The developmental origins of complex behavior and neuropsychiatric disease

Development is a period marked by a profound, prolonged maturation of the brain and attendant changes in behavior. It has also long been recognized that the seeds of psychiatric disease are planted early in life in the form of influential ontogenic events and as major life events (e.g., exposure to stress or drugs) that resonate throughout the lifespan. This issue of G2BREVIEWS brings the question of development into focus with a collection of reviews by researchers who are leading efforts to understand how brain and behavior are shaped during the formative years of early life, and decipher the mechanisms by which genes and early environmental experience impact risk for an array of mental illnesses. Autism is a canonical developmental disorder that has become a major focus in psychiatric genetics. The resultant findings have informed the generation of mice with engineered mutations in autism candidate genes and in turn necessitated reliable readouts of autism-relevant behaviors. Here, Kazdoba et al. (2015) review the current genetic models and behavioral assays for autism, many of which this group has pioneered. Their article provides an excellent overview and template for researchers delving into this field. The need for better phenotypic modeling is echoed by Cope et al. (2015) in the context of modeling cognitive deficits associated with neurodevelopmental diseases. These authors contend that the failure to translate preclinical findings to new pro-cognitive treatments results from the artificial strictures of diagnostic boundaries separating disorders, and they herald the adoption of dimensional approaches to diagnosis typified by the Research Domain Criteria as a framework for advancing cross-species behavioral assays. Schizophrenia is a mental illness with profound cognitive dysfunction that has been long thought to have its roots in development. Schoenrock and Tarantino (2015) consider the intriguing hypothesis, based on animal models as well as epidemiological data from clinical studies, that prenatal vitamin D deficiency may be a risk factor for schizophrenia and a potential explanation for the greater incidence of the disease in individuals born in seasons or environments with lower sunlight (and hence vitamin D production). A major neural system implicated in schizophrenia and other developmentally related disorders in is the midbrain dopaminergic system. Bissonette and Roesch (2015) review the significant advances that have been made in delineating the ontogeny of this neurotransmitter system. They also offer a valuable description of the myriad genetic and molecular factors that modulate the fate of dopamine neurons and their connectivity with forebrain regions mediating cognition, reward and emotion. Dopamine is of course also well known for its role in reward, drug abuse and addiction. Belin et al. (2015) discuss how the work they have helped lead has provided novel insight into how specific, genetically related traits, such as impulsivity, may represent predictive markers for addiction-like behaviors. They also argue that research aimed at interrogating the developmental trajectory of addiction, and the contribution of individual differences in dopamine function and other neural processes, would be greatly facilitated by the availability of sound phenotypic measures of addiction-like behavior in rodents (Belin et al., 2015). These findings have implications for studying a variety of mechanisms known to be involved in addictions, such as nicotinic acetylcholine receptors – the focus of the article by Melroy-Greif et al. (2015). These authors discuss the interesting observation that there are adaptations, notably functional upregulation, in nicotinic receptors expressed in reward-related circuits that vary as a function of developmental age (Melroy-Greif et al., 2015). They point out how this idiosyncratic feature of nicotinic receptor function may be particularly relevant to risk for addictions in view of genetic associations between nicotinic receptors and drug abuse. Like nicotinic receptors, endocannabinoids are defined as targets for a commonly used and abused drug, but have broad neurobiological functions. For instance, there is now a substantial body of research demonstrating a key role for endocannabinoids in regulating stress, anxiety and various emotional behaviors across species. Lee et al. (2015) have made many important discoveries in this regard and, here, underscore the parallels that exist between alterations in brain endocannabinoid signaling and learned fear behaviors across development. They also discuss the topical