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Critchley H.,Psychiatry | Critchley H.,Sussex Education Center Millview Hospital | Critchley H.,University of Sussex | Harrison N.,Psychiatry | And 2 more authors.
Neuron | Year: 2013

Mental processes and their neural substrates are intimately linked to the homeostatic control of internal bodily state. There are a set of distinct interoceptive pathways that directly and indirectly influence brain functions. The anatomical organization of these pathways and the psychological/behavioral expressions of their influence appear along discrete, evolutionarily conserved dimensions that are tractable to a mechanistic understanding. Here, we review the role of these pathways as sources of biases to perception, cognition, emotion, and behavior and arguably the dynamic basis to the concept of self.

Eccles J.A.,Psychiatry | Eccles J.A.,Sussex Partnership National Health Service Foundation Trust | Owens A.P.,University College London | Mathias C.J.,University College London | And 5 more authors.
Frontiers in Neuroscience | Year: 2015

This review explores the proposal that vulnerability to psychological symptoms, particularly anxiety, originates in constitutional differences in the control of bodily state, exemplified by a set of conditions that include Joint Hypermobility, Postural Tachycardia Syndrome and Vasovagal Syncope. Research is revealing how brain-body mechanisms underlie individual differences in psychophysiological reactivity that can be important for predicting, stratifying and treating individuals with anxiety disorders and related conditions. One common constitutional difference is Joint Hypermobility, in which there is an increased range of joint movement as a result of a variant of collagen. Joint hypermobility is over-represented in people with anxiety, mood and neurodevelopmental disorders. It is also linked to stress-sensitive medical conditions such as irritable bowel syndrome, chronic fatigue syndrome and fibromyalgia. Structural differences in "emotional" brain regions are reported in hypermobile individuals, and many people with joint hypermobility manifest autonomic abnormalities, typically Postural Tachycardia Syndrome. Enhanced heart rate reactivity during postural change and as recently recognized factors causing vasodilatation (as noted post-prandially, post-exertion and with heat) is characteristic of Postural Tachycardia Syndrome, and there is a phenomenological overlap with anxiety disorders, which may be partially accounted for by exaggerated neural reactivity within ventromedial prefrontal cortex. People who experience Vasovagal Syncope, a heritable tendency to fainting induced by emotional challenges (and needle/blood phobia), are also more vulnerable to anxiety disorders. Neuroimaging implicates brainstem differences in vulnerability to faints, yet the structural integrity of the caudate nucleus appears important for the control of fainting frequency in relation to parasympathetic tone and anxiety. Together there is clinical and neuroanatomical evidence to show that common constitutional differences affecting autonomic responsivity are linked to psychiatric symptoms, notably anxiety. © 2015 Eccles, Owens, Mathias, Umeda and Critchley.

Makovac E.,IRCCS Santa Lucia Foundation | Watson D.R.,Psychiatry | Meeten F.,Psychiatry | Meeten F.,King's College London | And 8 more authors.
Social Cognitive and Affective Neuroscience | Year: 2016

Generalized anxiety disorder (GAD) is characterized by excessive worry, autonomic dysregulation and functional amygdala dysconnectivity, yet these illness markers have rarely been considered together, nor their interrelationship tested longitudinally. We hypothesized that an individual's capacity for emotion regulation predicts longer-term changes in amygdala functional connectivity, supporting the modification of GAD core symptoms. Sixteen patients with GAD (14 women) and individually matched controls were studied at two time points separated by 1 year. Resting-state fMRI data and concurrent measurement of vagally mediated heart rate variability were obtained before and after the induction of perseverative cognition. A greater rise in levels of worry following the induction predicted a stronger reduction in connectivity between right amygdala and ventromedial prefrontal cortex, and enhanced coupling between left amygdala and ventral tegmental area at follow-up. Similarly, amplified physiological responses to the induction predicted increased connectivity between right amygdala and thalamus. Longitudinal shifts in a distinct set of functional connectivity scores were associated with concomitant changes in GAD symptomatology over the course of the year. Results highlight the prognostic value of indices of emotional dysregulation and emphasize the integral role of the amygdala as a critical hub in functional neural circuitry underlying the progression of GAD symptomatology. © The Author (2016).

Garfinkel S.N.,Psychiatry | Garfinkel S.N.,University of Sussex | Tiley C.,Brighton and Sussex Medical School | O'Keeffe S.,Brighton and Sussex Medical School | And 8 more authors.
Biological Psychology | Year: 2016

Emotions and affective feelings are influenced by one's internal state of bodily arousal via interoception. Autism Spectrum Conditions (ASC) are associated with difficulties in recognising others' emotions, and in regulating own emotions. We tested the hypothesis that, in people with ASC, such affective differences may arise from abnormalities in interoceptive processing. We demonstrated that individuals with ASC have reduced interoceptive accuracy (quantified using heartbeat detection tests) and exaggerated interoceptive sensibility (subjective sensitivity to internal sensations on self-report questionnaires), reflecting an impaired ability to objectively detect bodily signals alongside an over-inflated subjective perception of bodily sensations. The divergence of these two interoceptive axes can be computed as a trait prediction error. This error correlated with deficits in emotion sensitivity and occurrence of anxiety symptoms. Our results indicate an origin of emotion deficits and affective symptoms in ASC at the interface between body and mind, specifically in expectancy-driven interpretation of interoceptive information. © 2015 Elsevier B.V.

Luyten L.,Catholic University of Leuven | Vansteenwegen D.,Center for the Psychology of Learning and Experimental Psychopathology | Van Kuyck K.,Catholic University of Leuven | Gabriels L.,Psychiatry | Nuttin B.,Catholic University of Leuven
Cognitive, Affective and Behavioral Neuroscience | Year: 2011

Animal models of psychiatric disorders are important translational tools for exploring new treatment options and gaining more insight into the disease. Thus far, there is no systematically validated animal model for generalized anxiety disorder (GAD), a severely impairing and difficult-to-treat disease. In this review, we propose contextual conditioning (CC) as an animal model for GAD. We argue that this model has sufficient face validity (there are several symptom similarities), predictive validity (it responds to clinically effective treatments), and construct validity (the underlying mechanisms are comparable). Although the refinement and validation of an animal model is a never-ending process, we want to give a concise overview of the currently available evidence. We suggest that the CC model might be a valuable preclinical tool to enhance the development of new treatment strategies and our understanding of GAD. © 2011 Psychonomic Society, Inc.

Thompson W.K.,Psychiatry | Holland D.,University of California at San Diego | Rddey J.C.,University of California at San Diego | Blennow K.,Goteburg University | And 4 more authors.
Annals of Neurology | Year: 2011

The relationship between neurodegeneration and the 2 hallmark proteins of Alzheimer's disease, amyloid-b (Ab) and tau, is still unclear. Here, we examined 286 nondemented participants (107 cognitively normal older adults and 179 memory impaired individuals) who underwent longitudinal magnetic resonance (MR) imaging and lumbar puncture. Using mixed effects models, we investigated the relationship between longitudinal entorhinal cortex atrophy rate, cerebrospinal fluid (CSF) p-tau181p and CSF Ab1-42. We found a significant relationship between elevated entorhinal cortex atrophy rate and decreased CSF Ab1-42 only with elevated CSF ptau181p. Our findings indicate that Ab-associated volume loss occurs only in the presence of phospho-tau in humans at risk for dementia. © 2011 American Neurological Association.

Garfinkel S.N.,Psychiatry | Garfinkel S.N.,University of Sussex | Seth A.K.,University of Sussex | Barrett A.B.,University of Sussex | And 3 more authors.
Biological Psychology | Year: 2015

Interoception refers to the sensing of internal bodily changes. Interoception interacts with cognition and emotion, making measurement of individual differences in interoceptive ability broadly relevant to neuropsychology. However, inconsistency in how interoception is defined and quantified led to a three-dimensional model. Here, we provide empirical support for dissociation between dimensions of: (1) interoceptive accuracy (performance on objective behavioural tests of heartbeat detection), (2) interoceptive sensibility (self-evaluated assessment of subjective interoception, gauged using interviews/questionnaires) and (3) interoceptive awareness (metacognitive awareness of interoceptive accuracy, e.g. confidence-accuracy correspondence). In a normative sample (. N=. 80), all three dimensions were distinct and dissociable. Interoceptive accuracy was only partly predicted by interoceptive awareness and interoceptive sensibility. Significant correspondence between dimensions emerged only within the sub-group of individuals with greatest interoceptive accuracy. These findings set the context for defining how the relative balance of accuracy, sensibility and awareness dimensions explain cognitive, emotional and clinical associations of interoceptive ability. © 2014 The Authors.

Bagley S.C.,Psychiatry
Suicide & life-threatening behavior | Year: 2010

Military personnel and veterans have important suicide risk factors. After a systematic review of the literature on suicide prevention, seven (five in the U.S.) studies of military personnel were identified containing interventions that may reduce the risk of suicide. The effectiveness of the individual components was not assessed, and problems in methodology or reporting of data were common. Overall, multifaceted interventions for active duty military personnel are supported by consistent evidence, although of very mixed quality, and in some cases during intervals of declines in suicide rates in the general population. There were insufficient studies of U.S. Veterans to reach conclusions.

Quera-Salva M.-A.,Raymond Poincare Hospital | Lemoine P.,Psychiatry | Guilleminault C.,Stanford University
Human Psychopharmacology | Year: 2010

Background: Disturbance of sleep-wake cycles is common in major depressive disorder (MDD), usually as insomnia, but also as hypersomnia or reduced daytime alertness. Agomelatine, an MT1 and MT2 receptor agonist and 5-HT2C receptor antagonist, represents a novel approach in MDD, with proven antidepressant efficacy and a positive impact on the sleep-wake cycle. We review the effects of agomelatine 25/50 mg/day on objective and subjective measures of the sleep-wake cycle in MDD. Subjective measures: Agomelatine improved all aspects of the sleep-wake cycle from as early as 1 week in randomized trials versus selective serotonin reuptake inhibitors and venlafaxine, particularly getting off to sleep and quality of sleep, with an improvement in daytime alertness. Objective measures: Agomelatine's effect on sleep architecture in MDD has been measured by polysomnography (PSG). There were significant improvements in sleep efficiency, slow-wave sleep (SWS), and the distribution of delta activity throughout the night, but no change in amount or latency of rapid eye movement (REM) sleep. Furthermore, the slow-wave sleep was resynchronized to the first sleep cycle of the night. Conclusion: Agomelatine, a novel antidepressant, improves disturbed sleep-wake cycles in MDD. The improvement of both nighttime sleep and daytime functioning with agomelatine are promising features of this antidepressant regarding the management of MDD. Copyright © 2010 John Wiley & Sons, Ltd.

Berman M.I.,Psychiatry | Hegel M.T.,Psychiatry
Psychotherapy Research | Year: 2014

Objective: Recursive partitioning was applied to a longitudinal dataset of outpatient mental health clinic patients to identify empirically factors and interactions among factors that best predicted clinical improvement and deterioration in symptoms of depression across treatment. Method: Sixty-two variables drawn from an initial patient survey and from chart review were included as covariates in the analysis, representing nearly all of the demographic, treatment, symptom, diagnostic, and social history information obtained from patients at their initial evaluations. Trees estimated the probability of participants' having depression at their last assessment, improving to a clinically significant degree during treatment, or developing a new onset of significant depressive symptoms during treatment. Results: Initial pain, the presence of anxiety, and a history of multiple types of abuse were risk factors for poorer outcome, even among patients who did not initially have significant depressive symptoms. Conclusions: By examining multiple-related outcomes, we were able to create a series of overlapping models that revealed important predictors across trees. Limitations of the study included the lack of cross-validation of the trees and the exploratory nature of the analysis. © 2014, Society for Psychotherapy Research.

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