Developmental origins of child mental health disorders.

This special issue on pre and perinatal processes in child mental health and disease is timely because there has been a revival of theory and hypothesis of persistent effects of adverse early environments on mental as well as physical health. The articles included here offer interesting contributions and generate intriguing questions about the complexity inherent in this area that makes research very challenging to conduct. Our commentary is intended to provide a critical appraisal of the area of research as well as of the individual articles in this special section. As a framework for our commentary, we used background articles in the literature that formed the basis for a meeting of 20 eminent geneticists (Swanson, Wadhwa, & Sing, 2006) convened to address genes, environments, and human development, health, and disease (GEHDHD) (see https://webfiles.uci.edu/xythoswfs/webui/jmswanso/GEHDHD%20Irvine%20Meeting), and two selected articles from the literature that discuss the concept of biological programming (Rutter, O’Connor, and the English and Romanian Adoptees Study Team, 2004 and Gluckman, Hanson, & Spencer, 2007b). Rutter et al. (2004) provide historical context about the waxing and waning of the hypothesis about adverse effects of the early environment, with initial claims made that were later discounted by the continuity hypothesis (i.e., that early disadvantage was usually followed by later disadvantage, but could be overcome if the pattern was interrupted due to priority of effects of the current environment on outcome), which was followed by a relatively recent revival based on the biological programming hypothesis (i.e., that early disadvantage produces adaptations in structure and function of the brain with enduring effects). Gluckman et al. (2007b) describes one variant of this approach, the Developmental Origins of Health and Disease (DOHaD), which has become so popular that an international society has been formed and is actively promoting research and collaboration in this area (see http://www.mrc.soton.ac.uk/dohad/). One section of the GEHDHD meeting focused on epigenetic processes, the molecular mechanisms presumed to underlie some forms of biological programming (see Swanson et al., 2006). The DOHaD approach evolved from observations of enduring effects of the fetal environment on adult physical health and disease. Barker, Osmond, Winter, Margetts, and Simmonds (1989) noted that low birth weight was associated with adverse adult outcomes, such as coronary heart disease, stroke, high blood pressure, and type 2 diabetes. This stimulated detailed animal and human studies and sophisticated accounts of what is now called predictive adaptive programming (see Gluckman et al., 2007b). The basic premise of the DOHaD approach is that early phenotypes such as low birth weight are correlated with prenatal conditions that may elicit biological programming, which operates to shape the structure and function of organs for optimal performance in the fetal environment. For example, one predictive adaptive programming response to energy-poor fetal conditions (i.e., fetal malnutrition) may be to develop resistance to the effects of insulin that moves glucose out of the blood stream into tissues (Phillips, 1996). This may produce a ‘thrifty’ phenotype (Hales & Barker, 1992) characterized by small size and insulin resistance, which for a fetus receiving inadequate amounts of glucose may be adaptive (beneficial). One benefit that has been hypothesized is that this thrifty phenotype may protect the glucose supply to the brain (Bateson et al., 2004). However, the thriftiness conferred by the predictive adaptive response may lead to adverse effects manifested in subsequent stages of life if the experienced fetal environment does not match the predicted future environment of the child. That is, it may confer continued advantage in a postnatal environment that is energy-poor but may have adverse consequences (e.g., increased risk for obesity) in a nutritionally enriched postnatal environment. Gluckman, Hanson, and Beedle (2007a) outline several reasons why the DOHaD phenomenon represents physiological plasticity not pathology. Rather than disrupt normal development, this form of biological programming appears to modulate development and permit a range of phenotypes to be expressed from a given genotype. This allows for more rapid adaptation to changing environmental conditions (i.e., within a lifetime by sculpting thrifty phenotypes) than by classical genetic mechanisms (i.e., across many lifetimes by shaping of the species by survival of the fittest in stable environments that produces thrifty genotypes by Darwinian natural selection). Another account of biological programming is presented by Rutter et al. (2004). In the formulation of hypotheses about the long-term effects of severe deprivation of Romanian orphans after adoption, two classes of theory were contrasted: one was based on the notion of physiological plasticity due to biological programming that modulates normal development, and the other on the notion of pathology that may also result from some environmental exposures and disrupt normal development. Environmental risk factors during pregnancy, such as maternal smoking, alcohol consumption, or exposure to toxins (e.g., lead, pesticides, etc.), have been associated with brain pathology and adverse behavioral consequences (see Linnet et al., 2005; Jacobson & Jacobson, 2005; Braun, Kahn, Froehlich, Aulnger, & Lanphear, 2006; Nigg, 2006). One label attached to subtle brain pathology is minimal brain dysfunction (MBD), which has a long history (see Bax & MacKeith, 1962; Wender, 1971; Nichols & Chen, 1981). The initial use of this label was dismissed in part due to lack of specificity for any particular disorder, but a revival of the MBD approach has been proposed by Lou (1996) to specifically address attention-deficit/hyperactivity disorder (ADHD). This approach is based on the hypothesis that repeated bouts of prenatal hypoxia may damage developing dopamine neurons before the formation of dopamine-rich structures in the brain such as the striatum. In this model, the neurological basis for MBD is characterized by smaller brain structures (e.g., caudate) rather than differences in brain morphology. Some evidence from brain imaging studies using positron emission tomography Neto, Lou, Cumming, Pryds, & Gjedde (2002) and magnetic resonance spectroscopy (Jin, Zang, Zeng, Zhang, & Wang, 2001) support the revival of the MBD theory to account for an etiologic subtype of ADHD (see Swanson et al., 2007 for a review). We consider both approaches – the DOHaD approach based on plasticity and the MBD approach based on pathology – to be relevant to the discussion of the 9 empirical studies and 2 reviews articles in this special issue on ‘Pre- and Perinatal Processes in Child Mental Health and Disorder’. All of these articles face the very difficult task of addressing complexity inherent in the outcomes related to child mental health and disorder that are likely have multi-factorial etiology. To make matters more complex, some of the articles address the nature of combined effects of multiple etiological factors –whether they have additive or interactive effects on outcomes. Furthermore, outcome-specificity and predictor-specificity introduce more complexity: for any given outcome it is possible to get there from different starting points, and for any given risk factor (condition) it is possible to get to different outcomes. The two example reviews and theoretical accounts of biological programming make this point. For example, Rutter et al. (2004) formulated a hypothesis about enduring effects of severe postnatal deprivation on psychological outcome, and when considering contrasts of biological programming and neural damage, they noted that ‘we saw no clear way of differentiating between these two alternatives with the measures available to us’ (p. 84). Also, Gluckman et al. (2007) noted that even within one of these alternatives – predictive adaptive programming and plasticity – ‘a relatively similar phenotype can be induced by a variety of nutritional or hormonal manipulations acting either early or late in development’ (p. 7). What can be done in the face of such complexity? The empirical studies in the special issue attempt to address this in a variety of ways – some by utilizing large samples, some with moderate samples but designs to limit complexity based on timing of exposure to adversity, and some with fine-grained evaluation of exposures and outcomes with small but well-characterized samples. Here we will try to integrate these articles in a common framework based on some generic critical issues that are covered across the studies but not all by any of them separately. First, we will organize the eclectic set of articles and briefly summarize the primary conclusion of each one. In addition, we will illustrate a critical issue by presenting a question that is not meant to provide an additional review of the article but instead was meant to identify issues that might direct the next round of studies. Second, we will integrate the diverse studies based on a few organizing principles. Third, we will offer an appraisal and recommendations for the emerging area that this special section identifies and addresses.