http://www.biolmoodanxietydisord.com The latest research articles published by Biology of Mood & Anxiety Disorders 2012-05-18T00:00:00Z Background: In recent years, neuroimaging techniques such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) have played a significant role in elucidating the neural underpinnings of posttraumatic stress disorder (PTSD). However, a detailed understanding of the neural regions implicated in the disorder remains incomplete because of considerable variability in findings across studies. The aim of this meta-analysis was to identify consistent patterns of neural activity across neuroimaging study designs in PTSD to improve understanding of the neurocircuitry of PTSD. Methods: We conducted a literature search for PET and fMRI studies of PTSD that were published before February 2011. The article search resulted in 79 functional neuroimaging PTSD studies. Data from 26 PTSD peer-reviewed neuroimaging articles reporting results from 342 adult patients and 342 adult controls were included. Peak activation coordinates from selected articles were used to generate activation likelihood estimate maps separately for symptom provocation and cognitive-emotional studies of PTSD. A separate meta-analysis examined the coupling between ventromedial prefrontal cortex and amygdala activity in patients. Results: Results demonstrated that the regions most consistently hyperactivated in PTSD patients included mid- and dorsal anterior cingulate cortex, and when ROI studies were included, bilateral amygdala. By contrast, widespread hypoactivity was observed in PTSD including the ventromedial prefrontal cortex and the inferior frontal gyrus. Furthermore, decreased ventromedial prefrontal cortex activity was associated with increased amygdala activity. Conclusions: These results provide evidence for a neurocircuitry model of PTSD that emphasizes alteration in neural networks important for salience detection and emotion regulation. http://www.biolmoodanxietydisord.com/content/2/1/9 Jasmeet Hayes Scott Hayes Amanda Mikedis Biology of Mood & Anxiety Disorders 2012, null:9 2012-05-18T00:00:00Z doi:10.1186/2045-5380-2-9 /content/figures/2045-5380-2-9-toc.gif Biology of Mood & Anxiety Disorders 2045-5380 ${item.volume} 9 2012-05-18T00:00:00Z PDF Background: Most individuals exposed to a traumatic event do not develop post-traumatic stress disorder (PTSD), although many individuals may experience sub-clinical levels of post-traumatic stress symptoms (PTSS). There are notable individual differences in the presence and severity of PTSS among individuals who report seemingly comparable traumatic events. Individual differences in PTSS following exposure to traumatic events could be influenced by pre-trauma vulnerabilities for developing PTSS/PTSD. Methods: Pre-trauma psychological, psychophysiological and personality variables were prospectively assessed for their predictive relationships with post-traumatic stress symptoms (PTSS). Police and firefighter trainees were tested at the start of their professional training (i.e., pre-trauma; n=211) and again several months after exposure to a potentially traumatic event (i.e., post-trauma, n=99). Pre-trauma assessments included diagnostic interviews, psychological and personality measures and two psychophysiological assessment procedures. The psychophysiological assessments measured psychophysiologic reactivity to loud tones and the acquisition and extinction of a conditioned fear response. Post-trauma assessment included a measure of psychophysiologic reactivity during recollection of the traumatic event using a script-driven imagery task. Results: Logistic stepwise regression identified the combination of lower IQ, higher depression score and poorer extinction of forehead (corrugator) electromyogram responses as pre-trauma predictors of higher PTSS. The combination of lower IQ and increased skin conductance (SC) reactivity to loud tones were identified as pre-trauma predictors of higher post-trauma psychophysiologic reactivity during recollection of the traumatic event. A univariate relationship was also observed between pre-trauma heart rate (HR) reactivity to fear cues during conditioning and post-trauma psychophysiologic reactivity. Conclusion: The current study contributes to a very limited literature reporting results from truly prospective examinations of pre-trauma physiologic, psychologic, and demographic predictors of PTSS. Findings that combinations of lower estimated IQ, greater depression symptoms, a larger differential corrugator EMG response during extinction and larger SC responses to loud tones significantly predicted higher PTSS suggests that the process(es) underlying these traits contribute to the pathogenesis of subjective and physiological PTSS. Due to the low levels of PTSS severity and relatively restricted ranges of outcome scores due to the healthy nature of the participants, results may underestimate actual predictive relationships. http://www.biolmoodanxietydisord.com/content/2/1/8 Scott Orr Natasha Lasko Michael Macklin Suzanne Pineles Yuchiao Chang Roger Pitman Biology of Mood & Anxiety Disorders 2012, null:8 2012-05-18T00:00:00Z doi:10.1186/2045-5380-2-8 /content/figures/2045-5380-2-8-toc.gif Biology of Mood & Anxiety Disorders 2045-5380 ${item.volume} 8 2012-05-18T00:00:00Z PDF Background: The amygdala, hippocampus, medial prefrontal cortex (mPFC) and brain-stem subregions are implicated in fear conditioning and extinction, and are brain regions known to be sexually dimorphic. We used functional magnetic resonance imaging (fMRI) to investigate sex differences in brain activity in these regions during fear conditioning and extinction. Methods: Subjects were 12 healthy men comparable to 12 healthy women who underwent a 2-day experiment in a 3 T MR scanner. Fear conditioning and extinction learning occurred on day 1 and extinction recall occurred on day 2. The conditioned stimuli were visual cues and the unconditioned stimulus was a mild electric shock. Skin conductance responses (SCR) were recorded throughout the experiment as an index of the conditioned response. fMRI data (blood-oxygen-level-dependent [BOLD] signal changes) were analyzed using SPM8. Results: Findings showed no significant sex differences in SCR during any experimental phases. However, during fear conditioning, there were significantly greater BOLD-signal changes in the right amygdala, right rostral anterior cingulate (rACC) and dorsal anterior cingulate cortex (dACC) in women compared with men. In contrast, men showed significantly greater signal changes in bilateral rACC during extinction recall. Conclusions: These results indicate sex differences in brain activation within the fear circuitry of healthy subjects despite similar peripheral autonomic responses. Furthermore, we found that regions where sex differences were previously reported in response to stress, also exhibited sex differences during fear conditioning and extinction. http://www.biolmoodanxietydisord.com/content/2/1/7 Kelimer Lebron-Milad Brandon Abbs Mohammed Milad Clas Linnman Ansgar Rougemount-Bücking Mohammed Zeidan Daphne Holt Jill Goldstein Biology of Mood & Anxiety Disorders 2012, null:7 2012-04-16T00:00:00Z doi:10.1186/2045-5380-2-7 /content/figures/2045-5380-2-7-toc.gif Biology of Mood & Anxiety Disorders 2045-5380 ${item.volume} 7 2012-04-16T00:00:00Z PDF The number of neuroimaging studies has grown exponentially in recent years and their results are not always consistent. Meta-analyses are helpful to summarize this vast literature and also offer insights that are not apparent from the individual studies. In this review, we describe the main methods used for meta-analyzing neuroimaging data, with special emphasis on their relative advantages and disadvantages. We describe and discuss meta-analytical methods for global brain volumes, methods based on regions of interest (ROI), label-based reviews, voxel-based meta-analytic methods and online databases. ROI-based methods allow for optimal statistical analyses but are affected by a limited and potentially biased inclusion of brain regions, whilst voxel-based methods benefit from a more exhaustive and unbiased inclusion of studies but are statistically more limited. There are also relevant differences between the different available voxel-based meta-analytic methods, and the field is rapidly evolving to develop more accurate and robust methods. We suggest that in any meta-analysis of neuroimaging data, authors should aim to: a) only include studies exploring the whole brain; b) ensure that the same threshold throughout the whole brain is used within each included study; and c) explore the robustness of the findings via complementary analyses to minimize the risk of false positives. http://www.biolmoodanxietydisord.com/content/2/1/6 Joaquim Radua David Mataix-Cols Biology of Mood & Anxiety Disorders 2012, null:6 2012-03-08T00:00:00Z doi:10.1186/2045-5380-2-6 /content/figures/2045-5380-2-6-toc.gif Biology of Mood & Anxiety Disorders 2045-5380 ${item.volume} 6 2012-03-08T00:00:00Z PDF Background: Potassium channels have been proposed to play a role in mechanisms of neural plasticity, and the Kv4.2 subunit has been implicated in the regulation of action-potential back-propagation to the dendrites. Alterations in mechanisms of plasticity have been further proposed to underlie various psychiatric disorders, but the role of Kv4.2 in anxiety or depression is not well understood. Methods: In this paper, we analyzed the phenotype Kv4.2 knockout mice based on their neurological function, on a battery of behaviors including those related to anxiety and depression, and on plasticity-related learning tasks. Results: We found a novelty-induced hyperactive phenotype in knockout mice, and these mice also displayed increased reactivity to novel stimulus such as an auditory tone. No clear anxiety- or depression-related phenotype was observed, nor any alterations in learning/plasticity-based paradigms. Conclusions: We did not find clear evidence for an involvement of Kv4.2 in neuropsychiatric or plasticity-related phenotypes, but there was support for a role in Kv4.2 in dampening excitatory responses to novel stimuli. http://www.biolmoodanxietydisord.com/content/2/1/5 Carly Kiselycznyk Dax Hoffman Andrew Holmes Biology of Mood & Anxiety Disorders 2012, null:5 2012-03-02T00:00:00Z doi:10.1186/2045-5380-2-5 /content/figures/2045-5380-2-5-toc.gif Biology of Mood & Anxiety Disorders 2045-5380 ${item.volume} 5 2012-03-02T00:00:00Z XML Consistent evidence links major depression and its affective components to negative health outcomes. Although the pathways of these effects are likely complex and multifactorial, recent evidence suggests that innate inflammatory processes may play a role. An overview of current literature suggests that pathways between negative moods and inflammation are bi-directional. Indeed, negative moods activate peripheral physiologic mechanisms that result in an up regulation of systemic levels of inflammation. Conversely, peripheral inflammatory mediators signal the brain to affect behavioral, affective and cognitive changes that are consistent with symptoms of major depressive disorder. It is likely that these pathways are part of a complex feedback loop that involves the nervous, endocrine, and immune systems and plays a role in the modulation of peripheral inflammatory responses to central and peripheral stimuli, in central responses to peripheral immune activation and in the maintenance of homeostatic balance. Further research is warranted to fully understand the role of central processes in this feedback loop, which likely contributes to the pathophysiology of mental and physical health. http://www.biolmoodanxietydisord.com/content/2/1/4 Berhane Messay Alvin Lim Anna Marsland Biology of Mood & Anxiety Disorders 2012, null:4 2012-02-28T00:00:00Z doi:10.1186/2045-5380-2-4 /content/figures/2045-5380-2-4-toc.gif Biology of Mood & Anxiety Disorders 2045-5380 ${item.volume} 4 2012-02-28T00:00:00Z XML Convergent data from rodents and human studies have led to the development of models describing the neural mechanisms of fear extinction. Key components of the now well-characterized fear extinction network include the amygdala, hippocampus, and medial prefrontal cortical regions. These models are fueling novel hypotheses that are currently being tested with much refined experimental tools to examine the interactions within this network. Lagging far behind, however, is the examination of sex differences in this network and how sex hormones influence the functional activity and reactivity of these brain regions in the context of fear inhibition. Indeed, there is a large body of literature suggesting that sex hormones, such as estrogen, do modulate neural plasticity within the fear extinction network, especially in the hippocampus.After a brief overview of the fear extinction network, we summarize what is currently known about sex differences in fear extinction and the influence of gonadal hormones on the fear extinction network. We then go on to propose possible mechanisms by which sex hormones, such as estrogen, may influence neural plasticity within the fear extinction network. We end with a discussion of how knowledge to be gained from developing this line of research may have significant ramifications towards the etiology, epidemiology and treatment of anxiety disorders. http://www.biolmoodanxietydisord.com/content/2/1/3 Kelimer Lebron-Milad Mohammed Milad Biology of Mood & Anxiety Disorders 2012, null:3 2012-02-07T00:00:00Z doi:10.1186/2045-5380-2-3 /content/figures/2045-5380-2-3-toc.gif Biology of Mood & Anxiety Disorders 2045-5380 ${item.volume} 3 2012-02-07T00:00:00Z XML Depression in bipolar disorder has long been thought to be a state characterized by mental inactivity. However, recent research demonstrates that patients with bipolar disorder engage in rumination, a form of self-focused repetitive cognitive activity, in depressed as well as in manic states. While rumination has long been associated with depressed states in major depressive disorder, the finding that patients with bipolar disorder ruminate in manic states is unique to bipolar disorder and challenges explanations put forward for why people ruminate. We review the research on rumination in bipolar disorder and propose that rumination in bipolar disorder, in both manic and depressed states, reflects executive dysfunction. We also review the neurobiology of bipolar disorder and recent neuroimaging studies of rumination, which is consistent with our hypothesis that the tendency to ruminate reflects executive dysfunction in bipolar disorder. Finally, we relate the neurobiology of rumination to the neurobiology of emotion regulation, which is disrupted in bipolar disorder. http://www.biolmoodanxietydisord.com/content/2/1/2 Sharmin Ghaznavi Thilo Deckersbach Biology of Mood & Anxiety Disorders 2012, null:2 2012-01-23T00:00:00Z doi:10.1186/2045-5380-2-2 /content/figures/2045-5380-2-2-toc.gif Biology of Mood & Anxiety Disorders 2045-5380 ${item.volume} 2 2012-01-23T00:00:00Z XML Background: Individuals with major depressive disorder (MDD) process information with a bias towards negative stimuli. However, little is known on the link between vulnerability to MDD and brain functional anomalies associated with stimulus bias. Methods: A cohort of 38 subjects, of which 14 were patients with acute MDD and 24 were healthy controls (HC), were recruited and compared. The HC group included 10 healthy participants with a first degree family history of depression (FHP) and 14 volunteers with no family history of any psychiatric disease (FHN). Blood oxygen level dependence signals were acquired from functional magnetic resonance imaging (fMRI) during performance in a dot-probe task using fearful and neutral stimuli. Reaction times and the number of errors were also obtained. Results: Although MDD patients and HC showed no behavioral difference, the MDD group exhibited smaller activation in the left middle cingulum. The MDD group also showed smaller activation in the left insula when compared to the HC group or the FHN group. Finally, FHP participants exhibited higher activation in the right Heschl's gyrus compared to FHN participants. Conclusions: The present study shows that family risk for MDD is associated with increased activation in the Heschl's gyrus. Our results also suggest that acute MDD is linked to reduced activation in the insula and anterior cingulate cortex during processing of subliminal, not recognizable, masked fearful stimuli. Further research should confirm these results in a larger cohort of participants. http://www.biolmoodanxietydisord.com/content/2/1/1 Francesco Amico Angela Carballedo Danuta Lisiecka Andrew Fagan Gerard Boyle Thomas Frodl Biology of Mood & Anxiety Disorders 2012, null:1 2012-01-12T00:00:00Z doi:10.1186/2045-5380-2-1 /content/figures/2045-5380-2-1-toc.gif Biology of Mood & Anxiety Disorders 2045-5380 ${item.volume} 1 2012-01-12T00:00:00Z XML Background: Previous studies in healthy subjects have shown that strong attentional distraction prevents the amygdala from responding to threat stimuli. Here, we investigated the effects of attentional load on amygdala activation to threat-related stimuli in individuals suffering from an anxiety disorder. Methods: During functional magnetic resonance imaging, spider-phobicand healthy control subjects were presented with phobia-related and neutral stimuli while performing a distraction task with varying perceptual load (high vs low). Results: Our data revealed a pattern of simultaneously increased amygdala and visual cortical activation to threat vs neutral pictures in phobic individuals, compared with controls, occurring regardless of attentional load. Conclusions: These results suggest that, in contrast to studies in healthy subjects, amygdala activation to clinically relevant threat stimuli is more resistant to attentional load. http://www.biolmoodanxietydisord.com/content/1/1/12 Thomas Straube Judith Lipka Andreas Sauer Martin Mothes-Lasch Wolfgang Miltner Biology of Mood & Anxiety Disorders 2011, null:12 2011-12-16T00:00:00Z doi:10.1186/2045-5380-1-12 /content/figures/2045-5380-1-12-toc.gif Biology of Mood & Anxiety Disorders 2045-5380 ${item.volume} 12 2011-12-16T00:00:00Z XML