UK depression prevalence is increasing. In this study we appraised the relationships between psychological factors of derailment, self-criticism, self-reassurance and depression, to identify individual differences within the UK general population indicating those at higher risk. Participants completed self-report measures regarding these constructs. Relationships were assessed using correlation and path analyses. Derailment and self-criticism predicted depression positively, whereas self-reassurance predicted depression negatively. Self-criticism mediated derailment's relation to depression. Self-reassurance moderated derailment's relation to depression, with low self-reassurance indicating greater depression, though self-reassurance was not found to moderate the effect of derailment-associated self-criticism on depression. In depression treatment therefore derailment should be considered as a target factor to be reduced, since derailment indicates a risk of depression for individuals with high self-criticism or low self-reassurance.