Jordan Nechvatal

All Publications

• Long-term effects of intermittent early life stress on primate prefrontal-subcortical functional connectivity. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology Yuan, R., Nechvatal, J. M., Buckmaster, C. L., Ayash, S., Parker, K. J., Schatzberg, A. F., Lyons, D. M., Menon, V. 2021

  Abstract

  Correlational studies of humans suggest that exposure to early life stress has long-term effects on neural circuits involved in vulnerability and resilience to mental health disorders. Stress-related mental health disorders are more prevalent in women than in men. Here, female squirrel monkeys are randomized to intermittently stressful (IS) social separations or a non-separated (NS) control condition conducted from 17 to 27 weeks of age. Nine years later in mid-life adulthood, resting-state functional magnetic resonance imaging was employed to parcellate prefrontal cortex (PFC). Resulting subdivisions were then used to characterize functional connectivity within PFC, and between PFC subdivisions and subcortical regions that are known to be altered by stress. Extensive hyper-connectivity of medial and orbitofrontal PFC with amygdala, hippocampus, and striatum was observed in IS compared to NS monkeys. Functional hyper-connectivity in IS monkeys was associated with previously reported indications of diminished anxiety-like behavior induced by prepubertal stress. Hyper-connectivity of PFC with amygdala and with hippocampus was also associated with increased ventral striatal dopamine D2 and/or D3 receptor (DRD2/3) availability assessed with positron emission tomography (PET) of [11C]raclopride binding in adulthood. Ventral striatal DRD2/3 availability has been linked to cognitive control, which plays a key role in stress coping as an aspect of emotion regulation. These findings provide causal support for enduring neurobiological effects of early life stress and suggest novel targets for new treatments of stress-related mental health disorders.

  View details for DOI 10.1038/s41386-021-00956-0

  View details for PubMedID 33495547

• Integration of neural and epigenetic contributions to posttraumatic stress symptoms: The role of hippocampal volume and glucocorticoid receptor gene methylation PLOS ONE McNerney, M., Sheng, T., Nechvatal, J. M., Lee, A. G., Lyons, D. M., Soman, S., Liao, C., O'Hara, R., Hallmayer, J., Taylor, J., Ashford, J., Yesavage, J., Adamson, M. M. 2018; 13 (2): e0192222

  Abstract

  Many Veterans exposed to physical and psychological trauma experience symptoms of posttraumatic stress disorder (PTSD). As the etiology of PTSD symptoms is complex, a better understanding of the underlying biological mechanisms may improve preventative care and treatment for PTSD. Recent findings from the fields of neuroimaging and epigenetics offer important insights into the potential brain structures and biochemical pathways of modified gene expression associated with PTSD. We combined neuroimaging and epigenetic measures to assess current PTSD symptoms by measuring overall hippocampal volume and methylation of the glucocorticoid receptor (GR) gene (promoter region). Multiple regression analyses indicated that the hippocampal volume/GR methylation interaction was a predictor of PTSD symptoms. Our findings suggest that neuroimaging and epigenetic measures contribute interactively to PTSD symptoms. Incorporation of these metrics may aid in the identification and treatment of PTSD patients.

  View details for DOI 10.1371/journal.pone.0192222

  View details for Web of Science ID 000424325300060

  View details for PubMedID 29415058

  View details for PubMedCentralID PMC5802910

• Striatal dopamine D2/3 receptor regulation by stress inoculation in squirrel monkeys. Neurobiology of stress Lee, A. G., Nechvatal, J. M., Shen, B., Buckmaster, C. L., Levy, M. J., Chin, F. T., Schatzberg, A. F., Lyons, D. M. 2016; 3: 68-73

  Abstract

  Intermittent mildly stressful situations provide opportunities to learn, practice, and improve coping in a process called stress inoculation. Stress inoculation also enhances cognitive control and response inhibition of impulsive motivated behavior. Cognitive control and motivation have been linked to striatal dopamine D2 and/or D3 receptors (DRD2/3) in rodents, monkeys, and humans. Here, we study squirrel monkeys randomized early in life to stress inoculation with or without maternal companionship and a no-stress control treatment condition. Striatal DRD2/3 availability in adulthood was measured in vivo by [(11)C]raclopride binding using positron emission tomography (PET). DRD2/3 availability was greater in caudate and putamen compared to ventral striatum as reported in PET studies of humans and other non-human primates. DRD2/3 availability in ventral striatum was also consistently greater in stress inoculated squirrel monkeys compared to no-stress controls. Squirrel monkeys exposed to stress inoculation in the presence of their mother did not differ from squirrel monkeys exposed to stress inoculation without maternal companionship. Similar effects in different social contexts extend the generality of our findings and together suggest that stress inoculation increases striatal DRD2/3 availability as a correlate of cognitive control in squirrel monkeys.

  View details for PubMedID 27981179

• Coping changes the brain FRONTIERS IN BEHAVIORAL NEUROSCIENCE Nechvatal, J. M., Lyons, D. M. 2013; 7

  Abstract

  One of the earliest and most consistent findings in behavioral neuroscience research is that learning changes the brain. Here we consider how learning as an aspect of coping in the context of stress exposure induces neuroadaptations that enhance emotion regulation and resilience. A systematic review of the literature identified 15 brain imaging studies in which humans with specific phobias or post-traumatic stress disorder (PTSD) were randomized to stress exposure therapies that diminished subsequent indications of anxiety. Most of these studies focused on functional changes in the amygdala and anterior corticolimbic brain circuits that control cognitive, motivational, and emotional aspects of physiology and behavior. Corresponding structural brain changes and the timing, frequency, and duration of stress exposure required to modify brain functions remain to be elucidated in future research. These studies will advance our understanding of coping as a learning process and provide mechanistic insights for the development of new interventions that promote stress coping skills.

  View details for DOI 10.3389/fnbeh.2013.00013

  View details for Web of Science ID 000315183400001

  View details for PubMedID 23439935

  View details for PubMedCentralID PMC3579178