Philosophical aspects of neurobiological research on anxiety and anxiety disorders Gerrit Glas Purpose of review Neurobiological research literature on anxiety and anxiety disorders of the previous year (April 2003–June 2004) is investigated from the perspective of four conceptual questions: (1) is pathological anxiety an animal, a human or a layered phenomenon with aspects of both? (2) Is anxiety a unitary or a nonunitary phenomenon? (3) What is the relationship between different aspects, or ‘components’, of anxiety? (4) What is the relationship between scientific and clinical concepts of anxiety? Recent findings These questions are investigated in research papers in the areas of fear conditioning, delineation of neural pathways underlying aspects of anxiety (and anxiety disorder), and developmental plasticity. Most authors are inclined to a view in which both animal and human aspects are recognized and combined in some way (ad 1). Investigators are predominantly inclined to a nonunitary view, against the background model of multiple overlapping brain circuits (ad 2). The language of causal interaction between reified subsystems is avoided, leaving undiscussed the issue of the unity of brain functioning and the relationship of neural function and subjective experience (ad 3). The dominant framework seems to be noneliminative physicalist. There is a widely acknowledged conceptual gap between clinical and scientific understanding; however, newer methodologies enable a broader understanding, by taking into account that environmental factors play an important role in brain development and that study of regional circuitry is needed above study of neural loci (ad 4). Summary There is a paucity of papers on purely conceptual issues. The rich phenomenology of anxiety should serve as an incentive to deeper understanding. Conceptual rigor and refinement may have an important impact upon fundamental empirical research. Keywords philosophy, anxiety, neurobiology, anxiety disorder, concept, endophenotype Curr Opin Psychiatry 17:000–000. # 2004 Lippincott Williams & Wilkins. ????? Correspondence to Professor Gerrit Glas MD PhD, Zwolse Poort, PO Box 110, 8000 AC Zwolle, The Netherlands Tel: +31 38 4565 847/+31 6 1091 4513; e-mail: g.glas@zwolsepoort.nl Current Opinion in Psychiatry 2004, 17:000–000 Abbreviations mCPP m-chorophenylpiperazine OCD obsessive–compulsive disorder PTSD posttraumatic stress disorder # 2004 Lippincott Williams & Wilkins 0951-7367 Introduction The study of anxiety, more than of any emotion, has been a touchstone for sound thinking and conceptual clarity. It is evident why this is the case: the phenomenology of anxiety is elusive; its manifestations display an enormous variety; linguistic meanings are not sharply delineated and show considerable overlap; and there is a wide variety of disciplines, preclinical and clinical, in which the study of anxiety is undertaken – a variety which asks for creativity and interdisciplinary research. In this article I will first give a short introduction on some of the ‘large’ questions surrounding anxiety research. Then I will review those facets of recent neurobiological research on anxiety and anxiety disorders which in some way or other come close to a discussion of these questions. In the conclusion I will evaluate these developments by relating them to the ‘larger’ questions previously mentioned. Classical questions in anxiety research Any theory of anxiety has to face the following conceptual issues/questions. (1) Should anxiety be considered as an animal reaction or as a typically human emotional response or as a layered phenomenon with both animal and specific human elements? If anxiety is basically seen as an animal response, how are the typical human aspects related to this animal ‘core’? This question becomes even more difficult when applied to anxiety disorder. Do pathological forms of anxiety represent remnants of some ‘old’, animal way of brain functioning that has escaped from cortical control? And if so, does this mean that we should deny any psychological or existential relevance to the fears of anxiety disorder patients? This set of questions has been addressed by scientists who base their views on Paul MacLean’s work on the so- called triune brain (for a reappraisal, see Lambert [1 . ] and Ploog [2 . ]). A clear example of this approach can be found in an early paper by Jack Gorman et al. [3], who hypothesized that the symptoms of panic disorder (with agoraphobia) should be subdivided into three subsets representing dysfunctions of each of the three parts of the triune brain. The panic attack itself, especially its physiological and motor manifestations, was to be seen PY170613 1