Depression is one of the most common forms of mental illness. Despite decades of research, the mechanisms underlying this disorder remain unknown. To help elucidate the pathophysiology of depression, researchers are developing animal models of psychiatric disorders, including depression, and assessing for mood-related phenotypes. There are a limited number of behavioral assays available to assess depression-like behaviors in rodents but by far the most common is the forced swim test (FST). Although the FST is considered the gold standard for studying depression-like behaviors, there are strong reasons to question the interpretation that immobility represents ‘despair’ and escape-directed behaviors such as climbing represent the absence of a depression-like phenotype. It has recently been proposed that immobility in the FST is an adaptive learned response and reflects a switch from active to passive coping strategies (De Kloet and Molendijk, 2016). Although we agree with De Kloet and Molendijk (2016) that immobility is adaptive, we disagree on the interpretation of active versus passive coping strategies. Instead, we believe that escape-directed behaviors are driven by anxiety. We argue this perspective on the basis of comorbidity, gene targeting, and pharmacological studies.

Depression rarely strikes alone. In clinical populations, depression is highly comorbid with anxiety disorders, with estimates as high as 80% (Lamers et al, 2011). Despite the high degree of comorbidity between depression and anxiety in clinical populations, there are only a few studies examining individual differences in comorbidity between depression- and anxiety-like behaviors in rodents. One study found no relationship between performance on the FST and the elevated plus maze (EPM) (Ho et al, 2002), whereas another study reported an inverse relationship between performance on the FST and the EPM. In other words, animals that were high on measures of depression-like behaviors were low on measures of anxiety-like behaviors (Estanislau et al, 2011). More recently, we conducted a study looking at individual differences in depression- and anxiety-like behaviors where our results are more consistent with Estanislau et al (2011). The inverse relationship between depression- and anxiety-like behaviors is surprising as it is diametrically opposed to human clinical populations. There are two possible explanations for the discrepancies between human and animal research: either the underlying mechanisms driving depression and anxiety are distinct in humans and rodents or we are misinterpreting animal behavior. We believe the underlying mechanisms are conserved and therefore it is more likely due to interpretation error.

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