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Biomedical subjects

Christina M Hultman

Publications and source records attributed to Christina M Hultman.

8 recordsLinked to original sources

Phenotypic Impact of Rare Potentially Damaging Copy Number Variation in Obsessive-Compulsive Disorder and Chronic Tic Disorders.

BACKGROUND: Recent studies report an important-and previously underestimated-role of rare variation in risk of obsessive-compulsive disorder (OCD) and chronic tic disorders (CTD). Using data from a large epidemiological study, we evaluate the distribution of potentially damaging copy number variation (pdCNV) in OCD and CTD, examining associations between pdCNV and the phenotypes of probands, including a consideration of early- vs. late-diagnoses. METHOD: The Obsessive-Compulsive Inventory-Revised (OCI-R) questionnaire was used to ascertain psychometric profiles of OCD probands. CNV were identified genome-wide using chromosomal microarray data. RESULTS: For 993 OCD cases, 86 (9%) were identified as pdCNV carriers. The most frequent pdCNV found was at the 16p13.11 region. There was no significant association between pdCNV and the OCI-R total score. However, pdCNV was associated with Obsessing and Checking subscores. There was no significant difference in pdCNV frequency between early- vs. late-diagnosed OCD probands. Of the 217 CTD cases, 18 (8%) were identified as pdCNV carriers. CTD probands with pdCNV were significantly more likely to have co-occurring autism spectrum disorder (ASD). CONCLUSIONS: pdCNV represents part of the risk architecture for OCD and CTD. If replicated, our findings suggest pdCNV impact some OCD symptoms. Genes within the 16p13.11 region are potential OCD risk genes.

Humans↗

Incidence of hospitalization for postpartum psychotic and bipolar episodes in women with and without prior prepregnancy or prenatal psychiatric hospitalizations.

CONTEXT: Postpartum psychosis occurs in 1 to 2 cases per 1000 live births. Most studies have not distinguished postpartum psychosis from bipolar disorder or the proportion of the incidence attributable to prepregnancy psychiatric morbidity. OBJECTIVE: To determine the incidence of postpartum psychosis and bipolar disorder attributable to previous psychiatric hospitalization. DESIGN: Population-based study using linked registry data to determine postpartum onset of psychotic and bipolar episodes within 90 days after the first birth, by women with and without prepregnancy or prenatal psychiatric hospitalization. We assessed the type, number, and recency of previous hospitalizations on the incidence of hospitalization for postpartum psychotic and bipolar episodes. SETTING: Nationwide Swedish Hospital Discharge and Medical Birth registers. PATIENTS: Swedish women delivering a first live infant between January 1, 1987, and December 31, 2001. MAIN OUTCOME MEASURES: Postpartum hospitalization for psychosis or bipolar disorder. RESULTS: The cumulative incidences for postpartum psychotic and bipolar episodes (adjusted for age at first birth) were 0.07% and 0.03%, respectively. The incidence of psychiatric hospitalizations for postpartum psychotic or bipolar episodes among women without previous psychiatric hospitalizations was 0.04% and 0.01% of first births, respectively; for women with any psychiatric hospitalization before delivery, the incidence was 9.24% and 4.48%, respectively. For postpartum psychotic and bipolar episodes, the risk increased significantly with the recency of prepregnancy hospitalizations, number of previous hospitalizations, and length of most recent hospitalization. More than 40% of women hospitalized during the prenatal period for a bipolar or a psychotic condition were hospitalized again during the postpartum period. Approximately 90% of all postpartum psychotic and bipolar episodes occurred within the first 4 weeks after delivery. CONCLUSIONS: Almost 10% of women hospitalized for psychiatric morbidity before delivery develop postpartum psychosis after their first birth. This underscores the need for obstetricians to assess history of psychiatric symptoms and, with pediatric and psychiatric colleagues, to optimize the treatment of mothers with psychiatric diagnoses through childbirth.

Adult↗

Recurrence risks for schizophrenia in a Swedish national cohort.

OBJECTIVE: 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 Multi-Generation 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.

Adolescent↗

Fetal growth restriction and schizophrenia: a Swedish twin study.

Obstetric complications increase the risk of schizophrenia. However, it is not known whether there is a causal relation or whether the association is mediated by genetic and/or shared environmental effects. The aim of this study was to investigate the associations between birthweight, other birth characteristics, and schizophrenia. Twin pairs discordant for schizophrenia will also control for unmeasured genetic and shared environmental effects. Prospectively filed obstetric records were used for a cohort analysis of 11,360 same-sexed twins, and within-twin pair analyses were conducted on 90 twin pairs discordant for schizophrenia. The results from the cohort study showed that low birthweight (less than or equal to 1999 grams; odds ratio [OR] 1.67, 95% confidence interval [CI] 0.88-3.14 and 2000-2299 grams; OR 1.79, 95% CI 1.07-3.01) and small head circumference (less than or equal to 31.5 cm; OR 1.61, 95% CI 1.03-2.51) were associated with later development of schizophrenia. The associations remained in the within-pair analyses. The association between low birthweight and schizophrenia is partly a function of reduced fetal growth. Fetal growth restriction seems to be associated with risk of schizophrenia independently of familial factors.

Birth Weight↗

At issue: siblings of patients with schizophrenia: sibling bond, coping patterns, and fear of possible schizophrenia heredity.

Siblings of schizophrenia patients are from the patient's perspective important support providers, but most studies on family burden have focused on the parental role. This study aims to develop a detailed analysis of the psychological aspects of having a sibling with schizophrenia. We did a qualitative study with audiotaped semistructured interviews of 16 siblings. The reliability of the inductive categorization of data was high. A unifying theme appeared to be an emotional sibling bond characterized by feelings of love, sorrow, anger, envy, guilt, and shame. The major categories linked to coping with the situation were avoidance, isolation, normalization, caregiving, and grieving. A third major theme consisted of a fear of possible schizophrenia heredity. The siblings described concerns about the impact of a family history of psychiatric illness, a fear of becoming mentally ill, and reflections about "bad genes." Our findings support earlier findings of coping patterns but complement them by providing a model that includes awareness of genetic vulnerability as an important part of siblings' subjective burden.

Adaptation, Psychological↗

Women with schizophrenia: pregnancy outcome and infant death among their offspring.

Schizophrenia in the mother may imply an increased risk of adverse pregnancy outcome. However, inconclusive findings, unknown pathological mechanisms and possible confounding by social factors and smoking requests further explorations. The aim of this study were to (1) examine non-optimal pregnancy outcome using data from a population-based cohort, controlling for covariates known to influence fetal growth; and (2) perform separate analyses of women diagnosed before childbirth and women hospitalized for schizophrenia during pregnancy. The study sample comprised 2096 births by 1438 mothers diagnosed with schizophrenia (of whom 696 mothers were antenatal diagnosed and 188 admitted during pregnancy) and 1,555,975 births in the general population. We found significantly increased risks for stillbirth, infant death, preterm delivery, low birth weight, and small-for-gestational-age among the offspring of women with schizophrenia. Women with an episode of schizophrenia during pregnancy had the highest risks (e.g., low birth weight; OR 4.3, 95% CI 2.9-6.6 and stillbirth; OR 4.4, 95% CI 1.4-13.8). Controlling for a high incidence of smoking during pregnancy among schizophrenic women (51% vs. 24% in the normal population) and other maternal factors (single motherhood, maternal age, parity, maternal education, mothers' country of birth and pregnancy-induced hypertensive diseases) in a multiple regression model, reduced the risk estimates markedly. However, the risks for adverse pregnancy outcomes were even after adjustments generally doubled for women with an episode of schizophrenia during pregnancy compared to women in the control group (e.g., low birth weight; OR 2.3, 95% CI 1.5-3.5, preterm delivery; OR 2.4, 95% CI 1.5-3.8 and stillbirth; OR 2.5, 95% CI 0.8-7.9). The risks for preterm delivery and low birth weight were significantly elevated throughout the analyses. We conclude that schizophrenia in the mother implies an increased risk for poor perinatal outcome, not fully explained by maternal factors, and a need to consider a common familial (probably genetic) vulnerability for pre- and perinatal stress and schizophrenia.

Adult↗

Perinatal risk factors for infantile autism.

BACKGROUND: Etiologic hypotheses in infantile autism suggest a strong genetic component, as well as possible environmental risks linked to early fetal development. We evaluated the association of maternal, pregnancy, delivery, and infant characteristics and risk of infantile autism. METHODS: We conducted a case-control study nested within a population-based cohort (all Swedish children born in 1974-1993). We used prospectively recorded data from the Swedish Birth Register, which were individually linked to the Swedish Inpatient Register. Cases were 408 children (321 boys and 87 girls) discharged with a main diagnosis of infantile autism from any hospital in Sweden before 10 years of age in the period 1987-1994, plus 2,040 matched controls. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The risk of autism was associated with daily smoking in early pregnancy (OR = 1.4; CI = 1.1-1.8), maternal birth outside Europe and North America (OR = 3.0; CI = 1.7-5.2), cesarean delivery (OR = 1.6; CI = 1.1-2.3), being small for gestational age (SGA; OR = 2.1; CI = 1.1-3.9), a 5-minute Apgar score below 7 (OR = 3.2, CI = 1.2-8.2), and congenital malformations (OR = 1.8, CI = 1.1-3.1). No association was found between autism and head circumference, maternal diabetes, being a twin, or season of birth. CONCLUSIONS: Our findings suggest that intrauterine and neonatal factors related to deviant intrauterine growth or fetal distress are important in the pathogenesis of autism.

Asphyxia Neonatorum↗