CRE Publications

Hiles, S. A., Baker, A. L., deMalmanche, T., & Attia, J. (2013). 104. The inflammatory hypothesis of depression in the context of physical health: Depression and inflammatory markers in cardiovascular hospitalisations. Brain, Behavior, and Immunity, 32, Supplement(0), e30. doi


Separate studies identify depression and inflammatory markers as predictors of cardiovascular events such as myocardial infarction and stroke. Given the strong association between inflammatory markers and depression, these two factors may interact, or partially mediate each other, in predicting cardiovascular hospitalisations. We examined this in participants from a community-dwelling prospective cohort aged 55–85 years. Participants completed baseline questionnaires regarding depressive symptoms and lifestyle factors, and blood was drawn for assay of C-reactive protein (CRP) and interleukin-6. Participants were followed for cardiovascular-related hospitalisations. Potential sources of confounding from behaviour and disease characteristics were identified via directed acyclic graphs. Across approximately 5600 person-years of risk, there were 80 cardiovascular hospitalisations (4.2% of sample, total N = 1888). Depression score and logCRP were significantly associated with risk of cardiovascular event over time (HR = 1.03, 95%CI 1.01, 1.05; HR = 1.50, 95%CI 1.14, 1.99, respectively). However their interaction was not significant, and adjusting for the other did not substantially alter affect sizes. Results for interleukin-6 were similar. There was some evidence of effect modification, where participants with both elevated CRP  > 3 mg/L and high depressive symptoms had more cardiovascular events than expected (χ2 = 12.27, p = .03). Hazard ratios were no longer significant after controlling for confounding. Subclinical inflammation may not be the mediating factor between depression and cardiovascular events. Other shared factors such as high risk lifestyle behaviours may underlie the relationship between inflammation, depression and cardiovascular disease.

Hiles, S. A., Baker, A. L., Handley, T., de Malmanche, T., & Attia, J. (2013). 103. Statins, depression and the inflammatory hypothesis of depression: A meta-analysis of randomized controlled trials. Brain, Behavior, and Immunity, 32, Supplement(0), e30. doi


Early evidence from randomized controlled trials indicates that primary or adjunct treatment with anti-inflammatory medications improves outcomes for some patients with depression. One of the most highly prescribed classes of medications are statins, and evidence is mounting that these have anti-inflammatory effects. Consequently, we examined whether treatment with statins, compared with placebo, is associated with improved depression outcomes. Random effects meta-analysis was conducted on studies meeting eligibility criteria: randomized controlled trial of any type of statin vs. placebo, measured depression as a continuous score or binary outcome, in any patient group, published in a peer reviewed journal. Computerised searches of Embase, Medline, PsycInfo, Cochrane Library and Web of Science were undertaken using derivatives of terms related to depression, statins and randomized controlled trial. Two authors independently assessed eligibility and extracted data. Treatment with statins was associated with a significantly greater reduction in depressive symptoms compared with placebo treatment, d = −0.11 (95%CI −0.20, −0.02), p = .02, I2 = 0. Treatment with statins was also significantly associated with fewer depression adverse events, RR = 0.90 (95%CI 0.81, 1.00), p = .05, I2 = 0. Statin use was associated with improved depression outcomes across clinically diverse samples. The small benefits demonstrated may have substantial public health benefits, due to their widespread use. This data provides tentative support for the inflammatory hypothesis of depression. However, measuring inflammatory markers and depression simultaneously in future trials of statin use is warranted

Keywords: Depression

Handley, T. E., Kay-Lambkin, F. J., Baker, A. L., Lewin, T. J., Kelly, B. J., Inder, K. J., Kavanagh, D. J. (In press). Incidental treatment effects of CBT on suicidal ideation and hopelessness. Journal of affective disorders, 151(1), 275-283. doi:


Depression and alcohol misuse are among the most prevalent diagnoses in suicide fatalities. The risk posed by these disorders is exacerbated when they co-occur. Limited research has evaluated the effectiveness of common depression and alcohol treatments for the reduction of suicide vulnerability in individuals experiencing comorbidity. Participants with depressive symptoms and hazardous alcohol use were selected from two randomised controlled trials. They had received either a brief (1 session) intervention, or depression-focused cognitive behaviour therapy (CBT), alcohol-focused CBT, therapist-delivered integrated CBT, computer-delivered integrated CBT or person-centred therapy (PCT) over a 10-week period. Suicidal ideation, hopelessness, depression severity and alcohol consumption were assessed at baseline and 12-month follow-up. Three hundred three participants were assessed at baseline and 12 months. Both suicidal ideation and hopelessness were associated with higher severity of depressive symptoms, but not with alcohol consumption. Suicidal ideation did not improve significantly at follow-up, with no differences between treatment conditions. Improvements in hopelessness differed between treatment conditions; hopelessness improved more in the CBT conditions compared to PCT and in single-focused CBT compared to integrated CBT. Limitations Low retention rates may have impacted on the reliability of our findings. Combining data from two studies may have resulted in heterogeneity of samples between conditions. CBT appears to be associated with reductions in hopelessness in people with co-occurring depression and alcohol misuse, even when it is not the focus of treatment. Less consistent results were observed for suicidal ideation. Establishing specific procedures or therapeutic content for clinicians to monitor these outcomes may result in better management of individuals with higher vulnerability for suicide.

Glozier, N., Christensen, H., Naismith, S., Cockayne, N., Donkin, L., Neal, B., Hickie, I. (2013). Internet-Delivered Cognitive Behavioural Therapy for Adults with Mild to Moderate Depression and High Cardiovascular Disease Risks: A Randomised Attention-Controlled Trial. PLoS One, 8(3), e59139. doi:


Mild to moderate depression is common in those with cardiovascular disease and undertreated. We aimed to evaluate the effectiveness of internet-delivered Cognitive Behaviour Therapy (iCBT) on depressive symptom severity and adherence to medical advice and lifestyle interventions in adults with mild to moderate depression and high cardiovascular disease (CVD) risks. Randomised double-blind, 12 week attention-controlled trial comparing an iCBT programme (E-couch) with an internet-delivered attention control health information package (HealthWatch, n = 282). The primary outcome was depression symptom level on the nine-item Patient Health Questionnaire (PHQ-9) (trial registration: ACTRN12610000085077). 487/562 (88%) participants completed the endpoint assessment. 383/562 (70%) were currently treated for cardiovascular disease and 314/562 (56%) had at least one other comorbid condition. In ITT analysis of 562 participants iCBT produced a greater decline in the mean PHQ-9 score compared to the attention control of 1.06 (95% CI: 0.23–1.89) points, with differences between the two arms increasing over the intervention period (time by treatment effect interaction p = .012). There were also larger improvements in adherence (2.16 points; 95% CI: 0.33–3.99), reductions in anxiety (0.96 points; 95% CI: 0.19–1.73), and a greater proportion engaging in beneficial physical activity (Odds Ratio 1.91, 95%CI: 1.01–3.61) in the iCBT participants but no effect upon disability, or walking time/day. There were no withdrawals due to study related adverse events. In people with mild to moderate depression and high levels of CVD risk factors, a freely accessible iCBT programme ( produced a small, but robust, improvement in depressive symptoms, adherence and some health behaviours.

Donker, T., Batterham, P. J., Warmerdam, L., Bennett, K., Bennett, A., Cuijpers, P., Christensen, H. (2013). Predictors and moderators of response to internet-delivered Interpersonal Psychotherapy and Cognitive Behavior Therapy for depression. Journal of affective disorders, 151(1), 343-351. doi:


By identifying which predictors and moderators lead to beneficial outcomes, accurate selection of the best initial treatment will have significant benefits for depressed individuals. An automated, fully self-guided randomized controlled internet-delivered noninferiority trial was conducted comparing two new interventions (Interpersonal Psychotherapy [IPT; n=620] and Cognitive Behavioral Therapy [CBT; n=610]) to an active control intervention (MoodGYM; n=613) over a period of 4 weeks to spontaneous visitors of an internet-delivered therapy website (e-couch). A range of putative predictors and moderators (socio-demographic characteristics [age, gender, marital status, education level], clinical characteristics [depression/anxiety symptoms, disability, quality of life, medication use], skills [mastery and dysfunctional attitudes] and treatment preference) were assessed using internet-delivered self-report measures at baseline and immediately following treatment and at six months follow-up. Analyses were conducted using Mixed Model Repeated Measures (MMRM). Female gender, lower mastery and lower dysfunctional attitudes predicted better outcome at post-test and/or follow-up regardless of intervention. No overall differential effects for condition on depression as a function of outcome were found. However, based on time-specific estimates, a significant interaction effect of age was found. For younger people, internet-delivered IPT may be the preferred treatment choice, whereas older participants derive more benefits from internet-delivered CBT programs. Limitations Although the sample of participants was large, power to detect moderator effects was still lacking. Different e-mental health programs may be more beneficial for specific age groups. The findings raise important possibilities for increasing depression treatment effectiveness and improving clinical practice guidelines for depression treatment of different age groups.

Batterham, P. J., Calear, A. L., & Christensen, H. (2013). Correlates of Suicide Stigma and Suicide Literacy in the Community. Suicide and Life-Threatening Behavior. doi:


Public knowledge and attitudes toward suicide may influence help-seeking for suicidality. This study aimed to identify correlates of suicide attitudes and knowledge. Australian adults were invited to complete an online survey, with 1,286 responders. Less exposure to suicide, older age, male gender, less education, and culturally diverse backgrounds were associated with poorer knowledge; while younger age, male gender, and culturally diverse backgrounds were associated with more stigmatizing attitudes toward people who die by suicide. The results suggest suicide literacy and stigma reduction programs would benefit community members, particularly males and individuals from culturally diverse backgrounds.

Baker, A. L., Kay-Lambkin, F. J., Gilligan, C., Kavanagh, D. J., Baker, F., & Lewin, T. J. (2013). When does change begin following screening and brief intervention among depressed problem drinkers? Journal of substance abuse treatment, 44(3), 264-270. doi:


Brief interventions are effective for problem drinking and reductions are known to occur in association with screening and assessment. The present study sought to assess, among participants (N = 202) in a clinical trial, how much change occurred between baseline assessment and a one-session brief intervention (S1), and the predictors of early change. The primary focus was on changes in the Beck Depression Inventory Fast Screen scores and alcohol consumption (standard drinks per week) prior to random allocation to nine further sessions addressing either depression, alcohol, or both problems. There were large and clinically significant reductions between baseline and S1, with the strongest predictors being baseline scores in the relevant domain and change in the other domain. Client engagement was also predictive of early depression changes. Monitoring progress in both domains from first contact, and provision of empathic care, followed by brief intervention appear to be useful for this high prevalence comorbidity.

Berle, D., & Moulds, M. L. (2013). An experimental investigation of emotional reasoning processes in depression. British Journal of Clinical Psychology, 52(3), 316-329. doi:


Cognitive models of depression emphasize how distorted thoughts and interpretations contribute to low mood. Emotional reasoning is considered to be one such interpretative style. We used an experimental procedure to determine whether elevated levels of emotional reasoning characterize depression. Participants who were currently experiencing a major depressive episode (n = 27) were compared with those who were non-depressed (n = 25 who had never been depressed and n = 26 previously but not currently depressed) on an emotional reasoning task. Although there were some trends for depressed participants to show greater levels of emotional reasoning relative to non-depressed participants, none of these differences attained significance. Interestingly, previously depressed participants engaged in more non-self-referent emotional reasoning than never-depressed participants. Emotional reasoning does not appear to characterize mild to moderate levels of depression. The lack of significant differences in emotional reasoning between currently depressed and non-depressed participants may have been a consequence of the fact that participants in our currently depressed group were, for the most part, only mildly depressed. Non-self-referent emotional reasoning may nevertheless be a risk factor for subsequent depressive episodes, or else serve as a ‘cognitive scar’ from previous episodes. In contrast with the predictions of cognitive models of depression, emotional reasoning tendencies may not be especially prominent in currently depressed individuals. * Depressed individuals vary greatly in the degree to which they engage in emotional reasoning. * Individuals with remitted depression may show elevated of levels non-self-referent emotional reasoning compared with those who have never had a depressive episode, that is, rely on their emotions when forming interpretations about situations.  Our findings require replication using alternative indices of emotional reasoning. * Our currently depressed individuals were only mildly clinically depressed precluding conclusions about individuals with more severe levels of depression.

Keywords: Cognition, Depression

Connor, C., & Birchwood, M. (2013). Power and Perceived Expressed Emotion of Voices: Their Impact on Depression and Suicidal Thinking in Those Who Hear Voices. Clinical Psychology & Psychotherapy, 20(3), 199-205. doi:


Considerable focus has been given to the interpersonal nature of the voice-hearing relationship and how appraisals about voices may be linked with distress and depression (the ‘cognitive model’). Research hitherto has focused on appraisals of voice power, but the supportive and affiliative quality of voices, which may act to mitigate distress, is not understood. We explored appraisals of voices' power and emotional support to determine their significance in predicting depression and suicidal thought. We adapted the concept of expressed emotion (EE) and applied it to measure voice hearers' perception of the relationship with their voice(s). In a sample of 74 voice hearers, 55.4% were moderately depressed. Seventy-eight who rated their voices as high in both power and EE had a large and significant elevation in depression, suggesting that co-occurrence of these appraisals impacts on depression. Analysis of the relationship between power and EE revealed that many voices perceived as low in power were, nevertheless, perceived as high in EE. Those rating their voices as emotionally supportive showed the lowest levels of depression and suicidal thinking. These findings highlight the protective role that the supportive dimension of the voice/voice-hearer relationship may have. Copyright © 2011 John Wiley & Sons, Ltd. Key Practitioner Message * Appraisals of social rank and EE impact on the depressive and suicidal status of voice-hearers. * The emotionally supportive dimension of the voice-hearing relationship may have a protective role in the affective response of voice hearers. * Therapeutic interventions should consider the emotionally supportive needs of voice-hearers

Christensen, H., Batterham, P. J., Griffiths, K. M., Gosling, J., & Hehir, K. K. (2013). Research priorities in mental health. Australian and New Zealand Journal of Psychiatry, 47(4), 355-362. doi:


Over the last decade, Australia has seen an increase in investment in mental health services, primarily through the funding of headspace and Better Access to Mental Health Outcomes programs. Concurrently there has been a policy focus on prevention and early intervention, suicide reduction and ‘hard-to-target’ groups such as Indigenous groups. It is not clear, however, whether research funding targeting health services or prevention or promotion has been prioritized, or whether funding priorities in general have shifted over the last decade. A total of 1008 Australian-authored research publications and 126 competitive research grants in 2008 were coded in terms of their target of research, research goal setting and target group. These characteristics were compared with the research priorities of 570 stakeholders, burden of disease estimates and similar data collected 10 years earlier. The proportion of research funding for affective disorders, dementia and psychosis has increased, but not for anxiety disorders or suicide. Funding for childhood disorders has decreased. Funding for prevention and promotion is low and decreasing. With respect to research publications, substance abuse was associated with the most publications, followed by affective disorders, anxiety disorders and psychosis. When publications and funding are compared to stakeholder priorities and the burden of disease, the areas of suicide and self-harm, personality disorders, anxiety disorders, childhood conditions and dementia are all insufficiently funded. Despite mental health policy reforms through the last decade, there has been little change in the focus of research funding or publication output. There is modest evidence for a shift in support towards affective disorders as a major focus for research. However, the remaining gaps were very similar to those identified 10 years earlier showing that suicide, personality disorders and anxiety disorders are under-researched.

Calear, A. L., Christensen, H., Mackinnon, A., & Griffiths, K. M. (2013). Adherence to the MoodGYM program: Outcomes and predictors for an adolescent school-based population. Journal of affective disorders, 147(1–3), 338-344. doi:


Program adherence has been associated with improved intervention outcomes for mental and physical conditions. The aim of the current study is to investigate adolescent adherence to an Internet-based depression prevention program in schools to identify the effect of adherence on outcomes and to ascertain the predictors of program adherence. Data for the current study (N=1477) was drawn from the YouthMood Project, which was conducted to test the effectiveness of the MoodGYM program in reducing and preventing symptoms of anxiety and depression in an adolescent school-based population. The current study compares intervention effects across three sub-groups: high adherers, low adherers and the wait-list control condition. When compared to the control condition, participants in the high adherence intervention group reported stronger intervention effects at post-intervention and 6-month follow-up than participants in the low adherence group for anxiety (d=0.34–0.39 vs. 0.11–0.22), and male (d=0.43–0.59 vs. 0.26–0.35) and female depression (d=0.13–0.20 vs. 0.02–0.04). No significant intervention effects were identified between the high and low adherence groups. Being in Year 9, living in a rural location and having higher pre-intervention levels of depressive symptoms or self-esteem were predictive of greater adherence to the MoodGYM program. The program trialled is Internet-based and therefore the predictors of adherence identified may not generalise to face-to-face interventions. The current study provides preliminary support for the positive relationship between program adherence and outcomes in a school environment. The identification of significant predictors of adherence will assist in identifying the type of user who will engage most with an online depression prevention program.

Bailey, R. C., & Baillie, A. J. (2013). The relationship between placebo alcohol and affect: Motives for drinking. Drug and Alcohol Review, 32, 162-169. doi:


Although alcohol is often used in an attempt to alleviate negative affect, alcohol oftentimes exacerbates depressive symptoms. Therefore the relationship between alcohol and affect, and the role of motives for drinking remain unclear. The present study hypothesised that placebo alcohol would blunt affective responding and that desire to drink would increase in individuals who expected alcohol to help them cope after a negative experience. The present study also explored whether motives and reasons for drinking altered after a negative experience. Participants (36 first-year psychology students and 41 community members) were randomly assigned to one of four experimental groups, being soft drink or placebo alcohol, neutral or negative mood induction.Two repeated measures analyses indicated that placebo alcohol did not significantly blunt affective responding after the negative mood induction.T-tests showed that desire to drink did not significantly increase post negative mood induction for participants who endorsed coping motives for drinking. However, interestingly coping-depression and enhancement motives decreased after negative mood induction, and participants misattributed the majority of their mood to other life events. The findings indicate that motives for drinking are amendable with prior learning, providing support for expectancy challenge procedures.The study also provides some evidence for alcohol’s effect on emotional lability. [Bailey RC, Baillie AJ. The relationship between placebo alcohol and affect: Motives for drinking. Drug Alcohol Rev 2013;32:162–169]

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