Panic disorder

Aetiology

 What happens in the brain
 Neurochemical involvement

What happens in the brain?

The areas of the brain implicated are the forebrain  and limbic system .

The forebrain is the area most affected in people with anxiety disorders, including panic disorder (PD). The limbic system is involved in storing memories and creating emotions and is thought to play a central role in processing all anxiety-related information. Both the locus coeruleus  and the dorsal  raphe project to the septohippocampal circuit, which in turn projects to other areas of the limbic system that mediate anxiety. The hippocampus  and amygdala  are of particular importance in that they are interconnected and also project to both subcortical and cortical nuclei.

Neurochemical involvement

Most researchers have emphasised the role of noradrenergic mechanisms in PD. However, serotonin-related findings in PD, such as the documented antipanic potential of SSRIs, are lending support to there also being a serotonergic dysfunction occurring (Humble et al., 1989; Humble and Wistedt, 1992; DeVane, 1997).

The three neurochemical pathways that have been most studied are those related to benzodiazepines (BZD) and g-amino-butyric acid (GABA) function, noradrenergic function, and serotonergic function. There seems to be evidence of serotonin involvement in the GABA-BZD and the noradrenergic systems (Kahn et al., 1990). Serotonin may influence the GABA system in the raphe nuclei and median raphe sites in the brainstem , while the serotonin and noradrenergic systems have complex interconnections in the locus coeruleus. These facts, with the evidence of the efficacy of the SSRIs in PD treatment, contribute to the hypothesis that serotonin dysfunction may be a primary pathological element in PD (Bell and Nutt, 1998).

Further evidence for the involvement of serotonin in PD derives from the abnormal cerebrospinal fluid levels of 5-hydroxyindoleacetic acid (5-HIAA) (Eriksson et al., 1991), and anxiety induced by the serotonin receptor  agonist m-chlorophenylpiperazine (m-CPP) (Klein et al., 1991). The superior efficacy of serotonin antidepressants compared with noradrenergic drugs in treatment studies has also suggested a role for other receptors in panic. In general, serotonergic agents are more effective than purely noradrenergic agents (Mavissakalian et al., 1998; Bell and Nutt, 1998; den Boer and Westenberg, 1988). At clinically effective doses of imipramine and clomipramine, the most serotonergic tricyclic antidepressents, levels of serotonin reuptake inhibition correlate with clinical efficacy in PD (Humble and Wistedt, 1992).

The role of GABA has been supported by the initial effects of BZDs on panic, and the subsequent rebound effect and panic exacerbation on withdrawal of the BZD.