Christopher G. Beevers

Neural mechanisms of the cognitive model of depression

In the 40 years since Aaron Beck first proposed his cognitive model of depression, the elements of this model — biased attention, biased processing, biased thoughts and rumination, biased memory, and dysfunctional attitudes and schemas — have been consistently linked with the onset and maintenance of depression. Although numerous studies have examined the neural mechanisms that underlie the cognitive aspects of depression, their findings have not been integrated with Becks cognitive model. In this Review, we identify the functional and structural neurobiological architecture of Becks cognitive model of depression. Although the mechanisms underlying each element of the model differ, in general the negative cognitive biases in depression are facilitated by increased influence from subcortical emotion processing regions combined with attenuated top-down cognitive control.

Effectiveness of a Novel Integrative Online Treatment for Depression (Deprexis): Randomized Controlled Trial

BACKGROUND Depression is associated with immense suffering and costs, and many patients receive inadequate care, often because of the limited availability of treatment. Web-based treatments may play an increasingly important role in closing this gap between demand and supply. We developed the integrative, Web-based program Deprexis, which covers therapeutic approaches such as behavioral activation, cognitive restructuring, mindfulness/acceptance exercises, and social skills training. OBJECTIVE To evaluate the effectiveness of the Web-based intervention in a randomized controlled trial. METHODS There were 396 adults recruited via Internet depression forums in Germany, and they were randomly assigned in an 80:20 weighted randomization sequence to either 9 weeks of immediate-program-access as an add-on to treatment-as-usual (N = 320), or to a 9-week delayed-access plus treatment-as-usual condition (N = 76). At pre- and post-treatment and 6-month follow-up, we measured depression (Beck Depression Inventory) as the primary outcome measure and social functioning (Work and Social Adjustment Scale) as the secondary outcome measure. Complete analyses and intention-to-treat analyses were performed. RESULTS Of 396 participants, 216 (55%) completed the post-measurement 9 weeks later. Available case analyses revealed a significant reduction in depression severity (BDI), Cohens d = .64 (CI 95% = 0.33 - 0.94), and significant improvement in social functioning (WSA), Cohens d = .64, 95% (CI 95% = 0.33 - 0.95). These improvements were maintained at 6-month follow-up. Intention-to-treat analyses confirmed significant effects on depression and social functioning improvements (BDI: Cohens d = .30, CI 95% = 0.05 - 0.55; WSA: Cohens d = .36, CI 95% = 0.10 - 0.61). Moreover, a much higher percentage of patients in the intervention group experienced a significant reduction of depression symptoms (BDI: odds ratio [OR] = 6.8, CI 95% = 2.90 - 18.19) and recovered more often (OR = 17.3, 95% CI 2.3 - 130). More than 80% of the users felt subjectively that the program had been helpful. CONCLUSIONS This integrative, Web-based intervention was effective in reducing symptoms of depression and in improving social functioning. Findings suggest that the program could serve as an adjunctive or stand-alone treatment tool for patients suffering from symptoms of depression.

Biased attention and dysphoria: Manipulating selective attention reduces subsequent depressive symptoms

Selective attention for dysphoric stimuli has been observed in individuals with depression and those at risk for depression. To date, no studies have investigated the effects of directly manipulating selective attention for dysphoric stimuli on depressive symptoms. Mild to moderately depressed college students (N=34) were randomly assigned to complete 4 sessions of either attention training (AT) or no training (NT) during a two-week period. Participants completed self-reported assessments of depressive symptoms at baseline, post-training, and follow-up. Participants in the AT condition had a significantly greater decrease in depressive symptoms from baseline to follow-up than participants in the NT condition. This group difference was mediated by change in attention bias. Our findings suggest that biased attention may have a causal role in the maintenance of depressive symptoms.

Serotonin transporter genetic variation and biased attention for emotional word stimuli among psychiatric inpatients.

The short allele in a variable repeat sequence of the promoter region of the serotonin transporter gene (5-HTTLPR) has been associated with stronger activation in brain regions critical for processing emotional stimuli. The authors examined whether variants of the 5-HTTLPR promoter polymorphism were also associated with individual differences in attentional biases for emotional stimuli. Words related to anxious and dysphoric emotional states were presented to psychiatric inpatients in a standard dot-probe reaction time task. Compared with participants with two long alleles, carriers of the short 5-HTTLPR allele exhibited a stronger attentional bias for anxious word stimuli. No genetic group difference was observed for dysphoric word stimuli. Findings from this preliminary study highlight the potential for integrating genetic and cognitive models of psychopathology.

Association of the Serotonin Transporter Gene Promoter Region (5-HTTLPR) Polymorphism with Biased Attention for Emotional Stimuli

A deletion polymorphism in the serotonin transporter-linked polymorphic region (5-HTTLPR) has been associated with vulnerability to affective disorders, yet the mechanism by which this gene confers vulnerability remains unclear. Two studies examined associations between the 5-HTTLPR polymorphism and attentional bias for emotional stimuli among nondepressed adults. Biased attention, attention engagement, and difficulty with attention disengagement were assessed with a spatial cuing task using emotional stimuli. Results from Study 1 (N = 38) indicated that short 5-HTTLPR allele carriers experienced greater difficulty disengaging their attention from sad and happy stimuli compared with long allele homozygotes. Study 2 participants (N = 144) were genotyped for the 5-HTTLPR polymorphism, including single nucleotide polymorphism rs25531 in the long allele of the 5-HTTLPR. Consistent with Study 1, individuals homozygous for the low-expressing 5-HTTLPR alleles (i.e., S and LG) experienced greater difficulty disengaging attention from sad, happy, and fear stimuli than high-expressing 5-HTTLPR homozygotes. Because this association exists in healthy adults, it may represent a susceptibility factor for affective disorders that becomes problematic during stressful life experiences.

Attentional Bias and Mood Persistence as Prospective Predictors of Dysphoria

This study examined whether either a negative attentional bias or mood persistence would interact with intervening life stress to predict future increases in dysphoria among college students (N = 77). Dysphoria was assessed in the lab, and then attentional bias was measured with a dot-probe task before and after a negative mood induction. Mood recovery following the induction was also assessed. Seven weeks later, dysphoria and intervening life stress were measured. Prior shifts in attention toward negative information following a negative mood induction interacted with intervening life stress to predict increases in dysphoria 7 weeks later. Slower mood recovery following the mood induction also combined with intervening life stress to predict increased dysphoria at follow-up. These vulnerabilities each explained unique variance in follow-up dysphoria. Results suggest that both attentional bias and mood persistence may have significant roles in depression susceptibility.

Discontinuities and Cognitive Changes in an Exposure-Based Cognitive Therapy for Depression

Significant shifts or discontinuities in symptom course can mark points of transition and reveal important change processes. The authors investigated 2 patterns of change in depression-the rapid early response and a transient period of apparent worsening that the authors call a depression spike. Participants were 29 patients diagnosed with major depressive disorder who enrolled in an open trial of an exposure-based cognitive therapy. Hierarchical linear modeling revealed an overall cubic shape of symptom change and that both the rapid response and spike patterns predicted lower posttreatment depression. Patients wrote weekly narratives about their depression. Early narratives of rapid responders were coded as having more hope than those of nonrapid responders. The narratives of patients with a depression spike had more cognitive-emotional processing during this period of arousal than those without a spike. Findings are discussed in the context of cognitive-emotional processing theories in depression and anxiety disorders.

Frontal-Limbic White Matter Pathway Associations with the Serotonin Transporter Gene Promoter Region (5-HTTLPR) Polymorphism

Variation in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) has been associated with heightened neural activity in limbic and prefrontal regions in response to emotional stimuli. The current study examined whether the 5-HTTLPR polymorphism is also associated with alterations in microstructure of frontal-limbic white matter (WM) tracts. Thirty-seven (mean age, 20.51 years; range, 13–28) female participants were genotyped for the 5-HTTLPR polymorphism. Diffusion MRI was collected and a probabilistically defined tract of the uncinate fasciculus (UF), a WM pathway connecting the amygdala to medial and orbital prefrontal cortex, was used to generate fractional anisotropy (FA) values for participants. Regression analyses indicated a significant inverse association between number of low-expressing 5-HTTLPR alleles and FA values for the left frontal UF region, β = − 0.42, p = 0.005. Furthermore, there was a positive association between age and FA values for bilateral frontal regions of the UF; these effects explained 39 and 20% of the variance in FA values for left and right frontal regions, respectively. 5-HTTLPR genotype and age appear to independently influence the WM microstructure of the UF. The observed reduction in FA values among low-expressing 5-HTTLPR allele carriers may contribute to biased regulation of emotional stimuli.

Association of Predeployment Gaze Bias for Emotion Stimuli With Later Symptoms of PTSD and Depression in Soldiers Deployed in Iraq

OBJECTIVE Biased processing of emotion stimuli is thought to confer vulnerability to psychopathology, but few longitudinal studies of this link have been conducted. The authors examined the relationship between predeployment gaze bias for emotion stimuli and later symptoms of posttraumatic stress disorder (PTSD) and depression in soldiers deployed to Iraq. METHOD An eye-tracking paradigm was used to assess line of gaze in 139 soldiers while they viewed a two-by-two matrix of fearful, sad, happy, and neutral facial expressions before they were deployed to Iraq. Once they were deployed, the soldiers periodically reported on their levels of war zone stress exposure and symptoms of PTSD and depression. RESULTS War zone stress exposure predicted higher scores on PTSD and depression symptom measures; however, eye gaze bias moderated this relationship. In soldiers with war zone stress exposure, shorter mean fixation time when viewing fearful faces predicted higher PTSD symptom scores, and greater total fixation time and longer mean fixation time for sad faces predicted higher depressive symptom scores. CONCLUSIONS Biased processing of emotion stimuli, as measured by gaze bias, appears to confer vulnerability to symptoms of PTSD and depression in soldiers who experience war zone stress.

DEPRESSION SYMPTOMS AND COGNITIVE CONTROL OF EMOTION CUES: A FUNCTIONAL MAGNETIC RESONANCE IMAGING STUDY

Few studies have examined associations between depressive symptoms and alterations in neural systems that subserve cognitive control. Cognitive control was assessed with an exogenous cueing task using happy, sad, and neutral facial expressions as cues among women with mild to moderate symptoms of depression and a non-depressed control group while functional magnetic resonance imaging (fMRI) measured brain activity. Amygdala and medial/orbital prefrontal cortex (PFC) response to valid emotion cues did not differ as a function of depression symptoms. However, significant depression group differences were observed when task demands required cognitive control. Participants with elevated depression symptoms showed weaker activation in right and left lateral PFC and parietal regions when shifting attentional focus away from invalid emotion cues. No depression group differences were observed for invalid non-emotional cues. Findings suggest that mild to moderate depression symptoms are associated with altered function in brain regions that mediate cognitive control of emotional information.