizophrenia and associated disturbances and affects short-term visual memory functions. This finding should stimulate studies aiming at the molecular characterization of how the specific alleles of DISC1 affect the visual memory functions and eventually participates in the development of schizophrenia.

Aged↗
PubMed2004

Health care contacts before and after attempted suicide among adolescent and young adult versus older suicide attempters.

BACKGROUND: The pattern of all health care contacts among young people before and after attempted suicide is not well documented. Neither is it known if the health care contacts of young suicide attempters differ from those of older suicide attempters. This study investigated the age-related clinical characteristics of suicide attempters and the pattern of their contacts with health care before and after attempted suicide in different age groups, particularly adolescence and young adulthood. METHOD: All consecutive 1198 suicide attempters treated in hospital emergency rooms in Helsinki between January 1997 and January 1998 were identified and divided into three age groups (15-24 years, 25-39 years, 40 years and over). Data were gathered on all health care contacts 1 year before and after the index attempt. RESULTS: Although adolescent and young adult suicide attempters suffered from severe mental disorders, a remarkable proportion of them were left without psychiatric consultation and aftercare recommendation following the attempt. Two-thirds of 15-19-year-old male suicide attempters had no treatment contact during the month before the attempt, while a quarter of them were referred to psychiatric consultation and a half had no healthcare contact in the month following the attempt. CONCLUSIONS: These findings indicate considerable scope for improvement in the assessment of young suicide attempters and their referral to aftercare.

Adolescent↗
PubMed2004

Replication of 1q42 linkage in Finnish schizophrenia pedigrees.

Chromosome 1q has been implicated in the etiology of schizophrenia in several independent studies. However, the peak linkage findings have been dispersed over a large chromosomal region, with negative findings in this region also being reported. Our group has previously observed linkage on chromosome 1q42, maximizing within the DISC1 gene, which has also been implied in the etiology of schizophrenia based on functional studies. In the study presented here, we genotyped 300 polymorphic markers on chromosome 1 using a study sample of 70 families with multiple individuals affected with schizophrenia or related conditions, independent of the study samples in our previous reports. We again found evidence for linkage on 1q42 maximizing within the DISC1 gene (rs1000731, lod=2.70). Further, a haplotype containing the most strongly linked markers showed some evidence of association with the disease. This replicates the previous linkage finding in the same region and constitutes supportive evidence for a susceptibility gene in this region.

Chromosome Mapping↗
PubMed2004

Time patterns and seasonal mismatch in suicide.

OBJECTIVE: Physical time-givers may have a modifying effect on the time patterns of death from suicide. METHOD: Data on a total of 1397 suicides in Finland over a year were collected using the method of psychological autopsy. We linked versatile information on each individual to meteorological data adjusted for local weather conditions, and to the universal astronomic data. RESULTS: The number of suicides with seasonal mismatch was greater than the expected in the northernmost region of the country (P = 0.03). The northern location was the most significant predictor of such suicides (P = 0.001). They were associated with the changes in ambient temperature during the preceding day (P < 0.00001), the changes to colder preceding suicides in the spring. CONCLUSION: Our findings show that mismatch between the changes in ambient temperature and those in the length of day may precede death from suicide in some individuals.

Adolescent↗
PubMed2002

Maintenance and manipulation in spatial working memory: dissociations in the prefrontal cortex.

Two experiments were conducted to compare thec ries of the functional organization of spatial working memory within the human prefrontal cortex. In Experiment I, memory set size for locations was parametrically varied, allowing for the assessment of BOLD signal across maintenance requirements. In the sec ond experiment, manipulation of spatial information held in working memory was contrasted with simple maintenance of that information. Both experiment evoked significant activity in a distributed spatia working memory network. Although dorsolateral prefrontal activation increased monotonically with memory set size, this region was differentially engaged in task conditions involving explicit manipulation of in ternal representations. Activation in the superior frontal sulcal region was associated with maintenance of spatial information, increasing with memory se size. In contrast, ventrolateral prefrontal activation was present only at the highest memory set size, possibly due to the differential use of organizational strategies with more complex stimuli. These results sup port claims that the dorsolateral prefrontal cortex is involved in the manipulation of internal representa tions and that the superior frontal sulcal region is involved in the maintenance of spatial information but they suggest a complex role for the ventrolatera prefrontal region.

Algorithms↗
PubMed2002

Bright-light exposure combined with physical exercise elevates mood.

BACKGROUND: Physical exercise alleviates depressive symptoms, as does exposure to bright light, especially in those with seasonal variation. Our objective was to compare the effect of exercise alone or combined with morning bright light on mood and the health-related quality of life in healthy subjects. METHODS: Study subjects were working-age adults, randomized in two groups (n=80): exercise in bright light (group A), or exercise in normal indoor illumination (group B). Intervention lasted for 8 weeks and questionnaire data on mood and the health-related quality of life were collected at study entry, and at weeks 4 and 8. RESULTS: Physical exercise both in normal indoor illumination and in bright light was effective at alleviating depressive symptoms. The exercise was significantly more effective at alleviating so-called atypical depressive symptoms when combined with bright-light exposure. LIMITATIONS: There was no active placebo condition, but a comparative, randomized trial was executed. CONCLUSIONS: Physical exercise in bright light had a positive effect on mood and health-related quality of life in a sample of healthy, working-age people. Further research is needed to explore the mechanisms of the apparent additive effect of exercise and light.

Adult↗
PubMed2002

Major depressive episode among young adults: CIDI-SF versus SCAN consensus diagnoses.

BACKGROUND: We aimed to evaluate the diagnostic accuracy of a highly structured diagnostic interview in relation to a semi-structured diagnostic procedure. We compared the World Health Organization Composite International Diagnostic Interview Short Form (CIDI-SF) in diagnosing major depressive episode (MDE) to consensus diagnoses based on the SCAN interview (Schedules for Clinical Assessment in Neuropsychiatry). METHOD: Subjects comprised a follow-up sample of 239 20-24-year-old former high-school students who were administered the SCAN and immediately thereafter the CIDI-SF. Concordance was estimated for 12-month MDE, using different cut-points of the CIDI-SF and for any affective disorders. RESULTS: Correspondence between instruments was moderate for MDE (kappa = 0.43, sensitivity 0.71, specificity 0.82), but better for any affective disorder (kappa = 0.60, sensitivity 0.70, specificity 0.90). Most false negatives suffered from their depression as much as those correctly identified by the CIDI-SF. False negativity was mainly due to not endorsing the stem questions of the CIDI-SF. Of the false positives almost half had an affective disorder other than MDE. CONCLUSIONS: The CIDI-SF seems to function best in identifying a broader category of affective disorders. It could be useful in large-scale community surveys where more extensive psychiatric interviews are not feasible.

Adult↗
PubMed2002

Bipolar disorder susceptibility region on Xq24-q27.1 in Finnish families.

Bipolar disorder (BPD) is a common disorder characterized by episodes of mania, hypomania and depression. The genetic background of BPD remains undefined, although several putative loci predisposing to BPD have been identified. We have earlier reported significant evidence of linkage for BPD to chromosome Xq24-q27.1 in an extended pedigree from the late settlement region of the genetically isolated population of Finland. Further, we established a distinct chromosomal haplotype covering a 19 cM region on Xq24-q27.1 co-segregating with the disorder. Here, we have further analyzed this X-chromosomal region using a denser marker map and monitored X-chromosomal haplotypes in a study sample of 41 Finnish bipolar families. Only a fraction of the families provided any evidence of linkage to this region, suggesting that a relatively rare gene predisposing to BPD is enriched in this linked pedigree. The genome-wide scan for BPD predisposing loci in this large pedigree indicated that this particular X-chromosomal region provides the best evidence of linkage genome-wide, suggesting an X-chromosomal gene with a major role for the genetic predisposition of BPD in this family.

Bipolar Disorder↗
PubMed2001

Genome-wide scan in a nationwide study sample of schizophrenia families in Finland reveals susceptibility loci on chromosomes 2q and 5q.

We have previously carried out two genome-wide scans in samples of Finns ascertained for schizophrenia from national epidemiological registers. Here, we report data from a third genome scan in a nationwide Finnish schizophrenia study sample of 238 pedigrees with 591 affected individuals. Of the 238 pedigrees, 53 originated from a small internal isolate (IS) on the eastern border of Finland with a well established genealogical history and a small number of founders, who settled in the community 300 years ago. The total study sample of over 1200 individuals were genotyped, using 315 markers. In addition to the previously identified chromosome 1 locus, two new loci were identified on chromosomes 2q and 5q. The highest LOD scores were found in the IS families with marker D2S427 (Z(max) = 4.43) and in the families originating from the late settlement region with marker D5S414 (Z(max) = 3.56). In addition to 1q, 2q and 5q, some evidence for linkage emerged at 4q, 9q and Xp, the regions also suggested by our previous genome scans, whereas, in the nationwide study sample, the region at 7q failed to show further evidence of linkage. The chromosome 5q finding is of particular interest, since several other studies have also shown evidence for linkage in the vicinity of this locus.

Chromosomes, Human, Pair 1↗
PubMed2001

Chromosome 1 loci in Finnish schizophrenia families.

We have earlier reported evidence for linkage to two regions on chromosome 1q32--q42 in schizophrenia families collected for two separate studies in Finland. Here we report the results of a fine mapping effort aimed at further definition of the chromosomal region of interest using a large, population-based study sample (221 families, 557 affected individuals). Most affecteds (78%) had a DSM-IV schizophrenia diagnosis and the remaining had schizophrenia spectrum disorders. We genotyped a total of 147 microsatellite markers on a wide 45 cM region of chromosome 1q. The results were analyzed separately for families originating from an internal isolate of Finland and for families from the rest of Finland, as well as for all families jointly. We used traditional two-point linkage analysis, SimWalk2 multipoint analysis and a novel gamete-competition association/linkage method. Evidence for linkage was obtained for one locus in the combined sample (Z(max) = 2.71, D1S2709) and in the nuclear families from outside the internal isolate (Z(max) = 3.21, D1S2709). In the families from the internal isolate the strongest evidence for linkage was obtained with markers located 22 cM centromeric from this marker (Z(max) = 2.30, D1S245). Multipoint analysis also indicated these loci. Some evidence for association with several markers was observed using the gamete-competition method. Interestingly, the strongest evidence for linkage in the combined study sample was obtained for marker D1S2709, which is an intragenic marker of the DISC1 gene, previously suggested as a susceptibility gene for schizophrenia. These results are consistent with the presence of susceptibility gene(s) in this chromosomal region, a result also implied in other recent family studies of schizophrenia.

Adult↗
PubMed2001

Female homicide offenders have greatly increased mortality from unnatural deaths.

The mortality of female homicidal offenders has scarcely been studied. Our aim was to examine the mortality of homicidal women in Finland using a representative nation-wide material. The data consisted of all 132 women who underwent forensic psychiatric examinations after committing homicide or attempted homicide in 1982-1992. We analysed their rate and cause of death during follow-up using standardised mortality ratios (SMRs) and the official classification of death. The mean follow-up time for dead subjects was 7 years (S.D. 4), and for the rest 11 years (S.D. 3). There were 22 observed deaths, the expected value being 1.3 (SMR 17.4). The SMR for unnatural deaths was 226 and for suicides 425. The SMRs for women below 40 years were over 220. In conclusion, homicidal women have an over 200-fold risk of unnatural death, rising to over 400-fold for suicide. This should be taken into consideration in planning discharge programmes for homicidal offenders.

Accidents↗
PubMed2001

Correlates of initiation to cannabis use: a 5-year follow-up of 15-19-year-old adolescents.

Initiation to cannabis is often the first step in the use of illicit drugs. We studied the correlates of initiation in a 5-year follow-up study. A total of 21.4% of the subjects reported using cannabis at some time. Of the 139 users, 89.2% had tried cannabis not more than once or a few times. This initiation to cannabis was related to male gender, absence of mother, frequent lack of interest and early age at first sexual intercourse in logistic regression analysis. These factors seem to be useful in predicting initiation to cannabis.

Adolescent↗
PubMed2001

The Schizophrenia Suicide Risk Scale (SSRS): development and initial validation.

BACKGROUND: Estimations about the lifetime risk of suicide in schizophrenia vary between 4 and 10%. At present, there does not exist a suicide risk scale developed particularly for schizophrenic patients. The aims of the present study were to: (1) develop a clinically useful semi-structured scale for the estimation of short-term suicide risk among schizophrenic patients, and (2) to carry out an initial validation of the scale. METHODS: A 25-item Schizophrenia Suicide Risk Scale (SSRS) was constructed on the base of the literature. The SSRS scores of 69 living schizophrenic patients (LS group) were compared with the scores of 69 schizophrenic suicides (SS group) whose data had been collected previously from The Finnish nationwide and representative psychological autopsy study. Internal consistency of the SSRS was evaluated with Cronbach alpha. The most important SSRS items predicting suicide were identified with a logistic regression analysis. Sensitivity, specificity, positive predictive value, and negative predictive value of the SSRS in predicting suicide with various cut-off scores were calculated. RESULTS: In the final logistic regression model, the following SSRS items significantly predicted suicide: suicide plans communicated to someone during the past 3 months; one or more previous suicide attempts; loss of professional skills demanding job; depression observed during an interview; and suicide plans communicated during an interview. With high cut-off scores the specificity of the SSRS became satisfactory, but the sensitivity dropped below 32%. Internal consistency of the anamnestic history of the SSRS was low, which suggests that anamnestic risk factors for suicide in schizophrenia are multifactorial. Internal consistency of the interview-based items was high, and present state risk factors seemed to consist of two separate factors, depression-anxiety and irritability. CONCLUSIONS: The SSRS may be clinically useful in identifying schizophrenic patients with a particularly high risk for suicide. However, the SSRS seems not to be a practical screening instrument for suicide risk in schizophrenia, and it is probably impossible to construct a suicide risk scale with both high sensitivity and high specificity in this disorder.

Adolescent↗
PubMed2001

Incidence of cancer among persons with schizophrenia and their relatives.

BACKGROUND: It has repeatedly been reported that the risk for cancer in patients with schizophrenia is different from that of the general population, specifically a lower risk for lung cancer despite increased smoking. Confirmation of these associations could lead to hypotheses on shared risk or protective factors, either genetic or environmental. METHODS: From Finland's National Hospital Discharge and Disability Pension registers, Helsinki, we identified a cohort of 26 996 individuals born between 1940 and 1969 and treated for schizophrenia between 1969 and 1991. They were followed up for cancer from 1971 to 1996 by record linkage with the Finnish Cancer Registry, yielding 446 653 person-years at risk, and standardized incidence ratios (SIRs) were calculated. Likewise, 39 131 parents and 52 976 siblings of the patients with schizophrenia were followed up to explore familial genetic hypotheses on deviations in cancer risk. RESULTS: In patients with schizophrenia, an increased overall cancer risk was found (724 cases observed vs 619 expected; SIR, 1.17; 95% confidence interval [CI], 1.09-1.25). Half of the excess cases were attributable to lung cancer (SIR, 2.17; 95% CI, 1.78-2.60), and the strongest relative increase in risk was in pharyngeal cancer (SIR, 2.60; 95% CI, 1.25-4.77). Cancer incidence in siblings (SIR, 0.89; 95% CI, 0.83-0.94) and parents (SIR, 0.91; 95% CI, 0.89-0.93) was consistently lower than that in the general population. CONCLUSION: Although specific lifestyle factors, particularly tobacco smoking and alcohol consumption, probably account for the increased cancer risk in patients with schizophrenia, the decreased risk in relatives would be compatible with a postulated genetic risk factor for schizophrenia offering selective advantage to unaffected relatives.

Alcohol Drinking↗
PubMed2001

Excess mortality of suicide attempters.

BACKGROUND: Excessive mortality of suicide attempters has emerged from many follow-up studies. Completed suicide is the main cause of excess deaths, but the increased risk of deaths from other unnatural and natural causes is also of major public health concern. We lack follow-up studies of the different causes of death in cohorts of suicide attempters. The present study aimed to determine the mortality by suicide and other causes of death and to investigate risk factors. METHODS: This mean 5.3-year follow-up study was based on an unselected cohort of suicide attempts by both violent and non-violent methods, treated in hospitals in a well-defined urban catchment area in Helsinki. In total, 2782 patients aged 15 years and over admitted to the emergency rooms after suicide attempt between 1989 and 1996 were included in the follow-up analysis. Standardised mortality ratios (SMR) for suicide, disease, accident, homicide, and undetermined death were calculated. RESULTS: Mortality from all causes was 15 times higher than that expected among men and nine times higher in women. SMRs in men were 5402 (95% CI 4339-6412) for suicide, 2480 (95% CI 925-4835) for homicide, and 11,139 (95% CI 6884-16,680) for undetermined cause, and for women 7682 (95% CI 5423-9585), 3763 (95% CI 52-5880) and 15,681 (95% CI 6894-22,294), respectively. Fifteen percent of all suicide attempters died during the average 5.3-year follow-up of the index attempt. Deaths from suicide accounted for 37% of all excess deaths in men and 44% in women. The mortality ratio was highest during the 1st follow-up year. The total number of lost years of life among the 413 suicide attempters who died during follow-up was 13,883. The risk factors for all causes of death were male sex, single, retirement, drug overdose as a method, an index attempt not involving alcohol, and a repeated attempt. CONCLUSION: A suicide attempt indicates a severe risk of premature death, and suicide is the main cause of excess deaths. However, it appears that concentrating efficient treatment only on the most suicidal patients could prevent no more than two of five premature deaths. More effort is therefore needed to prevent the excess mortality of suicide attempters by also addressing causes of death other than suicide.

Adolescent↗
PubMed2001

Attempted suicide rates and trends during a period of severe economic recession in Helsinki, 1989-1997.

BACKGROUND: This study investigated attempted suicide trends during a deep economic recession in the 1990s in a well-defined urban catchment area. METHODS: The data covered every suicide attempt treated in health care during sample periods in 1989-1997 in Helsinki, Finland. Annual rates were estimated, 3-year moving averages for trends calculated, and significances tested. RESULTS: The overall attempted suicide rate remained stable over the 9-year study period. Against expectations, male rates decreased significantly (P < 0.01), especially among those aged 15-34. There was a convergence of female and male rates, although male rates remained higher. The proportion of poisonings as method increased (P < 0.01). CONCLUSIONS: Despite the deep economic recession, with rapidly rising unemployment attempted suicide rates remained unexpectedly stable. The total attempted suicide rate did not increase as might have been anticipated, and the male rate even decreased.

Adolescent↗