Holger J. Sørensen

Association Between Prenatal Exposure to Bacterial Infection and Risk of Schizophrenia

Recent research suggests that prenatal exposure to nonviral infection may be associated with increased risk of schizophrenia, and we hypothesized an association between maternal bacterial infection during pregnancy and elevated offspring risk of schizophrenia. Data on maternal infections from the Copenhagen Perinatal Cohort were linked with the Danish National Psychiatric Register. Offspring cases of narrowly defined schizophrenia (International Classification of Diseases, Eighth Revision [ICD-8]) and more broadly defined schizophrenia (ICD-8 and ICD-10) were identified before the ages of 32-34 and 45-47 years, respectively. The effect of prenatal exposure to bacterial infections was adjusted for prenatal exposure to analgesics and parental social status. In a risk set of 7941 individuals, 85 cases (1.1%) of ICD-8 schizophrenia were identified by the age of 32-34 years and 153 cases (1.9%) of more broadly defined schizophrenia by the age of 45-47 years. First-trimester exposure conferred an elevated risk of ICD-8 schizophrenia (odds ratio 2.53; 95% confidence interval [CI] 1.07-5.96) and also of broadly defined schizophrenia (odds ratio 2.14; 95% CI 1.06-4.31). Second-trimester exposure also conferred a significantly elevated risk of schizophrenia but only in unadjusted analyses. These findings suggest a relationship between maternal bacterial infection in pregnancy and offspring risk of schizophrenia, and this effect was somewhat stronger for ICD-8 schizophrenia with earlier onset. Post hoc analyses showed that upper respiratory tract and gonococcal infections were associated with elevated risk of the disease. An association between risk of schizophrenia and prenatal exposure to bacterial infections might be mediated through transplacental passage of maternally produced cytokines in response to bacterial infections.

Early developmental milestones and risk of schizophrenia: A 45-year follow-up of the Copenhagen Perinatal Cohort

The aim of the present study was to investigate the relationship between age of neuromotor milestone attainment and risk of adult schizophrenia. 5765 mothers of the Copenhagen Perinatal Cohort recorded 12 developmental milestones during the childs first year of life. Cohort members were followed until they were 46-48 years old through record linkage with the Danish Psychiatric Central Research Register. The age at which milestones were met in the 92 individuals who later developed schizophrenia was compared with milestone attainment in the 691 individuals who developed other psychiatric disorders and in the 4982 cohort controls who were never admitted to a psychiatric department. Group comparisons were adjusted for gender, mothers age, fathers age, parental social status, breadwinners education, single mother status and parity. Individuals who developed schizophrenia reached all developmental milestones later than controls and differed significantly from the controls with respect to the mean age of reaching the 12 milestones. Five developmental milestones in particular (smiling, lifting head, sitting, crawling, and walking) differed significantly. Individuals who later developed psychiatric disorders other than schizophrenia reached most developmental milestones earlier than those who developed schizophrenia, but later than the controls. The two psychiatric groups only differed significantly with respect to age of walking without support. The findings corroborate and methodologically extend previous research from prospective longitudinal cohort studies suggesting developmental delays observable as early as within the first year of life. These early developmental delays may not only characterize schizophrenia, but may be associated with a range of psychiatric disorders.

Childhood Motor Coordination and Adult Schizophrenia Spectrum Disorders

OBJECTIVE The authors examined whether motor coordination difficulties assessed in childhood predict later adult schizophrenia spectrum outcomes. METHOD A standardized childhood neurological examination was administered to a sample of 265 Danish children in 1972, when participants were 10-13 years old. Adult diagnostic information was available for 244 members of the sample. Participants fell into three groups: children whose mothers or fathers had a psychiatric hospital diagnosis of schizophrenia (N=94); children who had at least one parent with a psychiatric record of hospitalization for a nonpsychotic disorder (N=84); and children with no parental records of psychiatric hospitalization (N=66). Psychiatric outcomes of the offspring were assessed through psychiatric interviews in 1992 when participants were 31-33 years of age, as well as through a scan of national psychiatric registers completed in May 2007. RESULTS Children who later developed a schizophrenia spectrum disorder (N=32) displayed significantly higher scores on a scale of coordination deficits compared with those who did not develop a mental illness in this category (N=133). CONCLUSIONS Results from this study provide further support for the neurodevelopmental hypothesis of schizophrenia and underscore the potential role of cerebellar and/or basal ganglia abnormalities in the etiology and pathophysiology of schizophrenia.

Perspective-taking deficits in people with schizophrenia spectrum disorders : a prospective investigation

BACKGROUND This study examined data from a Danish prospective longitudinal project in attempt to address the state/trait controversy regarding theory of mind deficits in schizophrenia. Deficits in perspective-taking--a component of theory of mind--were investigated prospectively among children who developed schizophrenia spectrum disorders as adults in comparison to children who did not develop schizophrenia spectrum disorders. METHOD A total of 265 high risk and control subjects were studied in 1972. At the time of initial assessment, the Role-Taking Task (RTT) was administered. Two hundred and forty-two of these children were evaluated in 1992 during follow-up examinations. Sixteen developed schizophrenia, 10 developed a schizophrenia spectrum disorder, 70 had outcomes of other psychopathology, and 146 did not develop a mental illness. RESULTS Children who later developed schizophrenia or a schizophrenia spectrum disorder had lower RTT scores, controlling for verbal IQ and age, compared to those who did not develop any mental illness. Although in the expected direction, RTT scores for those with schizophrenia spectrum disorders were not significantly different from those who developed a non-psychotic disorder. CONCLUSIONS Deficits in perspective-taking among children who later developed schizophrenia spectrum disorders suggest that a facet of theory of mind is impaired prior to development of schizophrenia. Our findings lend support to the hypothesis that theory of mind deficits in schizophrenia are trait markers of the disorder.

Association Between Prepartum Maternal Iron Deficiency and Offspring Risk of Schizophrenia: Population-Based Cohort Study With Linkage of Danish National Registers

Recent findings suggest that maternal iron deficiency may increase the risk of schizophrenia-spectrum disorder in offspring. We initiated this study to determine whether maternal prepartum anemia influences offspring risk of schizophrenia. We conducted a population-based study with individual record linkage of the Danish Civil Registration System, the Danish Psychiatric Central Register, and the Danish National Hospital Register. In a cohort of 1,115,752 Danish singleton births from 1978 to 1998, cohort members were considered as having a maternal history of anemia if the mother had received a diagnosis of anemia at any time during the pregnancy. Cohort members were followed from their 10th birthday until onset of schizophrenia, death, or December 31, 2008, whichever came first. Adjusted for relevant confounders, cohort members whose mothers had received a diagnosis of anemia during pregnancy had a 1.60-fold (95% confidence interval = 1.16-2.15) increased risk of schizophrenia. Although the underlying mechanisms are unknown and independent replication is needed, our findings suggest that maternal iron deficiency increases offspring risk of schizophrenia.

Preventing repetition of attempted suicide—II. The Amager Project, a randomized controlled trial

Repetition after attempted suicide is high but only few effect studies have been carried out. The Baerum Model from Norway offers practical and affordable intervention for those not being offered psychiatric treatment. During a period from 2005–2007, all attempted suicide patients except those with major psychiatric diagnoses (schizophrenia, bipolar disorder, severe/psychotic depression), were offered participation. The intervention group received the OPAC programme (outreach, problem solving, adherence, continuity) and the control group received treatment as usual (TAU). The intervention period was 6 months. After this intervention period, all patients were followed passively for an extra 6 months. The design was an intent-to-treat one. The outcomes were: 1) repetition of attempted suicide or suicide, and 2) total number of suicidal acts. A total of 200 patients were offered participation, 67 refused. Of the 133 participants, 69 were randomized to the OPAC programme and 64 to the (non-intervention) control group. Four in each group dropped out after initial participation. There was a significant lower proportion who repeated a suicide attempt the intervention group (proportion 8.7%) than in the control group (proportion 21.9%) and the number of repetitive acts was also significant lower (eight repetitions in the intervention group vs. 22 in the control group). In conclusion, our findings suggest a protective effect of the OPAC programme on the proportion who repeated a suicide attempt and on the total number of repetitions during the follow-up.

Suicide and mental illness in parents and risk of suicide in offspring : A birth cohort study

BackgroundA family history of completed suicide and psychiatric illness has been identified as risk factors for suicide.AimsTo examine the risk of offspring suicide in relation to parental history of suicide and other parental risk factors.MethodThe study population consisted of 7,177 adult offspring born 1959–1961 and their parents from the Copenhagen Perinatal Cohort. Cohort members and their parents who had committed suicide were identified in the Danish Causes of Death Registry (follow-up until December 31, 2005), while information on psychiatric hospitalisation history was obtained from the Danish Psychiatric Central Research Register.ResultsForty-eight cohort members, 77 mothers and 133 fathers had committed suicide during the follow-up. Independent of parental psychiatric illness and social status, parental suicide significantly increased suicide risk in offspring (hazard ratio 4.40 with 95% CI 1.81–10.69). A stronger effect of parental suicide was observed in offspring without a history of psychiatric hospitalisation.ConclusionParental history of suicide is a risk factor for suicide in offspring, but primarily in offspring without psychiatric hospitalisation.

Premorbid childhood ocular alignment abnormalities and adult schizophrenia-spectrum disorder

This study examined the relation between childhood ocular alignment deficits and adult psychiatric outcomes among children at high-risk for schizophrenia and controls. A sample of 265 Danish children was administered a standardized eye exam assessing strabismus and related ocular alignment deficits. All children whose mothers or fathers had a psychiatric diagnosis of schizophrenia comprised the first group (N=90). Children who had at least one parent with a diagnosis other than schizophrenia comprised the first matched control group (N=93). The second control group consisted of children with no parental diagnoses (N=82). In 1992, adult psychiatric outcome data were obtained for 242 of the original subjects. It was found that children who later developed a schizophrenia-spectrum disorder had significantly higher eye exam scale and strabismus scale scores compared to children who developed other non-psychotic psychopathology and children who did not develop a mental illness. The mean rank for children in the high-risk group (offspring of parents with schizophrenia) on the eye scale and the strabismus scale was greater than the mean rank for children in the matched control groups (both offspring of parents with other non-psychotic disorder and no mental illness), although the results failed to reach statistical significance. Results from this study suggest a premorbid relation between ocular deficits and schizophrenia-spectrum disorders in childhood prior to onset of psychopathology in adulthood. Strabismus may serve as a premorbid marker for spectrum disorders and may have implications for the understanding of early aberrant neurological development related to later schizophrenia-spectrum disorders.

Height, weight and body mass index in early adulthood and risk of schizophrenia

Objective:  To illuminate the possible associations between height, weight, and body mass index (BMI) during early adulthood and the development of schizophrenia.

Breastfeeding and risk of schizophrenia in the Copenhagen Perinatal Cohort

Objective:  The aim was to study whether early weaning from breastfeeding may be associated with increased risk of schizophrenia.