Two primary lines of research:
1. The effects of developmental stress exposure:
The prenatal period and adolescence are two phases of development consistently linked with adult psychiatric illness. For example, when a woman experiences extreme stress during pregnancy, her offspring have an increased risk for psychiatric problems such as anxiety, depression, and schizophrenia[1-3]. In contrast, adolescence is the time when many psychiatric illnesses tend to emerge. However, the relationship between adolescent development and psychiatric illness remains poorly understood. Therefore, we aim to understand how the timing of stress exposure across development determines brain and behavioral development.
2. Organizing actions of gonadal steroid hormones on brain and behavioral development:
Pubertal timing varies widely between individuals, and whether individuals undergo pubertal development early or late relative to their peers increases risk for mental illness . In general, late maturing boys and early maturing girls are at greatest increased risk for psychopathologies such as depression[6-9] disordered eating[10, 11], substance abuse, and disruptive behavioral disorder.
Scientific explanations of the relationship between pubertal timing and mental illness have primarily focused on the social and emotional consequences of off-time pubertal development relative to one’s peers in boys and girls. However, pubertal gonadal steroid hormones also alter the trajectory of brain development during adolescence. We’ve recently proposed a biological model in which nervous system sensitivity to gonadal steroid hormones decreases across adolescent development [14-16]. In this framework, the developing adolescent brain is a moving target for the effects of gonadal steroid hormones, and shifts in pubertal timing may alter the course of brain development toward increased vulnerability.
Neural mechanisms: Nicotinic Acetylcholine Receptors (nAChRs) and Mental Illness
Nicotinic receptor dysfunction is common across many mental illnesses[5, 6]. Nicotine activates nicotinic acetylcholine receptors in the same way as the endogenous neurotransmitter acetylcholine. Rates of smoking are significantly higher amongst depressed, anxious, and schizophrenic individuals compared to the general population, suggesting individuals may be “self-medicating” to alleviate some of their symptoms. In support of this possibility, nicotine has anxiolytic actions in humans, and nicotine also ameliorates sensory gating attentional deficits in schizophrenia patients. There are several nicotinic receptor subtypes, and the two most widely found in the brain and implicated in psychiatric disorders are the high affinity nicotinic alpha4 beta2 receptors and the low affinity nicotinic alpha7 receptors. Animal studies demonstrate that alpha7 or alpha4 beta2 nicotinic receptor activation facilitates memory performance in a variety of testing paradigms[10, 11]. There is also evidence to suggest that disrupting the balance of hippocampal alpha7 and alpha4 beta2 receptor activity alters memory function in rats[10, 11]. In addition, both alpha7 and alpha4 beta2 hippocampal receptors have been shown to influence anxiety and depressive-like behaviors in rodents. Taken together, these data suggest that alpha7 and alpha4 beta2 nicotinic receptors in the hippocampus play a key role in both cognitive and affective behavioral function.
Recent lab studies:
Behavioral effects of prenatal stress
Prenatal stress has wide-ranging effects on the behavior of rodents. Dozens of published papers demonstrate that prenatal stress increases anxiety and depressive-related behaviors, and decrease memory function. Interestingly, these effects tend to be sexually dimorphic in nature. In our laboratory, we observe prenatal stress-induced increases in anxiety-related behaviors in females but not in males, and decreased memory function in males but not in females.
Choline as a Stress Intervention
Choline is an essential nutrient and an important structural component of all cell membranes. Therefore, a women's need for choline increases during pregnacy because the fetus requires high choline levels to build new cells. Although choline is abundant in protein-rich foods such as eggs, meats, and beans, about 25% of women do not meet the recommended levels of choline during pregnancy, and are consequently at a 4-fold greater risk of having a child with neural tube defects. Interestingly, choline is also a neurotransmitter in the brain and acts directly on the nAChRs that are altered by prenatal stress. As such, we tested whether perinatal dietary choline supplementation counteracts the detrimental effects of prenatal stress. Specifically, we fed stressed and nonstressed dams a choline-supplemented or control diet during pregnancy and lactation, and measured anxiety-related behaviors in adulthood.
Determining whether adolescence is a discrete sensitive period for the organizing actions of gonadal steroid hormones on cognitive and emotional behavioral function.
Does dietary choline protect against the deleterious effects of adolescent stress on adult behavior?
Determining the effects of prenatal stress and perinatal dietary choline on brain AChR levels.
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