Certainly the preponderance of evidence suggests there is a genetic contribution to the predisposition to develop panic attacks and agoraphobia. There are increased rates of panic disorder in first-degree relatives with 7.9 to 41 per cent versus 8 per cent or less in control populations. The overall increased risk in first-degree relatives ranges from two- to 20-fold with the median seven- to eightfold. Overall, studies suggest that another affected relative can be found 25 to 50 per cent of the time, two times as commonly in female relatives. The increased familial aggregation is specific for panic disorder. (43) These findings are certainly consistent with a modest genetic transmission with relatively high specificity.
Although twin studies are limited, Torgersen (44) did find increased concordance in monozygotic twins (31 per cent versus zero). Skre et al.(45) found a twofold increase of panic disorder in monozygotic twins, while Andrews et al.(46) failed to find an increased incidence. In the largest sample of interviewed female twins, a several-fold increase was again found (23.9 per cent versus 10.9 per cent). (47)
Overall, evidence from family and twin studies suggests that panic disorder involves modest inheritability of around 30 to 40 per cent. The best model suggests 50 per cent genetic and 50 per cent environmental influences.(48) Recent linkage studies to confirm these hypotheses have been contradictory but do suggest that single-gene transmission is unlikely. This leaves the possibilities of either heterogeneity across families and/or a polygenic inheritance.
Several converging lines do link childhood anxiety with adult anxiety, consistent with a genetic predisposition. (49> This is particularly true for separation anxiety in children.(50) Kagan et al/51 have prescribed that 10 per cent of Caucasian children are born with heightened anxiety which they call behavioural inhibition. Behavioural inhibition is higher in children of anxiety-disordered parents, (52) and there are high rates of anxiety disorders in children of adults with panic disorder. (53) As behaviourally inhibited children have aged, they have been found to show higher rates of anxiety and phobic disorders. Currently, this is probably the best model of an inherited anxiety predisposition. A variant of this type model proposes that there is an ethological factor involving an evolutionarily determined vulnerability to unfamiliar territory.(54) This might explain why the seemingly inherited anxiety is to specific situations. This is also consistent with the high rate of precipitating events prior to the onset of clinical difficulties. In this model an evolutionarily/genetically determined vulnerability, would be clinically 'activated' by critical stressors in genetically vulnerable individuals.
Precipitating events have been reported in 60 to 96 per cent of cases. These have often centred on separation or loss, relationship difficulties, taking on new responsibility, and physiological stressors (e.g. childbirth, surgery, hyperthyroidism). (55) This is certainly consistent with a diathesis/vulnerability model with the illness being precipitated in a predisposed individual in adulthood.
There are also many studies suggesting that traumatic early events may figure in the vulnerability leading to panic disorder. The majority of children in some studies have experienced early parental separation.(42) A traumatic event in childhood has been retrospectively reported in at least two-thirds of children, a threefold increase/56» Early sexual abuse before the age of 5 may even be specific for the subsequent development of panic disorder. (57) The most common adult disorder following sexual abuse before the age of 5 is in fact a 44 per cent incidence of agoraphobia. (58)
There is some evidence in a prospective study involving over 3000 individuals that dependent personality traits were later associated with the development of anxiety disorders/59 There are also retrospective data that adult panic disorder patients describe their parents as being overly protective and less caring. (60) It is difficult to separate the effects on individuals of the anxiety disorders themselves which create dependent behaviour, or overprotectiveness in the parents producing dependent personality traits.
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