Anxiety disorders neurotransmitters

FIGURE 37-1. Neurocircuitry and key neurotransmitters involved in mediating anxiety disorders. 

Another major focus of interest for the investigation of anxiety disorders is the monoamine neurotransmitter serotonin (5-HT see also chapter by Mohler et al., this volume) because of reduced levels of 5-HT receptors found in patients... 

There has been a plethora of linkage and association studies attempting to identify genes for anxiety disorders. The neurotransmitter systems that have been implicated in anxiety disorders include adenosine, adrenaline, noradrenaline, dopamine, serotonin, cholecystokinin, and y-aminobutyric acid (GABA). In... 

Polymorphisms in genes controlling the function of neurotransmitter systems (e.g., transporters, receptors, etc.) are thought to be related to the pathogenesis of many psychiatric disorders including anxiety disorders as well as temper-... 

GABA is formed by the decarboxylation of glutamate, and is the major inhibitory neurotransmitter, hi recent years the GABAa receptor has been identified as the mediator of the anxiolytic and sedative effects of drugs such as alcohol and the benzodiazepines. Abnormahties of this receptor have been identified in humans with anxiety disorders (Nutt and Mahzia 2001). 

This group includes compounds with actions on a range of neurotransmitter systems. Their antidepressant efficacy is mediated by reuptake inhibition of serotonin and noradrenaline, although side-effects such as sedation may also be useful. Their use in anxiety disorders is supported by a long history of clinical experience and a reasonable evidence base from controlled trials. Studies support the use of clomipramine (a potent serotonin reuptake inhibitor) in panic disorder and OCD (Lecrubier et al. 1997 Clomipramine Collaborative Study Group 1991), of imipramine in panic disorder and GAD (Cross-National Collaborative Panic Study 1992 Rickels et al. 1993), and of amitriptyline in PTSD (Davidson et al. 1993a). No controlled studies support the use of TCAs in social anxiety disorder. 

Pharmacology has provided powerful tools to characterize the neurochemical pathways of stress and anxiety in the brain, and how these pathways are involved in the pathophysiology and treatment of anxiety disorders. In the past, this work has largely focused on classical neurotransmitter systems, including the synthesis, release, and metabolism of monoamines and receptor subtypes that control presynaptic release of neurotransmitters and their postsynaptic effects. Increasing the specihcity of drugs but also the combination of mechanisms has been pursued to improve anxiolytic drugs. 

Buspirone has been shown to be very effective in treating generalized anxiety disorder (GAD). It is especially useful when combined with a benzodiazepine, probably because using these two drugs together causes the activation of two neurotransmitter systems (GABA and serotonin). 

Currently, the most often prescribed class of drugs for the treatment of anxiety disorders is the SSRIs. Although several neurotransmitters have been linked to mood and affect, serotonin has received most of the interest in the last decade. 

Benzodiazepine—A drug used to treat anxiety disorders by increasing the ability of the neurotransmitter GABA to inhibit cells in the brain. 

The complexity of the pathobiology of anxiety disorders and the diversified treatment choices are further emphasized by the examination of the role of neuropeptides [NPs] in anxiety and their possible application as treatment modalities [see Tollefson, Chapter 26, in this volume]. More than 50 NPs have been identified many of them interact with conventional neurotransmitter systems as well as with each other. Some of them or their mimetics... 

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