Increased sensitivity to stress and episode recurrence in spontaneous recurrence of methamphetamine psychosis

Increased sensitivity to stress associated with noradrenergic hyperactivity and dopaminergic changes may precipitate stress-related psychiatric disorders. The present study examines the relation between this increased sensitivity and vulnerability to subsequent spontaneous recurrences of methamphetamine (MAP) psychosis (i.e. flashbacks). Plasma monoamine metabolite levels were assayed in 18 subjects with flashbacks, of whom ten experienced a single flashback and eight experienced further subsequent flashbacks; in 21 subjects with a history of MAP psychosis who did not experience flashbacks; and 33 controls. A square-root transformation was applied to monoaminergic values, rendering the distribution normal. The subjects with flashbacks had undergone frightening stressful experiences during previous MAP use. The dominant factor triggering flashbacks was a mild fear of other people. During flashbacks, plasma noradrenaline levels markedly increased and 3-methoxytyramine levels, an indicator of dopamine release, were elevated. Among the 18 subjects with flashbacks, the ten with subsequent flashbacks had markedly increased noradrenaline levels during flashbacks, whereas the eight with a single flashback displayed small increases in noradrenaline levels as well as 3-methoxytyramine levels. Thus, a mild fear of other people may have elicited memories of MAP psychosis, related to frightening stressful experiences through increased sensitivity to stress associated with noradrenergic hyperactivity, involving increased dopamine release. Robust noradrenergic hyperreactivity to mild stress may predispose subjects to subsequent flashbacks.