Schizophrenia: do all roads lead to dopamine or is this where they start? Evidence from two epidemiologically informed developmental rodent models

The idea that there is some sort of abnormality in dopamine (DA) signalling is one of the more enduring hypotheses in schizophrenia research. Opinion leaders have published recent perspectives on the aetiology of this disorder with provocative titles such as ‘Risk factors for schizophrenia—all roads lead to dopamine' or ‘The dopamine hypothesis of schizophrenia—the final common pathway'. Perhaps, the other most enduring idea about schizophrenia is that it is a neurodevelopmental disorder. Those of us that model schizophrenia developmental risk-factor epidemiology in animals in an attempt to understand how this may translate to abnormal brain function have consistently shown that as adults these animals display behavioural, cognitive and pharmacological abnormalities consistent with aberrant DA signalling. The burning question remains how can in utero exposure to specific (environmental) insults induce persistent abnormalities in DA signalling in the adult? In this review, we summarize convergent evidence from two well-described developmental animal models, namely maternal immune activation and developmental vitamin D deficiency that begin to address this question. The adult offspring resulting from these two models consistently reveal locomotor abnormalities in response to DA-releasing or -blocking drugs. Additionally, as adults these animals have DA-related attentional and/or sensorimotor gating deficits. These findings are consistent with many other developmental animal models. However, the authors of this perspective have recently refocused their attention on very early aspects of DA ontogeny and describe reductions in genes that induce or specify dopaminergic phenotype in the embryonic brain and early changes in DA turnover suggesting that the origins of these behavioural abnormalities in adults may be traced to early alterations in DA ontogeny. Whether the convergent findings from these two models can be extended to other developmental animal models for this disease is at present unknown as such early brain alterations are rarely examined. Although it is premature to conclude that such mechanisms could be operating in other developmental animal models for schizophrenia, our convergent data have led us to propose that rather than all roads leading to DA, perhaps, this may be where they start

Cross-national Comparison of Prenatal Methamphetamine Exposure on Infant and Early Child Physical Growth: A Natural Experiment

The current study seeks to compare the effects of prenatal methamphetamine exposure (PME) on infant and child physical growth between the United States (US) and New Zealand (NZ). This cross-national comparison provides a unique opportunity to examine the potential impact of services provided to drug using mothers on child health. METHODS: The longitudinal Infant Development, Environment and Lifestyle (IDEAL) study of PME from birth to 36 months was conducted in the US and NZ. The US cohort included 204 children with PME and 212 non-PME matched comparisons (NPME); the NZ cohort included 108 children with PME and 115 NPME matched comparisons. Latent growth curve models were used to examine effects of PME, country of origin, and the country × PME interaction on growth in length/height and weight. RESULTS: In regard to length/height, PME and country of origin were associated with initial length and growth over time. There was also a significant interaction effect, such that children with PME in the US were shorter at birth than children with PME in NZ after controlling for other prenatal exposures, infant set, socioeconomic status, and maternal height. In regard to weight, there was only an effect of country of origin. CONCLUSIONS: Effects of PME on infant and child growth were shown to differ across countries, with exposed children in NZ faring better than exposed children in the US. Implications for prevention programs and public policy are discussed