Biology of mood & anxiety disorders最新文献

{"title":"Temporal factors in the extinction of fear in inbred mouse strains differing in extinction efficacy.","authors":"Kathryn MacPherson,&nbsp;Nigel Whittle,&nbsp;Marguerite Camp,&nbsp;Ozge Gunduz-Cinar,&nbsp;Nicolas Singewald,&nbsp;Andrew Holmes","doi":"10.1186/2045-5380-3-13","DOIUrl":"https://doi.org/10.1186/2045-5380-3-13","url":null,"abstract":"<p><strong>Background: </strong>Various neuropsychiatric conditions, including posttraumatic stress disorder (PTSD), are characterized by deficient fear extinction, but individuals differ greatly in risk for these. While there is growing evidence that fear extinction is influenced by certain procedural variables, it is unclear how these influences might vary across individuals and subpopulations. To model individual differences in fear extinction, prior studies identified a strain of inbred mouse, 129S1/SvImJ (S1), which exhibits a profound deficit in fear extinction, as compared to other inbred strains, such as C57BL/6J (B6).</p><p><strong>Methods: </strong>Here, we assessed the effects of procedural variables on the impaired extinction phenotype of the S1 strain and, by comparison, the extinction-intact B6 strain. The variables studied were 1) the interval between conditioning and extinction, 2) the interval between cues during extinction training, 3) single-cue exposure before extinction training, and 4) extinction of a second-order conditioned cue.</p><p><strong>Results: </strong>Conducting extinction training soon after ('immediately') conditioning attenuated fear retrieval in S1 mice and impaired extinction in B6 mice. Spacing cue presentations with long inter-trial intervals during extinction training augmented fear in S1 and B6 mice. The effect of spacing was lost with one-trial fear conditioning in B6, but not S1 mice. A single exposure to a conditioned cue before extinction training did not alter extinction retrieval, either in B6 or S1 mice. Both the S1 and B6 strains exhibited robust second-order fear conditioning, in which a cue associated with footshock was sufficient to serve as a conditioned exciter to condition a fear association to a second cue. B6 mice extinguished the fear response to the second-order conditioned cue, but S1 mice failed to do so.</p><p><strong>Conclusions: </strong>These data provide further evidence that fear extinction is strongly influenced by multiple procedural variables and is so in a highly strain-dependent manner. This suggests that the efficacy of extinction-based behavioral interventions, such as exposure therapy, for trauma-related anxiety disorders will be determined by the procedural parameters employed and the degree to which the patient can extinguish.</p>","PeriodicalId":89532,"journal":{"name":"Biology of mood & anxiety disorders","volume":"3 1","pages":"13"},"PeriodicalIF":0.0,"publicationDate":"2013-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-5380-3-13","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31559322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping anhedonia onto reinforcement learning: a behavioural meta-analysis.","authors":"Quentin Jm Huys,&nbsp;Diego A Pizzagalli,&nbsp;Ryan Bogdan,&nbsp;Peter Dayan","doi":"10.1186/2045-5380-3-12","DOIUrl":"https://doi.org/10.1186/2045-5380-3-12","url":null,"abstract":"<p><strong>Background: </strong>Depression is characterised partly by blunted reactions to reward. However, tasks probing this deficiency have not distinguished insensitivity to reward from insensitivity to the prediction errors for reward that determine learning and are putatively reported by the phasic activity of dopamine neurons. We attempted to disentangle these factors with respect to anhedonia in the context of stress, Major Depressive Disorder (MDD), Bipolar Disorder (BPD) and a dopaminergic challenge.</p><p><strong>Methods: </strong>Six behavioural datasets involving 392 experimental sessions were subjected to a model-based, Bayesian meta-analysis. Participants across all six studies performed a probabilistic reward task that used an asymmetric reinforcement schedule to assess reward learning. Healthy controls were tested under baseline conditions, stress or after receiving the dopamine D2 agonist pramipexole. In addition, participants with current or past MDD or BPD were evaluated. Reinforcement learning models isolated the contributions of variation in reward sensitivity and learning rate.</p><p><strong>Results: </strong>MDD and anhedonia reduced reward sensitivity more than they affected the learning rate, while a low dose of the dopamine D2 agonist pramipexole showed the opposite pattern. Stress led to a pattern consistent with a mixed effect on reward sensitivity and learning rate.</p><p><strong>Conclusion: </strong>Reward-related learning reflected at least two partially separable contributions. The first related to phasic prediction error signalling, and was preferentially modulated by a low dose of the dopamine agonist pramipexole. The second related directly to reward sensitivity, and was preferentially reduced in MDD and anhedonia. Stress altered both components. Collectively, these findings highlight the contribution of model-based reinforcement learning meta-analysis for dissecting anhedonic behavior.</p>","PeriodicalId":89532,"journal":{"name":"Biology of mood & anxiety disorders","volume":"3 1","pages":"12"},"PeriodicalIF":0.0,"publicationDate":"2013-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-5380-3-12","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31518121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"D-Cycloserine as an augmentation strategy for cognitive behavioral therapy of anxiety disorders.","authors":"Stefan G Hofmann, Jade Q Wu, Hannah Boettcher","doi":"10.1186/2045-5380-3-11","DOIUrl":"10.1186/2045-5380-3-11","url":null,"abstract":"<p><p>The goal of this review is to examine the clinical studies on d-cycloserine, a partial glutamatergic N-methyl-D-aspartate agonist, as an augmentation strategy for exposure procedures during cognitive behavioral therapy for anxiety disorders. Although cognitive behavioral therapy and anxiolytic medications are more effective than placebo for treating anxiety disorders, there is still considerable room for further improvement. Traditional combination strategies typically yield disappointing results. However, recent studies based on translational research have shown promise to augment the neural circuitry underlying fear extinction with pharmacological means. We discuss the current state of the literature, including inconsistencies of findings and issues concerning the drug mechanism, dosing, and dose timing. D-cycloserine is a promising combination strategy for cognitive behavioral therapy of anxiety disorders by augmenting extinction learning. However, there is also evidence to suggest that d-cycloserine can facilitate reconsolidation of fear memory when exposure procedures are unsuccessful.</p>","PeriodicalId":89532,"journal":{"name":"Biology of mood & anxiety disorders","volume":"3 1","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2013-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3686620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31507547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diminished rostral anterior cingulate cortex activation during trauma-unrelated emotional interference in PTSD.","authors":"Reid Offringa,&nbsp;Kathryn Handwerger Brohawn,&nbsp;Lindsay K Staples,&nbsp;Stacey J Dubois,&nbsp;Katherine C Hughes,&nbsp;Danielle L Pfaff,&nbsp;Michael B Vanelzakker,&nbsp;F Caroline Davis,&nbsp;Lisa M Shin","doi":"10.1186/2045-5380-3-10","DOIUrl":"https://doi.org/10.1186/2045-5380-3-10","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Findings: </strong>While 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).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":89532,"journal":{"name":"Biology of mood & anxiety disorders","volume":"3 1","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2013-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-5380-3-10","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31521576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anxiety genetics - findings from cross-species genome-wide approaches.","authors":"Ewa Sokolowska,&nbsp;Iiris Hovatta","doi":"10.1186/2045-5380-3-9","DOIUrl":"https://doi.org/10.1186/2045-5380-3-9","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":89532,"journal":{"name":"Biology of mood & anxiety disorders","volume":"3 1","pages":"9"},"PeriodicalIF":0.0,"publicationDate":"2013-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-5380-3-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31418184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early experiences and the development of emotional learning systems in rats.","authors":"Bridget L Callaghan,&nbsp;Rick Richardson","doi":"10.1186/2045-5380-3-8","DOIUrl":"https://doi.org/10.1186/2045-5380-3-8","url":null,"abstract":"<p><p>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. </p>","PeriodicalId":89532,"journal":{"name":"Biology of mood & anxiety disorders","volume":"3 ","pages":"8"},"PeriodicalIF":0.0,"publicationDate":"2013-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-5380-3-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31349714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anterior cingulate cortex and insula response during indirect and direct processing of emotional faces in generalized social anxiety disorder.","authors":"Heide Klumpp,&nbsp;David Post,&nbsp;Mike Angstadt,&nbsp;Daniel A Fitzgerald,&nbsp;K Luan Phan","doi":"10.1186/2045-5380-3-7","DOIUrl":"https://doi.org/10.1186/2045-5380-3-7","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":89532,"journal":{"name":"Biology of mood & anxiety disorders","volume":" ","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2013-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-5380-3-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40243116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meeting report: \"Depression and Anxiety Spectrum disorders: from basic science to the clinic and back\".","authors":"Suzanne N Haber,&nbsp;Ziad Safadi,&nbsp;Mohammad R Milad","doi":"10.1186/2045-5380-3-6","DOIUrl":"https://doi.org/10.1186/2045-5380-3-6","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":89532,"journal":{"name":"Biology of mood & anxiety disorders","volume":"3 1","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2013-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-5380-3-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31310191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is there less to social anxiety than meets the eye? Behavioral and neural responses to three socio-emotional tasks.","authors":"Michal Ziv,&nbsp;Philippe R Goldin,&nbsp;Hooria Jazaieri,&nbsp;Kevin S Hahn,&nbsp;James J Gross","doi":"10.1186/2045-5380-3-5","DOIUrl":"https://doi.org/10.1186/2045-5380-3-5","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":89532,"journal":{"name":"Biology of mood & anxiety disorders","volume":"3 1","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2013-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2045-5380-3-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31272107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapygenetics: Using genetic markers to predict response to psychological treatment for mood and anxiety disorders.","authors":"Kathryn J Lester, Thalia C Eley","doi":"10.1186/2045-5380-3-4","DOIUrl":"10.1186/2045-5380-3-4","url":null,"abstract":"<p><p> 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.</p>","PeriodicalId":89532,"journal":{"name":"Biology of mood & anxiety disorders","volume":"3 1","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2013-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31221052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}