Anxiety/fear is a normal reaction to threatening situations and it represents a physiologically protective function. Anxiety/fear is often manifested as avoidance and is also characterized by overt sympathetic reactions. Pathological anxiety is a level of anxiety that is disproportionate to the threat and can be manifested even in the absence of threat. In clinical practice, categorical systems set the boundary at which a particular level of anxiety becomes an anxiety disorder.

Although a genetic contribution to anxiety disorders has long been suspected, it is only recently that genetic polymorphisms in various neurotransmitter and neuromodulatory systems have been linked to anxiety disorders. Still, the contribution of these factors is relatively small to the overall disease phenotype and the complex interaction between genetic factors and the environment will ultimately explain the development of susceptibility to anxiety.

Genetic and biochemical studies, combined with the analysis of mouse strains with induced genetic mutations implicate multiple neurobiological processes in anxiety disorders. Although the association of neurotransmitters and their receptors with anxiety-like behavior is not surprising, cytokines and cell adhesion molecules were also identified as modulators of anxiety. Furthermore, intracellular signaling pathways and their target genes were linked to anxiety allowing the assembly of specific “anxiety” pathways. It is apparent that anxiety-related pathways and processes involve communication between various neurons that, via signaling pathways, eventually converge onto regulation of transcription and/or translation. The proper function of these pathways is especially crucial during early postnatal development and one can hypothesize that abnormalities in these pathways at any level lead to, via altered gene expression, to changes in neuronal morphology and/or function. Importantly, all commonly used anxiolytic drugs can be integrated into this model implying that anxiolytic drugs target and modulate the molecular and cellular pathways which establish and/or control the level of anxiety.