Modulation of naturalistic maladaptive memories using behavioural and pharmacological reconsolidation-interfering strategies: a systematic review and meta-analysis of clinical and 'sub-clinical' studies

BACKGROUND: Consolidated memories can undergo enduring modification through retrieval-dependent treatments that modulate reconsolidation. This represents a potentially transformative strategy for weakening or overwriting the maladaptive memories that underlie substance use and anxiety/trauma-related disorders. However, modulation of naturalistic maladaptive memories may be limited by 'boundary conditions' imposed on the reconsolidation process by the nature of these memories. METHODS: We conducted a systematic review and meta-analyses of behavioural and pharmacological studies examining retrieval-dependent modulation of reward- and threat-related memories in (sub) clinical substance use and anxiety/trauma, respectively. RESULTS: Of 4938 publications assessed for eligibility, 8 studies of substance use and 10 of anxiety (phobia)- and trauma-related symptoms were included in the meta-analyses. Overall, the findings were in the predicted direction, with most studies favouring the 'retrieval + treatment' condition. However, the magnitude of effects was dependent upon the nature of treatment, with pharmacological interventions showing a medium-sized effect (g = 0.59, p = 0.03) and behavioural treatments, a relatively small effect (g = 0.32, p = 0.10) in studies of phobia/trauma. Among studies of substance use, post-retrieval behavioural interventions yielded a larger effect (g = 0.60, p < 0.001) relative to pharmacological treatments (g = - 0.03, p = 0.91), with treatment type being a statistically significant moderator (χ2(1) = 4.20, p = 0.04). CONCLUSION: Modification of naturalistic maladaptive memories during reconsolidation appears to be a viable treatment strategy for substance use and phobias/trauma disorders. However, high levels of heterogeneity and methodological variation limit the strength of conclusions that can be drawn from the reviewed studies at this stage

Prospects for reconsolidation-focused treatments of substance use and anxiety-related disorders

Memories are often conceptualized as permanent entities; however, retrieval of memories via stimulus prompts can return them to an active state, which initiates a period of lability before the memories are reconsolidated into long-term storage. Importantly, during this period, memories can be disrupted/altered. A growing body of work has focused on translating animal and experimental science into reconsolidation-based interventions for clinical disorders maintained by maladaptive memories. Interventions targeting reward-based and fear-based memories undergirding substance use and anxiety-related disorders, respectively, have shown significant potential. There are several promising pharmacological agents and behavioral approaches that have been used to therapeutically target memory reconsolidation. Here, we discuss the current state of science with special emphasis on the clinical utility of these approaches