Social relationships significantly influence physiology and behavior, including the hypothalamo-pituitary-adrenal axis, anxiety, and mental health. Disruption of social bonds through separation or death often results in profound grieving, depression, and physical illness. As the monogamous prairie vole forms enduring, selective pair bonds with the mating partner, they provide an animal model to study the physiological consequences of pair bonding and, thus, the loss of the bonded partner. Male prairie voles were paired with a novel female or male sibling. After 5 days, half of the males of each group were separated from the partner. Elevated plus-maze, forced swim, and tail suspension tests were used to assess anxiety-like and passive stress-coping behaviors indicative of depressive-like behavior. Following 4 days of separation from the female but not the male partner, experimental males displayed increased passive stress-coping. This effect was abolished by long-term intracerebroventricular infusion of a nonselective corticotropin-releasing factor (CRF) receptor antagonist without disrupting the bond itself. Both CRF type 1 and 2 receptors were involved in the emergence of passive stress-coping behavior. Furthermore, pairing with a female was associated with elevated CRF mRNA in the bed nucleus of the stria terminalis, and partner loss elicited a pronounced increase in circulating corticosteroid and adrenal weight. We speculate that the CRF system may mediate an aversive affect following separation from the female partner, which may facilitate proximity seeking between the pair-bonded individuals. Hence, the prairie vole model may provide insights into brain mechanisms involved in the psychopathological consequences of partner loss.

Corticotropin-releasing factor (CRF) receptor subtypes 1 and 2 have been implicated in rodent models of anxiety, but much less is known about the CRF system and social behavior. Both corticosterone and central CRF receptors modulate pair bonding in the monogamous prairie vole. Using receptor autoradiography, we mapped CRFR(1) and CRFR(2) in the brains of two monogamous vole species, the prairie vole and pine vole, and two promiscuous vole species, the meadow vole and montane vole. We found markedly different patterns of brain CRFR(1) and CRFR(2) binding among the four species, including species differences in the olfactory bulb, nucleus accumbens, lateral septum, hippocampus, laterodorsal thalamus, cingulate cortex, superior colliculus, and dorsal raphe. Interestingly, we also observed striking sex differences in voles: CRFR(2) binding was higher in the encapsulated bed nucleus of the stria terminalis in males than females for all four vole species. These results suggest possible sites of action for CRF-induced facilitation of pair bond formation in prairie voles, as well as potential sex differences in the CRF modulation of pair bonding. Further examination of CRF receptors in vole species may reveal a novel role for CRF in social behavior. Ultimately, our results identify several brain regions with conserved CRF receptor patterns across rodent and primate species, in contrast to several brain regions with phylogenetically plastic CRF receptor patterns, and have interesting implications for the evolution of CRF receptor patterns and behavior.

Vasopressin regulates complex behaviors such as anxiety, parenting, social engagement and attachment and aggression in a species-specific manner. The capacity of vasopressin to modulate these behaviors is thought to depend on the species-specific distribution patterns of vasopressin 1a receptors (V1aRs) in the brain. There is considerable individual variation in the pattern of V1aR binding in the brains of the prairie vole species, Microtus ochrogaster. We hypothesize that this individual variability in V1aR expression levels is associated with individual variation in a polymorphic microsatellite in the 5 0 regulatory region of the prairie vole v1ar gene. Additionally, we hypothesize that individual variation in V1aR expression contributes to individual variation in vasopressin-dependent behaviors. To test these hypotheses, we first screened 20 adult male prairie voles for behavioral variation using tests that measure anxiety-related and social behaviors. We then assessed the brains of those animals for V1aR variability with receptor autoradiography and used polymerase chain reaction to genotype the same animals for the length of their 5 0 microsatellite polymorphism in the v1ar gene. In this report, we describe the results of this discovery-based experimental approach to identify potential gene, brain and behavior interrelationships. The analysis reveals that V1aR levels, in some but not all brain regions, are associated with microsatellite length and that V1aR levels in those and other brain regions correlate with anxiety-related and social behaviors. These results generate novel hypotheses regarding neural control of anxiety-related and social behaviors and yield insight into potential mechanisms by which non-coding gene polymorphisms may influence behavioral traits. In the mammalian brain, the neuropeptide vasopressin contributes to the regulation of behaviors such as learning and memory, stress and anxiety, and social behaviors, through its action at the vasopressin 1a receptor (V1aR) (Bielsky et al.

The New York City terrorist attacks on Sept 11, 2001 (9/11), killed nearly 2800 people and thousands more had subsequent health problems. In this Review of health effects in the short and medium terms, strong evidence is provided for associations between experiencing or witnessing events related to 9/11 and post-traumatic stress disorder and respiratory illness, with a correlation between prolonged, intense exposure and increased overall illness and disability. Rescue and recovery workers, especially those who arrived early at the World Trade Center site or worked for longer periods, were more likely to develop respiratory illness than were other exposed groups. Risk factors for post-traumatic stress disorder included proximity to the site on 9/11, living or working in lower Manhattan, rescue or recovery work at the World Trade Center site, event-related loss of spouse, and low social support. Investigators note associations between 9/11 exposures and additional disorders, such as depression and substance use; however, for some health problems association with exposures related to 9/11 is unclear.

Respiratory illness1---9 and posttraumatic stress disorder (PTSD) 6,7,9---12 are 2 of the most commonly reported health outcomes related to the September 11, 2001 terrorist attacks on the New York City World Trade Center (WTC). Only recently, however, have studies addressed their co-occurrence among 9/11 disaster---exposed individuals. 13 Comorbidity is increasingly seen as the norm rather than the exception in primary care settings 14 and can significantly affect diagnosis, treatment, and prognosis of a given disease, 15 including respiratory illness. 16---20 Co-occurring physical illness may also affect the diagnosis, treatment, and prognosis of PTSD. Therefore, understanding the epidemiology of co-occurring respiratory illness and PTSD can have important implications for ongoing public health outreach and treatment efforts aimed at individuals exposed to the 9/11 disaster as well as individuals in the general population with respiratory or mental illness. The burden of co-occurring respiratory illness and PTSD among individuals directly exposed to the 9/11 disaster is likely to be high because of shared 9/11-related risk factors 6 and because of the close, reciprocal association between PTSD and physical health. Individuals with PTSD are at greater risk for long-term physical illness 20---30 partly because of lifestyle and health behaviors associated with PTSD and partly because of physiological dysregulation linked to PTSD. 30The latter might also underlie the well-documented association between PTSD and somatization. 31 Because symptoms can arise from interacting physical and psychological factors, a single, causative disease might not be found, 15 highlighting the importance of examining comorbid conditions and symptomatology in 9/11-exposed individuals.In this study we have described the prevalence, risk factors, and severity of illness associated with co-occurring lower respiratory symptoms (LRS) and probable PTSD 5 to 6 years after the 9/11 disaster among lower Manhattan residents, area workers, and passersby enrolled in the World Trade Center Health Registry. To better understand the burden of undiagnosed illness, we focused on symptoms. We hypothesized that severe dust cloud exposure and returning to homes or workplaces with dust or damage from the disaster would be associated with co-occurring LRS and PTSD. We also hypothesized that (1) independent of these risk factors LRS and PTSD would be risk factors for each other, (2) individuals with LRS who had comorbid PTSD would have worse respiratory illness and a higher prevalence of diagnosed asthma than would those with LRS alone, (3) those with PTSD who had cooccurring LRS would report more PTSD symptoms and have greater odds of comorbid mental health conditions than would those with PTSD alone, and (4) co-occurring LRS and PTSD would be associated with worse health-related quality of life (QOL) and more unmet health care needs after controlling for diagnosed respiratory and mental health conditions. METHODSThe Registry, a longitudinal cohort of per...