Dennis K. Kinney

Prenatal stress and risk for autism.

This paper reviews several converging lines of research that suggest that prenatal exposure to environmental stress may increase risk for Autistic Disorder (AD). We first discuss studies finding that prenatal exposure to stressful life events is associated with significantly increased risk of AD, as well as other disorders, such as schizophrenia and depression. We then review evidence from animal and human studies that prenatal stress can produce both (a) abnormal postnatal behaviors that resemble the defining symptoms of AD, and (b) other abnormalities that have elevated rates in AD, such as learning deficits, seizure disorders, perinatal complications, immunologic and neuroinflammatory anomalies, and low postnatal tolerance for stress. We explain why an etiologic role for prenatal stress is compatible with genetic factors in AD, and describe how stress can disrupt fetal brain development. Finally, we discuss implications for understanding underlying processes in AD, including potential gene-environment interactions, and developing new therapies and early prevention programs.

Environmental risk factors for autism: Do they help cause de novo genetic mutations that contribute to the disorder?

Recent research has discovered that a number of genetic risk factors for autism are de novo mutations. Advanced parental age at the time of conception is associated with increased risk for both autism and de novo mutations. We investigated the hypothesis that other environmental factors associated with increased risk for autism might also be mutagenic and contribute to autism by causing de novo mutations. A survey of the research literature identified 9 environmental factors for which increased pre-conceptual exposure appears to be associated with increased risk for autism. Five of these factors--mercury, cadmium, nickel, trichloroethylene, and vinyl chloride--are established mutagens. Another four--including residence in regions that are urbanized, located at higher latitudes, or experience high levels of precipitation--are associated with decreased sun exposure and increased risk for vitamin D deficiency. Vitamin D plays important roles in repairing DNA damage and protecting against oxidative stress--a key cause of DNA damage. Factors associated with vitamin D deficiency will thus contribute to higher mutation rates and impaired repair of DNA. We note how de novo mutations may also help explain why the concordance rate for autism is so markedly higher in monozygotic than dizygotic twins. De novo mutations may also explain in part why the prevalence of autism is so remarkably high, given the evidence for a strong role of genetic factors and the low fertility of individuals with autism--and resultant selection pressure against autism susceptibility genes. These several lines of evidence provide support for the hypothesis, and warrant new research approaches--which we suggest--to address limitations in existing studies. The hypothesis has implications for understanding possible etiologic roles of de novo mutations in autism, and it suggests possible approaches to primary prevention of the disorder, such as addressing widespread vitamin D deficiency and exposure to known mutagens.

Pre- and perinatal complications and risk for bipolar disorder: a retrospective study

BACKGROUND Many studies have reported that obstetric complications are risk factors for schizophrenia, but few studies have examined whether complications increase risk for bipolar disorder. METHODS Bipolar-disorder probands and their adult siblings were diagnosed using DSM-III-R criteria. Obstetrical data from maternal reports were scored, blind to diagnosis, applying published scales that take into account number and severity of complications. RESULTS Obstetric complication scores were significantly worse in probands than siblings without mood disorders. LIMITATIONS Probands had relatively severe symptoms; research using more heterogeneous samples is needed. CONCLUSION Results suggest obstetric complications are etiologically significant in bipolar disorder.

Mood Swings and Creativity

ABSTRACT: This article evaluates recent evidence for an association between creativity and bipolar mood disorders. Eminent creativity and everyday creativity are distinguished, with high rates of major mood disorders‐particularly bipolar disorders— appearing among eminent creators in the arts. However, among everyday persons, including the 4–5% of the population that may develop a bipolar “spectrum”; disorder and their relatives, it is those with relatively milder mood disorders and normalcy who may show the greatest creative advantage. These seemingly conflicting results are reconciled through comparison of research designs and the creativity and diagnostic variables studied. Evidence regarding mood states that enhance creativity is also considered, both for eminent and everyday creators, and some preliminary results from a study of patients are presented. Here, milder mood elevations were tied most closely to the experience of creativity, although other patterns can exist. Three patterns are examined in...

Hard neurologic signs and psychopathology in relatives of schizophrenic patients

Previous research found more hard neurologic signs (i.e., signs that have localizing significance and exclude likely artifacts) in the nonschizophrenic relatives of schizophrenic patients than in control subjects, and in the psychiatrically normal relatives of schizophrenic patients compared with their ill relatives. Using interview-based DSM-III-R diagnoses and standard clinical neurological examinations on new samples, we found a trend to more hard signs in the 52 nonschizophrenic relatives of schizophrenic patients than in 20 control subjects, and significantly more signs in psychiatrically normal relatives than in ill ones. When pooled with previous data, signs were significantly higher in (1) relatives vs. controls and (2) normal vs. ill relatives, suggesting neurologic signs reflect an etiologic factor that often runs in families of schizophrenic patients.

An Evolutionary Hypothesis of Depression and Its Symptoms, Adaptive Value, and Risk Factors

Major depression is an evolutionary paradox: it carries great disadvantages for survival and reproduction of both patients and their relatives, yet it is common and has significant heritability. We propose a new hypothesis to help explain many of depressions symptoms and its risk factors, most of them not explained by previous evolutionary theories. We hypothesize that the evolutionary costs of depression are offset by its benefits in combating existing infections and avoiding new ones. As our hypothesis predicts, depression can be elicited by various infections as well as by environmental stressors that compromise immune function. Moreover, many depressive symptoms tend to aid immune function and reduce exposure to new infections and stressors. The hypothesis makes many predictions about the epidemiology and physiology of depression that are supported by available evidence. The hypothesis also suggests that possible underlying infectious and immune factors deserve greater consideration in prevention and treatment of depression.

Prenatal Stress and Risk for Schizophrenia

Evidence from several complementary types of studies suggests that prenatal exposure to maternal distress can increase a persons risk of developing schizophrenia. This includes (a) indirect evidence, from both human and animal studies, that prenatal stress can affect postnatal behavior and brain chemistry, and ( b ) more direct evidence, from several studies that have found that people with schizophrenia are more likely than controls to have been in utero when their mothers were exposed to stressful events.

Relationship of neurological abnormalities in schizophrenics to family psychopathology

Competing etiological models make opposite predictions as to the relationship between focal neurological abnormalities in schizophrenics and the prevalence of psychosis in their families. In previous studies of neurological abnormalities in schizophrenia, the authors found an increased prevalence of focal neurological signs in both patients and their nonschizophrenic relatives. The current study examines the relationship between neurological abnormalities in 24 schizophrenic patients and psychopathology in their families. A family history of psychotic psychopathology was found to be associated with an increased prevalence of focal neurological abnormalities in the schizophrenics. The results are relevant to current models of the potential role of neurological factors in the etiology of schizophrenia and illustrate how family studies of the joint distribution of psychiatric and neurological data can potentially help to distinguish between different etiological models.

Abnormal immune system development and function in schizophrenia helps reconcile diverse findings and suggests new treatment and prevention strategies

Extensive research implicates disturbed immune function and development in the etiology and pathology of schizophrenia. In addition to reviewing evidence for immunological factors in schizophrenia, this paper discusses how an emerging model of atypical immune function and development helps explain a wide variety of well-established - but puzzling - findings about schizophrenia. A number of theorists have presented hypotheses that early immune system programming, disrupted by pre- and perinatal adversity, often combines with abnormal brain development to produce schizophrenia. The present paper focuses on the hypothesis that disruption of early immune system development produces a latent immune vulnerability that manifests more fully after puberty, when changes in immune function and the thymus leave individuals more susceptible to infections and immune dysfunctions that contribute to schizophrenia. Complementing neurodevelopmental models, this hypothesis integrates findings on many contributing factors to schizophrenia, including prenatal adversity, genes, climate, migration, infections, and stress, among others. It helps explain, for example, why (a) schizophrenia onset is typically delayed until years after prenatal adversity, (b) individual risk factors alone often do not lead to schizophrenia, and (c) schizophrenia prevalence rates actually tend to be higher in economically advantaged countries. Here we discuss how the hypothesis explains 10 key findings, and suggests new, potentially highly cost-effective, strategies for treatment and prevention of schizophrenia. Moreover, while most human research linking immune factors to schizophrenia has been correlational, these strategies provide ethical ways to experimentally test in humans theories about immune function and schizophrenia. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease.

Eye-tracking dysfunction and birth-month weather in schizophrenia.

The prevalence of eye-tracking dysfunction (ETD) is significantly elevated in individuals with a diagnosis of schizophrenia and in their nonschizophrenic relatives, suggesting that ETD marks a familial (most likely genetic) risk factor for schizophrenia. Birth in a season with intemperate weather is also a widely reported risk factor for schizophrenia and is particularly marked for the subgroup with no family history of the disorder. This study examined how these two risk factors covaried in 78 patients with a Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; American Psychiatric Association, 1987) diagnosis of schizophrenia. Eye tracking and birth-month weather were independently assessed. As hypothesized, patients without ETD were significantly more likely to be born in months with intemperate weather (both hot and cold) than either patients with ETD or people in the general population. Etiologic factors associated with severe weather near birth may be important sources of nonfamilial schizophrenia.