Jill M. Newby

The neural correlates and role of D1 dopamine receptors in renewal of extinguished alcohol-seeking

We used an ABA renewal design to study the neural correlates, and role of D1 dopamine receptors, in contextual control over extinguished alcohol-seeking. Rats were trained to respond for 4% beer in one context (A), extinguished in a different (B) context, and then tested for responding in the original training context (A) or the extinction context (B). ABA renewal was mediated by D1 dopamine receptors because it was prevented by SCH23390. ABA renewal of alcohol-seeking was associated with selective increases in c-Fos protein induction in basolateral amygdala, ventral accumbens shell, and lateral hypothalamus (renewal-associated Fos). By contrast, being tested was associated with increased c-Fos induction in anterior cingulate, prelimbic and infralimbic cortex, rostral agranular insula, dorsomedial accumbens shell, and accumbens core (test-associated Fos). Renewal-associated Fos in ventral accumbens shell and lateral hypothalamus, but not basolateral amygdala, was D1 dopamine receptor dependent. Double immunofluorescence showed that renewal-associated Fos was expressed in orexin-negative lateral hypothalamic neurons. However, c-Fos induction in either lateral hypothalamic orexin-negative or orexin-positive neurons was positively and significantly correlated with alcohol-seeking. Test-associated c-Fos induction was observed in orexin-positive perifornical neurons. In both regions, c-Fos expression was dependent on D1 dopamine receptors. These results suggest that renewal of extinguished alcohol-seeking depends on a distributed neural circuit involving basolateral amygdala, ventral accumbens shell, and lateral hypothalamus that involves D1 dopamine receptors. Comparison with our previous results [Hamlin AS, Blatchford KE, McNally GP (2006) Renewal of an extinguished instrumental response: Neural correlates and the role of D1 dopamine receptors. Neuroscience 143:25-38] permits identification of similarities and differences in the correlates of renewal of extinguished drug- and natural-reward seeking.

Systematic review and meta-analysis of transdiagnostic psychological treatments for anxiety and depressive disorders in adulthood

A broad array of transdiagnostic psychological treatments for depressive and anxiety disorders have been evaluated, but existing reviews of this literature are restricted to face-to-face cognitive behavioural therapy (CBT) protocols. The current meta-analysis focused on studies evaluating clinician-guided internet/computerised or face-to-face manualised transdiagnostic treatments, to examine their effects on anxiety, depression and quality of life (QOL). Results from 50 studies showed that transdiagnostic treatments are efficacious, with large overall mean uncontrolled effects (pre- to post-treatment) for anxiety and depression (gs=.85 and .91 respectively), and medium for QOL (g=.69). Uncontrolled effect sizes were stable at follow-up. Results from 24 RCTs that met inclusion criteria showed that transdiagnostic treatments outperformed control conditions on all outcome measures (controlled ESs: gs=.65, .80, and .46 for anxiety, depression and QOL respectively), with the smallest differences found compared to treatment-as-usual (TAU) control conditions. RCT quality was generally poor, and heterogeneity was high. Examination of the high heterogeneity revealed that CBT protocols were more effective than mindfulness/acceptance protocols for anxiety (uncontrolled ESs: gs=.88 and .61 respectively), but not depression. Treatment delivery format influenced outcomes for anxiety (uncontrolled ESs: group: g=.70, individual: g=.97, computer/internet: g=.96) and depression (uncontrolled ESs: group: g=.89, individual: g=.86, computer/internet: g=.96). Preliminary evidence from 4 comparisons with disorder-specific treatments suggests that transdiagnostic treatments are as effective for reducing anxiety, and may be superior for reducing depression. These findings show that transdiagnostic psychological treatments are efficacious, but higher quality research studies are needed to explore the sources of heterogeneity amongst treatment effects.

Health anxiety in Australia: prevalence, comorbidity, disability and service use

BACKGROUND Health anxiety is associated with high distress, disability and increased health service utilisation. However, there are relatively few epidemiological studies examining the extent of health anxiety or the associated sociodemographic and health risk factors in the general population. AIMS To provide epidemiological data on health anxiety in the Australian population. METHOD Lifetime and current prevalence estimates, associations between comorbid disorders, psychological distress, impairment, disability and mental health service utilisation were generated using the Australian 2007 National Survey of Mental Health and Wellbeing. RESULTS Health anxiety affects approximately 5.7% of the Australian population across the lifespan and 3.4% met criteria for health anxiety at the time of the interview. Age, employment status, smoking status and comorbid physical conditions were significantly related to health anxiety symptoms. Health anxiety was associated with significantly more distress, impairment, disability and health service utilisation than that found in respondents without health anxiety. CONCLUSIONS Health anxiety is non-trivial; it affects a significant proportion of the population and further research and clinical investigation of health anxiety is required.

Physical activity in the treatment of Post-traumatic stress disorder: A systematic review and meta-analysis

People with PTSD experience high levels of cardiovascular disease and comorbid mental health problems. Physical activity (PA) is an effective intervention in the general population. We conducted the first systematic review and meta-analysis to determine the effect of PA on PTSD. We searched major electronic databases from inception till 03/2015 for RCTs of PA interventions among people with PTSD. A random effects meta-analysis calculating hedges g was conducted. From a potential of 812 hits, four unique RCTs met the inclusion criteria (n=200, mean age of participants 34-52 years). The methodological quality of included trials was satisfactory, and no major adverse events were reported. PA was significantly more effective compared to control conditions at decreasing PTSD and depressive symptoms among people with PTSD. There was insufficient data to investigate the effect on anthropometric or cardiometabolic outcomes. Results suggest that PA may be a useful adjunct to usual care to improve the health of people with PTSD. Although there is a relative paucity of data, there is reason to be optimistic for including PA as an intervention for people with PTSD, particularly given the overwhelming evidence of the benefits of PA in the general population. Robust effectiveness and implementation studies are required.

School-based depression and anxiety prevention programs for young people: A systematic review and meta-analysis.

Depression and anxiety often emerge for the first time during youth. The school environment provides an ideal context to deliver prevention programs, with potential to offset the trajectory towards disorder. The aim of this review was to provide a comprehensive evaluation of randomised-controlled trials of psychological programs, designed to prevent depression and/or anxiety in children and adolescents delivered in school settings. Medline, PsycINFO and the Cochrane Library were systematically searched for articles published until February 2015. Eighty-one unique studies comprising 31,794 school students met inclusion criteria. Small effect sizes for both depression (g=0.23) and anxiety (g=0.20) prevention programs immediately post-intervention were detected. Small effects were evident after 12-month follow-up for both depression (g=0.11) and anxiety (g=0.13). Overall, the quality of the included studies was poor, and heterogeneity was moderate. Subgroup analyses suggested that universal depression prevention programs had smaller effect sizes at post-test relative to targeted programs. For anxiety, effect sizes were comparable for universal and targeted programs. There was some evidence that externally-delivered interventions were superior to those delivered by school staff for depression, but not anxiety. Meta-regression confirmed that targeted programs predicted larger effect sizes for the prevention of depression. These results suggest that the refinement of school-based prevention programs have the potential to reduce mental health burden and advance public health outcomes.

A clinical audit of changes in suicide ideas with internet treatment for depression.

Objectives To examine reductions in suicidal ideation among a sample of patients who were prescribed an internet cognitive behavior therapy (iCBT) course for depression. Design Effectiveness study within a quality assurance framework. Setting Primary care. Participants 299 patients who were prescribed an iCBT course for depression by primary care clinicians. Intervention Six lesson, fully automated cognitive behaviour therapy course delivered over the internet. Primary outcome: suicidal ideation as measured by question 9 on the Patient Health Questionnaire (PHQ-9). Results Suicidal ideation was common (54%) among primary care patients prescribed iCBT treatment for depression but dropped to 30% post-treatment despite minimal clinician contact and the absence of an intervention focused on suicidal ideation. This reduction in suicidal ideation was evident regardless of sex and age. Conclusions The findings do not support the exclusion of patients with significant suicidal ideation.

Effectiveness of transdiagnostic internet cognitive behavioural treatment for mixed anxiety and depression in primary care

BACKGROUND Internet-delivered cognitive behavioural treatment (iCBT) has been shown to be effective for the combined treatment of depression and anxiety in randomised controlled trials. The degree to which these findings generalise to patients in primary care awaits further investigation. METHODS Using an open-trial design, we investigated adherence to, and effectiveness of a 6-lesson therapist-assisted iCBT program for mixed anxiety and depression for patients (n = 707) who completed the program under the supervision of primary care clinicians (general practitioners, psychologists and other allied health professionals). Primary outcome measures were the PHQ-9 (depression), GAD-7 (generalised anxiety), K-10 (distress), WHODAS-II (disability), mini-SPIN (social anxiety) and panic disorder severity scale self-report version (PDSS). RESULTS Adherence to the iCBT program was modest (47.3%), but within-subjects effect sizes ranged from medium (0.51 for PDSS) to large (1.20 for PHQ-9). LIMITATIONS The lack of control group, limited post-treatment data due to drop-out, and short follow-up period. CONCLUSIONS iCBT is an effective treatment for mixed depression and anxiety when delivered in primary care settings. Methods to increase adherence are needed to optimise the benefits to patients.

Transdiagnostic computerised cognitive behavioural therapy for depression and anxiety: A systematic review and meta-analysis

An increasing number of computerised transdiagnostic cognitive behavioural therapy programs (TD-cCBT) have been developed in the past decade, but there are no meta-analyses to explore the efficacy of these programs, nor moderators of the effects. The current meta-analysis focused on studies evaluating TD-cCBT interventions to examine their effects on anxiety, depression and quality of life (QOL). Results from 17 RCTs showed computerised TD-cCBT outperformed control conditions on all outcome measures at post-treatment, with large effect sizes for depression (gs=.84), and medium effect sizes for anxiety (g=.78) and QOL (g=.48). RCT quality was generally good, although heterogeneity was moderate to high. Further analyses revealed that studies comparing TD-cCBT to waitlist controls had the largest differences (g=.93) compared to active (g=.59) and usual care control groups (g=.37) on anxiety outcomes, but there was no influence of control group subtype on depression outcomes. Treatment length, symptom target (mixed versus anxiety only), treatment design (standardised versus tailored), and therapist experience (students versus qualified therapists) did not influence the results. Preliminary evidence from 4 comparisons with disorder-specific treatments suggests transdiagnostic treatments are as effective for reducing anxiety, and there may be small but superior outcomes for TD-cCBT programs for reducing depression (g=.21) and improving QOL (g=.21) compared to disorder-specific cCBT. These findings show that TD-cCBT programs are efficacious, and have comparable effects to disorder-specific cCBT programs.

Characteristics of intrusive memories in a community sample of depressed, recovered depressed and never-depressed individuals

An accumulating body of evidence has revealed that intrusive autobiographical memories of negative events play a role in depression. Despite increasing understanding of the phenomenological experience of these memories, previous research in this area has been conducted in either nonclinical samples, or in clinical samples without an adequate control group. This study aimed to replicate and extend findings with dysphoric samples by comparing the content and characteristics of intrusive memories in clinically depressed (n=25), recovered (n=30) and never-depressed (n=30) participants. Participants completed mood measures, and a battery of self-report questionnaires that indexed intrusive memory frequency, avoidance and characteristics. Intrusive memories were common and shared strikingly similar characteristics across the three groups. The key finding was that depressed participants reported higher levels of intrusion-related distress, associated emotions (especially sadness and helplessness), interference as a result of the memories and memory vividness compared to the never-depressed group. Despite similar levels of intrusion, there were group differences in avoidance such that depressed participants reported higher levels of avoidance than the never-depressed group. These results provide further support for the proposal that clinical interventions for depression could usefully incorporate components that aim to reduce intrusive autobiographical memories and target avoidance strategies.

Does Internet-based guided-self-help for depression cause harm?: An individual participant data meta-analysis on deterioration rates and its moderators in randomized controlled trials

BACKGROUND Almost nothing is known about the potential negative effects of Internet-based psychological treatments for depression. This study aims at investigating deterioration and its moderators within randomized trials on Internet-based guided self-help for adult depression, using an individual patient data meta-analyses (IPDMA) approach. METHOD Studies were identified through systematic searches (PubMed, PsycINFO, EMBASE, Cochrane Library). Deterioration in participants was defined as a significant symptom increase according to the reliable change index (i.e. 7.68 points in the CES-D; 7.63 points in the BDI). Two-step IPDMA procedures, with a random-effects model were used to pool data. RESULTS A total of 18 studies (21 comparisons, 2079 participants) contributed data to the analysis. The risk for a reliable deterioration from baseline to post-treatment was significantly lower in the intervention v. control conditions (3.36 v. 7.60; relative risk 0.47, 95% confidence interval 0.29-0.75). Education moderated effects on deterioration, with patients with low education displaying a higher risk for deterioration than patients with higher education. Deterioration rates for patients with low education did not differ statistically significantly between intervention and control groups. The benefit-risk ratio for patients with low education indicated that 9.38 patients achieve a treatment response for each patient experiencing a symptom deterioration. CONCLUSIONS Internet-based guided self-help is associated with a mean reduced risk for a symptom deterioration compared to controls. Treatment and symptom progress of patients with low education should be closely monitored, as some patients might face an increased risk for symptom deterioration. Future studies should examine predictors of deterioration in patients with low education.