This issue contains two reviews, one on the concept of recovery in major depression and one on internet-based cognitive behavioural therapy (CBT) for depression and anxiety. Four papers report findings from randomized controlled trials (RCT) of interventions for depression and other sets of papers examine various aspects of depression, suicide, and co-morbid generalized anxiety disorder (GAD) and major depression (MD).

Background. There is increasing literature on the unsatisfactory degree of remission that current therapeutic strategies yield in unipolar depression. The aims of this review were to survey the available literature on residual symptoms of depression, to introduce new targets for therapy and to outline a more stringent definition of recovery.

Method. Studies were identified by using MEDLINE (English language articles published from 1967 to June 2006; keywords: recovery, remission, residual symptoms, sequential treatment, drugs and psychotherapy, related to depressive disorder and depression) and a manual search of the literature and Index Medicus for the years 1960–2006.

Results. Most patients report residual symptoms despite apparently successful treatment. Residual symptoms upon remission have a strong prognostic value. There appears to be a relationship between residual and prodromal symptomatology. The concept of recovery should involve psychological well-being.

Conclusions. Appraisal of subclinical symptomatology in depression has important implications for pathophysiological models of disease and relapse prevention. New therapeutic strategies for improving the level of remission, such as treatment on residual symptoms that progress to become prodromes of relapse, may yield more lasting benefits.

Background. We studied to what extent internet-based cognitive behaviour therapy (CBT) programs for symptoms of depression and anxiety are effective.

Method. A meta-analysis of 12 randomized controlled trials.

Results. The effects of internet-based CBT were compared to control conditions in 13 contrast groups with a total number of 2334 participants. A meta-analysis on treatment contrasts resulted in a moderate to large mean effect size [fixed effects analysis (FEA) d=0·40, mixed effects analysis (MEA) d=0·60] and significant heterogeneity. Therefore, two sets of post hoc subgroup analyses were carried out. Analyses on the type of symptoms revealed that interventions for symptoms of depression had a small mean effect size (FEA d=0·27, MEA d=0·32) and significant heterogeneity. Further analyses showed that one study could be regarded as an outlier. Analyses without this study showed a small mean effect size and moderate, non-significant heterogeneity. Interventions for anxiety had a large mean effect size (FEA and MEA d=0·96) and very low heterogeneity. When examining the second set of subgroups, based on therapist assistance, no significant heterogeneity was found. Interventions with therapist support (n=5) had a large mean effect size, while interventions without therapist support (n=6) had a small mean effect size (FEA d=0·24, MEA d=0·26).

Conclusions. In general, effect sizes of internet-based interventions for symptoms of anxiety were larger than effect sizes for depressive symptoms; however, this might be explained by differences in the amount of therapist support.

Background. Non-professional treatment programmes are presumed to relieve the extensive need for care of anxiety and depression disorders. This study investigates the effectiveness of cognitive self- therapy (CST) in the treatment of depression or generalized anxiety disorder.

Method. Patients (n=151) were randomized to receive CST or treatment as usual (TAU) in a trial lasting for 18 months, measuring symptoms (SCL-90; main outcome), social functions, quality of life and utilization of care.

Results. Patients in both conditions improved significantly, but no difference was found between the conditions. Reduction of symptoms, improvement of social functions and medical utilization were maintained at the end of the 18 months. Medical care utilization (therapist contact and hospitalization) was lower for CST than for TAU. No suicides occurred.

Conclusions. Cognitive self-therapy is likely to decrease the need for care of chronic depression and anxiety disorders, but it has not been proven to be more effective than treatment as usual.

Background. Studies of repetitive transcranial magnetic stimulation (rTMS) in depression have mostly involved once-daily treatment, with positive but modest clinical results. This study tested the efficacy and safety of twice-daily rTMS over 2 weeks.

Method. Thirty-eight depressed subjects enrolled in a double-blind, sham-controlled trial of twice-daily rTMS (left prefrontal cortex, 10 Hz, 110% intensity, 1500 stimuli per session) over 2 weeks. Mood and neuropsychological functioning were assessed weekly by blind raters, using the Montgomery–Asberg Depression Rating Scale (MADRS) as the primary outcome measure, plus the Hamilton Rating Scale for Depression (HRSD) and self-report measures. After the blind period, 22 subjects continued with once-daily rTMS to receive a total of 6 weeks of active rTMS.

Results. Subjects were moderately treatment resistant. Active treatment resulted in significantly greater improvement than sham over the 2-week blind period on one outcome measure only (MADRS p<0·05). Subjects showed further improvement over the 6 weeks of active rTMS. Neuropsychological test scores did not change significantly.

Conclusions. rTMS given twice daily was effective and safe, with no adverse neuropsychological effects.

Background. Major depression has far-reaching consequences for work functioning and absenteeism. In most cases depression is treated by medication and clinical management. The addition of occupational therapy (OT) might improve outcome. We determined the cost-effectiveness of the addition of OT to treatment as usual (TAU).

Method. Sixty-two adults with major depression and a mean absenteeism of 242 days were randomized to TAU (out-patient psychiatric treatment) or TAU+OT [6 months, including (i) diagnostic phase with occupational history and work reintegration plan, and (ii) therapeutic phase with individual sessions and group sessions]. Main outcome domains were depression, work resumption, work stress and costs. Assessments were at baseline and at 3, 6, 12 and 42 months.

Results. The addition of OT to TAU: (i) did not improve depression outcome, (ii) resulted in a reduction in work-loss days during the first 18 months, (iii) did not increase work stress, and (iv) had a 75·5% probability of being more cost-effective than TAU alone.

Conclusion. Addition of OT to good clinical practice does not improve depression outcome, improves productivity without increasing work stress and is superior to TAU in terms of cost-effectiveness.

Background. Depression is an important cause of disability worldwide, with many people experiencing their first depressive episode before the age of 18. University students are particularly vulnerable to depression. Depression can be treated successfully in most patients. However, for treatment to be successful, depressed people need to recognize their symptoms as illness, present to medical care, and be aware that effective treatment is available. A thoughtful health campaign might therefore increase the likelihood of successful treatment.

Method. A cluster randomized controlled trial was conducted to determine the effectiveness of an educational intervention. A total of 3313 undergraduate students participated in the study. The intervention consisted of postcards and posters on depression and its treatment. The primary outcome was student awareness that depression can be treated effectively. Secondary outcomes included the proportion of students reading the postcards, recognition of symptoms and knowledge of treatments.

Results. The postcards were read by 69% of students. Less than half of participants reported that depression could be treated effectively, and there was no evidence of a difference between the intervention and control groups [341 (49·1%) v. 379 (49·7%), difference −0·7, p=0·8, 95% confidence interval (CI) −5·1 to 3·7]. However, intervention group participants were more likely than control group participants to recognize depressive symptoms and to report that antidepressants are not addictive.

Conclusions. Many university students lack knowledge about depression and its treatment. Simple and cheap media, such as postcards and posters, might help to improve awareness in areas where current knowledge is low.

Background. Despite an increased prevalence of depression among people of low socio-economic position, it remains unclear whether their treatment with antidepressants appropriately matches their increased need compared with people from more affluent backgrounds. This study examined socio-economic differences in antidepressant prescriptions and mortality related to depressive disorders.

Method. A longitudinal register study of 17947 male and 47458 female local government employees with linked information on socio-economic indicators (education and occupational status) and data on antidepressant use and mortality associated with depressive disorder (suicide, alcohol-related deaths) during the years 1994 to 2000.

Results. In men, antidepressant treatment was less common among low educational groups than among high educational groups (OR 0·87, 95% CI 0·76–0·99) and a corresponding difference was seen between occupational statuses (OR for manual v. upper non-manual 0·72, 95% CI 0·62–0·84). In women, socio-economic position was not associated with antidepressant use. However, both among the men and women, employees with low socio-economic position had increased risk for mental-health-related mortality, as indicated by suicides, deaths from alcohol-related causes, and all-cause mortality.

Conclusions. These data suggest a mismatch in the treatment of depression relative to apparent clinical need, with the lowest levels of treatment concentrated in the lower socio-economic groups, despite evidence of their increased prevalence of depression and suicide.

Background. Vascular depression is regarded as a subtype of depression, especially in, but not entirely restricted to, the elderly, characterized by a specific clinical presentation and an association with (cerebro)vascular risk and disease. It could have major implications for treatment if subjects at risk for such a depression could be easily identified by their clinical presentation in general practice.

Method. We studied the symptom profile of depression in subjects with and without vascular risk factors in two large Dutch community-based studies, the Rotterdam Study and the Amsterdam Study of the Elderly (AMSTEL).

Results. We could not confirm the specific symptom profile in depressed subjects with vascular risk factors in either of the two cohorts. Depressed subjects with vascular risk factors showed more loss of energy and more physical disability than those without vascular risk factors. However, presumed specific symptoms of vascular depression, namely psychomotor retardation and anhedonia, were not significantly associated with any of the vascular risk indicators. Loss of energy was significantly associated with myocardial infarction and peripheral arterial disease.

Conclusions. In these two large community-based studies we identified some differences between vascular and non-vascular depressed subjects but found no evidence for a specific symptom profile of vascular depression as previously defined.

Background. Past research has demonstrated that depression is associated with dysfunctional processing of emotional information. Recent studies demonstrate that a bias in the attentional processing of negative information may be an important cognitive vulnerability factor underlying the onset and maintenance of depression. However, to date, the nature of this attentional bias is still poorly understood and further exploration of this topic to advance current knowledge of attentional biases in depression seems imperative.

Method. This study examined attentional biases for angry facial expressions presented for 1000 ms in 20 patients with major depressive disorder (MDD) and 20 non-depressed control participants (NC) matched for age and gender using an emotional modification of the Exogenous Cueing task.

Results. Patients with MDD showed maintained attention for angry faces compared with neutral faces. In comparison with non-depressed participants they showed a stronger attentional engagement for angry faces. In contrast, the NC group directed attention away from angry faces, more rapidly disengaging their attention compared with neutral faces.

Conclusions. This pattern of results supports the assumption that MDD is characterized by deficits in the attentional processing of negative, interpersonal information and suggests a ‘protective’ bias in non-depressed individuals. Implications in relation to previous research exploring cognitive and interpersonal functioning in depression are discussed.

Background. Biases in the processing of emotional information have been shown to be abnormal in subjects with major depression, both during an episode and after full recovery. However, it is unclear whether these biases are a cause or an effect of the depression. This study set out to explore whether such biases represent a vulnerability factor for depression by looking at unaffected first-degree relatives of those with major depressive disorder. We also measured waking salivary cortisol, as the regulation of the hypothalamo–pituitary–adrenal (HPA) axis is thought to be impaired in depressive disorder.

Method. Twenty-five female relatives and 21 age-matched controls completed a facial expression recognition task, an emotional categorization task with positive and negative personality characteristics, and had their waking salivary cortisol measured on a work day and a non-work day.

Results. The depressed relative group was significantly faster to recognize facial expressions of fear than controls. The depressed relative group also showed significantly increased reaction time to recognize positive versus negative personality characteristics in the categorization task. There was no difference in waking salivary cortisol between groups, although there was an effect of work day versus non-work day.

Conclusions. Subtle biases in the processing of emotional information may exist in the unaffected first-degree relatives of those with depression. As such, this may represent a familial vulnerability factor to developing a depressive illness.

Background. Abnormal serotonergic neurotransmission has long been demonstrated in suicidal behavior. The dorsal and median raphe nuclei housing the main serotonergic cell bodies and the prefrontal cortex (PFC), particularly the ventral part innervated by the serotonergic system, have therefore been studied extensively in suicidal behavior research. However, only a few studies have described neuropsychological function impairment in suicidal patients. We investigated PFC-related neuropsychological function in patients with suicidal behavior, separating dorsolateral PFC (DLPFC)- and orbitofrontal cortex (OFC)-related functions.

Method. We compared 30 euthymic patients with suicidal behavior aged 18–65 years with 39 control subjects, for the following neuropsychological domains: global intellectual functioning, reward sensitivity, initiation, inhibition, and working memory. Patients and controls were compared by means of univariate and multivariate analyses, adjusting for age at interview, level of education and mood state at the time of evaluation. Trait impulsivity, measured with the Barratt Impulsivity Scale version 10 (BIS-10), was also included as a covariate in a subset of analyses.

Results. Multivariate comparisons demonstrated significant executive function deficits in patients with suicidal behavior. In particular, we observed impairment in visuospatial conceptualization (p<0·0001), spatial working memory (p=0·001), inhibition (Hayling B–A, p=0·04; go anticipations, p=0·01) and visual attention (or reading fluency) (p=0·002). Similar results were obtained following adjustment for motor impulsivity as a covariate, except for spatial working memory.

Conclusions. These deficits are consistent with prefrontal dysfunction in patients with suicidal behavior. Differentiation between DLPFC- and OFC-related neuropsychological functions showed no specific dysfunction of the orbitofrontal region in patients with suicidal behavior in our sample.

Background. Suicide is expressly condemned in the Qu'ran, and traditionally few Islamic countries have reported suicide. Undetermined deaths are classified by the World Health Organization (WHO) as Other Violent Deaths (OVD) in ICD-9, or Other External Causes (OEC) in ICD-10. It has been suggested that to avoid under-reporting of suicides, both formal suicide verdicts and OVD should be considered together because OVD may contain ‘hidden’ suicides.

Method. The latest WHO mortality data, by age and gender, were analysed and tested by χ2 tests. Levels of suicide and OVD in 17 Islamic countries were examined and contextually compared with UK rates. The regional Islamic cultural differences in Middle Eastern, South Asian, European Islam countries and those of the former Union of Socialist Soviet Republics (FUSSR) were analysed separately to test the hypotheses that there would be no difference between regional suicide and OVD rates per million (pm) and 17 Islamic countries and UK rates.

Results. Suicide rates were higher for males than females, and ‘older’ (65+) higher than ‘younger’ (15–34) rates in every country reviewed. The rate for Middle Eastern males was 0–36 pm, South Asian 0–12 pm, European 53–177 pm and FUSSR 30–506 pm, with three countries exceeding the UK rate of 116 pm. The Western male average OVD rate was 22 pm; the UK 55 pm rate was highest. Middle Eastern OVD was 1–420 pm, South Asian 0–166 pm, European 1–66 pm and FUSSR 11–361 pm. OVD rates in 10 Islamic countries were considerably higher than the Western average and eight had OVD rates considerably higher than their suicide rates.

Conclusions. Islamic suicide rates varied widely and the high OVD rates, especially the Middle Eastern, may be a repository for hiding culturally unacceptable suicides.

Background. The aim of this study was to estimate the extent to which anxiety disorders contribute to an increase in suicidal behaviour after controlling for both observed and non-observed sources of confounding.

Method. Data were collected from the Christchurch Health and Development Study (CHDS), a 25-year longitudinal study of over 1000 participants. Measures of anxiety disorders [phobia, generalized anxiety disorder (GAD), panic disorder], major depression (MD), substance use disorders, conduct/antisocial personality disorder, stressful life events, unemployment, and suicidal ideation/attempts for subjects aged 16–18, 18–21 and 21–25 years were used to fit random and fixed effects regression models of the associations between anxiety disorders and suicidal behaviours.

Results. Anxiety disorders were strongly associated with suicidal ideation/attempts. Any single anxiety disorder increased the odds of suicidal ideation by 7·96 times [95% confidence interval (CI) 5·69–11·13] and increased the rate of suicide attempts by 5·85 times (95% CI 3·66–9·32). Control for co-occurring mental disorders, non-observed fixed confounding factors and life stress reduced these associations [suicidal ideation odds ratio (OR) 2·80, 95% CI 1·71–4·58; suicide attempts incidence rate ratio (IRR) 1·90, 95% CI 1·07–3·39]. Rates of suicidal behaviour also increased with the number of anxiety disorders. Estimates of the population attributable risk suggested that anxiety disorders accounted for 7–10% of the suicidality in the cohort.

Conclusions. Anxiety disorders may be a risk factor for suicidality, even after controlling for confounding, with risks increasing with multiple anxiety disorders. Management of anxiety disorders may be an important component in strategies to reduce population rates of suicide.

Background. The close association between generalized anxiety disorder (GAD) and major depressive disorder (MDD) prompts questions about how to characterize them in future diagnostic systems. We tested whether risk factors for MDD and GAD are similar or different.

Method. The representative 1972–73 Dunedin birth cohort of 1037 males and females was followed to age 32 with 96% retention. Adult GAD and MDD were diagnosed at ages 18, 21, 26, and 32 years, and juvenile anxiety/depression were also taken into account. Thirteen prospective risk measures indexed domains of family history, adverse family environment, childhood behavior, and adolescent self-esteem and personality traits.

Results. Co-morbid MDD+GAD was antedated by highly elevated risk factors broadly across all domains. MDD+GAD was further characterized by the earliest onset, most recurrence, and greatest use of mental health services and medication. Pure GAD had levels of risk factors similar to the elevated levels for co-morbid MDD+GAD; generally, pure MDD did not. Pure GAD had risks during childhood not shared by pure MDD, in domains of adverse family environment (low SES, somewhat more maltreatment) and childhood behavior (internalizing problems, conduct problems, somewhat more inhibited temperament). Pure MDD had risks not shared by pure GAD, in domains of family history (of depression) and personality (low positive emotionality).

Conclusions. Specific antecedent risk factors for pure adult MDD versus GAD may suggest partly different etiological pathways. That GAD and co-morbid MDD+GAD share many risk markers suggests that the presence of GAD may signal a pathway toward relatively more severe internalizing disorder.

Background. Prior studies report high levels of co-morbidity between major depression (MD) and generalized anxiety disorder (GAD) and suggest that these disorders are closely related genetically. The personality trait of neuroticism (N) is substantially correlated with risk for MD and GAD.

Method. Bivariate twin models were applied to lifetime diagnoses of modified DSM-IV diagnosis of MD and GAD obtained at personal interview in 1998–2003 with 37296 twins from the population-based Swedish Twin Registry. A trivariate Cholesky model with N, MD and GAD was applied to a subset (23280 members of same-sex twin pairs) who completed a self-report questionnaire assessing N in 1972–1973.

Results. In the best-fit bivariate model, the genetic correlation between MD and GAD was estimated at +1·00 in females and +0·74 in males. Individual-specific environmental factors were also shared between the two disorders with an estimated correlation of +0·59 in males and +0·36 in females. In the best-fit trivariate Cholesky model, genetic factors indexed by N impacted equally on risk for MD and GAD in males and females. However, in both sexes, genetic risk factors indexed by N contributed only around 25% to the genetic correlation between MD and GAD.

Conclusion. Genetic risk factors for lifetime MD and GAD are strongly correlated, with higher correlations in women than in men. Although genetic risk factors indexed by the personality trait of N contribute substantially to risk for both MD and GAD, the majority of genetic covariance between the two disorders results from factors not shared with N.