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It remains uncertain whether generalized anxiety disorder (GAD) and major depressive disorder (MDD) represent two separate diagnostic entities. The goal of this study was to examine whether comorbid MDD distinguishes individuals with GAD on a psychophysiological level during an experimentally-induced worrying procedure. Participants included 39 individuals with GAD, 14 of whom met the criteria for MDD. During the experimental procedure, participants were asked to worry or relax after an initial baseline phase while measuring their heart rate, high frequency heart rate variability (HF-HRV), skin conductance level, and subjective level of anxiety. The two groups did not differ in their subjective anxiety, heart rate response, and skin conductance levels. However, participants with comorbid MDD had greater HF-HRV values throughout the experiment than did those without MDD. At baseline, HF-HRV was significantly correlated with a self-report measure of depression. These results suggest that individuals with comorbid GAD and MDD can be distinguished based on HF-HRV from individuals with GAD but without MDD. These results support the distinction between GAD and MDD.

Generalized anxiety disorder (GAD) and major depressive disorder (MDD) are highly comorbid, as suggested by a number of epidemiological studies (Breslau et al., 1995, Kessler et al., 1996 and Kessler et al., 2005). Approximately two thirds of patients with a lifetime diagnosis of GAD retrospectively report MDD, but only approximately one fifth of patients with a lifetime diagnosis of MDD retrospectively report GAD (Kessler et al., 1999), suggesting that generalized anxiety tends to precede depression and eventually develops into depression. However, a recent prospective longitudinal cohort study from New Zealand challenged this notion, because the reverse temporal relationship occurs almost as often (Moffitt et al., 2007). The authors further concluded that the relationship between GAD and MDD is strong, suggesting that the disorders could be classified in one category of distress disorders. GAD was first defined in DSM-III and was characterized by fluctuating levels of uncontrollable worry associated with fatigue, insomnia, muscle tension, poor concentration, and irritability, which are also typical symptoms of depression. In DSM-III, individuals could not receive a diagnosis of an anxiety disorder if the anxiety symptoms occurred during episodes of depression. This hierarchy rule was eliminated in the DSM-III-R for all anxiety disorders except GAD. According to DSM-IV, GAD can only be assigned in individuals with MDD if the GAD symptoms also occur outside a depressive episode. Thus, DSM-IV precludes the diagnosis of GAD for individuals who experience symptoms of GAD only during depressive episodes. These nosological rules reflect the uncertainty as to whether GAD and MDD represent two separate diagnostic entities and whether the comorbidity between the two disorders identifies a unique group of individuals (Mineka et al., 1998 and Zahn-Waxler et al., 2000). The empirical evidence to inform the upcoming DSM-V criteria on the overlap between GAD and MDD are primarily based on interview and questionnaire data from epidemiological surveys (see Hettema, 2008, for a review).