Differential modulation of emotion processing brain regions by noradrenergic and serotonergic antidepressants

Rationale: Most widely used antidepressant drugs affect the serotonergic and noradrenergic pathways. However, there are currently no neurobiological criteria for selecting between these targets and predicting the treatment response in individual depressed patients. Objectives: The current study is aimed at differentiating brain regions known to be pathophysiologically and functionally involved in depression-related emotion processing with respect to their susceptibility to serotonergic and noradrenergic modulation. Methods: In a single-blind pseudo-randomized crossover study, 16 healthy subjects (out of 21 enrolled) were included in analysis after ingesting a single dose of citalopram (a selective serotonin-reuptake inhibitor, 40mg), reboxetine (a selective noradrenaline-reuptake inhibitor, 8mg), or placebo at three time points prior to functional magnetic resonance imaging (fMRI). During fMRI, subjects anticipated and subsequently viewed emotional pictures. Effects of serotonergic and noradrenergic modulation versus placebo on brain activity during the perception of negative pictures were analyzed with a repeated measures ANOVA in the whole brain and in specific regions of interest relevant to depression. Results: Noradrenergic modulation by reboxetine increased brain activity in the thalamus, right dorsolateral prefrontal cortex and occipital regions during the perception of negative emotional stimuli. Citalopram primarily affected the ventrolateral prefrontal cortical regions. Conclusion: The brain regions involved in the processing of negative emotional stimuli were differentially modulated by selective noradrenergic and serotonergic drugs: thalamic activity was increased by reboxetine, whereas citalopram primarily affected ventrolateral prefrontal regions. Thus, dysfunction in these regions, which could be identified in depressed patients, may predict treatment responses to either noradrenergic or serotonergic antidepressant

Drugs, games, and devices for enhancing cognition: implications for work and society.

As work environments change, the demands on working people change. Cognitive abilities in particular are becoming progressively more important for work performance and successful competition in a global environment. However, work-related stress, performance over long hours, lack of sleep, shift work, and jet lag affect cognitive functions. Therefore, an increasing number of healthy people are reported to use cognitive-enhancing drugs, as well as other interventions, such as noninvasive brain stimulation, to maintain or improve work performance. This review summarizes research on pharmacological and technical methods as well as cognitive training, including game apps for the brain, in healthy people. In neuropsychiatric disorders, impairments in cognitive functions can drastically reduce the chances of returning to work; therefore, this review also summarizes findings from pharmacological and cognitive-training studies in neuropsychiatric disorders.All cited psychopharmacological work from Professor Sahakian laboratory was funded by a Wellcome Trust Grant (089589/Z/09/Z) awarded to T.W. Robbins, B.J. Everitt, A.C. Roberts, J.W. Dalley, and B.J. Sahakian, and it was conducted at the Behavioural and Clinical Neuroscience Institute, which is supported by a joint award from the Medical Research Council and Wellcome Trust (G00001354). ABB was supported by a grant from the The Wallitt Foundation.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1111/nyas.1304

Making sense of real-time functional magnetic resonance imaging (rtfMRI) and rtfMRI neurofeedback

This review explains the mechanism of functional magnetic resonance imaging in general and specifically introduces real-time functional magnetic resonance imaging as a method for training self-regulation of brain activity. Using real-time functional magnetic resonance imaging neurofeedback, participants can acquire control over their own brain activity. In patients with neuropsychiatric disorders, this control can potentially have therapeutic implications. In this review, the technical requirements are presented and potential applications and limitations are discussed

Neuroethical issues in cognitive enhancement: Modafinil as the example of a workplace drug?

The use of cognitive-enhancing drugs by healthy individuals has been a feature for much of recorded history. Cocaine and amphetamine are modern cases of drugs initially enthusiastically acclaimed for enhancing cognition and mood. Today, an increasing number of healthy people are reported to use cognitive-enhancing drugs, as well as other interventions, such as non-invasive brain stimulation, to maintain or improve work performance. Cognitive-enhancing drugs, such as methylphenidate and modafinil, which were developed as treatments, are increasingly being used by healthy people. Modafinil not only affects 'cold' cognition, but also improves 'hot' cognition, such as emotion recognition and task-related motivation. The lifestyle use of 'smart drugs' raises both safety concerns as well as ethical issues, including coercion and increasing disparity in society. As a society, we need to consider which forms of cognitive enhancement (e.g. pharmacological, exercise, lifelong learning) are acceptable and for which groups under what conditions and by what methods we would wish to improve and flourish

Neuroethical issues in cognitive enhancement: Modafinil as the example of a workplace drug?

The use of cognitive-enhancing drugs by healthy individuals has been a feature for much of recorded history. Cocaine and amphetamine are modern cases of drugs initially enthusiastically acclaimed for enhancing cognition and mood. Today, an increasing number of healthy people are reported to use cognitive-enhancing drugs, as well as other interventions, such as non-invasive brain stimulation, to maintain or improve work performance. Cognitive-enhancing drugs, such as methylphenidate and modafinil, which were developed as treatments, are increasingly being used by healthy people. Modafinil not only affects 'cold' cognition, but also improves 'hot' cognition, such as emotion recognition and task-related motivation. The lifestyle use of 'smart drugs' raises both safety concerns as well as ethical issues, including coercion and increasing disparity in society. As a society, we need to consider which forms of cognitive enhancement (e.g. pharmacological, exercise, lifelong learning) are acceptable and for which groups under what conditions and by what methods we would wish to improve and flourish

Neuroimaging in social anxiety disorder—a meta-analytic review resulting in a new neurofunctional model.

Social anxiety disorder (SAD) is one of the most frequent anxiety disorders. The landmark meta-analysis of functional neuroimaging studies by Etkin and Wager (2007) revealed primarily the typical fear circuit as overactive in SAD. Since then, new methodological developments such as functional connectivity and more standardized structural analyses of grey and white matter have been developed. We provide a comprehensive update and a meta-analysis of neuroimaging studies in SAD since 2007 and present a new model of the neurobiology of SAD. We confirmed the hyperactivation of the fear circuit (amygdala, insula, anterior cingulate and prefrontal cortex) in SAD. In addition, task-related functional studies revealed hyperactivation of medial parietal and occipital regions (posterior cingulate, precuneus, cuneus) in SAD and a reduced connectivity between parietal and limbic and executive network regions. Based on the result of this meta-analysis and review, we present an updated model of SAD adopting a network-based perspective. The disconnection of the medial parietal hub in SAD extends current frameworks for future research in anxiety disorders.This is the author's accepted manuscript. The final version is printed by Elsevier in Neuroscience & Biobehavioral Reviews here: http://www.sciencedirect.com/science/article/pii/S0149763414002012

Neural correlates of personality dimensions and affective measures during the anticipation of emotional stimuli

Neuroticism and extraversion are proposed personality dimensions for individual emotion processing. Neuroticism is correlated with depression and anxiety disorders, implicating a common neurobiological basis. Extraversion is rather inversely correlated with anxiety and depression. We examined neural correlates of personality in relation to depressiveness and anxiety in healthy adult subjects with functional magnetic resonance imaging during the cued anticipation of emotional stimuli. Distributed particularly prefrontal but also other cortical regions and the thalamus were associated with extraversion. Parieto-occipital and temporal regions and subcortically the caudate were correlated with neuroticism and affective measures. Neuroticism-related regions were partially cross-correlated with anxiety and depression and vice versa. Extraversion-related activity was not correlated with the other measures. The neural correlates of extraversion compared with those of neuroticism and affective measures fit with concepts of different neurobiological bases of the personality dimensions and point at predispositions for affective disorder

Psychiatry in the Digital Age: A Blessing or a Curse?

Social distancing and the shortage of healthcare professionals during the COVID-19 pandemic, the impact of population aging on the healthcare system, as well as the rapid pace of digital innovation are catalyzing the development and implementation of new technologies and digital services in psychiatry. Is this transformation a blessing or a curse for psychiatry? To answer this question, we conducted a literature review covering a broad range of new technologies and eHealth services, including telepsychiatry; computer-, internet-, and app-based cognitive behavioral therapy; virtual reality; digital applied games; a digital medicine system; omics; neuroimaging; machine learning; precision psychiatry; clinical decision support; electronic health records; physician charting; digital language translators; and online mental health resources for patients. We found that eHealth services provide effective, scalable, and cost-efficient options for the treatment of people with limited or no access to mental health care. This review highlights innovative technologies spearheading the way to more effective and safer treatments. We identified artificially intelligent tools that relieve physicians from routine tasks, allowing them to focus on collaborative doctor-patient relationships. The transformation of traditional clinics into digital ones is outlined, and the challenges associated with the successful deployment of digitalization in psychiatry are highlighted

Amphibians and plant-protection products: what research and action is needed?

Background: The majority of Swiss amphibians are threatened. There is a range of factors which have been discussed as possible causes for their decline, including plant protection products (PPPs). Results: The influence of PPPs on amphibian populations has not yet been studied to any great extent, neither for active ingredients nor for the wetting agents, breakdown products or tank mixtures. A further topic of discussion was how to better protect amphibians by reducing their exposure to PPPs in agricultural fields. Conclusion: Experts at a workshop concluded that further research is needed

SSRI Treatment Response Prediction in Depression Based on Brain Activation by Emotional Stimuli

Introduction: The prediction of antidepressant treatment response may improve outcome. Functional magnetic resonance imaging (fMRI) of emotion processing in major depressive disorder (MDD) may reveal regional brain function serving as predictors of response to treatment with selective serotonin reuptake inhibitor (SSRI). Methods: We examined the association between pre-treatment neural activity by means of fMRI during the perception of emotional stimuli in 22 patients with MDD and the treatment outcome after 6 weeks' medication with an SSRI. A whole brain correlation analysis with Beck Depression Inventory (BDI) change between pre- to post-treatment was conducted to identify neural regions associated with treatment response. Results: During the perception of positive stimuli, responders were characterized by more activation in posterior cingulate cortex (PCC), medial prefrontal cortex, and thalamus as well as middle temporal gyrus. During perception of negative stimuli, PCC, and pregenual anterior cingulate cortex showed the highest correlation with treatment response. Furthermore, responders exhibited higher activation to emotional stimuli than to neutral stimuli in all the above-mentioned regions, while non-responders demonstrated an attenuated neural response to emotional compared to neutral stimuli. Conclusion: Our data suggest that the activity of distinct brain regions is correlated with SSRI treatment outcome and may serve as treatment response predictor. While some regions, in which activity was correlated with treatment response, can be assigned to networks that have been implied in the pathophysiology of depression, most of our regions of interest could also be matched to the default mode network (DMN). Higher DMN activity has been associated with increased rumination as well as negative self-referential processing in previous studies. This may suggest our responders to SSRI to be characterized by such dysregulations and that SSRIs might modify the function associated with this network