http://www.biolmoodanxietydisord.com The latest research articles published by Biology of Mood & Anxiety Disorders 2013-05-14T00:00:00Z Background: Previous research suggests that individuals with posttraumatic stress disorder (PTSD) preferentially attend to trauma-related emotional stimuli and have difficulty completing unrelated concurrent tasks. Compared to trauma-exposed control groups, individuals with PTSD also exhibit lower rostral anterior cingulate cortex (rACC) activation during tasks involving interference from trauma-related stimuli. However, it is not clear whether relatively diminished rACC activation in PTSD also occurs during interference tasks involving trauma-unrelated emotional stimuli. The present study employed functional magnetic resonance imaging (fMRI) and an interference task that involves emotional facial expressions and elicits rACC activation in healthy participants.FindingsWhile performing a trauma-unrelated emotional interference task, participants with PTSD (n=17) showed less rACC activation than trauma-exposed non-PTSD (TENP; n=18) participants. In the PTSD group, rACC activation was negatively correlated with the severity of re-experiencing symptoms. The two groups did not significantly differ on behavioral measures (i.e., response times and error rates). Conclusions: These findings suggest that relatively diminished rACC activation in PTSD can be observed in interference tasks involving trauma-unrelated emotional stimuli, indicating a more general functional brain abnormality in this disorder. Future neuroimaging studies need not employ trauma-related stimuli in order to detect rACC abnormalities in PTSD. http://www.biolmoodanxietydisord.com/content/3/1/10 Reid Offringa Kathryn Handwerger Brohawn Lindsay Staples Stacey Dubois Katherine Hughes Danielle Pfaff Michael VanElzakker F Davis Lisa Shin Biology of Mood & Anxiety Disorders 2013, null:10 2013-05-14T00:00:00Z doi:10.1186/2045-5380-3-10 /content/figures/2045-5380-3-10-toc.gif Biology of Mood & Anxiety Disorders 2045-5380 ${item.volume} 10 2013-05-14T00:00:00Z PDF Anxiety disorders are complex diseases, which often occur in combination with major depression, alcohol use disorder, or general medical conditions. Anxiety disorders were the most common mental disorders within the EU states in 2010 with 14% prevalence. Anxiety disorders are triggered by environmental factors in genetically susceptible individuals, and therefore genetic research offers a great route to unravel molecular basis of these diseases. As anxiety is an evolutionarily conserved response, mouse models can be used to carry out genome-wide searches for specific genes in a setting that controls for the environmental factors. In this review, we discuss translational approaches that aim to bridge results from unbiased genome-wide screens using mouse models to anxiety disorders in humans. Several methods, such as quantitative trait locus mapping, gene expression profiling, and proteomics, have been used in various mouse models of anxiety to identify genes that regulate anxiety or play a role in maintaining pathological anxiety. We first discuss briefly the evolutionary background of anxiety, which justifies cross-species approaches. We then describe how several genes have been identified through genome-wide methods in mouse models and subsequently investigated in human anxiety disorder samples as candidate genes. These studies have led to the identification of completely novel biological pathways that regulate anxiety in mice and humans, and that can be further investigated as targets for therapy. http://www.biolmoodanxietydisord.com/content/3/1/9 Ewa Sokolowska Iiris Hovatta Biology of Mood & Anxiety Disorders 2013, null:9 2013-05-09T00:00:00Z doi:10.1186/2045-5380-3-9 /content/figures/2045-5380-3-9-toc.gif Biology of Mood & Anxiety Disorders 2045-5380 ${item.volume} 9 2013-05-09T00:00:00Z XML Research first reported nearly 50 years ago demonstrated that infant and young animals (including humans) exhibit profoundly faster rates of forgetting (i.e., infantile amnesia) than do adults. In addition to these differences in retention, more recent research has shown that inhibition of fear learning is also very different in infancy than in adulthood. Specifically, extinction of fear early in life is much more resistant to relapse than is extinction later in life. Both of these findings suggest that young animals should be especially resilient to the emergence of mental health disorders, which appears to be at odds with the view that early-life experiences are particularly important for the development of later psychopathologies (such as anxiety disorders) and with the finding that the majority of anxiety disorders first emerge in adolescence or childhood. This apparent paradox might be resolved, however, if exposure to chronic stress early in life affects the maturation of the fear retention and extinction systems, leading to a faster transition to the adult form of each (i.e., long-lasting fear memories and relapse-prone extinction). In several recent studies we have found exactly this pattern; that is, infant rats exposed to maternal-separation stress exhibit adult-like fear and extinction learning early in development. Further, we have demonstrated that some of these effects can be mimicked by exposing the mother to the stress hormone corticosterone in their drinking water (in lieu of the separation procedure). These findings suggest that early-life exposure to stress and stress hormones may act as a general signal that can alter the developmental trajectory of emotional systems and potentially place animals at greater risk for the development of anxiety. The implications of these recent findings for our understanding of the developmental origins of health and disease, and for enhancing preventative and therapeutic treatments across the lifespan, are considered. http://www.biolmoodanxietydisord.com/content/3/1/8 Bridget Callaghan Rick Richardson Biology of Mood & Anxiety Disorders 2013, null:8 2013-04-10T00:00:00Z doi:10.1186/2045-5380-3-8 /content/figures/2045-5380-3-8-toc.gif Biology of Mood & Anxiety Disorders 2045-5380 ${item.volume} 8 2013-04-10T00:00:00Z XML Background: Generalized social anxiety disorder (gSAD) is associated with a heightened neural sensitivity to signals that convey threat, as evidenced by exaggerated amygdala and/or insula activation when processing face stimuli that express negative emotions. Less clear in the brain pathophysiology of gSAD are cortical top down control mechanisms that moderate reactivity in these subcortical emotion processing regions. This study evaluated amygdala, insula, and anterior cingulate cortex (ACC) activity in gSAD with a novel “Emotional Faces Shifting Attention Task” (EFSAT), an adaptation of perceptual assessment tasks well-known to elicit amygdala response. In healthy volunteers, the task has been shown to engage the amygdala when attention is directed to emotional faces and the ACC when attention is directed to shapes, away from emotional faces. Methods: During functional MRI, 29 participants with gSAD and 27 healthy controls viewed images comprising a trio of faces (angry, fear, or happy) alongside a trio of geometric shapes (circles, rectangles, or triangles) within the same field of view. Participants were instructed to match faces or match shapes, effectively directing attention towards or away from emotional information, respectively. Results: Participants with gSAD exhibited greater insula, but not amygdala, activation compared to controls when attending to emotional faces. In contrast, when attention was directed away from faces, controls exhibited ACC recruitment, which was not evident in gSAD. Across participants, greater ACC activation was associated with less insula activation. Conclusions: Evidence that individuals with gSAD exhibited exaggerated insula reactivity when attending to emotional faces in EFSAT is consistent with other studies suggesting that the neural basis of gSAD may involve insula hyper-reactivity. Furthermore, greater ACC response in controls than gSAD when sustained goal-directed attention is required to shift attention away from social signals, together with a negative relationship between ACC and bilateral insula activity, indicate the ACC may have served a regulatory role when the focus of attention was directed to shapes amidst emotional faces. http://www.biolmoodanxietydisord.com/content/3/1/7 Heide Klumpp David Post Mike Angstadt Daniel Fitzgerald K Phan Biology of Mood & Anxiety Disorders 2013, null:7 2013-04-02T00:00:00Z doi:10.1186/2045-5380-3-7 /content/figures/2045-5380-3-7-toc.gif Biology of Mood & Anxiety Disorders 2045-5380 ${item.volume} 7 2013-04-02T00:00:00Z XML In March, 2012 we held the first Mideast conference on “Depression and Anxiety Spectrum disorders: from basic science to the clinic and back”, at the University of Amman, Jordan. This event brought together both clinical and basic scientists with expertise in depression and anxiety spectrum disorders. The meeting took place in a large lecture hall at the University of Jordan Medical School. The audience included faculty, residents, and students. The Dean of the Medical School opened the meeting, welcoming the guest speakers and participants. http://www.biolmoodanxietydisord.com/content/3/1/6 Suzanne Haber Ziad Safadi Mohammad Milad Biology of Mood & Anxiety Disorders 2013, null:6 2013-03-05T00:00:00Z doi:10.1186/2045-5380-3-6 /content/figures/2045-5380-3-6-toc.gif Biology of Mood & Anxiety Disorders 2045-5380 ${item.volume} 6 2013-03-05T00:00:00Z XML Background: Social anxiety disorder (SAD) is widely thought to be characterized by heightened behavioral and limbic reactivity to socio-emotional stimuli. However, although behavioral findings are clear, neural findings are surprisingly mixed. Methods: Using functional magnetic resonance imaging (fMRI), we examined behavioral and brain responses in a priori emotion generative regions of interest (amygdala and insula) in 67 patients with generalized SAD and in 28 healthy controls (HC) during three distinct socio-emotional tasks. We administered these socio-emotional tasks during one fMRI scanning session: 1) looming harsh faces (Faces); 2) videotaped actors delivering social criticism (Criticism); and 3) written negative self-beliefs (Beliefs). Results: In each task, SAD patients reported heightened negative emotion, compared to HC. There were, however, no SAD versus HC differential brain responses in the amygdala and insula. Between-group whole-brain analyses confirmed no group differences in the responses of the amygdala and insula, and indicated different brain networks activated during each of the tasks. In SAD participants, social anxiety symptom severity was associated with increased BOLD signal in the left insula during the Faces task. Conclusions: The similar responses in amygdala and insula in SAD and HC participants suggest that heightened negative emotion responses reported by patients with SAD may be related to dysfunction in higher cognitive processes (e.g., distorted appraisal, attention biases, or ineffective cognitive reappraisal). In addition, the findings of this study emphasize the differential effects of socio-emotional experimental tasks. http://www.biolmoodanxietydisord.com/content/3/1/5 Michal Ziv Philippe Goldin Hooria Jazaieri Kevin Hahn James Gross Biology of Mood & Anxiety Disorders 2013, null:5 2013-03-01T00:00:00Z doi:10.1186/2045-5380-3-5 /content/figures/2045-5380-3-5-toc.gif Biology of Mood & Anxiety Disorders 2045-5380 ${item.volume} 5 2013-03-01T00:00:00Z XML Considerable variation is evident in response to psychological therapies for mood and anxiety disorders. Genetic factors alongside environmental variables and gene-environment interactions are implicated in the etiology of these disorders and it is plausible that these same factors may also be important in predicting individual differences in response to psychological treatment. In this article, we review the evidence that genetic variation influences psychological treatment outcomes with a primary focus on mood and anxiety disorders. Unlike most past work, which has considered prediction of response to pharmacotherapy, this article reviews recent work in the field of therapygenetics, namely the role of genes in predicting psychological treatment response. As this is a field in its infancy, methodological recommendations are made and opportunities for future research are identified. http://www.biolmoodanxietydisord.com/content/3/1/4 Kathryn Lester Thalia Eley Biology of Mood & Anxiety Disorders 2013, null:4 2013-02-07T00:00:00Z doi:10.1186/2045-5380-3-4 /content/figures/2045-5380-3-4-toc.gif Biology of Mood & Anxiety Disorders 2045-5380 ${item.volume} 4 2013-02-07T00:00:00Z XML Background: Recent studies implicate individual differences in regulatory focus as contributing to self-regulatory dysfunction, particularly not responding to positive outcomes. How such individual differences emerge, however, is unclear. We conducted a proof-of-concept study to examine the moderating effects of genetically driven variation in dopamine signaling, a key modulator of neural reward circuits, on the association between regulatory focus and reward cue responsiveness.MethodHealthy Caucasians (N=59) completed a measure of chronic regulatory focus and a probabilistic reward task. A common functional genetic polymorphism impacting prefrontal dopamine signaling (COMT rs4680) was evaluated. Results: Response bias, the participants’ propensity to modulate behavior as a function of reward, was predicted by an interaction of regulatory focus and COMT genotype. Specifically, self-perceived success at achieving promotion goals predicted total response bias, but only for individuals with the COMT genotype (Val/Val) associated with relatively increased phasic dopamine signaling and cognitive flexibility. Conclusions: The combination of success in promotion goal pursuit and Val/Val genotype appears to facilitate responding to reward opportunities in the environment. This study is among the first to integrate an assessment of self-regulatory style with an examination of genetic variability that underlies responsiveness to positive outcomes in goal pursuit. http://www.biolmoodanxietydisord.com/content/3/1/3 Elena Goetz Ahmad Hariri Diego Pizzagalli Timothy Strauman Biology of Mood & Anxiety Disorders 2013, null:3 2013-02-01T00:00:00Z doi:10.1186/2045-5380-3-3 /content/figures/2045-5380-3-3-toc.gif Biology of Mood & Anxiety Disorders 2045-5380 ${item.volume} 3 2013-02-01T00:00:00Z XML Background: Posttraumatic stress disorder (PTSD) is a debilitating anxiety disorder. Surveys of the general population suggest that while 50-85% of Americans will experience a traumatic event in their lifetime, only 2-50% will develop PTSD. Why some individuals develop PTSD following trauma exposure while others remain resilient is a central question in the field of trauma research. For more than half a century, the role of genetic influences on PTSD has been considered as a potential vulnerability factor. However, despite the exponential growth of molecular genetic studies over the past decade, limited progress has been made in identifying true genetic variants for PTSD. Methods: In an attempt to aid future genome wide association studies (GWAS), this paper presents a systematic review of 28 genetic association studies of PTSD. Inclusion criteria required that 1) all participants were exposed to Criterion A traumatic events, 2) polymorphisms of relevant genes were genotyped and assessed in relation to participants’ PTSD status, 3) quantitative methods were used, and 4) articles were published in English and in peer-reviewed journals. In the examination of these 28 studies, particular attention was given to variables related to trauma exposure (e.g. number of traumas, type of trauma). Results: Results indicated that most articles did not report on the GxE interaction in the context of PTSD or present data on the main effects of E despite having data available. Furthermore, some studies that did consider the GxE interaction had significant findings, underscoring the importance of examining how genotypes can modify the effect of trauma on PTSD. Additionally, results indicated that only a small number of genes continue to be studied and that there were marked differences in methodologies across studies, which subsequently limited robust conclusions. Conclusions: As trauma exposure is a necessary condition for the PTSD diagnosis, this paper identifies gaps in the current literature as well as provides recommendations for how future GWAS studies can most effectively incorporate trauma exposure data in both the design and analysis phases of studies. http://www.biolmoodanxietydisord.com/content/3/1/2 Julia DiGangi Guia Guffanti Katie McLaughlin Karestan Koenen Biology of Mood & Anxiety Disorders 2013, null:2 2013-01-03T00:00:00Z doi:10.1186/2045-5380-3-2 /content/figures/2045-5380-3-2-toc.gif Biology of Mood & Anxiety Disorders 2045-5380 ${item.volume} 2 2013-01-03T00:00:00Z XML Since the initial publication of the review article [Cusin C and Dougherty DD, 2012], a number of readers have contacted us to clarify potential erroneous information in the article. These comments focused on our review of the use of transcranial magnetic stimulation (TMS) for treatment-resistant depression (TRD). In the initial article, we concluded that TMS is well-tolerated and has been approved by the FDA for adults who have failed to respond to one antidepressant, but that its use in TRD was not yet supported by rigorous double-blind randomized clinical trials. It should be noted, that for the article, we searched PubMed and based our review on the several meta-analyses we found during this search. http://www.biolmoodanxietydisord.com/content/3/1/1 Cristina Cusin Darin Dougherty Biology of Mood & Anxiety Disorders 2013, null:1 2013-01-01T00:00:00Z doi:10.1186/2045-5380-3-1 /content/figures/2045-5380-3-1-toc.gif Biology of Mood & Anxiety Disorders 2045-5380 ${item.volume} 1 2013-01-01T00:00:00Z XML