The weight- versus cognitive-symptom outcome conundrum
The symptom profile in AN comprises both physiological and cognitive features, although the central distinction between weight-based versus cognitive symptomatology has historically been underreported in AN treatment trials and long-term course-of-illness studies, with weight status alone being the most widely favoured index of recovery. In studies adopting weight as an exclusive or primary metric of outcome, potentially important differences may go undetected, as may their implications for our understanding of both disorder- and treatment-specific mechanisms. Without question, an essential first step in the treatment of AN is the reversal of the acute effects of starvation, which may be most readily indexed by weight status. However, inferring from positive increments in our patients’ weight that we have effectively engaged the target mechanism of treatment and achieved change in corresponding broader symptom domains, belies the complex and interwoven network of maintaining factors that underpin AN. Moreover, the implicit assumption that weight-based recovery is a proxy for broader cognitive recovery is not supported by evidence, as the constellation of cognitive and affective challenges facing those with AN, including the fear of weight gain, body dissatisfaction, emotional dysregulation, and an ongoing fear of calorie-dense foods, frequently persist after significant weight gain has been achieved . Thus, relying on weight outcomes alone in drawing conclusions from randomized controlled trials (RCT) or course-of-illness studies could inadvertently inflate the interpretation of positive results. For instance, long-term naturalistic follow-up data over approximately 20 years illustrate remission rates ranging from 62% when considering weight status as the sole criterion for a ‘good outcome , to just 40% when including both weight and cognitive symptoms .
More recently, an increasing number of clinical trials have begun to report treatment outcomes as an aggregated function of both weight status and cognitive AN psychopathology, yielding categorical outcome groupings. For instance, “full” remission is typically achieved by attaining both (i) 95% of expected body weight plus (ii) a score within 1 standard deviation of community norms on gold standard measures of cognitive and behavioural ED psychopathology; “partial” remission can be defined by meeting either of those criteria, but not both; and no remission would reflect an absence of the two criteria. While this approach represents an improvement over exclusively weight-based outcomes, there are potential discrepancies between these component dimensions. Conflating weight-based and cognitive symptom status into unitary outcome measures represents a missed opportunity to elucidate their distinct pathways, which in turn can stymie ongoing attempts to locate precise mechanisms of treatment. Moreover, varying definitions of what constitutes a ‘good outcome’, even when applied to a single clinical trial, yields remission rates ranging from 2% - 96% , which has precluded meaningful between-trial comparisons.