A Comparison of Selected Risk Factors for Unipolar Depressive Disorder, Bipolar Affective Disorder, Schizoaffective Disorder, and Schizophrenia From a Danish Population-Based Cohort

Aarhus University, Aarhus, Central Jutland, Denmark
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 12/2007; 68(11):1673-81. DOI: 10.4088/JCP.v68n1106
Source: PubMed


Growing evidence of an etiologic overlap between schizophrenia and bipolar disorder has become increasingly difficult to disregard. In this study, we examined paternal age, urbanicity of place of birth, being born "small for gestational age," and parental loss as risk factors for primarily schizophrenia and bipolar disorder, but also unipolar depressive disorder and schizo-affective disorder. Furthermore, we examined the incidence of the disorders in a population-based cohort and evaluated our results in the context of the Kraepelinian dichotomization.
We established a register-based cohort study of more than 2 million persons born in Denmark between January 1, 1955, and July 1, 1987. Overall follow-up began on January 1, 1973 and ended on June 30, 2005. Relative risks for schizophrenia, bipolar disorder, unipolar depressive disorder, and schizoaffective disorder (ICD-8 or ICD-10) were estimated by survival analysis, using Poisson regression.
Differences were found in age-specific incidences. Loss of a parent (especially by suicide) was a risk factor for all 4 disorders. High paternal age and urbanization at birth were risk factors for schizophrenia. Children born pre-term had an excess risk of all disorders except schizophrenia if they were born "small for gestational age."
An overlap in the risk factors examined in this study was found, and the differences between the phenotypes were quantitative rather than qualitative, which suggests a genetic and environmental overlap between the disorders. However, large gender differences and differences in the age-specific incidences in the 4 disorders were present, favoring the Kraepelinian dichotomization.

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    • "While many studies have identified alleles associated with depression, to our knowledge no study has shown an association between increased mutation rate and MDD. In one sample, for instance, paternal age was shown to be a risk factor for schizophrenia, but not unipolar depressive disorder (Laursen et al., 2007). This suggests that MDD is less likely than other psychiatric disorders to be caused by de novo genetic mutations that lead to biological malfunction. "
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    ABSTRACT: Major depressive disorder (MDD) presents with a variety of symptoms and responds to a wide range of treatment interventions. Diagnostic criteria collapse multiple syndromes with distinct etiologies into the same disorder. MDD is typically understood as a malfunction of neurotransmission or brain circuitry regulating mood, pleasure and reward, or executive function. However, research from an evolutionary perspective suggests that the “normal” functioning of adaptations may also generate symptoms meeting diagnostic criteria. Functioning adaptations may be an underappreciated etiological pathway to MDD. Many adaptive functions for depressive symptoms have been suggested: biasing cognition to avoid losses, conserving energy, disengaging from unobtainable goals, signaling submission, soliciting resources, and promoting analytical thinking. We review the potential role of these adaptive functions and how they can lead to specific clusters of depressive symptoms. Understanding MDD from such a perspective reduces the heterogeneity of cases and may help to select the best intervention for each patient. We discuss the implications of different adaptive and maladaptive etiological pathways for the use of antidepressants and various modes of psychotherapy. In particular, instances of MDD caused by functioning adaptations may benefit most from treatments that support the adaptive function, or that target the precipitating causal stressor. We conclude that an evolutionary approach to the study of MDD may be one of the more promising approaches to reduce its heterogeneity and to better match patients and treatment.
    Full-text · Article · Sep 2014 · Journal of Affective Disorders
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    • "However, to our knowledge, no previous study has offered a lifecourse perspective examining whether the possible effects of late preterm birth on mental disorders extend across adult ages from young to old adulthood. Some studies suggest that the increased risk for mental disorders associated with preterm birth may characterize especially those preterm individuals who were born small for gestational age [SGA; defined as birth size at 42 standard deviations (S.D.s) or below the 5th or 10th percentile of that predicted by their gestational age; Laursen et al. 2007; Räikkönen et al. 2008; Strang-Karlsson et al. 2008; Monfils Gustafsson et al. 2009]. In fact, previous studies have shown that at least until young adulthood, individuals born SGA are at increased risk of severe mental disorders independently of their gestational age (Abel et al. 2010; Niederkrotenthaler et al. 2012; Nosarti et al. 2012). "
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    ABSTRACT: Background: Late preterm births constitute the majority of preterm births. However, most evidence suggesting that preterm birth predicts the risk of mental disorders comes from studies on earlier preterm births. We examined if late preterm birth predicts the risks of severe mental disorders from early to late adulthood. We also studied whether adulthood mental disorders are associated with post-term birth or with being born small (SGA) or large (LGA) for gestational age, which have been previously associated with psychopathology risk in younger ages. Method: Of 12 597 Helsinki Birth Cohort Study participants, born 1934-1944, 664 were born late preterm, 1221 post-term, 287 SGA, and 301 LGA. The diagnoses of mental disorders were identified from national hospital discharge and cause of death registers from 1969 to 2010. In total, 1660 (13.2%) participants had severe mental disorders. Results: Individuals born late preterm did not differ from term-born individuals in their risk of any severe mental disorder. However, men born late preterm had a significantly increased risk of suicide. Post-term birth predicted significantly increased risks of any mental disorder in general and particularly of substance use and anxiety disorders. Individuals born SGA had significantly increased risks of any mental and substance use disorders. Women born LGA had an increased risk of psychotic disorders. Conclusions: Although men born late preterm had an increased suicide risk, late preterm birth did not exert widespread effects on adult psychopathology. In contrast, the risks of severe mental disorders across adulthood were increased among individuals born SGA and individuals born post-term.
    Full-text · Article · Sep 2014 · Psychological Medicine
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    • "High scores on psychotic experiences in childhood (age 11) were shown to be an indication of an increased risk of developing a psychotic disorder later in life (age 26)[4]. However, it is typically not until adolescence/early adulthood that psychotic symptoms first emerge [6] and the association between psychotic experiences and a number of psychiatric disorders strengthens [7]. In a study conducted by Kelleher et al. [7] prevalence of psychotic experiences have been shown to decrease over time, from 21% in early adolescence (11–13 year olds) to 7% in mid-adolescence (13–16 year olds). "
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    ABSTRACT: Psychosis has been hypothesised to be a continuously distributed quantitative phenotype and disorders such as schizophrenia and bipolar disorder represent its extreme manifestations. Evidence suggests that common genetic variants play an important role in liability to both schizophrenia and bipolar disorder. Here we tested the hypothesis that these common variants would also influence psychotic experiences measured dimensionally in adolescents in the general population. Our aim was to test whether schizophrenia and bipolar disorder polygenic risk scores (PRS), as well as specific single nucleotide polymorphisms (SNPs) previously identified as risk variants for schizophrenia, were associated with adolescent dimension-specific psychotic experiences. Self-reported Paranoia, Hallucinations, Cognitive Disorganisation, Grandiosity, Anhedonia, and Parent-rated Negative Symptoms, as measured by the Specific Psychotic Experiences Questionnaire (SPEQ), were assessed in a community sample of 2,152 16-year-olds. Polygenic risk scores were calculated using estimates of the log of odds ratios from the Psychiatric Genomics Consortium GWAS stage-1 mega-analysis of schizophrenia and bipolar disorder. The polygenic risk analyses yielded no significant associations between schizophrenia and bipolar disorder PRS and the SPEQ measures. The analyses on the 28 individual SNPs previously associated with schizophrenia found that two SNPs in TCF4 returned a significant association with the SPEQ Paranoia dimension, rs17512836 (p-value = 2.57×10-4) and rs9960767 (p-value = 6.23×10-4). Replication in an independent sample of 16-year-olds (N = 3,427) assessed using the Psychotic-Like Symptoms Questionnaire (PLIKS-Q), a composite measure of multiple positive psychotic experiences, failed to yield significant results. Future research with PRS derived from larger samples, as well as larger adolescent validation samples, would improve the predictive power to test these hypotheses further. The challenges of relating adult clinical diagnostic constructs such as schizophrenia to adolescent psychotic experiences at a genetic level are discussed.
    Full-text · Article · Apr 2014 · PLoS ONE
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