Kross et al. (pages 361–366) provide new insight into the human tendency to ruminate on previous life events. In their study, participants were scanned using functional magnetic resonance imaging (fMRI) as they focused on negative autobiographical memories using strategies designed to facilitate or interfere with rumination. The authors report that conditions that promoted ruminating increased the activity of brain regions implicated in self-reflection, including subgenual anterior cingulate cortex and medial prefrontal cortex.
Reappraisal is a relatively adaptive form of coping with stress, compared to attempting to suppress one's stress response. Drabant et al. (pages 367–373) found that the tendency to use reappraisal as a strategy to cope with stress was related to the pattern of brain activity that emerged when people watched pictures of people expressing emotional distress. Specifically, the extensive use of reappraisal was associated with relatively greater activity in a region associated with cognitive control, the dorsolateral prefrontal cortex, and relatively less activity in a brain region that modulates the intensity of emotion, the amygdala. These data suggest that the strategies that people use to cope with negative emotion influence their pattern of brain activity and, perhaps, their capacity to successfully cope with stress.
The Biology of Stress Response Systems
McTeague et al. (pages 374–382) report findings that suggest that the clinical features of social phobia in particular patients are related to the pattern of their physiologically increased reactivity to a variety of imagined situations. For example, patients with performance anxiety showed increased startle response while imagining situations that involved public performance. In contrast, patients with generalized social anxiety reacted broadly to imagined social situations.
Noradrenaline may have been the first neural substance linked to stress response. However, recent research is drawing attention to neuropeptides that may be released with noradrenaline by noradrenergic neurons, such as galanin and neuropeptide Y. In this report, Kozlovsky et al. (pages 383–391) show that in rodents, the administration of a galanin-like substance, galnon, following exposure to the scent of a predator prevented the emergence of stress-related behavioral changes and other stress-related neurochemical changes in the brain. These data further implicate galanin in the neurobiology of stress and stress-related disorders, such as posttraumatic stress disorder (PTSD). These data also raise the possibility that drugs that stimulate galanin receptors might play a role in the treatment of PTSD.
Hajszan et al. (pages 392–400) report that, in the rat learned helplessness paradigm, depressive symptoms are associated with loss of synapses in the hippocampal brain area, which could be reversed by antidepressant treatment. This study provides the first electron microscopic evidence for synapse loss in association with depressive-like behavior in rodents, indicating that this cellular mechanism may be an important component in the neurobiology of stress-related disorders.
Shanahan et al. (pages 401–408) show that features of obsessive compulsive disorder (OCD), including deficient prepulse inhibition and perseverative motor behavior, are induced by 5-HT1B agonists in mice. In addition, they found that these effects are blocked by chronic serotonin reuptake inhibitor treatment or knockout of the serotonin transporter. These findings suggest that the serotonin transporter and 5-HT1B receptors interact to modulate OCD-related behaviors.
Early Adversity: Gene x Environment Interactions
Family stress interacts with genetic factors in influencing stress response early in life. Ouellet-Morin et al. (pages 409–416) studied the patterns of cortisol levels in 6-month old twins. The authors report an interaction between the number of “challenges” that a family faced (single parenthood, low income, low maternal education, high levels of maternal hostility, etc.) and morning cortisol levels in the infants. Among families with higher numbers of challenges, presumably more stress, the genetic impact upon morning cortisol was greater. These data are consistent with the view that the impact of “risk genes” is more pronounced at higher levels of stress.
Weder et al. (pages 417–424) present new data supporting the link between variation in the monoamine oxidase (MAO) gene and maltreatment in contributing to the risk for antisocial personality traits. Here, the authors report that a lower activity MAO genotype increased the risk for displaying aggressive behavior among children with mild-moderate levels of maltreatment. However, at severe levels of maltreatment, all children showed increased rates of aggression, regardless of MAO genotype.
Geller et al. (pages 432–437) investigated the role of age, sex and major life experiences (independent life events [ILE]) on the structural development of cortical-limbic-striatal pathways in children with or without bipolar I disorder. The authors report that among all of the children studied, greater numbers of ILE's were associated with smaller volumes of the amygdala and nucleus accumbens volumes. Furthermore, in males, there was a significant interaction of age and diagnosis, such that there was a decrease in the volumes of these two brain regions with age in patients with bipolar disorder that was not seen in healthy males.
Rnf41: Anxiety Candidate Gene
Using mouse models of fearful behavior, Kim et al. (pages 425–431) identified a new candidate risk gene with the intriguing name of “Really Interesting New Gene (RING) Finger 41” or Rnf41, a novel E3 ubiquitin ligase. The authors used yeast two-hybrid studies to identify NoGoA as a potential binding partner for Rnf41. The authors then show that Rnf41 gene expression levels are reduced in post-mortem prefrontal cortex tissue from individuals with depression or bipolar disorder. Together these data implicate Rnf41 and the proteins that interact with it in the risk for mood and anxiety disorders.
Disrupting Fear: New Therapies?
A model for PTSD posits that fear conditioning occurs immediately after trauma exposure. Animal studies indicate that acute administration of morphine attenuates fear conditioning. Bryant et al. (pages 438–440) report a longitudinal study of 120 adults hospitalized for traumatic injury and found that a morphine dose in the initial 48 hours after trauma exposure was associated with fewer PTSD symptoms 3 months later. This finding suggests that morphine may limit fear conditioning after trauma.
While glucocorticoids, the adrenal hormones released during stress, increase the excitability of neurons in the basolateral complex of the amygdala, estrogen decreases it. Rodrigues and Sapolsky (pages 441–444) show that expression of a chimeric gene that contains the glucocorticoid and estrogen receptors in the amygdala disrupts auditory and contextual fear memory consolidation in rats. These data show that dual gene therapy might be a useful tool for understanding the role of steroid hormones in the storage of traumatic memories.
Early Indicators of Anxiety Risk
Children who display behavioral inhibition (BI) are at risk for later-life anxiety. Using a longitudinal design incorporating event-related potential methodology, McDermott et al. (pages 445–448) found evidence that adolescents with a history of childhood BI monitored their behavior excessively compared to adolescents without a history of BI. Furthermore, the combination of high childhood BI and enhanced response monitoring in adolescence indicated heightened risk for anxiety disorders.
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