http://www.biolmoodanxietydisord.com The most accessed research articles published by Biology of Mood & Anxiety Disorders 2012-04-16T00:00:00Z 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 Background: Cognitive models of depression suggest that major depression is characterized by biased facial emotion processing, making facial stimuli particularly valuable for neuroimaging research on the neurobiological correlates of depression. The present review provides an overview of functional neuroimaging studies on abnormal facial emotion processing in major depression. Our main objective was to describe neurobiological differences between depressed patients with major depressive disorder (MDD) and healthy controls (HCs) regarding brain responsiveness to facial expressions and, furthermore, to delineate altered neural activation patterns associated with mood-congruent processing bias and to integrate these data with recent functional connectivity results. We further discuss methodological aspects potentially explaining the heterogeneity of results. Methods: A Medline search was performed up to August 2011 in order to identify studies on emotional face processing in acutely depressed patients compared with HCs. A total of 25 studies using functional magnetic resonance imaging were reviewed. Results: The analysis of neural activation data showed abnormalities in MDD patients in a common face processing network, pointing to mood-congruent processing bias (hyperactivation to negative and hypoactivation to positive stimuli) particularly in the amygdala, insula, parahippocampal gyrus, fusiform face area, and putamen. Furthermore, abnormal activation patterns were repeatedly found in parts of the cingulate gyrus and the orbitofrontal cortex, which are extended by investigations implementing functional connectivity analysis. However, despite several converging findings, some inconsistencies are observed, particularly in prefrontal areas, probably caused by heterogeneities in paradigms and patient samples. Conclusions: Further studies in remitted patients and high-risk samples are required to discern whether the described abnormalities represent state or trait characteristics of depression. http://www.biolmoodanxietydisord.com/content/1/1/10 Anja Stuhrmann Thomas Suslow Udo Dannlowski Biology of Mood & Anxiety Disorders 2011, null:10 2011-11-07T00:00:00Z doi:10.1186/2045-5380-1-10 /content/figures/2045-5380-1-10-toc.gif Biology of Mood & Anxiety Disorders 2045-5380 ${item.volume} 10 2011-11-07T00:00:00Z 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 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 Background: The amygdala and medial prefrontal cortex (mPFC) comprise a key corticolimbic circuit that helps shape individual differences in sensitivity to threat and the related risk for psychopathology. Although serotonin (5-HT) is known to be a key modulator of this circuit, the specific receptors mediating this modulation are unclear. The colocalization of 5-HT1A and 5-HT2A receptors on mPFC glutamatergic neurons suggests that their functional interactions may mediate 5-HT effects on this circuit through top-down regulation of amygdala reactivity. Using a multimodal neuroimaging strategy in 39 healthy volunteers, we determined whether threat-related amygdala reactivity, assessed with blood oxygen level-dependent functional magnetic resonance imaging, was significantly predicted by the interaction between mPFC 5-HT1A and 5-HT2A receptor levels, assessed by positron emission tomography. Results: 5-HT1A binding in the mPFC significantly moderated an inverse correlation between mPFC 5-HT2A binding and threat-related amygdala reactivity. Specifically, mPFC 5-HT2A binding was significantly inversely correlated with amygdala reactivity only when mPFC 5-HT1A binding was relatively low. Conclusions: Our findings provide evidence that 5-HT1A and 5-HT2A receptors interact to shape serotonergic modulation of a functional circuit between the amygdala and mPFC. The effect of the interaction between mPFC 5-HT1A and 5-HT2A binding and amygdala reactivity is consistent with the colocalization of these receptors on glutamatergic neurons in the mPFC. http://www.biolmoodanxietydisord.com/content/1/1/2 Patrick Fisher Julie Price Carolyn Meltzer Eydie Moses-Kolko Carl Becker Sarah Berga Ahmad Hariri Biology of Mood & Anxiety Disorders 2011, null:2 2011-09-27T00:00:00Z doi:10.1186/2045-5380-1-2 /content/figures/2045-5380-1-2-toc.gif Biology of Mood & Anxiety Disorders 2045-5380 ${item.volume} 2 2011-09-27T00:00:00Z XML 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 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 Background: Both fear and pain processing are altered in post-traumatic stress disorder (PTSD), as evidenced by functional neuroimaging studies showing increased amygdala responses to threats, and increased insula, putamen and caudate activity in response to heat pain. Using psychophysiology and functional magnetic resonance imaging, we studied conditioned and unconditioned autonomic and neuronal responses in subjects with PTSD versus trauma-exposed non-PTSD control (TENC) subjects. A design using an electric shock selected by subjects to be 'highly annoying but not painful' as an unconditioned stimulus (US) with partially reinforced cues allowed us to partly disentangle the expectancy- and prediction-error components from sensory components of the unconditioned response. Results: Whereas responses to the conditioned stimulus (CS) were similar in PTSD and TENC, the former displayed higher putamen, insula, caudate and amygdala responses to the US. Reactivity to the US in the anterior insula correlated with PTSD symptom severity. Functional connectivity analyses using the putamen as a seed region indicated that TENC subjects had increased amygdala-putamen connectivity during US delivery; this connection was disengaged in PTSD. Conclusions: Our results indicate that although neural processing of fear learning in people with PTSD seems to be comparable with controls, neural responses to unconditioned aversive stimuli in PTSD seem to be increased. http://www.biolmoodanxietydisord.com/content/1/1/8 Clas Linnman Thomas Zeffiro Roger Pitman Mohammed Milad Biology of Mood & Anxiety Disorders 2011, null:8 2011-11-01T00:00:00Z doi:10.1186/2045-5380-1-8 /content/figures/2045-5380-1-8-toc.gif Biology of Mood & Anxiety Disorders 2045-5380 ${item.volume} 8 2011-11-01T00:00:00Z XML 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 Background: Abnormalities of the striatum and frontal cortex have been reported consistently in studies of neural structure and function in major depressive disorder (MDD). Despite speculation that compromised connectivity between these regions may underlie symptoms of MDD, little work has investigated the integrity of frontostriatal circuits in this disorder. Methods: Functional magnetic resonance images were acquired from 21 currently depressed and 19 never-disordered women during wakeful rest. Using four predefined striatal regions-of-interest, seed-to-whole brain correlations were computed and compared between groups. Results: Compared to controls, depressed participants exhibited attenuated functional connectivity between the ventral striatum and both ventromedial prefrontal cortex and subgenual anterior cingulate cortex. Depressed participants also exhibited stronger connectivity between the dorsal caudate and dorsal prefrontal cortex, which was positively correlated with severity of the disorder. Conclusions: Depressed individuals are characterized by aberrant connectivity in frontostriatal circuits that are posited to support affective and cognitive processing. Further research is required to examine more explicitly the link between patterns of disrupted connectivity and specific symptoms of depression, and the extent to which these patterns precede the onset of depression and normalize with recovery from depressive illness. http://www.biolmoodanxietydisord.com/content/1/1/11 Daniella Furman J Hamilton Ian Gotlib Biology of Mood & Anxiety Disorders 2011, null:11 2011-12-08T00:00:00Z doi:10.1186/2045-5380-1-11 /content/figures/2045-5380-1-11-toc.gif Biology of Mood & Anxiety Disorders 2045-5380 ${item.volume} 11 2011-12-08T00:00:00Z XML