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A brief summary of the articles appearing in this issue of Biological Psychiatry

        Biological Responses and Vulnerabilities to Stress

        Telomere length has been used as a marker of cellular aging. Wikgren et al. (pages 294–300) investigated leukocyte telomere length and hypothalamic-pituitary-adrenal (HPA) axis measurements in patients with major depressive disorder and healthy controls. They found that telomere length was shorter in patients compared with controls, and that telomere length was shorter among both patients and controls who exhibited a hypocortisolemic HPA axis profile. These findings support the concept of telomere length as a measure of stress and the idea that stress contributes to the aging process.
        Chronic exposure to stress may precipitate affective disorders in vulnerable subjects, some of which are characterized by hyper-reactivity of stress-related neuronal networks. Using a chronic stress model in rats, Miklós and Kovács (pages 301–308) report quantitative and spatial changes of synaptic contacts on the corticotropin-releasing hormone neurons that modulate the pituitary-adrenal response, providing evidence that stress-induced morphological plasticity may be involved in the enhanced activity of the HPA axis and development of stress-related disorders.
        van Zuiden et al. (pages 309–316) investigated whether glucocorticoid receptor (GR) pathway components assessed in leukocytes before military deployment could predict the subsequent development of posttraumatic stress disorder symptoms. Their results demonstrate that several GR pathway components, including high GR number, low FKBP5 mRNA expression and high GILZ mRNA expression, are vulnerability factors for subsequent development of posttraumatic stress disorder symptoms in male soldiers.
        Abnormal regulation of corticotropin-releasing factor (CRF) is associated with stress-related psychopathologies including anxiety disorders and depression. Regev et al. (pages 317–326) used genetic manipulation in adult mice to show that CRF in the central amygdala is pivotal for adequate behavioral responses to stress and for basal, but not stress-induced, corticosterone levels. These viral tools may represent a novel approach for further understanding the role of central CRF in mediating behavioral and neuroendocrine responses to stress.
        The bed nucleus of the stria terminalis (BNST) has been linked with aversive responses, but only minimally associated with reward despite its anatomical link with brain reward systems. Using subsecond catecholamine measurements, Park et al. (pages 327–334) show that norepinephrine and dopamine release in the rat BNST have a reciprocal relationship in response to rewarding and aversive stimuli, suggesting that the catecholamine systems in the BNST may balance the responses to reward and aversion.
        Mild traumatic brain injury (TBI) is a risk factor for developing anxiety disorders including posttraumatic stress disorder, but the mechanisms underlying this association are not well understood. Reger et al. (pages 335–343) examined fear-related symptoms in mild TBI rats utilizing fear conditioning and examined markers of brain excitation and inhibition. Mild TBI produced enhanced fear learning and a molecular change indicative of increased excitation and learning in the amygdala, suggesting mild TBI predisposes individuals toward acquiring anxiety disorders.

        Long-Term Effects of Childhood Maltreatment

        Individual differences in stress reactivity are considered potentially important in long-term health and disease, but little is known about the sources of these differences. Lovallo et al. (pages 344–349) used a laboratory stress test in healthy young adults, some of whom had one or more adverse experiences in childhood and adolescence. Adverse experiences predicted smaller heart rate and cortisol responses, indicating a long-term impact of stressful life experience on the reactivity of the stress axis.
        Dannlowski et al. (pages 286–293) investigated long-term effects of childhood maltreatment on brain morphology and function in healthy adult participants. Although psychologically healthy, participants with a history of childhood maltreatment showed abnormalities in brain areas responsible for learning and emotion processing, including amygdala responsiveness and reduced hippocampal volumes, similar to prior findings in patients with depression. These long-term effects may predispose such individuals to developing emotional disorders in later life.
        Cross-sectional studies report that low and high activity MAOA genotypes interact with child maltreatment to protect against depression and alcohol abuse. In a prospective cohort study, Nikulina et al. (pages 350–357) followed individuals with substantiated cases of child maltreatment into adulthood to assess mental health status. Results showed that MAOA interacts with specific types of maltreatment to predict alcohol abuse, depression, and dysthymia symptoms, but these relationships varied by sex and race.

        Evaluating Genetic Expressions of Stress

        Food restriction increases motivation and reward responding. Guarnieri et al. (pages 358–365) investigated changes in gene expression after altered food intake in mice to identify the neural mechanisms underlying these responses. They identified a set of genes that are upregulated during food restriction in brain reward circuits, and demonstrate that the stress hormone corticosterone is important for these gene changes. These results indicate that stress hormones mediate both molecular and behavioral responses to food restriction.
        Antoni et al. (pages 366–372) present evidence that cognitive behavioral stress management can reverse a pattern of threat- and anxiety-related changes in immune cell gene expression in women undergoing treatment for breast cancer. These findings mirror those of previous studies of human beings confronting major adversity. These results may also have significant implications for the etiology of anxiety via effects of leukocyte-expressed cytokines on the brain.
        Pergamin-Hight et al. (pages 373–379) performed a meta-analysis and report that allele variants of the promoter region of the serotonin transporter gene are associated with selective attention to negative stimuli. Carriers of the low transmission efficacy genotype display attentional vigilance toward negatively valenced stimuli, a pattern not found in the intermediate and high efficacy genotypes. With additional research, these results may promote the development of more comprehensive etiological models of anxiety vulnerability, and enhance specificity in treatment development.

        Memory Reconsolidation Impairments by Propranolol

        After their reactivation, memories undergo a reconsolidation process during which they can be modified. Schwabe et al. (pages 380–386) found that administration of a beta-adrenergic receptor antagonist before reactivation selectively impairs the subsequent memory for emotional events in healthy volunteers. Using functional magnetic resonance imaging, they also show that this emotional memory impairment is accompanied by systematic changes in the amygdala and hippocampus, structures that were also recruited during reactivation.