Behavioral inhibition (BI) is a temperament identified in early childhood that is a risk factor for later social anxiety. However, mechanisms underlying the development of social anxiety remain ...unclear. To better understand the emergence of social anxiety, longitudinal studies investigating changes at behavioral neural levels are needed.
BI was assessed in the laboratory at 2 and 3 years of age (N = 268). Children returned at 12 years, and an electroencephalogram was recorded while children performed a flanker task under 2 conditions: once while believing they were being observed by peers and once while not being observed. This methodology isolated changes in error monitoring (error-related negativity) and behavior (post-error reaction time slowing) as a function of social context. At 12 years, current social anxiety symptoms and lifetime diagnoses of social anxiety were obtained.
Childhood BI prospectively predicted social-specific error-related negativity increases and social anxiety symptoms in adolescence; these symptoms directly related to clinical diagnoses. Serial mediation analysis showed that social error-related negativity changes explained relations between BI and social anxiety symptoms (n = 107) and diagnosis (n = 92), but only insofar as social context also led to increased post-error reaction time slowing (a measure of error preoccupation); this model was not significantly related to generalized anxiety.
Results extend prior work on socially induced changes in error monitoring and error preoccupation. These measures could index a neurobehavioral mechanism linking BI to adolescent social anxiety symptoms and diagnosis. This mechanism could relate more strongly to social than to generalized anxiety in the peri-adolescent period.
Anxiety disorders are common, serious and a growing health problem worldwide. However, the causative factors, aetiology and underlying mechanisms of anxiety disorders, as for most psychiatric ...disorders, remain relatively poorly understood. Animal models are an important aid in giving insight into the aetiology, neurobiology and, ultimately, the therapy of human anxiety disorders. The approach, however, is challenged with a number of complexities. In particular, the heterogeneous nature of anxiety disorders in humans coupled with the associated multifaceted and descriptive diagnostic criteria, creates challenges in both animal modelling and in clinical research. In this paper, we describe some of the more widely used approaches for assessing the anxiolytic activity of known and potential therapeutic agents. These include ethological, conflict‐based, hyponeophagia, vocalization‐based, physiological and cognitive‐based paradigms. Developments in the characterization of translational models are also summarized, as are the challenges facing researchers in their drug discovery efforts in developing new anxiolytic drugs, not least the ever‐shifting clinical conceptualization of anxiety disorders. In conclusion, to date, although animal models of anxiety have relatively good validity, anxiolytic drugs with novel mechanisms have been slow to emerge. It is clear that a better alignment of the interactions between basic and clinical scientists is needed if this is to change.
LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue‐4
Anxiety Disorders in the Elderly Andreescu, Carmen; Lee, Soyoung
Advances in experimental medicine and biology,
2020, Volume:
1191
Journal Article
Peer reviewed
Recent data has linked anxiety and its disorders in late life to increased morbidity and mortality, especially related to a higher cardiovascular burden and an increased cognitive decline. ...Clinically, anxiety symptoms may be more difficult to elicit in older adults who are less accurate in identifying anxiety symptoms and tend to minimize symptoms and to attribute symptoms to physical illness. Although SSRIs have proven more effective than psychotherapy in late-life anxiety, many elderly anxious subjects prefer psychotherapeutic interventions. These interventions appear to work best when tailored for the needs, expectations, and cultural background of older anxious subjects.
Substantial evidence from various studies suggests a preeminent role for early adverse experiences in the development of psychopathology. The most recent studies reviewed here suggest that early life ...stressors are associated with an increased risk for anxiety disorders in adulthood. Early life stress predisposes individuals to develop a number of psychiatric syndromes, particularly affective disorders, including anxiety disorders, and is therefore a significant health problem.This review examines the emerging literature on the relationship between stress, hypothalamic-pituitary-adrenal (HPA) axis function, and generalized anxiety disorder (GAD), panic disorder, and phobias and the role of early life stress as an important risk factor for HPA axis dysfunction.The most consistent findings in the literature show increased activity of the HPA axis in depression associated with hypercortisolemia and reduced inhibitory feedback. In addition to melancholic depression, a spectrum of other conditions may be associated with increased and prolonged activation of the HPA axis, including panic, GAD, phobias and anxiety. Moreover, HPA axis changes appear to be state-dependent, tending to improve upon resolution of the anxiety syndrome. Interestingly, persistent HPA hyperactivity has been associated with higher rates of relapse. These studies suggest that an evaluation of the HPA axis during treatment may help identify patients who are at a higher risk for relapse. These findings suggest that this dysfunction of the HPA axis is partially attributable to an imbalance between glucocorticoid and mineralocorticoid receptors. Evidence has consistently demonstrated that glucocorticoid receptor function is impaired in anxiety disorders. Moreover, normal basal cortisol levels and hyper-responsiveness of the adrenal cortex during a psychosocial stressor are observed in social phobics. Finally, abnormal HPA axis activity has also been observed in generalized anxiety disordered patients. Early stressful life events may provoke alterations of the stress response and thus of the HPA axis that can endure during adulthood, predisposing individuals to develop psychopathology.
ABSTRACTA double-blind, randomized, active placebo-controlled pilot study was conducted to examine safety and efficacy of lysergic acid diethylamide (LSD)-assisted psychotherapy in 12 patients with ...anxiety associated with life-threatening diseases. Treatment included drug-free psychotherapy sessions supplemented by two LSD-assisted psychotherapy sessions 2 to 3 weeks apart. The participants received either 200 μg of LSD (n = 8) or 20 μg of LSD with an open-label crossover to 200 μg of LSD after the initial blinded treatment was unmasked (n = 4). At the 2-month follow-up, positive trends were found via the State-Trait Anxiety Inventory (STAI) in reductions in trait anxiety (p = 0.033) with an effect size of 1.1, and state anxiety was significantly reduced (p = 0.021) with an effect size of 1.2, with no acute or chronic adverse effects persisting beyond 1 day after treatment or treatment-related serious adverse events. STAI reductions were sustained for 12 months. These results indicate that when administered safely in a methodologically rigorous medically supervised psychotherapeutic setting, LSD can reduce anxiety, suggesting that larger controlled studies are warranted.
The translational neural circuitry of anxiety Robinson, Oliver J; Pike, Alexandra C; Cornwell, Brian ...
Journal of neurology, neurosurgery and psychiatry,
12/2019, Volume:
90, Issue:
12
Journal Article
Peer reviewed
Open access
Anxiety is an adaptive response that promotes harm avoidance, but at the same time excessive anxiety constitutes the most common psychiatric complaint. Moreover, current treatments for anxiety—both ...psychological and pharmacological—hover at around 50% recovery rates. Improving treatment outcomes is nevertheless difficult, in part because contemporary interventions were developed without an understanding of the underlying neurobiological mechanisms that they modulate. Recent advances in experimental models of anxiety in humans, such as threat of unpredictable shock, have, however, enabled us to start translating the wealth of mechanistic animal work on defensive behaviour into humans. In this article, we discuss the distinction between fear and anxiety, before reviewing translational research on the neural circuitry of anxiety in animal models and how it relates to human neuroimaging studies across both healthy and clinical populations. We highlight the roles of subcortical regions (and their subunits) such as the bed nucleus of the stria terminalis, the amgydala, and the hippocampus, as well as their connectivity to cortical regions such as dorsal medial and lateral prefrontal/cingulate cortex and insula in maintaining anxiety responding. We discuss how this circuitry might be modulated by current treatments before finally highlighting areas for future research that might ultimately improve treatment outcomes for this common and debilitating transdiagnostic symptom.
The primary goal of this study was to examine the associations between baseline body image dissatisfaction (BID) and subsequent anxiety trajectories in a diverse, community sample of adolescent girls ...and boys. Participants were 581 adolescents (baseline age: M = 16.1, SD = 0.7; 58% female; 65% non-Hispanic White) from U.S. public high schools. Self-report questionnaires were administered during school at 3 annual assessment waves. Latent growth curve modeling examined the association between baseline BID and growth factors of anxiety disorder symptom trajectories. Covariates included baseline gender, age, race/ethnicity, parental education attainment, body mass index standard scores, and depressive symptoms. Higher BID at baseline was significantly associated with higher initial symptoms of generalized anxiety disorder (GAD), panic disorder (PD), social anxiety disorder (SAD), and significant school avoidance (SSA; ps = .001-.04) but was unrelated to initial separation anxiety disorder (SEP) symptoms (p = .27). Higher baseline BID also was associated with attenuated decreases in SAD symptoms across time (p = .001). Among adolescents with low baseline anxiety symptoms only, higher BID was associated with more attenuated decreases in SAD symptoms (p = .01) and greater increases in PD symptoms (p = .02). BID was unrelated to changes in GAD, SEP, and SSA symptoms (ps = .11-.94). Findings suggest that BID is associated with concurrent symptoms of multiple anxiety disorders and may have a prospective link to SAD and PD symptoms during adolescence. As such, assessing body image issues may be important to assess when identifying adolescents at risk for exacerbated SAD and PD symptoms.
Purpose of Review
The current review aims at providing an overview of relevant aspects of anxiety symptoms and anxiety disorders (AD) in adults patients with epilepsy (PWE).
Recent Findings
Firstly, ...the appropriate diagnosis of type of anxiety symptoms and AD in PWE will be presented. Anxiety symptoms are often peri-ictal and classified in relation to their temporal occurrence to seizures. Anxiety symptoms are of three types: preictal (preceding a seizure), ictal (presenting as part of the seizure symptoms and signs), and postictal (occurring within 72 h of a seizure). AD are diagnosed in the interictal period and occur independently of seizures. Four specific AD in PWE can be objectified: anticipatory anxiety of epileptic seizures (AAS), seizure phobia, epileptic social phobia, and epileptic panic disorder. Secondly, the bidirectional pathophysiological relationship between anxiety and epilepsy will be described. Anxiety is a trigger for seizures in some patients, and the notion of stress and arousal is essential to understand the relationship between anxiety and seizure. Moreover, seizures arising from the limbic network especially involving amygdala, which may express fear-related semiology, provide insight into the pathophysiology of AD comorbidities. Thirdly, the methods of screening for AD and anxiety symptoms will be detailed. Fourthly, the pharmacological and psychobehavioral management of anxiety symptoms and AD in PWE will be presented. Arousal-based approaches for preictal and ictal symptoms and anxiety-based approaches for postictal and interictal symptoms will be presented.
Summary
Despite lack of evidence-based approaches, it is recognized that management of epilepsy is not only about controlling seizures, but also depends heavily on detecting, correctly diagnosing, and appropriately managing anxiety symptoms and AD comorbidities, in order to maximize quality of life. Improving self-control and self-efficacy is of fundamental importance in the management of PWE. Further rigorously designed studies focusing on anxiety symptoms and AD are essential to improve the overall care of PWE.
Abstract
Introduction
We previously demonstrated that sleep disordered breathing was related to behavioral problem in primary school children (Naoko S. et al. Sleep 2017; 40:1–8). However, ...association between snoring and anxiety among community dwelling school children in Japan remains to be elucidated.
Methods
A cross sectional study on whole primary school children in a city in Japan was conducted. A questionnaire, which included questions regarding a history of snoring, anxiety and variables: such as sex, grade, height, weight, tonsil hypertrophy and asthma, was delivered to parents or guardians of all the children (26,599) via the schools, and their responses were collected by teachers. Anxiety was evaluated with the subscale of Strengths and Difficulties Questionnaire (SDQ); the scores for emotional symptoms. Score 0 to 3 was defined as ‘no anxiety’, and score 4 to 10 as ‘having anxiety’. Univariable and multivariable regression and logistic analyses adjusted for the variables were conducted, using SAS version 9.4 software.
Results
In total, 17,859 children were included in this analysis. The prevalence of children ‘having anxiety’ in ‘no snoring’, in ‘snoring once/twice a week’ and in ‘snoring more than three times a week’ were 6.0%(n=573), 9.7%(658) and 12.5%(176), respectively. The Odds Ratios(95% Confidence interval) for ‘having anxiety’ of ‘snoring once/twice a week’ and ‘snoring more than three times a week’ referenced to ‘no snoring’ were 1.67(1.49–1.88) and 2.19(1.82–2.63), respectively (P for trend<0.0001).
Conclusion
Frequency of snoring was significantly associated with anxiety among community-dwelling school children.
Support (If Any):
This review brings together recent research from molecular, neural circuit, animal model, and human studies to help understand the neurodevelopmental mechanisms underlying social anxiety disorder. ...Social anxiety disorder is common and debilitating, and it often leads to further psychopathology. Numerous studies have demonstrated that extremely behaviorally inhibited and temperamentally anxious young children are at marked risk of developing social anxiety disorder. Recent work in human and nonhuman primates has identified a distributed brain network that underlies early-life anxiety including the central nucleus of the amygdala, the anterior hippocampus, and the orbitofrontal cortex. Studies in nonhuman primates have demonstrated that alterations in this circuit are trait-like in that they are stable over time and across contexts. Notably, the components of this circuit are differentially influenced by heritable and environmental factors, and specific lesion studies have demonstrated a causal role for multiple components of the circuit. Molecular studies in rodents and primates point to disrupted neurodevelopmental and neuroplastic processes within critical components of the early-life dispositional anxiety neural circuit. The possibility of identifying an early-life at-risk phenotype, along with an understanding of its neurobiology, provides an unusual opportunity to conceptualize novel preventive intervention strategies aimed at reducing the suffering of anxious children and preventing them from developing further psychopathology.