Anxiety Disorders: Winslow JT

Nelson EE, Winslow JT. · Mood and Anxiety Disorders Program, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA. · Neuropsychopharmacology. · Pubmed #18800061 No free full text.

Abstract: Non-human primates have been used to model psychiatric disease for several decades. The success of this paradigm has issued from comparable cognitive skills, brain morphology, and social complexity in adult monkeys and humans. Recently, interest in biological psychiatry has focused on similar brain, social, and emotional developmental processes in monkeys. In part, this is related to evidence that early postnatal experiences in human development may have profound implications for subsequent mental health. Non-human primate studies of postnatal phenomenon have generally fallen into three basic categories: experiential manipulation (largely manipulations of rearing), pharmacological manipulation (eg drug-induced psychosis), and anatomical localization (defined by strategic surgical damage). Although these efforts have been very informative each of them has certain limitations. In this review we highlight general findings from the non-human primate postnatal developmental literature and their implications for primate models in psychiatry. We argue that primates are uniquely capable of uncovering interactions between genes, environmental challenges, and development resulting in altered risk for psychopathology.

Barrett CE, Noble P, Hanson E, Pine DS, Winslow JT, Nelson EE. · Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, MD 20892, United States. · Psychoneuroendocrinology. · Pubmed #19268477 No free full text.

Abstract: Monkeys separated from their mothers soon after birth and raised with peers display many disturbances in emotional behavior that are similar to human mood and anxiety disorders. In addition to emotional disturbances, both mood and anxiety disorders are often characterized by disruptions in normal sleep-wake cycles, a behavior that has not been well characterized in adversely reared non-human primates. Because polysomnographic measures are difficult to obtain in unrestrained monkeys we used 24-h actigraphy measures to assess probable sleep-wake patterns in juvenile nursery- and mother-reared rhesus macaques (Macaca mulatta, N=16) over several days in the home cage. In addition we assayed plasma cortisol in the morning, afternoon, and evening. Relative to mother-reared (MR) monkeys, actigraphic algorithms indicated that nursery-reared (NR) animals had shorter durations of nocturnal sleep, earlier morning waking, and longer periods of sleep during the active period, specifically in the mid morning. No shift in diurnal patterns of cortisol was observed, but NR animals displayed an overall elevation in cortisol. Finally a significant interaction was found between cortisol and actigraphic determination of sleep efficiency in the two groups. A strong positive relationship (r(2)>0.8) was found between mean cortisol levels and sleep efficiency for the MR monkeys, but a significant negative relationship was found between these same variables for the NR monkeys, indicating a fundamentally different relationship between waking cortisol and actigraphy patterns in these two groups.

Winslow JT, Noble PL, Davis M. · National Institute of Mental Health, Intramural Research Program, Bethesda, Maryland 20892, USA. · Learn Mem. · Pubmed #18230674 links to  free full text

Abstract: Individuals with anxiety disorders often do not respond to safety signals and hence continue to be afraid and anxious. Consequently, it is important to develop paradigms in animals that can directly study brain systems involved in learning about, and responding to, safety signals. We previously developed a discrimination procedure in rats of the form AX+/BX-, where cues A and X presented together are paired with an aversive stimulus and cues B and X presented together predict the absence of an aversive stimulus. The present experiment adapted this procedure to the fear-potentiated startle paradigm in rhesus monkeys.

Sánchez MM, Noble PM, Lyon CK, Plotsky PM, Davis M, Nemeroff CB, Winslow JT. · Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia, USA. · Biol Psychiatry. · Pubmed #15705353 No free full text.

Abstract: BACKGROUND: Early adverse experiences represent risk factors for the development of anxiety and mood disorders. Studies in nonhuman primates have largely focused on the impact of protracted maternal and social deprivation, but such intense manipulations also result in severe social and emotional deficits very difficult to remediate. This study attempts to model more subtle developmental perturbations that may increase the vulnerability for anxiety/mood disorders but lack the severe deficits associated with motherless rearing. METHODS: We investigated the consequences of repeated maternal separations between 3 to 6 months of age on rhesus monkeys' hypothalamic-pituitary-adrenal (HPA) axis function and acoustic startle reactivity. RESULTS: Repetitive maternal separation led to increased cortisol reactivity to the separation protocol in female infants and alterations in mother-infant interaction. It also resulted in a flattened diurnal rhythm of cortisol secretion and increased acoustic startle reactivity at later ages. CONCLUSIONS: Macaques with adverse rearing exhibited short-term and long-term alterations in HPA axis function and increased acoustic startle response comparable with changes associated with mood/anxiety disorders. The magnitude of HPA axis reactivity to the separations and the alterations in mother-infant relationship detected during the separation protocol predicted some of the alterations in HPA axis and emotionality exhibited later in life.