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  • James Shaffery, PhD

     shaffery, james.jpg

    Associate Professor, Psychiatry and Human Behavior
    Small Grant Principal Investigator
    Assistant Professor, Pharmacology and Toxicology
    Phone: (601) 984-6684



    • BA - Psychology, Castleton State College, Castleton, VT, 1978
    • DPhil - Ethology, zoology department, University of Oxford, UK, 1984


    • Postdoctoral training, Psychiatry Department, UT Southwestern Medical Center, Dallas, TX, 1988-93
    • Instructor, Psychiatry Department, UT Southwestern Medical Center, Dallas, TX, 1993-94
    • Assistant professor, Psychiatry Department, UT Southwestern Medical Center, Dallas, TX, 1994-95
    • Assistant professor, Department of Psychiatry and Human Behavior, UMMC School of Medicine, Jackson, MS, 1995-2002
    • Associate professor, Department of Psychiatry and Human Behavior, UMMC School of Medicine, Jackson, MS, 2002-present

    Special interests

    The rapid eye-movement (REM) sleep state appears to be necessary for proper brain maturation. Research in the Animal Sleep Laboratory is currently aimed at working out the neurophysiological and biochemical mechanisms which allow the REM sleep state to affect maturation of the central nervous system.

    Recent publications

    Key research personnel

    • Roseanne Armitage, PhD, Clinical mentor
    • Ian A. Paul, PhD, Consultant

    Laboratory personnel

    • Katherine O. Hall, Researcher II

    Small grant 3

    Title: Effects of Early-Life Sleep Abnormalities in the Production of Depressive-Like Features in a Rat Model of Human Major Depressive Disorder (MMOD)

    Mental health is the normal, expectable endpoint of brain maturation. Recent work shows that early-life rapid eye-movement sleep deprivation (ELRD) has long-lasting effects on synaptic plasticity mechanisms underlying CNS maturation, e.g., extending critical periods for brain development, in part, by altering expression of several neural signaling proteins. Other data implicate sleep in the etiology of major depressive disorder (MDD). Sleep electroencelopgraph (EEG) rhythmicity, sleep homeostasis as measured by slow-wave activity (SWA) in non-REM (NREM) sleep, rapid eye-movement (REM) sleep, as well as REM/NREM stage-cycle circadian timing are all abnormal when assessed at the time of early onset MDD. Similar abnormalities have been reported in children deemed at high risk for depression on the basis of maternal family history of MDD and likely reflect increased biological vulnerability to development of MDD in adolescence.

    Moreover, there is now good evidence that such sleep abnormalities are sex-dependent, namely greater biological rhythm disturbance in depressed women but less SWA in depressed men. Further, mild sleep deprivation provokes a very large SWA response in MDD women and a blunted response in MDD men, compared to healthy controls. These data point to impairments in sleep homeostasis at the core of sleep complaints in MDD. More generally, these findings have been interpreted to reflect greater neural plasticity in females than in males. In this project we plan to examine whether sleep deprivation increases the risk for MDD-like behaviors in particular critical periods of brain development and whether gender also impacts this risk. We will use an established rat model and focus on the relative permanence of ELRD effects upon brain maturation. We hypothesize that early ELRD predisposes developing brains to exhibit measurable, abnormal CNS signs in early adulthood that are proxies for CNS signs of MDD in people

    Another goal of this work is to determine whether a sex bias prevails in the CNS consequences of ELRD in rodents as it does in humans in terms of incidence of MDD. One major modification to the rat model is a focus on sleep homeostasis as measured by the SWA response to sleep deprivation. We raise the possibility that it is the effects of ELRD on sleep homeostasis and the recovery function of sleep that that confers greatest risk for MDD.

    We will investigate in late-adolescent rats the effects of ELRD at two points during early and late perinatal development on subsequent brain maturation, sleep regulation and behavior compared to control animals exposed to REM deprivation (ELRD) in early adolescence, outside of the critical period. In addition, we will also compare sleep homeostasis and SWA response to sleep deprivation between both experimental groups and controls. Potential group differences in hippocampal synaptic plasticity, behavior and neurochemical changes in both hippocampus and prefrontal cortex will be contrasted between groups.

    • Aim 1 - To determine if early- and late-ELRD impairs sleep regulation and sleep homeostasis in subsequent adolescence, and if the effects are sex dependent. Hypothesis 1a: Male- and females in both ELRD conditions will have less SWA, shorter REM sleep latency and less total REMS than control rats. Hypothesis 1b: Early-ELRD rats will have less SWA, shorter REM sleep latency and less REMS than those animals with late-ELRD. Hypothesis 1c: ELRD males will show a more blunted SWA response to subsequent sleep deprivation in late adolescence than control males and ELRD females. Hypothesis 1d: ELRD females will show a greater SWA response to subsequent sleep deprivation than control females.
    • Aim 2 - Demonstrate that in vitro synaptic plasticity is developmentally delayed by early- and late-of hippocampal synaptic plasticity than control rats. Hypothesis 2b: Early-ELRD will produce greater changes in developmental synaptic plasticity than late-ELRD. Hypothesis 2c: Males will exhibit greater changes in hippocampal developmental synaptic plasticity measures than females (see Background).
    • Aim 3 - Determine in adolescent ELRD rats if a sex bias exists in play activity and/or preferences for novel objects in an open-field. Hypothesis 3a: Adolescent ELRD females will spend less time in the open-arena-sectors containing a novel object than in the other sectors compared to either ELRD males and/or normal rats. Hypothesis 3b: Late-adolescent ELRD males will spend less time engaged in play behavior than normal males. Hypothesis 3c: Stronger effects on both behavioral measures are predicted for early-ELRD rats than in late-ELRD rats.
    • Aim 4 - To determine if there are sex differences in developmental changes in CNS expression of protein levels of the serotonin transporter (SERT) and/or the 5-HT1A autoreceptor. Hypothesis 4a: Late-adolescent ELRD females will express lower levels of the 5-HT1A autoreceptor- and SERT proteins than control animals in hippocampus and prefrontal cortex, more so (Hypothesis 4b) in the early-ELRD- than late-ELRD animals.

    In future (translational) work, we also will determine whether SWA homeostasis and sleep EEG regulation in adolescent ELRD rats conform to the patterns seen in children at high risk for MDD (e.g., NIH R01). Further, results from the planned studies potentially offer direction in the design of drug intervention and other treatments that selectively target sex differences in sleep regulation to improve depression.