The Age of Anxiety, a six-part alliterative poem by the British-American poet Wystan Hugh (W.H.) Auden, portrays the pressing quest to find personal substance and identity, in countering lost faith and existential dread in a post-bellum, rapidly changing, tumultuous world.Reference Auden1 It won the Pulitzer Prize in 1948 and was the principal inspiration for the similarly titled and unsettling second symphony of Leonard Bernstein, which premiered the following year. Almost 50 years later, in a similarly titled endeavour, The Age of Anxiety, the writer and broadcaster Sarah Dunant and social historian Roy Porter invited contributors with backgrounds in philosophy, sociology, psychotherapy, literature, journalism and public relations to consider the effects of globalisation, consumerism, technological innovation, environmental degradation and changing family patterns on individual, community and international well-being.Reference Dunant and Porter2 These commentaries proved disconcerting reading for those seeking some balm from fear, unease and worry in the years of ‘pre-millennial tension’. Then, in her introduction to a supplement to The Sociological Review (entitled ‘The Age of Anxiety: Conspiracy Theory and the Human Sciences’), the sociologist Jane Parish tackled the undermining effects of loss of certainty and anticipated the insidious creep of opinion-based ‘alternative facts’ and contentious disputes over which sources of knowledge and expertise are valued or denigrated in public discourse.Reference Parish3
This themed issue comprises papers highlighting recent developments in our understanding of the nature, experience and causes of anxiety, which together may provide some signposts for future lines of research into potential treatments of the principal anxiety disorders seen in clinical settings, while also trying to place these developments within a broader sociocultural context. Although there have been advances in disentangling the causes of anxiety disorders in recent decades – including insights gained from research into epidemiology, epigenetics, neuropsychobiology and novel therapeutic approaches – much has remained uncertain. Similarly, despite the wide availability of a range of psychotherapeutic and pharmacological treatments, many of those who could benefit from them are neither recognised nor treated in primary care. In secondary care mental health services, anxiety disorders are often comorbid with other conditions but can be overlooked as psychiatrists and their colleagues focus on the hurly-burly of severe mental illness, despite evidence that unrecognised and untreated comorbid anxiety can adversely affect the prognosis of other conditions. The persisting limitations in our understanding of the aetiology of anxiety disorders and the mechanisms underlying current psychotherapeutic and pharmacological treatments may underpin the disappointing response rates in real-world clinical practice.
A rising tide
It is widely held that common mental health problems such as major depressive episodes and the anxiety disorders are increasing in prevalence, but there has been relatively little robust evidence to confirm or refute this contention. By analysing data from two cohorts (conducted in 2007–2009 and 2019–2022) within the Netherlands Mental Health Survey and Incidence Studies, with appropriate weighting for gender, age, partner status, urbanicity and education level, Brenda Penninx and colleagues provide strong evidence that the 12-month prevalence of all anxiety and mood disorders was significantly higher in the second cohort (anxiety disorders increased from 6.3 to 9.8%, mood disorders from 6.0 to 10.8%).Reference Gkitakou, Ten Have, Batelaan, Luik and Penninx4 These mental health problems were no less severe in the second cohort: indeed, they were more likely to be characterised by earlier onset, greater comorbidity and higher use of mental health services. The increase in prevalence is to some extent unexplained, because there was no significant increase in the prevalence or impact of 14 known risk factors, reflecting demographic variables, adverse experiences, ‘lifestyle’ or chronic physical conditions. Furthermore, it seems unlikely that the COVID-19 pandemic period (2020–2021) was responsible, because interviews conducted preceding pandemic onset yielded prevalence estimates similar to those undertaken once the pandemic and its ensuing restrictions had occurred.
Much scope for early intervention
If indeed anxiety disorders are becoming more prevalent and have an earlier onset, there is an enhanced need for early recognition and prompt intervention to prevent chronicity, the development of comorbidity and the accompanying greater likelihood of treatment resistance. Regrettably, anxiety disorders are often characterised by a long ‘duration of untreated illness’ (the period between onset of symptoms and the initiation of an evidence-based pharmacological or psychotherapeutic treatment), perhaps because the conditions typically have a gradual onset and are sometimes accompanied by marked avoidance of health professionals. The most striking example is social anxiety disorder (often damagingly misconstrued as mere shyness), where typically there is a delay in starting treatment of between 10 and 15 years, during a crucial time when academic studies are peaking, employment options are being considered and interpersonal relationships are being formed. Bernardo Dell’Osso and colleagues provide a cogent argument for prioritising a broad range of coordinated efforts to reduce the duration of untreated illness as an important public health policy initiative – including awareness-raising activities in schools and colleges and general medical settings.Reference Olivola, Macellaro and Dell’Osso5
Altered emotions and heightened eye movements
Alterations in perceptions of threat and disturbances in emotion processing may be important in the aetiology of anxiety disorders, and intriguing papers within this issue illustrate the difficulties in unravelling these influences. One functional neuroimaging study of neural directive connectivity during an emotional recognition task found that individuals with social anxiety disorder differed from healthy controls in connectivity within prefrontal regions: because the groups did not differ in patterns of amygdala–prefrontal connectivity, the findings suggest that altered emotion processing and regulation in social anxiety disorder may be linked to perturbations in intra-prefrontal circuits.Reference Schrammen, Jamieson, Meinert, Böhnlein, Slump, Vogler and Menze6 In a second functional neuroimaging study, of explicit and implicit threat processing in healthy volunteers, administered an opioid antagonist (naltrexone) in a double-blind, placebo-controlled, cross-over design, we found that naltrexone attenuated ventromedial prefrontal cortex, thalamus and caudate activation when viewing negative images and increased left middle frontal gyrus activity when viewing fearful faces, suggesting a nuanced role for the endogenous opioid system in ‘fine-tuning’ automatic appraisal and the regulation of emotional salience. Although anxiety disorders are associated with an attentional bias towards threat-related stimuli, there have been few investigations of other eye movement paradigms. Zhang et al therefore examined a broad range of eye movement parameters in patients with anxiety disorders, or depressive disorders, and healthy controls, and found that only anxiety disorders were associated with ‘aberrant eye movement control’ (with features including hyper-scanning during viewing of still images, hyper-pursuit of moving images and increased pupillary arousal): these were more pronounced among participants with more severe anxiety symptoms, leading to the suggestion that altered eye movements might represent a useful behavioural ‘biomarker’ for anxiety disorders.Reference Zhang, Li, Xu, Xu, Xu, Zheng and Hong7
Not just ‘in our genes’
Explanatory models of mental disorders can influence patient and clinician attitudes, preferences and treatment decisions, and may heighten or reduce stigma: a solely neurobiological essentialist account might reduce a sense of ‘personal blame’ but encourage an unduly fatalistic approach, whereas a solely environmental conceptualisation might favour psychosocial approaches but reduce access to effective medicines. A cluster-randomised controlled trial of the effects of a brief educational intervention for mental health professionals, which compared the presentation of evolutionary and genetic explanations of anxiety, suggests that the evolutionary-based conceptualisation was associated with more positive clinician attitudes towards psychosocial interventions, a greater anticipated willingness of the public to seek psychiatric help and enhanced optimism for patient recovery.Reference Hunt, Carpenter, Brar, Katiyar, Al-Shawaf, Gillet and Chaudhary8 The authors acknowledge some methodological limitations, including high attrition rates, and it is uncertain whether the findings of this attitudinal research might translate into beneficial changes in mental health service delivery: furthermore, the effect of a more comprehensive ‘biopsychosocial’ approach (with insights from epigenetic studies) to understanding anxiety disorders, probably endorsed by most clinicians, does not appear to have been evaluated.
Anxiolytics old and new
Many have sought – and many still seek – to relieve psychological distress through the use of alcohol, opium and cannabis, but synthetic pharmaceutical anxiolytics first became commercially available in the mid 19th century. The earlier compounds, including barbiturates and benzodiazepines, proved helpful in reducing anxiety and were soon widely prescribed, but increasing awareness of problems such as tolerance, dependence and withdrawal gradually came to limit their use in clinical practice. Selective serotonin reuptake inhibitors are now regarded as first-line pharmacological treatments for anxiety disorders, but they too cannot be considered ideal. Peter Haddad reviews the development of psychotropic medications for reducing anxiety and reminds us that a full appreciation of the balance of their benefits and risks may take a few decades:Reference Haddad9 looking forward, he highlights the therapeutic potential for neurosteroids and psychedelic drugs. Additionally, compounds with differing mechanisms of action, such as GABA-A receptor subtype selective ligands, orexin receptor antagonists and alpha-7-nicotinic receptor agonists, are all being explored as potential anxiolytics, and well-known medicines used in other clinical arenas may also be ‘repurposed’ for treating patients with anxiety disorders. Awareness of the role of chemosensory acid-sensing ion channels (ASICs) in detecting hypercapnia associated with supra-environmental carbon dioxide inhalation (which can elicit both panic attacks and symptoms of generalised anxiety), and in mediating the learning response to adversities, has encouraged us to evaluate the diuretic amiloride (a reversible antagonist at ASICs) in preclinical studies and experimental medicine models of anxiety: in theory, it might prevent or shorten panic attacks as an ‘as-required’ medication, but it will take some time to establish whether or not this potential could be realised in clinical practice.
A tragic loss
Research into anxiety disorders suffered an enormous loss when our valued research collaborator, esteemed colleague and mutual friend Professor Dan Stein passed away after a brief illness in December 2025, at the age of 63 years (https://www.ecnp.eu/news/in-memoriam-dan-stein/). More than anyone else, Dan embraced research and clinical practice in anxiety and related disorders with engaging curiosity and infectious enthusiasm, drawing on insights from anthropology, philosophy, psychotherapy, psychiatry and neuroscience. He had an extraordinary appreciation of human frailties and resourcefulness, and strived to enhance understanding of mental health problems and improve provisions for those whose lives are affected by adversity. His monographs The Philosophy of Psychopharmacology (2008) and Problems of Living (2021) can be regarded as essential reading for those wishing to consider the place of psychiatric practice within its broader sociocultural milieu.
Concerns for the future
Where next for anxiety disorders? There is much to be done. If they are becoming more prevalent, particularly in young people, we must understand why. There is a need to address concerns about the potentially damaging effects on mental health of excessive engagement with social media platforms and the widespread loss of confidence in the veracity of information. The clinical and cost-effectiveness of implementing public health initiatives and reshaping clinical services to effect early recognition and initiate prompt treatment needs to be determined. Global dissemination of the state of knowledge and of advances in research is essential. As one example, slide sets on ‘History, definitions, and diagnosis’, ‘Epidemiology and burden’, ‘Comorbidities’, ‘Course, natural history, and prognosis’, ‘Neurobiology and etiology’ and ‘Treatment principles’ of anxiety disorders with accompanying articles and videos, developed by an international panel, are free to download and use at the knowledge hub provided through a non-commercial, non-profit educational initiative (https://neurotorium.org/anxiety/). The persisting neglect of the causes of separation anxiety disorder in adults has to be rectified, and potential treatments evaluated through randomised controlled trials. Greater efforts should be made to iteratively integrate symptoms, behaviour and multi-level biological data (including epigenetics and neuroimaging) to comprehensively model the latent mechanisms and their dynamics that give rise to the phenotypes of anxiety disorders. The value of participation in peer-led initiatives, mutual aid organisations and ‘social prescribing’ activities for people with anxiety needs to be more fully evaluated. Psychotherapeutic treatments must be refined and more equitably delivered, and the effectiveness and acceptability of psychopharmacological treatments has to be improved.
Author contributions
D.S.B., N.T.M.H., S.J.C.D., N.L. and K.D. all contributed to the conceptualisation and drafting of this article.
Funding
D.S.B., N.T.M.H., S.J.C.D. and K.D. are members of the European College of Neuropsychopharmacology (ECNP) Anxiety Disorders Research Network (ADRN), which receives funding through the ECNP Network Initiative. N.L. is Chief Executive of Anxiety UK, a national registered charity.
Declaration of interest
The clinical service provided by D.S.B. is supported by the Office of Life Sciences and National Institute for Health and Social Care Research (NIHR) through the Mental Health Mission. He receives research support from the National Institute for Health Research Health Technology Assessment Programme. He is a medical patron of Anxiety UK and contributed to the Neurotorium programme. N.T.M.H. is Deputy Director of Education for the British Association for Psychopharmacology, for which he receives an honorarium, and is a NIHR clinical lecturer. He has received a speaker honorarium from Focus Gulf Conferences. N.L. contributed to the ECNP ADRN-led consensus panel on treatment-resistant anxiety disorders. K.D. is a member of the Neurotorium Editorial board, Lundbeck Foundation and has received speaker’s fees from Janssen Inc. and ROVI. S.J.C.D. has no further interests to declare. The views expressed in this publication are those of the authors and not necessarily those of NIHR, NHS or the UK Department of Health and Social Care. D.S.B., N.T.M.H., S.J.C.D., N.L. and K.D. are guest editors for the British Journal of Psychiatry but did not take part in the review or decision-making process of this paper.
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