Generalized anxiety disorder (GAD) is no longer considered to be a rare and benign affliction. According to DSM-5, it is fairly prevalent (the adult 12-month prevalence is 2.9% in the general community in the United States), with a lifetime morbidity risk of 9.0%. Besides, the core features of GAD— excessive anxiety and worry—can impair the individual’s capacity to function effectively to a greater extent than what was previously believed.

This issue begins with a State of the Art article by Borwin Bandelow and his colleagues, who review recommendations, based on guidelines, for the treatment of anxiety disorders. Their article appears particularly useful when one considers the evidence for substantial undertreatment of anxiety disorders.

The Clinical Research section begins with an article on the history of GAD as a diagnostic category by Marc-Antoine Crocq. “Pantophobia” had long been used as a diagnostic term in classic psychiatric texts. Generalized anxiety disorder (GAD) appeared as a diagnostic category in DSM-III in 1980, with the splitting of anxiety neurosis into GAD and Panic Disorder. In the interim period between DSM-III and DSM- 5, worry about multiple life circumstances has gradually been emphasized as the distinctive symptom of GAD. Maherra Khambaty and Rajesh M. Parikh offer a history of the perception of anxiety in India. They describe culture-specific syndromes such as dhat and koro, and review the wide range of therapeutic modalities practiced in India, such as pharmacotherapy, ayurveda, unani medicine, yoga, meditation, and mindfulness. The latter methods have now gained worldwide popularity. Dan J. Stein and his colleagues, who have conducted extensive research on the epidemiology of anxiety disorders, emphasize that anxiety disorders are the most prevalent class of psychiatric conditions. Epidemiological and comorbidity data have contributed to the optimization of diagnostic criteria in successive revisions of DSM, and have also influenced the nosological conceptualization of mood and anxiety disorders. Evin Aktar, Milica Nikolić, and Susan M. Bögels review various potential environmental pathways for parent-to-child transmission of GAD. They discuss the intergenerational transmission of two central cognitive features of GAD, ie, the experiential avoidance of strong negative emotions and the intolerance of uncertainty.

The Translational Research section is introduced by a comprehensive review of the biological markers of GAD by Eduard Maron and David Nutt. This article encompasses evidence from neuroimaging, genetic, and neurochemical data. In the following article, Michael G. Gottschalk and Katharina Domschke explore the genetics of GAD and related traits. The authors do not limit themselves to reporting the recent advances of linkage studies, genomewide- association studies, and candidate gene studies. Instead, they go on to analyze the genetics of anxiety-relevant endophenotypes. These constitute pathological worry, fear of uncertainty, and neuroticism. They cover the mechanisms of gene–environment interaction, investigating childhood trauma, environmental adversity, and stressful life events in relation to selected candidate genes. Gregory A. Fonzo and Amit Etkin review affective neuroimaging in GAD. Their article offers a meticulous description of extant studies and an overarching scientific discussion. The authors discuss findings suggesting that the brain in GAD functions with a striking level of inflexibility in response to changing environmental demands. Finally, Kimberly R. Lezak, Galen Missig, and William A. Carlezon Jr review behavioral methods to study anxiety in rodents. Their article describes historical methods and proceeds to newer approaches that align with recent conceptualizations of disease symptomatology. These may prove to be fruitful in facilitating the development of improved therapeutics.

In a Free paper, Candace Jones and colleagues focus on oxytocin as a potential therapeutic option for individuals with social anxiety. Animal research, both in primates and nonprimates, supports oxytocin’s anxiolytic effects and its role in the facilitation of prosocial behaviors.

This issue of Dialogues in Clinical Neuroscience concludes with a Brief Report by Lucas Borza focusing on cognitive-behavioral therapy, which is regarded as the type of psychotherapy with the highest level of evidence in GAD. The knowledge about the cognitive functioning of GAD sufferers has made considerable strides forward over the last years.

We wish you pleasant reading, free of worry or preoccupations!

Marc-Antoine Crocq, MD; Rajesh M. Parikh, MD, DPM, DipNBE