The impact of treatment with selective serotonin reuptake inhibitors on primate cardiovascular disease, behavior, and neuroanatomy.

Selective serotonin reuptake inhibitor (SSRI) use is ubiquitous because they are widely prescribed for a number of disorders in addition to depression. Depression increases the risk of coronary heart disease (CHD). Hence, treating depression with SSRIs could reduce CHD risk.

Reduced marker of vascularization in the anterior hippocampus in a female monkey model of depression.

Depression is a common and debilitating mood disorder that impacts women more often than men. The mechanisms that result in depressive behaviors are not fully understood; however, the hippocampus has been noted as a key structure in the pathophysiology of depression. In addition to neural implications of depression, the cardiovascular system is impacted.

Long term sertraline effects on neural structures in depressed and nondepressed adult female nonhuman primates.

Background: Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for mood and other disorders. However, their neural effects are difficult to study due to patient compliance and drug history variability, and rarely studied in those prescribed SSRIs for non-mood disorders. Here we evaluated SSRI effects on neural volumetrics in depressed and nondepressed monkeys.

Altered expression of glial and synaptic markers in the anterior hippocampus of behaviorally depressed female monkeys.

The anterior hippocampus is associated with emotional functioning and hippocampal volume is reduced in depression. We reported reduced neuropil volume and number of glia in the dentate gyrus (DG) and cornu ammonis (CA)1 of the anterior hippocampus in behaviorally depressed adult female cynomolgus macaques. To determine the biochemical correlates of morphometric and behavioral differences between behaviorally depressed and nondepressed adult female monkeys, glial and synaptic transcripts and protein levels were assessed in the DG, CA3 and CA1 of the anterior hippocampus.

Sertraline effects on cerebrospinal fluid monoamines and species-typical socioemotional behavior of female cynomolgus monkeys.

Rationale: Although widely prescribed, little is known about the effects of selective serotonin reuptake inhibitors (SSRIs) on social behavior and cerebrospinal fluid (CSF) monoamines in female primates.

Objective: The objective of this study was to determine the effects of sertraline on agonistic and affiliative behavior.

Methods: Twenty-one adult female cynomolgus monkeys were housed in small, stable social groups, trained to participate in oral dosing, and began a 5-week cumulative dose-response study.

Cell number and neuropil alterations in subregions of the anterior hippocampus in a female monkey model of depression.

Background: The anterior hippocampus is associated with emotional functioning and hippocampal volume is reduced in depression. More women are clinically depressed than men, yet the depressed female brain is little studied. We reported reduced anterior hippocampal volume in behaviorally depressed adult female cynomolgus macaques; the mechanisms contributing to that reduction are unknown.

Development of amyloid burden in African Green monkeys.

The vervet is an old world monkey increasingly being used as a model for human diseases. In addition to plaques and tangles, an additional hallmark of Alzheimer's disease is damage to neurons that synthesize noradrenaline (NA). We characterized amyloid burden in the posterior temporal lobe of young and aged vervets, and compared that with changes in NA levels and astrocyte activation.

Aging and physical mobility in group-housed Old World monkeys.

While indices of physical mobility such as gait speed are significant predictors of future morbidity/mortality in the elderly, mechanisms of these relationships are not understood. Relevant animal models of aging and physical mobility are needed to study these relationships. The goal of this study was to develop measures of physical mobility including activity levels and gait speed in Old World monkeys which vary with age in adults.

Modeling depression in adult female cynomolgus monkeys (Macaca fascicularis).

Depressive disorders are prevalent, costly, and poorly understood. Male rodents in stress paradigms are most commonly used as animal models, despite the two-fold increased prevalence of depression in women and sex differences in response to stress. Although these models have provided valuable insights, new models are needed to move the field forward.

Behavioral and neurobiological characteristics of social stress versus depression in nonhuman primates.

The focus of the review is on the behavioral and physiological manifestations of stress versus depression. The purpose of the review is to evaluate the conceptual approach of using stress models as surrogates for depression. Social stress and depression have many characteristics in common and promote each other.

Depression and altered serum lipids in cynomolgus monkeys consuming a Western diet.

Research over the past 15 years has suggested a high comorbidity of depression and coronary heart disease (CHD). However the mechanisms responsible for this relationship are poorly understood. This study was designed to examine the relationships between depressive behaviors and concentrations of circulating lipids and lipid signaling molecules that may be common to both CHD and depression in a cohort of cynomolgus monkeys (Macaca fascicularis) consuming a 'Western' diet, enriched with saturated fat and cholesterol.

Hippocampal volume in postmenopausal cynomolgus macaques with behavioral depression.

Objective: Magnetic resonance imaging (MRI) studies report hippocampal (HC) volume reductions in depression. Despite observations of functional heterogeneity and ovarian steroid influence in the hippocampus, few studies report regional volume alterations or control for menstrual cycle phase. Using in vitro methods, we recently observed reduced anterior HC volume in antidepressant-naive, ovarian-intact, behaviorally depressed adult female monkeys.

Anterior hippocampal volume is reduced in behaviorally depressed female cynomolgus macaques.

Hippocampal (HC) function and morphology have been implicated in the pathophysiology of depression. Reduced HC volume has been observed in depressed humans, although the effect is not always significant. Studies of functional differentiation of the HC have revealed that the anterior portion is associated with emotional and anxiety-related functioning, and the posterior portion with memory processing.

Stress, depression, and coronary artery disease: modeling comorbidity in female primates.

Depression and coronary heart disease (CHD) are leading contributors to disease burden in women. CHD and depression are comorbid; whether they have common etiology or depression causes CHD is unclear. The underlying pathology of CHD, coronary artery atherosclerosis (CAA), is present decades before CHD, and the temporal relationship between depression and CAA is unclear.

Depressive behavior and coronary artery atherogenesis in adult female cynomolgus monkeys.

Objective: To examine depressive behavior and early coronary artery atherogenesis in 36 socially housed female cynomolgus monkeys, an established model of atherogenesis and depression. Coronary heart disease (CHD) is caused by coronary artery atherosclerosis (CAA) and its sequelae which develop over a period of decades. Thus, in prospective studies of depression and CHD, CAA was likely present at baseline in most subjects who experienced cardiac events.

Hormone therapy effects on social behavior and activity levels of surgically postmenopausal cynomolgus monkeys.

The purpose of the experiments reported here was to investigate central nervous system effects of commonly prescribed postmenopausal hormone therapies in a primate model, the cynomolgus monkey (Macaca fascicularis). The results of two experiments are reported. In the first, ovariectomized adult cynomolgus monkeys were treated for eight weeks each with oral micronized 17beta-estradiol (E2) (n=23), E2+medroxyprogesterone acetate (MPA) (n=23), E2+progesterone (P4) (n=23), and placebo (n=23) using a crossover design.

Effects of chronic moderate alcohol consumption and novel environment on heart rate variability in primates (Macaca fascicularis).

Rationale: The effects of chronic moderate alcohol consumption on cardiac function are not understood. Acute stress may affect cardiac function by shifting autonomic cardiac regulation in favor of the sympathetic nervous system. Although alcohol consumption often increases at times of stress, the interactive effects of stress and chronic moderate alcohol consumption on cardiac regulation have not been studied.