Bio

Academic Appointments


Administrative Appointments


  • Affiliate Scientist, California National Primate Research Center (2012 - Present)

Honors & Awards


  • Advanced Leadership Development Program, Stanford University School of Medicine (2012-2013)
  • Faculty Fellows Leadership Program, Stanford University School of Medicine (2010-2011)
  • Young Investigator Award recipient, NARSAD (2007-2009)
  • Individual postdoctoral NRSA recipient, National Institute of Mental Health (2003-2006)
  • Distinguished Dissertation Award recipient, University of Michigan (2000)
  • Oustanding Instructor Award recipient, University of Michigan (1999)
  • Institutional predoctoral NRSA recipient, National Institute of Child Health and Human Development (1998-2000)

Boards, Advisory Committees, Professional Organizations


  • Editorial Board Member, Psychoneuroendocrinology (2013 - Present)
  • Member of BRLE Grant Review Panel, National Institutes of Health (2012 - Present)

Professional Education


  • Postdoctoral, Stanford University, Psychiatry Neuroscience
  • Ph.D., University of Michigan, Biological Psychology (2000)
  • A.B., University of Michigan, Psychology (1994)

Research & Scholarship

Current Research and Scholarly Interests


The core interest that guides the Parker Lab translational research program is to understand the biological underpinnings of typical and atypical social behavior in animal models and in patient populations. This interest is manifested in two overlapping lines of research:

1) Studies of neuropeptides (e.g., oxytocin, vasopressin) that support species-typical social functioning in animals, and how alterations in these systems produce social impairments in a monkey model and in patients with autism. This research also tests the effectiveness of intranasal neuropeptide administration to enhance social functioning in children with autism, and whether biomarkers can help predict responses to these treatments.

2) Investigations of how early social relationships, and their disruption, alter developing neurobiological systems that regulate affect, social cognition, and stress reactivity, thereby producing stress resilient or stress vulnerable animals. This research is conducted in several species of monkeys and informs our clinical studies of patients with major depression.

Clinical Trials


  • The Role of Vasopressin in the Social Deficits of Autism Recruiting

    Researchers at the Stanford University School of Medicine are seeking participants for a study examining the effectiveness of vasopressin, a neuropeptide, in treating children with autism spectrum disorder. Difficulty with social interactions is characteristic of people with autism, who often have problems interpreting facial expressions or maintaining eye contact while talking with someone. There are currently no effective medicines available to treat social problems in individuals with autism. Neuropeptides, such as vasopressin and oxytocin, are molecules used by neurons in the brain to communicate with one another. Vasopressin is closely related to oxytocin, which is currently being tested as a treatment for autism, and has been shown to enhance social functioning in animals. Animal studies have shown that when the proper functioning of vasopressin is experimentally altered, animals develop a variety of social deficits, including impaired memory for peers and a reduced interest in social interaction. Researchers found that when vasopressin was administered to mice with a genetically induced form of autism, their social functioning improved. Vasopressin is already approved by the Food and Drug Administration for use in humans, and has proved to be a successful treatment for some common pediatric conditions, including bedwetting. Similar to oxytocin, it also has been shown to improve social cognition and memory in people who do not have autism. The researchers will test the effects of vasopressin on social impairments in 50 boys and girls with autism, ages 6 to 12 years old. The study will last four weeks for each participant. Participants will receive either vasopressin or a placebo nasal spray. At the end of this phase of the study, those who received the placebo will have the option of participating in a four-week trial during which they will be given vasopressin. Stanford is the only site for the study. Participants do not need to live locally but will need to come to the Stanford University Department of Psychiatry and Behavioral Sciences for study visits.

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  • Intranasal Oxytocin Treatment for Social Deficits in Children With Autism Recruiting

    Autism is a pervasive developmental disorder characterized by core deficits in social behavior and communication, and the presence of repetitive or stereotyped behaviors. It is one of three recognized disorders in the autism spectrum which affects an estimated 1 in 88 children in the United States. At present, pharmacotherapies target only associated features of autism, with no effective drug treatments for the social impairments. Several lines of evidence now suggest that the neuropeptide oxytocin (OT) may be an effective treatment for the core social deficits in autism. Here we will test the effects of twice daily intranasal OT (24 IU) over a 4-week period for enhancing social deficits in male and female children aged 6-12 years with autism. This research has high potential to lead to the development of more effective treatments and earlier interventions for children with autism.

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Projects


  • See Lab website for current projects: http://parkerlab.stanford.edu/research/, Stanford University

    Location

    Stanford University; California National Primate Research Center; Caribbean Primate Research Center

    Collaborators

    • Antonio Hardan, Professor of Psychiatry and Behavioral Sciences at the Stanford University Medical Center
    • Joseph Garner, Associate Professor of Comparative Medicine and, by courtesy, of Psychiatry and Behavioral Sciences
    • Alan Schatzberg, Kenneth T. Norris, Jr. Professor of Psychiatry and Behavioral Sciences
    • Jennifer Phillips, Clinical Associate Professor, Psychiatry & Behavioral Science - Child and Adolescent Psychiatry
    • Joshua Elias, Assistant Professor, Chemical and Systems Biology
    • Rachel Manber, Professor of Psychiatry and Behavioral Sciences at the Stanford University Medical Center
    • Sonia Partap, Clinical Assistant Professor, Neurology & Neurological Sciences
    • David Lyons, Professor (Research) of Psychiatry & Behavioral Sciences

Teaching

2013-14 Courses


Postdoctoral Advisees


Publications

Journal Articles


  • Plasma oxytocin concentrations are lower in depressed vs. healthy control women and are independent of cortisol. Journal of psychiatric research Yuen, K. W., Garner, J. P., Carson, D. S., Keller, J., Lembke, A., Hyde, S. A., Kenna, H. A., Tennakoon, L., Schatzberg, A. F., Parker, K. J. 2014; 51: 30-36

    Abstract

    The neuropeptide oxytocin (OT) promotes social behavior and attenuates stress responsivity in mammals. Recent clinical evidence suggests OT concentrations may be dysregulated in major depression. This study extends previous research by testing whether: 1) OT concentrations vary systematically in depressive disorders with and without hypercortisolemia, 2) gender differences in OT concentrations are observed in depressed vs. healthy control participants, and 3) OT concentrations are predictive of clinical phenotypes. Plasma OT concentrations of psychotic major depressive (PMD; n = 14: 10 female, 4 male), non-psychotic major depressive (NPMD; n = 17: 12 female, 5 male), and non-depressed, healthy control (n = 19: 11 female, 8 male) participants were assayed at 2000, 2400, 0400, and 0800 h. Plasma cortisol concentrations were quantified at 2300 h, and clinical phenotypes were determined. As expected, PMD participants, compared to NPMD and healthy control participants, showed higher plasma cortisol concentrations. Although both depressed groups showed similar OT concentrations, a significant interaction effect between group and gender was observed. Specifically, depressed females exhibited lower mean OT concentrations than depressed males. Further, depressed vs. healthy control female participants exhibited lower mean OT concentrations, whereas depressed vs. healthy control male participants showed a trend in the opposite direction. OT concentrations were also predictive of desirability, drug dependence, and compulsivity scores as measured by the Million Clinical Multiaxial Inventory-III. All findings were independent of cortisol. These data suggest that OT signaling may provide a mechanism by which to better understand female-biased risk to develop depressive disorders and that plasma OT concentrations may be a useful biomarker of certain clinical phenotypes.

    View details for DOI 10.1016/j.jpsychires.2013.12.012

    View details for PubMedID 24405552

  • The three-hit concept of vulnerability and resilience: Toward understanding adaptation to early-life adversity outcome PSYCHONEUROENDOCRINOLOGY Daskalakis, N. P., Bagot, R. C., Parker, K. J., Vinkers, C. H., De Kloet, E. R. 2013; 38 (9): 1858-1873

    Abstract

    Stressful experiences during early-life can modulate the genetic programming of specific brain circuits underlying emotional and cognitive aspects of behavioral adaptation to stressful experiences later in life. Although this programming effect exerted by experience-related factors is an important determinant of mental health, its outcome depends on cognitive inputs and hence the valence an individual assigns to a given environmental context. From this perspective we will highlight, with studies in rodents, non-human primates and humans, the three-hit concept of vulnerability and resilience to stress-related mental disorders, which is based on gene-environment interactions during critical phases of perinatal and juvenile brain development. The three-hit (i.e., hit-1: genetic predisposition, hit-2: early-life environment, and hit-3: later-life environment) concept accommodates the cumulative stress hypothesis stating that in a given context vulnerability is enhanced when failure to cope with adversity accumulates. Alternatively, the concept also points to the individual's predictive adaptive capacity, which underlies the stress inoculation and match/mismatch hypotheses. The latter hypotheses propose that the experience of relatively mild early-life adversity prepares for the future and promotes resilience to similar challenges in later-life; when a mismatch occurs between early and later-life experience, coping is compromised and vulnerability is enhanced. The three-hit concept is fundamental for understanding how individuals can either be prepared for coping with life to come and remain resilient or are unable to do so and succumb to a stress-related mental disorder, under seemingly identical circumstances.

    View details for DOI 10.1016/j.psyneuen.2013.06.008

    View details for Web of Science ID 000325188300045

    View details for PubMedID 23838101

  • Neonatal CSF oxytocin levels are associated with parent report of infant soothability and sociability. Psychoneuroendocrinology Clark, C. L., St John, N., Pasca, A. M., Hyde, S. A., Hornbeak, K., Abramova, M., Feldman, H., Parker, K. J., Penn, A. A. 2013; 38 (7): 1208-1212

    Abstract

    Oxytocin (OT) has been linked to social behavior in rodents, non-human primates, and adult humans, but almost nothing is known about brain OT activity in human newborns or its impact on social development. To better understand the role of OT biology in human social functioning, a multi-disciplinary, longitudinal study was conducted. Cerebral spinal fluid (CSF) OT levels from 18 human neonates were evaluated and examined in relationship to social-seeking behavior at term, at 3 months, and at 6 months of age. Higher neonatal CSF OT levels were consistently associated with solicitation of parental soothing and interest in social engagement with others. This is the first study to link CSF OT levels to normative human social functioning. Research is now required to test whether early OT levels serve as a biomarker for subsequent social abnormalities.

    View details for DOI 10.1016/j.psyneuen.2012.10.017

    View details for PubMedID 23507187

  • Distinct Plasma Profile of Polar Neutral Amino Acids, Leucine, and Glutamate in Children with Autism Spectrum Disorders JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS Tirouvanziam, R., Obukhanych, T. V., Laval, J., Aronov, P. A., Libove, R., Banerjee, A. G., Parker, K. J., O'Hara, R., Herzenberg, L. A., Herzenberg, L. A., Hardan, A. Y. 2012; 42 (5): 827-836

    Abstract

    The goal of this investigation was to examine plasma amino acid (AA) levels in children with Autism Spectrum Disorders (ASD, N = 27) and neuro-typically developing controls (N = 20). We observed reduced plasma levels of most polar neutral AA and leucine in children with ASD. This AA profile conferred significant post hoc power for discriminating children with ASD from healthy children. Furthermore, statistical correlations suggested the lack of a typical decrease of glutamate and aspartate with age, and a non-typical increase of isoleucine and lysine with age in the ASD group. Findings from this limited prospective study warrant further examination of plasma AA levels in larger cross-sectional and longitudinal cohorts to adequately assess for relationships with developmental and clinical features of ASD.

    View details for DOI 10.1007/s10803-011-1314-x

    View details for Web of Science ID 000302771500017

    View details for PubMedID 21713591

  • Effects of intranasal oxytocin on social anxiety in males with fragile X syndrome PSYCHONEUROENDOCRINOLOGY Hall, S. S., Lightbody, A. A., McCarthy, B. E., Parker, K. J., Reiss, A. L. 2012; 37 (4): 509-518

    Abstract

    Fragile X syndrome (FXS) is a rare inherited genetic disorder causing severe intellectual disability and autistic-like symptoms. Individuals with FXS, males in particular, often exhibit extreme eye gaze avoidance and hyperarousal when they encounter stressful social situations. We investigated whether oxytocin (OT), a hormone with prosocial and anxiolytic effects, could alleviate symptoms of social anxiety in this population. A randomized double-blind placebo-controlled single-dose trial was performed with intranasal administration of placebo, 24 IU OT and 48 IU OT. Measures of eye gaze frequency, heart rate, respiratory sinus arrhythmia (RSA), heart rate variability (HRV) and salivary cortisol were obtained during a structured social challenge conducted 50 min following OT administration. Ten low-functioning males with FXS (aged 13-28 years) traveled to Stanford for the initial visit: 8 completed the study. Eye gaze frequency improved significantly in response to the 24 IU OT dose and salivary cortisol levels decreased significantly in response to the 48 IU OT dose. There was no effect of OT on heart rate, RSA or HRV although individual plots of the heart rate data suggested that OT increased heart rate in some participants and decreased heart rate in others. These findings suggest that intranasal administration of OT may ameliorate some symptoms of social anxiety in patients with FXS. Further double-blind placebo-controlled studies of OT, conducted in combination with behavioral treatment programs, may be warranted.

    View details for DOI 10.1016/j.psyneuen.2011.07.020

    View details for Web of Science ID 000302044800007

    View details for PubMedID 21862226

  • Hypothalamic-pituitary-adrenal axis physiology and cognitive control of behavior in stress inoculated monkeys INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT Parker, K. J., Buckmaster, C. L., Lindley, S. E., Schatzberg, A. F., Lyons, D. M. 2012; 36 (1): 45-52
  • Psychological Stress in Childhood and Susceptibility to the Chronic Diseases of Aging: Moving Toward a Model of Behavioral and Biological Mechanisms PSYCHOLOGICAL BULLETIN Miller, G. E., Chen, E., Parker, K. J. 2011; 137 (6): 959-997

    Abstract

    Among people exposed to major psychological stressors in early life, there are elevated rates of morbidity and mortality from chronic diseases of aging. The most compelling data come from studies of children raised in poverty or maltreated by their parents, who show heightened vulnerability to vascular disease, autoimmune disorders, and premature mortality. These findings raise challenging theoretical questions. How does childhood stress get under the skin, at the molecular level, to affect risk for later diseases? And how does it incubate there, giving rise to diseases several decades later? Here we present a biological embedding model, which attempts to address these questions by synthesizing knowledge across several behavioral and biomedical literatures. This model maintains that childhood stress gets "programmed" into macrophages through epigenetic markings, posttranslational modifications, and tissue remodeling. As a consequence these cells are endowed with proinflammatory tendencies, manifest in exaggerated cytokine responses to challenge and decreased sensitivity to inhibitory hormonal signals. The model goes on to propose that over the life course, these proinflammatory tendencies are exacerbated by behavioral proclivities and hormonal dysregulation, themselves the products of exposure to early stress. Behaviorally, the model posits that childhood stress gives rise to excessive threat vigilance, mistrust of others, poor social relationships, impaired self-regulation, and unhealthy lifestyle choices. Hormonally, early stress confers altered patterns of endocrine and autonomic discharge. This milieu amplifies the proinflammatory environment already instantiated by macrophages. Acting in concert with other exposures and genetic liabilities, the resulting inflammation drives forward pathogenic mechanisms that ultimately foster chronic disease.

    View details for DOI 10.1037/a0024768

    View details for Web of Science ID 000296471000004

    View details for PubMedID 21787044

  • A novel form of oxytocin in New World monkeys BIOLOGY LETTERS Lee, A. G., Cool, D. R., Grunwald, W. C., Neal, D. E., Buckmaster, C. L., Cheng, M. Y., Hyde, S. A., Lyons, D. M., Parker, K. J. 2011; 7 (4): 584-587

    Abstract

    Oxytocin is widely believed to be present and structurally identical in all placental mammals. Here, we report that multiple species of New World monkeys possess a novel form of oxytocin, [P8] oxytocin. This mutation arises from a substitution of a leucine to a proline in amino acid position 8. Further analysis of this mutation in Saimiri sciureus (squirrel monkey) indicates that [P8] oxytocin is transcribed and translated properly. This mutation is specific to oxytocin, as the peptide sequence for arginine vasopressin, a structurally related nonapeptide, is unaltered. These findings dispel the notion that all placental mammals possess a 'universal' oxytocin sequence, and highlight the need for research on the functional significance of this novel nonapeptide in New World monkeys.

    View details for DOI 10.1098/rsbl.2011.0107

    View details for Web of Science ID 000292639100031

    View details for PubMedID 21411453

  • Identifying key features of early stressful experiences that produce stress vulnerability and resilience in primates NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS Parker, K. J., Maestripieri, D. 2011; 35 (7): 1466-1483

    Abstract

    This article examines the complex role of early stressful experiences in producing both vulnerability and resilience to later stress-related psychopathology in a variety of primate models of human development. Two types of models are reviewed: Parental Separation Models (e.g., isolate-rearing, peer-rearing, parental separations, and stress inoculation) and Maternal Behavior Models (e.g., foraging demands, variation in maternal style, and maternal abuse). Based on empirical evidence, it is argued that early life stress exposure does not increase adult vulnerability to stress-related psychopathology as a linear function, as is generally believed, but instead reflects a quadratic function. Features of early stress exposure including the type, duration, frequency, ecological validity, sensory modality, and developmental timing, within and between species, are identified to better understand how early stressful experiences alter neurobiological systems to produce such diverse developmental outcomes. This article concludes by identifying gaps in our current knowledge, providing directions for future research, and discussing the translational implications of these primate models for human development and psychopathology.

    View details for DOI 10.1016/j.neubiorev.2010.09.003

    View details for Web of Science ID 000292428200003

    View details for PubMedID 20851145

  • Somatic and neuroendocrine responses to standard and biologically salient acoustic startle stimuli in monkeys PSYCHONEUROENDOCRINOLOGY Parker, K. J., Hyde, S. A., Buckmaster, C. L., Tanaka, S. M., Brewster, K. K., Schatzberg, A. F., Lyons, D. M., Woodward, S. H. 2011; 36 (4): 547-556

    Abstract

    The startle response, a simple defensive response to a sudden stimulus signaling proximal threat, has been well studied in rodents and humans, but has been rarely examined in monkeys. The first goal of the present studies was to develop a minimally immobilizing startle measurement paradigm and validate its usefulness by testing two core features of the startle response (habituation and graded responsivity) in squirrel monkey subjects. Two different types of startle stimuli were used: standard broad-band noise bursts, and species-specific alarm vocalizations ("yaps") which are elicited in response to threat in both wild and captive animals. The second goal of the present studies was to test whether yaps produce enhanced startle responsivity due to their increased biological salience compared to simple, non-biologically relevant noise bursts. The third goal of the present studies was to evaluate the hypothalamic-pituitary-adrenal (HPA) axis response to startle stimuli, as little is known about the stress-activating role of startle stimuli in any species. These experiments determined that the whole-body startle response in relatively unrestrained squirrel monkeys habituates across repeated stimulus presentations and is proportional to stimulus intensity. In addition, differential habituation was observed across biologically salient vs. standard acoustic startle stimuli. Responses to "yaps" were larger initially but attenuated more rapidly over trials. Responses to "yaps" were also larger in the early subepochs of the response window but then achieved a lower level than responses to noise bursts in the later subepochs. Finally, adrenocorticotropic hormone and cortisol concentrations were significantly elevated above baseline after startle stimuli presentation, though monkeys did not exhibit differential HPA axis responses to the two types of startle stimuli. The development of monkey startle methodology may further enhance the utility of this paradigm in translational studies of human stress-related psychiatric disorders.

    View details for DOI 10.1016/j.psyneuen.2010.08.009

    View details for Web of Science ID 000288922300013

    View details for PubMedID 20869176

  • Mu-opioid Receptor (OPRM1) Variation, Oxytocin Levels and Maternal Attachment in Free-Ranging Rhesus Macaques Macaca mulatta BEHAVIORAL NEUROSCIENCE Higham, J. P., Barr, C. S., Hoffman, C. L., Mandalaywala, T. M., Parker, K. J., Maestripieri, D. 2011; 125 (2): 131-136

    Abstract

    Understanding the genetic and neuroendocrine basis of the mother-infant bond is critical to understanding mammalian affiliation and attachment. Functionally similar nonsynonymous mu-opioid receptor (OPRM1) SNPs have arisen and been maintained in humans (A118G) and rhesus macaques Macaca mulatta (C77G). In rhesus macaques, variation in OPRM1 predicts individual differences in infant affiliation for mothers. Specifically, infants carrying the G allele show increased distress on separation from their mothers, and spend more time with them upon reunion, than individuals homozygous for the C allele. In humans, individuals possessing the G allele report higher perceptions of emotional pain on receiving rejection by social partners. We studied maternal behavior over the course of a year among free-ranging female rhesus macaques on Cayo Santiago, Puerto Rico. We then trapped females and collected blood samples from which we assessed OPRM1 genotype; we also collected cerebrospinal fluid samples from which we measured oxytocin (OT) levels. We show that females possessing the G allele restrain their infants more (i.e., prevent infants from separating from them by pulling them back) than females homozygous for the C allele. Females possessing the G allele also show higher OT levels when lactating, and lower OT levels when neither lactating nor pregnant, than females homozygous for the C allele. This is the first study to demonstrate an association between OPRM1 genotype and maternal attachment for infants, and is one of the first studies of any free-ranging primate population to link functional genetic variation to behavior via potentially related neuroendocrine mechanisms.

    View details for DOI 10.1037/a0022695

    View details for Web of Science ID 000289182000001

    View details for PubMedID 21463018

  • Oxytocin receptor gene polymorphism (rs2254298) interacts with familial risk for psychopathology to predict symptoms of depression and anxiety in adolescent girls PSYCHONEUROENDOCRINOLOGY Thompson, R. J., Parker, K. J., Hallmayer, J. F., Waugh, C. E., Gotlib, I. H. 2011; 36 (1): 144-147

    Abstract

    The nonapeptide oxytocin and its receptor have been implicated in the regulation of mammalian social behavior and stress physiology. Evidence is accumulating that the quality of the parental environment is associated with oxytocin biology in children. The present study was designed to examine the interaction of the single nucleotide polymorphism (SNP) rs2254298 within the oxytocin receptor (OXTR) gene and quality of parental environment in predicting children's psychosocial functioning. More specifically, in a sample of 92 Caucasian adolescent girls (9-14 years old), we examined whether adverse parental environment, operationalized as mothers' history of recurrent major depressive disorder, interacts with the rs2254298 SNP on the OXTR gene to predict daughters' symptoms of depression and anxiety. Caucasian girls who both were heterozygous for the OXTR rs2254298 polymorphism and had high early adversity reported the highest levels of symptoms of depression, physical anxiety, and social anxiety. These findings highlight the potential importance of this OXTR gene polymorphism in the etiology of depression and anxiety disorders.

    View details for DOI 10.1016/j.psyneuen.2010.07.003

    View details for Web of Science ID 000286299100016

    View details for PubMedID 20708845

  • Animal Models of Early Life Stress: Implications for Understanding Resilience DEVELOPMENTAL PSYCHOBIOLOGY Lyons, D. M., Parker, K. J., Schatzberg, A. F. 2010; 52 (7): 616-624

    Abstract

    In the mid-1950s, Levine and his colleagues reported that brief intermittent exposure to early life stress diminished indications of subsequent emotionality in rats. Here we review ongoing studies of a similar process in squirrel monkeys. Results from these animal models suggest that brief intermittent exposure to stress promotes the development of arousal regulation and resilience. Implications for programs designed to enhance resilience in human development are discussed.

    View details for DOI 10.1002/dev.20500

    View details for Web of Science ID 000283570400002

    View details for PubMedID 20957724

  • Preliminary evidence that plasma oxytocin levels are elevated in major depression PSYCHIATRY RESEARCH Parker, K. J., Kenna, H. A., Zeitzer, J. M., Keller, J., Blasey, C. M., Amico, J. A., Schatzberg, A. F. 2010; 178 (2): 359-362

    Abstract

    It is well established that the neuropeptide oxytocin (OT) is involved in regulating social behavior, anxiety, and hypothalamic-pituitary-adrenal (HPA) axis physiology in mammals. Because individuals with major depression often exhibit functional irregularities in these measures, we test in this pilot study whether depressed subjects (n=11) exhibit dysregulated OT biology compared to healthy control subjects (n=19). Subjects were hospitalized overnight and blood samples were collected hourly between 1800 and 0900h. Plasma levels of OT, the closely related neuropeptide argine-vasopressin (AVP), and cortisol were quantified. Results indicated that depressed subjects exhibit increased OT levels compared to healthy control subjects, and this difference is most apparent during the nocturnal peak. No depression-related differences in AVP or cortisol levels were discerned. This depression-related elevation in plasma OT levels is consistent with reports of increased hypothalamic OT-expressing neurons and OT mRNA in depressed patients. This present finding is likewise consistent with the hypothesis that dysregulated OT biology may be a biomarker of the emotional distress and impaired social relationships which characterize major depression. Additional research is required to elucidate the role of OT in the pathophysiology of this psychiatric disorder.

    View details for DOI 10.1016/j.psychres.2009.09.017

    View details for Web of Science ID 000279988900025

    View details for PubMedID 20494448

  • Effects of Age on Cerebrospinal Fluid Oxytocin Levels in Free-Ranging Adult Female and Infant Rhesus Macaques BEHAVIORAL NEUROSCIENCE Parker, K. J., Hoffman, C. L., Hyde, S. A., Cummings, C. S., Maestripieri, D. 2010; 124 (3): 428-433

    Abstract

    There is growing interest in examining oxytocin and social functioning in human and non-human primates. Studies of human oxytocin biology are typically restricted to peripheral assessments because opportunities to collect cerebrospinal fluid (CSF) are rare. Several studies have examined CSF oxytocin levels in captive adult primates, but none to our knowledge have been conducted under free-ranging conditions and inclusive of infants. The main goal of this study was to establish feasibility of quantifying CSF oxytocin levels in free-ranging adult female and infant rhesus monkeys living on Cayo Santiago, PR. CSF oxytocin levels were examined in relation to individuals' demographic and reproductive characteristics as well as plasma cortisol levels. CSF oxytocin concentrations ranged from 36.02 to 134.41 pg/ml in adult females (ages 7-26 years; N = 31) and 35.94 to 77.3 pg/ml in infants (ages 38-134 days; N = 17). CSF oxytocin levels were positively correlated with adult female age and negatively correlated with infant age. The former correlation was driven by reproductive status. CSF oxytocin levels were unrelated to dominance rank or plasma cortisol levels. In contrast to a previous study of plasma oxytocin concentrations in this population, CSF oxytocin levels did not differ significantly between lactating and non-lactating females. These findings: 1) provide feasibility data for examining CSF oxytocin levels in free-ranging non-human primates and 2) indicate that CSF oxytocin levels may be a biomarker of age-related central nervous system changes across lifespan development. Research is now required to examine CSF oxytocin levels in the context of social functioning in free-ranging rhesus monkeys.

    View details for DOI 10.1037/a0019576

    View details for Web of Science ID 000278466000015

    View details for PubMedID 20528088

  • FOR BETTER OR WORSE? STRESS INOCULATION EFFECTS FOR IMPLICIT BUT NOT EXPLICIT ANXIETY DEPRESSION AND ANXIETY Edge, M. D., Ramel, W., Drabant, E. M., Kuo, J. R., Parker, K. J., Gross, J. J. 2009; 26 (9): 831-837

    Abstract

    Severe early life stress (ELS) is associated with negative outcomes. It is not clear, however, what impact moderate ELS has. A growing stress inoculation literature suggests that moderate (vs. low or high) ELS is associated with diminished behavioral and physiological anxiety responses. At the same time, studies of trait anxiety suggest that moderate (vs. low) ELS is associated with greater self-reported anxiety. This study tested the hypothesis that stress inoculation effects are evident for implicit (nonconscious) but not explicit (conscious) aspects of anxiety.Ninety-seven healthy women were assessed for ELS and explicit anxiety using questionnaires and assessed for implicit anxiety using a version of the Implicit Association Test.Results indicated a quadratic relation between ELS and implicit anxiety, such that moderate ELS was associated with lower implicit anxiety levels than low or high ELS. By contrast, the relation between ELS and explicit anxiety was linear.These findings support the stress inoculation hypothesis and suggest that stress inoculation applies for implicit but not explicit aspects of anxiety.

    View details for DOI 10.1002/da.20592

    View details for Web of Science ID 000269685500008

    View details for PubMedID 19569055

  • Prefrontal Plasticity and Stress Inoculation-Induced Resilience DEVELOPMENTAL NEUROSCIENCE Katz, M., Liu, C., Schaer, M., Parker, K. J., Ottet, M., Epps, A., Buckmaster, C. L., Bammer, R., Moseley, M. E., Schatzberg, A. F., Eliez, S., Lyons, D. M. 2009; 31 (4): 293-299

    Abstract

    Coping with mild early life stress tends to make subsequent coping efforts more effective and therefore more likely to be used as a means of arousal regulation and resilience. Here we show that this developmental learning-like process of stress inoculation increases ventromedial prefrontal cortical volumes in peripubertal monkeys. Larger volumes do not reflect increased cortical thickness but instead represent surface area expansion of ventromedial prefrontal cortex. Expansion of ventromedial prefrontal cortex coincides with increased white matter myelination inferred from diffusion tensor magnetic resonance imaging. These findings suggest that the process of coping with early life stress increases prefrontal myelination and expands a region of cortex that broadly controls arousal regulation and resilience.

    View details for DOI 10.1159/000216540

    View details for Web of Science ID 000267787200006

    View details for PubMedID 19546566

  • Developmental cascades linking stress inoculation, arousal regulation, and resilience FRONTIERS IN BEHAVIORAL NEUROSCIENCE Lyons, D. M., Parker, K. J., Katz, M., Schatzberg, A. F. 2009; 3

    Abstract

    Stressful experiences that are challenging but not overwhelming appear to promote the development of arousal regulation and resilience. Variously described in studies of humans as inoculating, steeling, or toughening, the notion that coping with early life stress enhances arousal regulation and resilience is further supported by longitudinal studies of squirrel monkey development. Exposure to early life stress inoculation diminishes subsequent indications of anxiety, increases exploration of novel situations, and decreases stress-levels of cortisol compared to age-matched monkeys raised in undisturbed social groups. Stress inoculation also enhances prefrontal-dependent cognitive control of behavior and increases ventromedial prefrontal cortical volumes. Larger volumes do not reflect increased cortical thickness but instead represent surface area expansion of ventromedial prefrontal cortex. Expansion of ventromedial prefrontal cortex coincides with increased white matter myelination inferred from diffusion tensor magnetic resonance imaging. These findings suggest that early life stress inoculation triggers developmental cascades across multiple domains of adaptive functioning. Prefrontal myelination and cortical expansion induced by the process of coping with stress support broad and enduring trait-like transformations in cognitive, motivational, and emotional aspects of behavior. Implications for programs designed to promote resilience in humans are discussed.

    View details for DOI 10.3389/neuro.08.032.2009

    View details for Web of Science ID 000208031500032

    View details for PubMedID 19826626

  • Preliminary evidence that hippocampal volumes in monkeys predict stress levels of adrenocorticotropic hormone BIOLOGICAL PSYCHIATRY Lyons, D. M., Parker, K. J., Zeitzer, J. M., Buckmaster, C. L., Schatzberg, A. F. 2007; 62 (10): 1171-1174

    Abstract

    Hippocampal volumes previously determined in monkeys by magnetic resonance imaging are used to test the hypothesis that small hippocampi predict increased stress levels of adrenocorticotropic hormone (ACTH).Plasma ACTH levels were measured after restraint stress in 19 male monkeys pretreated with saline or hydrocortisone. Monkeys were then randomized to an undisturbed control condition or intermittent social separations followed by new pair formations. After 17 months of exposure to the intermittent social manipulations, restraint stress tests were repeated to determine test/retest correlations.Individual differences in postrestraint stress ACTH levels over the 17-month test/retest interval were remarkably consistent for the saline (r(s) = .82, p = .0004) and hydrocortisone (r(s) = .78, p = .001) pretreatments. Social manipulations did not affect postrestraint stress ACTH levels, but monkeys with smaller hippocampal volumes responded to restraint after saline pretreatment with greater increases in ACTH levels with total brain volume variation controlled as a statistical covariate (beta = -.58, p = .031). Monkeys with smaller hippocampal volumes also responded with diminished sensitivity to glucocorticoid feedback determined by greater postrestraint ACTH levels after pretreatment with hydrocortisone (beta = -.68, p = .010).These findings support clinical reports that small hippocampi may be a risk factor for impaired regulation of the hypothalamic-pituitary-adrenal axis in humans with stress-related psychiatric disorders.

    View details for DOI 10.1016/i.biopsych.2007.03.012

    View details for Web of Science ID 000250905800015

    View details for PubMedID 17573043

  • Early life stress and novelty seeking behavior in adolescent monkeys PSYCHONEUROENDOCRINOLOGY Parker, K. J., Rainwater, K. L., Buckmaster, C. L., Schatzberg, A. F., Lindley, S. E., Lyons, D. M. 2007; 32 (7): 785-792

    Abstract

    Recent evidence suggests that early exposure to mild stress promotes the development of novelty seeking behavior. Here we test this hypothesis in squirrel monkeys and investigate whether novelty seeking behavior is associated with differences in cerebrospinal fluid (CSF) levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5HIAA), the dopamine metabolite homovanillic acid (HVA), the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), and the neuropeptide corticotrophin-releasing factor (CRF). Monkeys were randomized early in life to either mild intermittent stress (IS) or no stress (NS) conditions, and subsequently presented with opportunities to interact with a familiar or novel object in a test box that was connected to each monkey's home cage. To further minimize the potentially stressful nature of the test situation, monkeys were acclimated to the test procedures prior to study initiation. Post-test plasma levels of cortisol in IS and NS monkeys did not differ significantly from baseline levels measured in undisturbed conditions. During testing, more IS than NS monkeys voluntarily left the home cage, and IS monkeys spent more time in the test box compared to NS monkeys. More IS than NS monkeys engaged in object exploration in the test box, and IS monkeys preferred to interact with the novel vs. familiar object. Novelty seeking was not associated with differences in 5HIAA, HVA, MHPG, or CRF, but correlated with differences in object exploration observed in a different test situation at an earlier age. These trait-like differences in novelty seeking appear to reflect mild early stress-induced adaptations that enhance curiosity and resilience.

    View details for DOI 10.1016/j.psyneuen.2007.05.008

    View details for Web of Science ID 000249510200003

    View details for PubMedID 17604913

  • Stress inoculatio n-induced indications of resilience in monkeys JOURNAL OF TRAUMATIC STRESS Lyons, D. M., Parker, K. J. 2007; 20 (4): 423-433

    Abstract

    The negative consequences of stress are well-recognized in mental health research. Exposure to early life stressors, for example, increases the risk for the development of mood, anger, anxiety, and substance abuse disorders. Interestingly, however, early life stressors have also been linked to the subsequent development of resilience. Variously described as inoculating, immunizing, steeling, toughening, or thriving, the hypothesis that early life stressors provide a challenge that, when overcome, induces adaptations that enhance emotional processing, cognitive control, curiosity, and neuroendocrine regulation is examined in this review of squirrel monkey research.

    View details for DOI 10.1002/jts.20265

    View details for Web of Science ID 000249183400006

    View details for PubMedID 17721972

  • Social stress-related behavior affects hippocampal cell proliferation in mice PHYSIOLOGY & BEHAVIOR Mitra, R., Sundlass, K., Parker, K. J., Schatzberg, A. F., Lyons, D. M. 2006; 89 (2): 123-127

    Abstract

    Although social stress inhibits neurogenesis in the adult hippocampus, the extent to which individual differences in stress-related behavior affect hippocampal cell proliferation is not well understood. Based on results from resident-intruder stress tests administered to adult male mice, here we report that individual differences in hippocampal cell proliferation are related to the frequency of defensive behavior, and not the amount of aggression received or the frequency of fleeing. In contrast, access to voluntary wheel-running exercise did not affect hippocampal cell proliferation in either stressed or non-stressed mice. Social stress-induced inhibition of cell proliferation was restricted to the hippocampus, as neither stress nor access to wheel-running exercise altered cell proliferation in the amygdala. These findings indicate that individual differences in stress-related behavior influence cell proliferation in the mouse hippocampus, and may have important implications for understanding structural and functional hippocampal impairments in human psychiatric patients.

    View details for DOI 10.1016/j.physbeh.2006.05.047

    View details for Web of Science ID 000240414300001

    View details for PubMedID 16837015

  • Maternal mediation, stress inoculation, and the development of neuroendocrine stress resistance in primates PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Parker, K. J., Buckmaster, C. L., Sundlass, K., Schatzberg, A. F., Lyons, D. M. 2006; 103 (8): 3000-3005

    Abstract

    The stress inoculation hypothesis presupposes that brief intermittent stress exposure early in life induces the development of subsequent stress resistance in human and nonhuman primates. Rodent studies, however, suggest a role for maternal care rather than stress exposure per se (i.e., the maternal mediation hypothesis). To investigate these two hypotheses, we examined maternal care and the development of stress resistance after exposure to brief intermittent infant stress (IS), mother-infant stress (MIS), or no stress (NS) protocols administered to 30 monkeys between postnatal weeks 17 and 27. Unlike rodents, the IS condition did not permanently increase primate maternal care, nor did measures of total maternal care predict subsequent offspring hypothalamic-pituitary-adrenal-axis responsivity. Although MIS infants received less maternal care than IS and NS infants, both IS and MIS monkeys developed subsequent stress resistance. These findings indicate that rearing differences in the development of stress resistance are more closely related to differences in prior stress exposure than to differences in maternal care. A second experiment confirmed this conclusion in a different cohort of 25 monkeys exposed as infants to high foraging-demand (HFD) or low foraging-demand (LFD) conditions. HFD infants exhibited intermittent elevations in cortisol levels and received less maternal care than LFD infants. In keeping with a key prediction of the stress inoculation hypothesis, HFD males responded to stress in adulthood with diminished hypothalamic-pituitary-adrenal-axis activation compared with LFD males. Results from both experiments demonstrate that stress inoculation, rather than high levels of maternal care, promotes the development of primate stress resistance.

    View details for DOI 10.1073/pnas.0506571103

    View details for Web of Science ID 000235554900093

    View details for PubMedID 16473950

  • Intranasal oxytocin administration attenuates the ACTH stress response in monkeys PSYCHONEUROENDOCRINOLOGY Parker, K. J., Buckmaster, C. L., Schatzberg, A. F., Lyons, D. M. 2005; 30 (9): 924-929

    Abstract

    Social relationships protect against the development of stress-related psychiatric disorders, yet little is known about the neurobiology that regulates this phenomenon. Recent evidence suggests that oxytocin (OT), a neuropeptide involved in social bond formation, may play a role. This experiment investigated the effects of chronic intranasal OT administration on acute stress-induced hypothalamic-pituitary-adrenal (HPA) axis activation in adult female squirrel monkeys. Subjects were randomized to one of two experimental conditions. Monkeys were intranasally administered either 50 microg oxytocin (N = 6 monkeys) or 0 microg oxytocin (N = 6 monkeys)/300 microl saline once a day for eight consecutive days. Immediately after drug administration on the eighth day, all monkeys were exposed to acute social isolation. Blood samples for determinations of adrenocorticotropic hormone (ACTH) and cortisol concentrations were collected after 30 and 90 min of stress exposure. Consistent with an anti-stress effect, OT-treated monkeys exhibited lower ACTH concentrations compared to saline-treated monkeys after 90 min of social isolation (F(1,7) = 6.891; P = 0.034). No drug-related differences in cortisol levels were observed, indicating that OT does not directly attenuate the adrenal stress response. Intranasal peptide administration has been shown to penetrate the central nervous system, and research must determine whether intranasally delivered OT exerts its effect(s) at a pituitary and/or brain level. This primate model offers critical opportunities to improve our understanding of the anti-stress effects of OT and may lead to novel pharmacological treatments for stress-related psychiatric disorders.

    View details for DOI 10.1016/j.psyneuen.2005.04.002

    View details for Web of Science ID 000231003800012

    View details for PubMedID 15946803

  • Mild early life stress enhances prefrontal-dependent response inhibition in monkeys BIOLOGICAL PSYCHIATRY Parker, K. J., Buckmaster, C. L., Justus, K. R., Schatzberg, A. F., Lyons, D. M. 2005; 57 (8): 848-855

    Abstract

    Severely stressful early experiences have been implicated in the pathophysiology of psychiatric disorders. In contrast, exposure to mild early life stress (i.e., stress inoculation) strengthens emotional and neuroendocrine resistance to subsequent stressors. Herein we extend this research to examine the effects of mild early life stress on cognition.Squirrel monkeys were randomized to a mild intermittent stress (IS; n = 11) or nonstress (NS; n = 9) condition from 17 to 27 weeks postpartum. At 1.5 years of age, monkeys were assessed for response inhibition on a test previously shown to reflect prefrontal-dependent cognitive function.IS monkeys demonstrated fewer response inhibition errors compared with NS monkeys. There were no rearing-related differences in aspects of performance that did not require inhibitory control. Compared with NS monkeys, IS monkeys had lower basal plasma pituitary-adrenal stress hormone levels. No rearing-related differences on neuroendocrine measures obtained 15 minutes after testing were found.Results from this experiment provide the first evidence that exposure to mildly stressful early experiences improves prefrontal-dependent response inhibition in primates. Combined with our previous data, findings from this animal model suggest that exposure to mild early life stress may enhance the development of brain systems that regulate emotional, neuroendocrine, and cognitive control.

    View details for Web of Science ID 000228280700004

    View details for PubMedID 15820705

  • Prospective investigation of stress inoculation in young monkeys ARCHIVES OF GENERAL PSYCHIATRY Parker, K. J., Buckmaster, C. L., Schatzberg, A. F., Lyons, D. M. 2004; 61 (9): 933-941

    Abstract

    Retrospective studies in humans have identified characteristics that promote stress resistance, including childhood exposure to moderately stressful events (ie, stress inoculation).Because of limited opportunities for prospective studies in children, we tested whether exposure to moderate stress early in life produces later stress resistance in a primate model.Twenty squirrel monkeys were randomized to intermittent stress inoculation (IS; n = 11) or a nonstress control condition (NS; n = 9) from postnatal weeks 17 to 27. At postnatal week 35, each mother-offspring dyad underwent testing in a moderately stressful novel environment for inferential measures of offspring anxiety (ie, maternal clinging, mother-offspring interactions, object exploration, and food consumption) and stress hormone concentrations (corticotropin [ACTH] and cortisol). At postnatal week 50, after acclimation to an initially stressful wire-mesh box attached to the home cage, independent young monkeys underwent testing for inferential measures of anxiety (ie, voluntary exploration and play) in the box.In the novel environment test, IS compared with NS offspring demonstrated diminished anxiety as measured by decreased maternal clinging (P =.02), enhanced exploratory behavior (P =.005), and increased food consumption (P =.02). Mothers of IS offspring accommodated offspring-initiated exploration (P =.009) and served as a secure base more often compared with NS mothers (P =.047). Compared with NS offspring, IS offspring had lower basal plasma ACTH (P =.001) and cortisol (P =.001) concentrations and lower corticotropin (P =.04) and cortisol (P =.03) concentrations after stress. In the subsequent home-cage wire-box test, IS offspring demonstrated enhanced exploratory (P<.001) and play (P =.008) behaviors compared with NS offspring.These results provide the first prospective evidence that moderately stressful early experiences strengthen socioemotional and neuroendocrine resistance to subsequent stressors. This preclinical model offers essential opportunities to improve our understanding and enhance prevention of human stress-related psychiatric disorders by elucidating the etiology and neurobiology of stress resistance.

    View details for Web of Science ID 000223726200009

    View details for PubMedID 15351772

  • Female meadow voles (Microtus pennsylvanicus) demonstrate same-sex partner preferences JOURNAL OF COMPARATIVE PSYCHOLOGY Parker, K. J., Lee, T. M. 2003; 117 (3): 283-289

    Abstract

    Female meadow voles (Microtus pennsylvanicus) are territorial during warm months but demonstrate social tolerance under low temperatures. In spring, females nest together and some pairs participate in communal nursing and rearing of young. Because communal nursing involves significant cooperation, selective pair-bonds may develop between 2 nestmates. Using a choice apparatus, the authors determined that (a) captive females demonstrated partner preferences for a nestmate; (b) partner preferences were enduring and persisted after dyadic separation; and (c) following the loss of a nestmate, females did not develop preferences for a new nestmate, even after extended cohabitation. Data support the hypothesis that captive meadow voles develop selective and enduring same-sex social bonds that may, under free-living conditions, facilitate communal nesting and cooperative rearing of young.

    View details for DOI 10.1037/0735-7036.117.3.283

    View details for Web of Science ID 000185458600006

    View details for PubMedID 14498804

  • Circadian and homeostatic regulation of hypocretin in a primate model: Implications for the consolidation of wakefulness JOURNAL OF NEUROSCIENCE Zeitzer, J. M., Buckmaster, C. L., Parker, K. J., Hauck, C. M., Lyons, D. M., Mignot, E. 2003; 23 (8): 3555-3560

    Abstract

    In humans, consolidation of wakefulness into a single episode can be modeled as the interaction of two processes, a homeostatic "hour-glass" wake signal that declines throughout the daytime and a circadian wake-promoting signal that peaks in the evening. Hypocretins, novel hypothalamic neuropeptides that are dysfunctional in the sleep disorder narcolepsy, may be involved in the expression of the circadian wake-promoting signal. Hypocretins (orexins) are wake-promoting peptides, but their role in normal human sleep physiology has yet to be determined. We examined the daily temporal pattern of hypocretin-1 in the cisternal CSF of the squirrel monkey, a New World primate with a pattern of wake similar to that of humans. Hypocretin-1 levels peaked in the latter third of the day, consistent with the premise that hypocretin-1 is involved in wake regulation. When we lengthened the wake period by 4 hr, hypocretin-1 concentrations remained elevated, indicating a circadian-independent component to hypocretin-1 regulation. Changes in the stress hormone cortisol were not correlated with hypocretin-1 changes. Although hypocretin-1 is at least partially activated by a reactive homeostatic mechanism, it is likely also regulated by the circadian pacemaker. In the squirrel monkey, hypocretin-1 works in opposition to the accumulating sleep drive during the day to maintain a constant level of wake.

    View details for Web of Science ID 000182475200052

    View details for PubMedID 12716965

  • Euroendocrine aspects of hyperportisolism in major depression HORMONES AND BEHAVIOR Parker, K. J., Schatzberg, A. F., Lyons, D. M. 2003; 43 (1): 60-66

    Abstract

    A consistent finding in biological psychiatry is that hypothalamic-pituitary-adrenal (HPA) axis physiology is altered in humans with major depression. These findings include hypersecretion of cortisol at baseline and on the dexamethasone suppression test. In this review, we present a process-oriented model for HPA axis regulation in major depression. Specifically, we suggest that acute depressions are characterized by hypersecretion of hypothalamic corticotropin-releasing factor, pituitary adrenocorticotropic hormone (ACTH), and adrenal cortisol. In chronic depressions, however, enhanced adrenal responsiveness to ACTH and glucocorticoid negative feedback work in complementary fashion so that cortisol levels remain elevated while ACTH levels are reduced. In considering the evidence for hypercortisolism in humans, studies of nonhuman primates are presented and their utility and limitations as comparative models of human depression are discussed.

    View details for DOI 10.1016/S0018-506X(02)00016-8

    View details for Web of Science ID 000182658400009

    View details for PubMedID 12614635

  • Interaction of photoperiod and testes development is associated with paternal care in Microtus pennsylvanicus (meadow voles) PHYSIOLOGY & BEHAVIOR Parker, K. J., Lee, T. M. 2002; 75 (1-2): 91-95

    Abstract

    During the summer breeding season, free-living meadow voles do not engage in paternal care. However, in fall when female territoriality declines, social nesting and breeding activity may overlap and adult males nest with females and young. In the laboratory, meadow voles housed under short day (SD) lengths exhibit more and better quality paternal care than those housed under long day (LD) lengths. This observation is commensurate with the hypothesis that SD paternal care may increase fitness by decreasing pup mortality during colder months. However, SD males also demonstrate variability in paternal care. We hypothesize that this variability may be due to male fertility status; SD infertile males, incapable of siring offspring, should be less likely to care for pups than fertile males, for whom paternal care may confer fitness benefits. The goal of this experiment was to determine whether paternal behavior differed between fertile LD males, fertile SD males (i.e. males that were gonadally photoperiod-unresponsive to SD lengths), and infertile SD males (i.e. males that were gonadally photoperiod-responsive to SD lengths), as indexed by paired testes weights and behavioral evaluation. Fertile SD males exhibited proportionally more paternal behavior than infertile SD males or fertile LD males, which did not differ from each other. Fertile SD males also exhibited paternal behavior faster, spent more time in contact with pups, and engaged in longer and more frequent bouts of pup-directed grooming and huddling than either infertile SD males or fertile LD males. Collectively, these data suggest that photoperiod and fertility status may interact to exert both inhibitory and permissive control over the expression of paternal behavior in adult meadow voles.

    View details for Web of Science ID 000175195300012

    View details for PubMedID 11890957

  • Social and environmental factors influence the suppression of pup-directed aggression and development of paternal behavior in captive meadow voles (Microtus pennsylvanicus) JOURNAL OF COMPARATIVE PSYCHOLOGY Parker, K. J., Lee, T. M. 2001; 115 (4): 331-336

    Abstract

    During summer, female meadow voles (Microtus pennsylvanicus) maintain territories and males do not engage in paternal care. As day length shortens, territories dissolve and males nest with females and young. Because paternal behavior has never been studied in free-living meadow voles during colder months or in the laboratory under short photoperiods, the authors examined whether males housed in short day (SD) lengths exhibited more frequent or better quality paternal behavior than males housed in long day (LD) lengths. Sexually and parentally inexperienced (naive) SD males exhibited proportionally more and qualitatively better paternal care than naive LD males. SD males were more responsive than LD males to classic social cues associated with prepartum aggression inhibition and paternal onset. SD sires also displayed qualitatively better paternal behavior than LD sires. These data suggest that meadow vole paternal state is regulated by specific social and environmental cues that may contain reliable information about ecological conditions that favor paternal care.

    View details for DOI 10.1037//0735-7036.115.4.331

    View details for Web of Science ID 000173402200001

    View details for PubMedID 11824895

  • Day length and sociosexual cohabitation alter central oxytocin receptor binding in female meadow voles (Microtus pennsylvanicus) BEHAVIORAL NEUROSCIENCE Parker, K. J., Phillips, K. M., Kinney, L. F., Lee, T. M. 2001; 115 (6): 1349-1356

    Abstract

    In voles (Microtus), central oxytocin (OT) receptor patterns are associated with interspecific social organization. Social, monogamous voles have more OT receptors in the extended amygdala than asocial, nonmonogamous voles. Nonmonogamous meadow voles (Microtus pennsylvanicus), which exhibit seasonal changes in social organization (long day [LD] females are territorial, short day [SD] females live socially), provide a model for examining whether OT receptor patterns are associated with seasonal changes in intraspecific social behaviors. The authors examined whether sexually inexperienced (naive) SD females had more OT receptor binding than naive LD females. Naive SD females had greater OT receptor binding in the lateral septum (LS), lateral amygdala (LatAmyg), and central amygdala (CenAmyg) than less social, naive LD females. Because both SD and LD females acquire partner preferences, the authors assessed whether OT receptor binding was associated with partner preference onset. For LD females, partner preference onset corresponded with greater OT receptor binding in the anterior olfactory nucleus, LS, and bed nucleus of the stria terminalis, compared with naive LD females. In contrast, naive SD females and those exhibiting partner preferences did not differ. However, SD females that failed to acquire partner preferences showed less OT binding in the LatAmyg and CenAmyg. This study is the first to show that central OT receptor patterns are associated with seasonal changes in intraspecific social organization and partner preference onset in a nonmonogamous rodent.

    View details for Web of Science ID 000172687600018

    View details for PubMedID 11770065

  • Paternal behavior is associated with central neurohormone receptor binding patterns in meadow voles (Microtus pennsylvanicus) BEHAVIORAL NEUROSCIENCE Parker, K. J., Kinney, L. F., Phillips, K. M., Lee, T. M. 2001; 115 (6): 1341-1348

    Abstract

    Paternal and nonpaternal voles (microtus) have different arginine-vasopressin (AVP) and oxytocin (OT) receptor patterns in the extended amygdala, a neural pathway associated with parental behavior. Using receptor autoradiography, the authors examined whether AVP and OT receptor patterns were associated with facultative paternal behavior in either sexually and parentally inexperienced or experienced meadow voles (Microtus pennsylvanicus). Experienced, in contrast to inexperienced, males had less AVP binding in the lateral septum (LS), more AVP binding in the anterior olfactory nucleus (AON), and more OT binding in the AON, bed nucleus of the stria terminalis, LS, and lateral amygdala. Thus, specific AVP receptor patterns, which co-occur with paternal care in consistently paternal voles, also may be associated with paternal care (when present) in typically nonpaternal species. This study also demonstrated a possible relationship between OT receptor patterns and paternal state in male mammals.

    View details for Web of Science ID 000172687600017

    View details for PubMedID 11770064

  • Central vasopressin administration regulates the onset of facultative paternal behavior in Microtus pennsylvanicus (Meadow voles) HORMONES AND BEHAVIOR Parker, K. J., Lee, T. M. 2001; 39 (4): 285-294

    Abstract

    Pharmacological experiments have implicated a role for central arginine vasopressin (AVP) in regulating paternal behavior in monogamous prairie voles. Although nonmonogamous meadow voles exhibit appreciable paternal care when housed under winter, short day lengths (SD), no research has examined whether the same neurobiological systems are involved in regulating paternal behavior in a nonmonogamous species when it behaves paternally. The goal of these experiments was to determine whether central administration of AVP, but not cerebrospinal fluid (CSF), affected the suppression of pup-directed aggression and/or the onset of paternal behavior in meadow voles. Data from experiment 1 implicated a role for AVP in facilitating changes in male behavior: central administration of 1 ng of AVP (but not 3 ng or CSF) inhibited pup-directed aggression in previously pup-aggressive males, and 3 ng of AVP (but not 1 ng or CSF) induced paternal behavior in previously nonpaternal males. In contrast, AVP (1 and 3 ng) did not enhance paternal behavior in already paternal males. Experiment 2 tested the specificity of AVP. Previous research indicated that 24 h of unmated cohabitation with a female reliably induced paternal behavior in SD males. Hence, experiment 2 examined whether administration of a V(1a) AVP antagonist (AVPA), but not CSF, prior to 24 h of unmated cohabitation would block the onset of paternal behavior. Males that received CSF displayed paternal behavior faster and engaged in more investigatory and paternal behaviors than males that received AVPA. Thus, pharmacological experiments support the hypothesis that AVP likely regulates paternal behavior in both facultatively and consistently paternal vole species.

    View details for DOI 10.1006/hbeh.2001.1655

    View details for Web of Science ID 000169257100005

    View details for PubMedID 11374914

  • Development of selective partner preferences in captive male and female Microtus pennsylvanicus (meadow voles) Animal Behaviour Parker KJ, Phillips KM, Lee TM 2001; 61 (6): 1217-1226

Conference Proceedings


  • Neural substrates of stress inoculation determined in vivo by brain imaging in monkeys Lyons, D. M., Parker, K. J., Katz, M., Buckmaster, C. L., Schatzberg, A. F. NATURE PUBLISHING GROUP. 2005: S59-S60

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