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  • 1.
    Hultman, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital.
    Torrång, Anna
    Tuvblad, Catherine
    Cnattingius, Sven
    Larsson, Jan-Olov
    Lichtenstein, Paul
    Birth weight and attention-deficit/hyperactivity symptoms in childhood and early adolescence: A prospective Swedish twin study2007In: Journal of the American Academy of Child and Adolescent Psychiatry, ISSN 0890-8567, E-ISSN 1527-5418, Vol. 46, no 3, p. 370-377Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To determine whether low birth weight increases the risk of attention-deficit/hyperactivity disorder (ADHD) in childhood and early adolescence. METHOD: In a population-based sample of 1,480 twin pairs born in the period 1985-1986 ascertained from the Swedish Twin Registry, birth weight was collected prospectively through the Medical Birth Registry. ADHD symptoms were measured with a 14-item checklist covering DSM-III-R criteria (parental rating) at age 8 to 9 years and 13 to 14 years. We used both a dichotomous approach for birth weight (>400 g or 15% weight difference) and ADHD (eight or more symptoms) and continuous measures to investigate between- and within-twin pair effects. RESULTS: Our results showed that low birth weight was a risk factor for symptoms of ADHD and the associations did not diminish when we controlled for genetic influence. The lighter twin in birth weight-discordant pairs had on average 13% higher ADHD symptom score at age 8 to 9 years (p = .006) and 12% higher ADHD score at age 13 to 14 years (p = .018) compared with the heavier twin. The genetic correlations suggest modest or no genetic overlap between birth weight and ADHD. CONCLUSIONS: The hypothesis that low birth weight is associated with the development of ADHD symptoms was supported in this prospective twin study. Fetal growth restriction seems to represent a modest but fairly consistent environmental influence on the development of ADHD symptoms.

  • 2. Lambe, Mats
    et al.
    Hultman, Christina
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Psykiatri Ulleråker.
    Torrång, Anna
    MacCabe, James
    Cnattingius, Sven
    Maternal smoking during pregnancy and school performance at age 152006In: Epidemiology, Vol. 17, no 5, p. 524-530Article in journal (Refereed)
  • 3. Lichtenstein, Paul
    et al.
    Björk, Camilla
    Hultman, Christina M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Scolnick, Edward
    Sklar, Pamela
    Sullivan, Patrick F.
    Recurrence risks for schizophrenia in a Swedish national cohort2006In: Psychological Medicine, ISSN 0033-2917, E-ISSN 1469-8978, Vol. 36, no 10, p. 1417-1425Article in journal (Refereed)
    Abstract [en]

    Background. Recurrence risk estimates for schizophrenia are fundamental to our understanding of this complex disease. Widely cited estimates are from small/older samples. If these estimates are biased upwards, then the rationale for molecular genetic studies of schizophrenia may not be as solid.

    Method. We created a population-based, Swedish national cohort by linking two Swedish national registers into a relational database (the Swedish Hospital Discharge Register and the MultiGeneration Register). Affection was defined as the lifetime presence of at least two in-patient hospitalizations with a core schizophrenia diagnosis.

    Results. Merging the Swedish national registers created a population-based cohort of 7 739 202 individuals of known parentage. The lifetime prevalence of the narrow definition of schizophrenia was 0(.)407% and we estimated that one in every 79 extended Swedish families had been impacted by schizophrenia. The proportion of affected families with multiple affected members was 3(.)81%. Recurrence risk estimates for all relative types were strikingly similar to those reported in smaller and older studies. For example, we estimated lambda(sibs) at 8(.)55 [95% confidence interval (CI) 7(.)86-9(.)57] compared with a literature estimate of 8(.)6.

    Conclusions. In the largest and most comprehensive sample yet studied, we confirm the accepted estimates of recurrence risks for schizophrenia, and provide more accurate estimates of recurrence risks of schizophrenia in relatives, an estimate of the familial impact of schizophrenia, and the multiplex proportion (essential for gauging the generalizability of findings from multiplex pedigrees). These data may be valuable for planning and interpreting genetic studies of schizophrenia.

  • 4.
    Nilsson, Björn
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Psykiatri, Ulleråker.
    Hultman, Christina
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Psykiatri, Ulleråker.
    Wiesel, Frits-Axel
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Psykiatri, Ulleråker.
    Niacin skin-flush response and electrodermal activity in patients with schizophrenia and healthy controls2006In: Prostaglandins, Leukotrines and Essential Fatty Acids, Vol. 74, p. 339-346Article in journal (Refereed)
  • 5. Nilsson, Emma
    et al.
    Stålberg, Gabriella
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Psykiatri Ulleråker.
    Lichtenstein, Paul
    Gnattingius, Sven
    Otterblad Olausson, Petra
    Hultman, Christina M
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Psykiatri Ulleråker.
    Fetal growth restriction and schizophrenia: A Swedish twin study.2005In: Twin Research and Human Genetics, Vol. 8, no 4, p. 402-408Article in journal (Refereed)
  • 6.
    Stålberg, Gabriella
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Psykiatri Ulleråker.
    Ekerwald, Hedda
    Hultman, Christina
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Psykiatri Ulleråker.
    Siblings of Patients With Schizophrenia: Sibling Bond, Coping Patterns, and Fear of Possible Schizophrenia Heredity2004In: Schizophrenia Bulletin, Vol. 30, no 2, p. 445-458Article in journal (Refereed)
  • 7. Svensson, Anna C.
    et al.
    Lichtenstein, Paul
    Sandin, Sven
    Hultman, Christina M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital.
    Fertility of first-degree relatives of patients with schizophrenia: A three generation perspective2007In: Schizophrenia Research, ISSN 0920-9964, E-ISSN 1573-2509, Vol. 91, no 1-3, p. 238-245Article in journal (Refereed)
    Abstract [en]

    We explored the fertility in three generations; fertility of parents, siblings and offspring to patients with schizophrenia, to test the hypothesis that the decreased reproductive rate in the patients is compensated by an increased rate in their first-degree relatives. A population-based national database was created by linking the Swedish Multi-Generation and Hospital Discharge Registers. To maximize follow-up time for schizophrenia and reproductive history, three birth cohorts were selected: parental generation, born 1918–1927 (n=274464); affected generation, born 1932–1941 (n=108502) and offspring to affected generation, born 1951–1960 (n=103105). Ratios of estimated mean number of offspring were measured (fertility ratios), comparing the study subjects to the general population. The fertility among males with schizophrenia was decreased by over 70% (fertility ratiopatients/population=0.29, 95% CI 0.25–0.35), whereas female patients had less than half as many offspring as the general female population (fertility ratiopatients/population=0.48, 95% CI 0.42–0.55). When accounting for selection bias of larger families, no statistically significant difference was found among parents of patients with and without a diagnosis of schizophrenia. Further, the fertility among siblings of schizophrenic patients did not differ from the general population. A reduction in fertility was found among offspring to patients with schizophrenia, male offspring had 12% fewer offspring (fertility ratiooffspring/population=0.88, 95%CI 0.77–1.01), while female offspring had 6% fewer offspring (fertility ratiooffspring/population=0.94, 95% CI 0.84–1.05). In conclusion, we found reduced fertility in patients with schizophrenia and among their offspring that was not compensated by higher parental or sibling fertility.

  • 8. Yip, Benjamin H
    et al.
    Björk, Camilla
    Lichtenstein, Paul
    Hultman, Christina M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital.
    Pawitan, Yudi
    Covariance component models for multivariate binary traits in family data analysis2008In: Statistics in Medicine, ISSN 0277-6715, E-ISSN 1097-0258, Vol. 27, no 7, p. 1086-1105Article in journal (Refereed)
    Abstract [en]

    For family studies, there is now an established analytical framework for binary-trait outcomes within the generalized linear mixed models (GLMMs). However, the corresponding analysis of multivariate binary-trait (MBT) outcomes is still limited. Certain diseases, such as schizophrenia and bipolar disorder, have similarities in epidemiological features, risk factor patterns and intermediate phenotypes. To have a better etiological understanding, it is important to investigate the common genetic and environmental factors driving the comorbidity of the diseases. In this paper, we develop a suitable GLMM for MBT outcomes from extended families, such as nuclear, paternal- and maternal-halfsib families. We motivate our problem with real questions from psychiatric epidemiology and demonstrate how different substantive issues of comorbidity between two diseases can be put into the analytical framework.

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