Background. We examine a ‘lock and key’ (‘L–K’) hypothesis to depression which posits that early adverse experiences establish locks that are activated by keys mirroring the earlier adverse experience to induce depression.

Methods. Two-hundred and seventy clinically depressed patients were examined with open-ended and pre-coded interview questions to ascertain both early adverse experiences and precipitating life events. Qualitative and quantitative data analyses examined for any associations between developmental ‘locks’ and precipitating ‘keys’.

Results. Qualitative assessment suggested ‘L–K’ links in almost one-third of the sample, and examples are provided. While quantitative analyses indicated significant associations between several identical ‘lock’ and ‘key’ constructs, evidence of specificity was rare. When individual ‘locks’ and ‘keys’ were consolidated into three higher-order constructs, variable models were suggested, including a non-specific link, a specific link and absence of any link. ‘L–K’ links appeared more likely in those with ‘non-melancholic’ (versus ‘melancholic’) depression, with the seemingly greater relevance to ‘reactive’ (versus ‘neurotic’) depression in the quantitative analyses inviting speculation that that ‘disorder’ may be more a reaction to a salient rather than a severe stressor.

Conclusions. This exploratory study suggests that early adverse experiences may variably establish specific and non-specific patterns of vulnerability to having depression triggered by exposure to salient mirroring life event stressors.