Depression affects people of all ages and has an estimated lifetime prevalence of 27%
. The personal and social costs associated with depression are difficult to measure, but currently available evidence indicates that direct financial loss is in the order of A$100,000 over the lifetime of a person and approximately A$15 billion per annum for the Australian society
. People with depression have more unplanned admissions to general hospitals and longer length of stay than people without depression and, once admitted, they have nearly twice the risk of death as those without past history of depression
. In other words, depression is a common, costly, and disabling disorder that reduces life expectancy. Consequently, the successful prevention of depression would lead to important health and socioeconomic benefits.
Currently available strategies to prevent depression: who should we target?
Various approaches have been used with the aim of reducing the prevalence of depression in the community. Some have focused on improving the identification of people with depression, while others have sought to increase the efficacy and effectiveness of existing management strategies. A meta-analysis of 16 randomised trials has shown that the systematic use of screening instruments or case-finding procedures increases the recognition of depression by a modest 27%, and this has no effect on the adoption of treatments or the clinical outcome of patients
. Similarly, the evidence to support the value of educational interventions targeting medical practitioners to enhance the treatment of depression is not robust
. In view of these limitations, increasing emphasis has been placed on the potential value of strategies that instead seek to reduce the prevalence of depression through prevention.
Recent pragmatic approaches to prevent depression have focused on the targeted delivery of programs to people with symptoms of depression that do not reach threshold for the diagnosis of a disorder, an approach known as indicated prevention
. The rationale, in this case, is that people with ‘subsyndromal depression’ are at greater risk of developing a full-blown major depressive episode than people who are free of depressive symptoms, and so may benefit most from interventions designed to reduce risk. Data from the PROSPECT trial, which recruited older adults from primary care practices in New York, Philadelphia, and Pittsburgh, showed that 10.4% of people with subsyndromal depression developed a major depressive episode within one year compared with 0.8% of participants who were free of these symptoms
. The PIKO study is a good illustration of a trial of indicated prevention
, where the investigators recruited 170 adults aged 75 years or over who scored 16 or more on the Center for Epidemiologic Studies Depression Scale (CES-D) but did not fulfil DSM-IV criteria for a depressive or anxiety disorder at the time of assessment or during the preceding 12 months. They implemented a stepped care intervention that consisted of ‘watchful waiting’ for the first 3 months, then potentially progressing to bibliotherapy (if subsequent CES-D ≥16), followed by problem solving therapy and, lastly, treatment with antidepressant medications. The relative risk of developing a depressive or anxiety disorder among people receiving the intervention compared with usual care was 0.49 (95% confidence interval = 0.24–0.98) by the end of 12 months. During this period, 4 participants met criteria for a depressive disorder, 3 for an anxiety disorder, and 2 for mixed anxiety and depression in the intervention group compared with 10 cases of depressive disorder, 5 of anxiety, and 5 mixed states in the usual care group. However, there was no statistically significant difference between the groups when the outcome of the study was limited to depression. In addition, dropout was higher in the intervention than in the usual care group (24/86 vs. 8/84), suggesting problems with the acceptability of the intervention by participants.
The value of indicated prevention approaches in reducing the risk of major depression is not restricted to older adults. A recent review of studies across the lifespan reported data on 33 trials of indicated or selective prevention (for example, post-stroke patients), most of which used cognitive behavioural therapy (CBT) or problem solving as the active intervention
. There was an overall benefit of the interventions (about 25% relative risk reduction of clinically significant depression), although the non-independence of some studies was not taken into account in the analyses (i.e., trials with more than one intervention group were treated as separate studies).
In summary, existing evidence indicates that adults with subsyndromal symptoms of depression have substantially greater risk of developing a major depressive episode over the subsequent year compared with people free of these symptoms. Averting the onset of major depression in people at risk seems feasible, but clearly effective preventive strategies are yet to be established.
Biased thinking patterns are both markers and predictors of depression
The theoretical framework underpinning CBT posits that depressed mood is produced by a set of biased thinking processes that commonly involve preferential attention to negative aspects of experience and an inflated tendency to attribute negative interpretations to ambiguous events. Such a bias in the processing of information initiates the cycle of negative thinking, dysfunctional beliefs, withdrawal, and psychomotor changes that are characteristic of depression
. CBT challenges negative thoughts about the self, others, and the future, by teaching patients to rationally appraise these thoughts and to generate more accurate and functional alternatives. Effective shifts of dysfunctional biased beliefs have been associated with a robust response to treatment and a decreased risk of relapse of symptoms
. Importantly, such a pattern of biased beliefs and negative thinking are strong predictors of the development of future depression. For example, children with no history of depression, but known to be at high risk on the basis of a parent’s history, exhibit the same biased pattern of negative thinking and beliefs
. In a longitudinal study carried out over a 2.5 year period with 347 college students, those who initially displayed negatively biased thinking were 3 to 7 times as likely as controls to develop an episode of major depression
. These findings indicate that if the mechanisms that give rise to negatively biased thoughts and beliefs could be identified and effectively targeted, this could protect against the future development of depression in high-risk individuals.
Emerging empirical and clinical findings are consistent with the hypothesis that selective biases in attention and interpretation, operating to favour the processing of emotionally negative information, represent the psychological basis of disordered mood
[14–16]. For example, adults with mood disorders shown a series of faces on a computer screen selectively direct their attention to sad faces, but show no such a bias when presented with angry or happy faces
. Moreover, people without a history of depression, but known to be at heightened risk (e.g., daughters of depressed mothers), display this same attentional bias to negative information
. Such findings are consistent with the idea that attentional bias precedes and potentially contributes to the precipitation of depressive episodes. In addition, when faced with ambiguity, people with depressed mood favour negative interpretations of stimuli. For example, when presented the ambiguous cue word ‘GROWTH’, people with low mood are faster to then complete fragments of target words semantically related to the negative rather than the non-negative meanings of the ambiguous cue: C_NC_ER and GR_AT_R (cancer and greater)
. Once again, such bias has been found to characterise people with no history of depression known to be at high risk of developing this disorder
. These results confirm that attentional and interpretation biases are not only associated with concurrent disturbances of mood, but also represent risk factors for future mood disorders. They also invite the question: are these biases amenable to change?
Cognitive bias modification (CBM) procedures are effective at extinguishing selective processing bias
MacLeod and colleagues introduced the most widely used approach worldwide to modify attentional bias
. The procedure exposes participants to pairs of words or images on a computer screen for 500 ms, with each pair including one emotionally negative and one neutral item. Immediately after the words/images disappear, a single small visual probe (vertical or horizontal white line) is presented in the same spatial position where one of the original stimuli had been displayed. Participants are required to indicate, as quickly as possible, the orientation of this probe (horizontal or vertical), and their speed to accurately do so is recorded over dozens of trials. People who display an attentional bias to the more negative information are faster to make discrimination judgments for probes that appear in the same area as the negative stimuli, compared to probes in the area of the neutral stimuli
. Cognitive bias modification for attention (CBM-A) delivers hundreds to thousands of trials in which all probes are consistently presented where the neutral rather than the negative stimuli had just appeared, in order to encourage development of an attentional avoidance of negative response to information. A control condition presents probes with equal frequency to each of these two areas. In CBM designed to reduce negative interpretations (CBM-I), participants are exposed to trials that present ambiguous information, followed by a target word fragment that must be completed in a semantically consistent manner. CBM-I delivers hundreds of trials in which target fragments can yield only words consistent with non-negative interpretations of the ambiguity, thus encouraging the tendency to interpret ambiguity in a benign manner. Hence, the ambiguous text “When you chat to people at a party they are soon chuckling, because you are so”, will be followed by the fragment W_T_Y (yielding WITTY). A control condition employs fragments that equally often yield words consistent with negative (e.g., S_L_Y) or non-negative interpretation of the ambiguity.
CBM reduces anxiety and improves mood
Emerging research shows that CBM-A attenuates anxiety reactions to stressful life events
, reduces recurrent negative thought intrusions in chronic worriers
, decreases avoidant behaviours
, and mitigates the intensity of depressive symptoms among dysphoric patients over a 2-week period
. However, negative findings have also been reported, with an internet-based intervention failing to improve symptoms associated with social anxiety over a period of 4 weeks
. A recent, as yet unpublished, meta-analysis concluded that CBM is associated with small beneficial effects on symptoms of anxiety and depression, but that the quality and size of the trials published to date is suboptimal (personal communication). In addition, CBM-A normalises the cortisol awakening response that is characteristic of depressive disorders
. The results of CBM-I interventions indicate that they too reduce negative emotions following stress
[28, 29]. There is preliminary evidence that combining CBM-A and CBM-I may be useful in reducing existing emotional dysfunction. For example, Beard and colleagues randomly assigned 32 adults with social anxiety disorder to 16 sessions of combined CBM over a period of 8 weeks: participants exposed to this combined CBM experienced a significantly greater reduction of anxiety symptoms than controls
. However, it remains to be established if this combination of CBM-A and CBM-I can reduce the risk of a novel episode of major depression when delivered to participants known to be at increased risk for the disorder.
The primary aim of this trial is to determine if CBM designed to attenuate negative attentional and interpretive biases decreases the one-year onset of major depressive episodes among adults with subsyndromal symptoms of depression. The primary hypothesis of this trial is that a lower proportion of participants assigned active compared with control CBM will develop a depressive episode over a period of one year. The study will also test whether, compared with the control group, CBM reduces the severity of depressive symptoms and lowers the frequency of antidepressant and benzodiazepine use, as well as reducing negative attentional and interpretive biases.