Depression is a very common mental illness that is highly recurrent in individuals. In addition, it is a disorder with substantial personal and public health consequences. Thus, there is great interest in the development of strategies that might reduce the recurrence of depression. Important to the development of preventive interventions is a basic understanding of the factors that predict and contribute to recurrence. However, research in this area is rife with methodological variability. First, there are different definitions for “depression” in use in the literature, from diagnosed DSM or ICD Major Depressive Disorder, to high scores on depression inventories such as the BDI or Hamilton Rating Scale. However, these differences do not seem to have an impact on study findings because study results do not appear to vary according to the method used to identify depressed people. Second, there have been differing definitions of recurrence, although this is less of a problem since the publication of proposed consensus terms by Frank and colleagues (1991)
, and now most recent research employs these standard definitions. In addition, there has also been confusion about whether recurrence refers to a recurrent episode or whether it refers to a recurrent subtype of depression. Third, studies have varied in whether they include only individuals with unipolar depression, or whether they also include those with bipolar disorder who have experienced recurrent depressive episodes; this difference may account for some of the divergent findings reviewed in this paper, especially in studies using clinical samples where rates of bipolar disorder are often higher. Fourth, studies have varied in whether they include individuals with only unipolar depression and no comorbid psychopathology, which represent unusually “clean” cases of depression that are not representative of the general population of individuals with depression (Kessler et al., 1996
). Alternatively, some studies only examine hospital readmission rates, which may represent only unusually severe cases of depression and may be missing the presence of less severe recurrent episodes which do not lead to re-hospitalization. Both of these factors may play a role in some of the divergent findings across studies. Fifth, investigations have varied in the extent to which they address the potential influence of maintenance therapy, psychotherapy or antidepressants, on recurrence. Finally, many studies note the high attrition rates that occur in research on depression, which might be influencing all of the reviewed research.
Despite these methodological differences, some variables have consistently been found to relate to recurrence of depression, while for other variables the evidence is more mixed. There is considerable evidence that demographic variables are related to first-onset of depression. However, this is not the case for recurrence. Instead, from the studies reviewed, it appears that sex, SES, and marital status are not risk factors for depression recurrence.
Several clinical and family history variables do appear to be related to increased risk for recurrence, however. For example, there is evidence that both age at onset and number of prior episodes are related to recurrence, although their importance relative to one another has been difficult to determine due to their moderate intercorrelation. In addition, the severity of the first or index episode (as measured by number of symptoms or presence of suicidal thinking, but not duration) has been linked to increased risk for recurrence in adults but not in children. The presence of comorbid psychopathology, especially other affective disorders, also is related to recurrence risk in adults but not children. However, more research is necessary to determine which specific non-affective disorders confer increased risk for depression recurrence. Family history of psychopathology, particularly depression or other affective disorders, is also associated with increased risk for recurrence in those of all ages, although again more research is necessary regarding the role of non-affective disorders in increasing risk for recurrence of depression.
In addition, several psychological and psychosocial variables have been proposed as risk factors for recurrent depression, including negative cognitions, high neuroticism, poor social support, and stressful life events. There appears to be ample evidence from the studies reviewed that each of these variables is related not only to risk for first onset of depression, but also for recurrent depression. However, it is important to note that there is recent evidence supporting common genetic vulnerability to both recurrent depression and neuroticism or social support, and thus this might not be a directly causal relationship.
Thus, many variables appear to be related to risk for recurrence of depression. Many researchers, it seems, interpret these findings to mean that these risk factors are causally related to depression recurrence, and that if they could be somehow ameliorated, then recurrent episodes could potentially be avoided. A problem with this assumption is that it does not consider the possibility that these “risk factors” could actually be manifestations of the underlying liability to depression in general. Research on liability to depression has shown that it is due to genetic influences (h2
=40%) as well as to nonshared environmental factors. Research has also shown that depression liability may be better conceptualized as an underlying liability to internalizing disorders in general (e.g., Krueger, 1999
). It is possible that those individuals who have inherited a greater risk for depression are at risk not only for an early age at first onset and for comorbid psychopathology, particularly other internalizing disorders, but also for a family history of depression, increased neuroticism, more stressful life events, and for greater numbers of episodes in their lifetime. On the other hand, individuals with a small inherited risk for depression would have later ages at first onset, fewer numbers of lifetime episodes, less neuroticism, fewer stressful life events, and less comorbid psychopathology in themselves and in their family members. Analyses on genetically informative samples will be necessary to determine if these clinical variables are indeed good candidate targets for preventative interventions, or if they might be better conceptualized as markers of the severity of the underlying liability to depression in general.
Finally, several scar theories were also reviewed. They are all similar in that they propose that something, presumably encoded at the biological level, changes during an episode of depression, which then makes future episodes more likely. There was virtually no evidence to support the existence of a psychosocial scar, but there was slight evidence in favor of the occurrence of a scar on cognitions, although only in children and adolescents, but not adults. Research on a personality scar suggested a very subtle impact of depression on later neuroticism, although it was not clear that the slight change in neuroticism scores could truly be considered a scar and that this finding did not more simply reflect neuroticism’s status as a risk factor for depression in general. Regarding stressful life events, there was considerable research to support SLEs as a risk factor for recurrent depression. In addition, there was some evidence to support the idea that sensitization to SLEs occurs, although it was not definitive. There was also some evidence of stress generation occurring. A direct comparison of these two hypotheses regarding SLEs would make an interesting future study.
One problem with the scar theories in general, however, is that they do not address the concern that the “cut-off” for depression risk may have already been met even before the first episode. For example, individuals with high levels of neuroticism are already at increased risk for a first-onset of depression. Just because one episode of depression increases their neuroticism scores, on average, this does not mean that their subsequent risk for depression is automatically increased; instead, it could be that they are at the same risk for recurrence because they already had sufficient levels of neuroticism in order to lead to depression in the first place. This is relevant for the other scar theories as well. Furthermore, it is important to note that the scar theories suppose that due to the greater rates of depression in those who have a history of depression compared to those who have no such history, it must be the case that depression itself somehow increases the vulnerability to becoming depressed again. However, a more parsimonious explanation may instead be that individuals at high risk for multiple episodes already possessed the necessary characteristics to make them prone to recurrent depression, and that these necessary characteristics existed even before their first episode. For example, individuals at high risk for a recurrent subtype of depression may already have higher levels of neuroticism or SLEs, even before their first episode; any changes in these domains that occur after a depressive episode may simply be reflecting a sequela of depression rather than a scar per se. Given the largely null findings in the area of scar theories, this is a highly plausible alternative. More specifically, the mechanism conferring premorbid risk for recurrent depression could involve an underlying genetic liability.
In conclusion, the prevention of recurrence is a daunting but important task. To date, several variables have been identified as risk factors for recurrence in adults deriving from the clinical picture (age at onset/number of episodes, severity, comorbidity), family history, cognitions, personality (neuroticism), poor social support, and stressful life events. Research to date, however, has not supported demographic variables (gender, SES, marital status) or duration of first/index episode as risk factors for recurrence. Finally, it should be noted that there is little evidence to support the idea that any of these risk factors operate through scarring.
It is also important to note that the literature has yielded somewhat different results for children and adolescents. While age at onset, family history of psychopathology, personality, and SLEs appear to act as risk factors for recurrence in both children and adults, severity of the first episode and comorbidity of other forms of psychopathology do not appear to be related to increased risk for recurrence in children and adolescents. Furthermore, there is some evidence to suggest that there is scarring on cognitions in children and adolescents with depression, whereas in adults cognitions are more likely risk factors rather than scars. Thus, these different findings regarding risk for recurrence of depression in children versus adults certainly deserves further exploration from researchers.
Another important issue, however, is the question of why this pattern of risk factors has emerged. The putative risk factors for recurrence may simply be reflecting an underlying vulnerability to a recurrent subtype of depression. That is, those at underlying risk for recurrent depression may also, even before their first episode onset, be at risk for the risk factors reviewed herein. More specifically, it is hypothesized that individuals inherit a level of risk for recurrent depression. If they are high in this underlying genetic vulnerability, they are also likely to have an earlier age at onset, greater numbers of depressive episodes, more severe episodes, greater comorbidity, a stronger family history of depression, higher neuroticism scores, more SLEs, a depressogenic cognitive style, and less social support. While this is not to say that there is genetic predeterminism and that this genetic risk for recurrence and its associated risk factors cannot be modified through environmental mechanisms in order to alter the course of recurrences, it is likely that genetic factors may be strongly at play in the recurrent subtype of depression. It is this hypothesis regarding the underlying genetic vulnerability for recurrence and the putative risk factors reviewed herein that is most in need of further testing. There is a dearth of research on recurrence of depression using genetically informative samples, but it is with such samples that the most information can be obtained. Further research on the genetic underpinnings of recurrent depression, as well as how this relates to the putative risk factors reviewed earlier, is the most promising line of research for us to learn more about the etiology of recurrent depression.