Although self-help interventions are effective in treating depression, less is known about the factors that determine effectiveness (i.e. moderators of effect). This study sought to determine whether the content of self-help interventions, the study populations or aspects of study design were the most important moderators.

Randomized trials of the effectiveness of self-help interventions versus controls in the treatment of depressive symptoms were identified using previous reviews and electronic database searches. Data on moderators (i.e. patient populations, study design, intervention content) and outcomes were extracted and analysed using meta-regression.

Thirty-four studies were identified with 39 comparisons. Study design factors associated with greater effectiveness were unclear allocation concealment, observer-rated outcome measures and waiting-list control groups. Greater effectiveness was also associated with recruitment in non-clinical settings, patients with existing depression (rather than those ‘at risk’), contact with a therapist (i.e. guided self-help) and the use of cognitive behavioural therapy (CBT) techniques. However, only guided self-help remained significant in the multivariate analysis [regression coefficient 0·36, 95% confidence interval (CI) 0·05–0·68, p=0·03]. In the subset of guided studies, there were no significant associations between outcomes and the session length, content, delivery mode or therapist background.

The results provide some insights into moderators of self-help interventions, which might assist in the design of future interventions. However, the present study did not provide a comprehensive description, and other research methods might be required to identify factors associated with the effectiveness of self-help.

Despite increasing awareness of the extent and severity of cognitive deficits in major depressive disorder (MDD), trials of cognitive remediation have not been conducted. We conducted a 10-week course of cognitive remediation in patients with long-term MDD to probe whether deficits in four targeted cognitive domains, (i) memory, (ii) attention, (iii) executive functioning and (iv) psychomotor speed, could be improved by this intervention.

We administered a computerized cognitive retraining package (PSSCogReHab) with demonstrated efficacy to 12 stable patients with recurrent MDD. Twelve matched patients with MDD and a group of healthy control participants were included for comparison; neither comparator group received the intervention that involved stimulation of cognitive functions through targeted, repetitive exercises in each domain.

Patients who received cognitive training improved on a range of neuropsychological tests targeting attention, verbal learning and memory, psychomotor speed and executive function. This improvement exceeded that observed over the same time period in a group of matched comparisons. There was no change in depressive symptom scores over the course of the trial, thus improvement in cognitive performance occurred independent of other illness variables.

These results provide preliminary evidence that improvement of cognitive functions through targeted, repetitive exercises is a viable method of cognitive remediation in patients with recurrent MDD.

Undertreatment of depression in primary care is common. Efforts to address this tend to overlook the role of patient attitudes. Our aim was to validate and describe responses to a questionnaire about attitudes to depression and its treatment in a sample with experience of moderate and severe depressive episodes.

Cross-sectional survey of 866 individuals with a confirmed history of an ICD-10 depressive episode in the 12 months preceding interview, recruited from 7271 consecutive general practitioner (GP) attendees in 36 general practices in England and Wales. Attitudes to and beliefs about depression were assessed using a 19-item self-report questionnaire.

Factor analysis resulted in a three-factor solution: factor 1, depression as a disabling, permanent state; factor 2, depression as a medical condition responsive to support; and factor 3, antidepressants are addictive and ineffective. Participants who received and adhered to antidepressant medication and disclosed their depression to family and friends had significantly lower scores on factors 1 and 3 but higher scores on factor 2.

People with moderate or severe depressive episodes have subtle and divergent views about this condition, its outcome, and appropriate help. Such beliefs should be considered in primary care as they may significantly impact on help seeking and adherence to treatment.

Within Beck's cognitive model of depression, little is known about the mechanism(s) by which activated self-schemas result in the production of negative thoughts. Recent research has demonstrated that inhibitory dysfunction is present in depression, and this deficit is likely valence-specific. However, whether valence-specific inhibitory deficits are associated with increased negative cognition and whether such deficits are specific to depression per se remains unexamined. The authors posit the theory that inhibitory dysfunction may influence the degree to which activated self-schemas result in the production of depressive cognition.

Individuals with major depressive disorder (MDD, n=43) versus healthy (n=36) and non-depressed anxious (n=32) controls were assessed on the Prose Distraction Task (PDT), a measure of cognitive inhibition, and the Stop-Signal Task (SST), a measure of motor response inhibition. These two tasks were modified in order to present emotionally valenced semantic stimuli (i.e. negative, neutral, positive).

Participants with MDD demonstrated performance impairments on the PDT, which were most pronounced for negatively valenced adjectives, relative to both control groups. Moreover, these impairments correlated with self-report measures of negative thinking and rumination. Conversely, the performance of the MDD participants did not differ from either control group on the SST.

Implications of these findings for understanding the mechanisms underlying the development and maintenance of depressive cognition are discussed.

It has recently been proposed that major depression disorder (MDD) may, in a heterogeneous population-based cohort, be interpreted in terms of a random-mood model. Mood fluctuations are thought to result from stressors that occur randomly in time. We have investigated whether this concept also holds for more homogeneous groups, defined by known determinants for MDD, and whether the model's parameters, susceptibility (Z) and relaxation time (T), may be evaluated and used to differentiate between subcohorts.

From a large epidemiological survey, the Netherlands Mental Health Survey and Incidence Study (NEMESIS), data on the duration of MDD were obtained for subcohorts, based on gender, severity of depression, recurrence and co-morbidity with dysthymia, anxiety and somatic disorder, and were compared with random-mood simulation calculations.

Susceptibility, Z, is empirically found to be proportional to incidence and may be identified with a risk ratio. A second scaling rule states the proportionality of mean duration with the product of Z and T. This Z–T classification proves to be more sensitive than conventional significance tests. Notably for men/women and for co-morbid anxiety, differences are seen that have previously gone unnoticed.

Depression may be conceptualized as a disorder resulting from random-mood fluctuations, the response to which is influenced by a large variety of determinants or risk factors. The model's parameters can be evaluated and may be used in differentiating between risk factor-defined subgroups.

The relationship of postnatal (postpartum) depression (PND) to episodes of depression occurring at other times is not well understood. Despite a number of studies of clinical presentation, there is little consistency in the literature. We have undertaken within- and between-individual comparisons of the clinical presentation of postnatal (PN) and non-postnatal (NPN) depressive episodes in women with recurrent depression.

In a sample of well-characterized, parous women meeting DSM-IV and ICD-10 criteria for recurrent major depressive disorder, the clinical presentation of episodes of major depression with onset within 4 weeks of giving birth (PND group, n=50) were compared with (i) the non-postnatal episodes of women with PND, and (ii) episodes of major depression in parous women who had not experienced episodes of mood disorder in relation to childbirth (NPND group, n=132). In addition, the non-postnatal episodes of the PND group of women were compared with the depressive episodes of the NPND group.

The small number of differences found between PN and NPN depressive episodes, such as reduced early morning wakening in postnatal episodes, are likely to be explicable by the context of having a new baby rather than by any difference in the nature of the underlying depression.

The results do not point to substantial differences in clinical presentation between episodes of major depression occurring in relation to childbirth and at other times. Other avenues of research are therefore required to demonstrate a specific relationship between childbirth and depression.

Cognitive theories associate depression with negative biases in information processing. Although negatively biased cognitions are well documented in depressed patients and to some extent in recovered patients, it remains unclear whether these abnormalities are present before the first depressive episode.

High neuroticism (N) is a well-recognized risk factor for depression. The current study therefore compared different aspects of emotional processing in 33 high-N never-depressed and 32 low-N matched volunteers. Awakening salivary cortisol, which is often elevated in severely depressed patients, was measured to explore the neurobiological substrate of neuroticism.

High-N volunteers showed increased processing of negative and/or decreased processing of positive information in emotional categorization and memory, facial expression recognition and emotion-potentiated startle (EPS), in the absence of global memory or executive deficits. By contrast, there was no evidence for effects of neuroticism on attentional bias (as measured with the dot-probe task), over-general autobiographical memory, or awakening cortisol levels.

These results suggest that certain negative processing biases precede depression rather than arising as a result of depressive experience per se and as such could in part mediate the vulnerability of high-N subjects to depression. Longitudinal studies are required to confirm that such cognitive vulnerabilities predict subsequent depression in individual subjects.

Intellectual disability (ID) is highly prevalent in tuberous sclerosis (TS). Putative neurobiological risk factors include indices of cortical tuber (CT) load and epilepsy. We have used univariate and multivariate analyses, including both CT and epilepsy measures as predictors, in an attempt to clarify the pattern of cross-sectional associations between these variables and ID in TS.

Forty-eight children, adolescents and young adults with TS were identified through regional specialist clinics. All subjects underwent thorough history taking and examination, and had brain magnetic resonance imaging (MRI) scans. The number and regional distribution of CTs was recorded. Subjects were assigned to one of nine ordered intellectual quotient (IQ) categories (range <25 to >130) using age-appropriate tests of intelligence.

On univariate analyses, ID was significantly associated with both a history of infantile spasm (IS) (Z=−2·49, p=0·01) and total CT count (Spearman's ρ=−0·30, p=0·04). When controlling for total CT count, the presence of CTs in frontal (regression coefficient=−2·43, p=0·02) and temporal (regression coefficient=−1·60, p=0·02) lobes was significantly associated with ID. In multivariate analyses the association between IS and ID was rendered insignificant by the inclusion of the presence of CTs in temporal and frontal lobes, both of which remained associated (p=0·05 and p=0·06 respectively) with ID.

The presence of CTs in specific brain regions as opposed to a history of IS was associated with ID in TS. The significance of these findings is discussed in relation to previous work in TS, and the neural basis of intelligence.

Studies have found associations between psychological distress (PD) and increased risk of myocardial infarction (MI). However, it is not clear whether the relationship reflects the subtle influence of pre-existing illness on both PD and MI. This study examines the association between PD and MI in a prospective epidemiological study of 1864 middle-aged men to examine if the association is explained by existing illness.

This study was a prospective cohort study modelling the association between PD, measured using the 30-item General Health Questionnaire (GHQ) and non-fatal myocardial infarction (NFMI) and fatal/non-fatal myocardial infarction (FNFMI).The relationship was modelled in a series of logistic regression models adjusted for age, then cigarette smoking, then social position, and finally for all sociodemographic characteristics, coronary heart disease (CHD) risk factors, and baseline CHD.

PD was associated with a 70% and 68% increased risk of NFMI and FNFMI in fully adjusted analysis. However, PD was not associated with an increased risk of NFMI and FNFMI in analyses excluding those with baseline CHD. Further, being psychologically distressed and physically ill was associated with a greater than twofold risk of NFMI and FNFMI, 2·37 (95% CI 1·33–4·20) and 2·33 (95% CI 1·32–4·12) respectively.

This study suggests that PD is a moderator of the increased risk of MI associated with existing physical illness. PD in men who are physically ill is a marker of an underlying chronic physical illness. The prospective association of PD with MI is not independent of baseline physical illness.

Prenatal exposure to diethylstilboestrol (DES) may induce neurodevelopmental disturbances potentially mediating an increased risk of psychiatric disorders in exposed subjects. Most findings of an increased prevalence of psychiatric disorders in men and women prenatally exposed to DES are not easy to interpret because of selection biases.

Information on hormonal treatment during pregnancy and on offspring's medical outcome was collected from women participating in the Etude Epidemiologique de femmes de la Mutuelle Générale de l'Education Nationale (E3N) prospective cohort who completed consecutive postal questionnaires on a range of medical events since 1990. Information on hormonal treatment during pregnancy was collected in 1992 and on offspring's medical outcome in 2004. The psychiatric outcome of subjects prenatally exposed to DES was compared to that of their unexposed siblings.

A total of 1352 mothers with DES treatment for at least one pregnancy provided information on 1680 exposed children and 1447 unexposed siblings. After adjustment for duration of follow-up, educational level, history of obstetric complication, prenatal exposure to progestagen drugs or other hormones and parental history of psychiatric hospitalization, no association was found between prenatal exposure to DES and occurrence of strictly defined serious psychiatric outcome (suicide or psychiatric hospitalization) [adjusted odds ratio (OR) 0·8, 95% confidence interval (CI) 0·5–1·2], or of broadly defined serious psychiatric outcome (same events plus psychiatric or psychological consultation) (adjusted OR 1·0, 95% CI 0·8–1·2).

These findings suggest that the impact of prenatal DES exposure on foetal brain development, if any, is unlikely to increase the risk of serious psychiatric disorders.

Perinatal problems may be associated with an increased risk for psychological and physical health problems in adulthood, although it is unclear which perinatal problems (low birthweight, preterm birth, low Apgar scores, and small head circumference), or what clusters of problems, are more likely to be associated with later health problems. It is also not known whether perinatal problems (singly or together) are associated with co-morbidity between psychological and physical health problems.

A regional random sample (from Baltimore) of mothers and their children (n=1525) was followed from birth to adulthood (mean age 29 years). Perinatal conditions were measured at delivery. Psychological problems (depression and suicidal ideation) were measured with the General Health Questionnaire-28 (GHQ-28) and physical problems (asthma and hypertension) with the RAND-36 Health Status Inventory.

Children with perinatal problems were generally at increased risk for depression, suicidal ideation and hypertension, and co-morbid depression and hypertension even after controlling for confounders. One possible underlying condition, preterm low birthweight (LBW), extracted by cluster analysis, considering all of the four perinatal problems, was associated with increased risk for psychological and physical health outcomes as well as co-morbidity of the two.

LBW, preterm birth and small head circumference singly increased the risk for both psychological and physical health problems, as well as co-morbid depression and hypertension, while low Apgar scores were only associated with psychological problems. Delineating different etiological processes, such as preterm LBW, considering various perinatal problems simultaneously, might be of benefit to understanding the fetal origin of adult illness and co-morbidity.

Sternberg's Memory Scanning Test (MST) is a useful paradigm for evaluating the speed and efficiency of information processing in working memory. Unfortunately, the classical MST has major drawbacks for use in applied settings such as the clinic. For example, its administration time is long and the test is too difficult for older people or people with cognitive disorders. It would be advantageous to have a test for the assessment of information processing in working memory for use in applied settings, for example in differential diagnostics in clinical settings.

The MST was modified into a format that makes it more appropriate for use in the clinic, the Paper & Pencil MST (P&P MST). The influence of age and age-extrinsic factors on the P&P MST was evaluated in a large sample (n=1839) of healthy and cognitively intact adults (24–81 years) to establish the normal range of performance.

Age and education affected all components of information processing in working memory. Gender did not affect the non-memory processing stages in the P&P MST, but affected the speed of memory scanning. An Age×Gender interaction was observed, which suggested that females who were aged below 55 scanned working memory faster than males, and vice versa for people aged above 55.

The established P&P MST norms provide a useful tool in applied settings when a person's memory scanning and non-memory processes in working memory are to be evaluated.

DSM-IV criteria for illicit drug abuse and dependence are largely based on criteria developed for alcohol use disorders and there is a lack of research evidence on the psychometric properties of these symptoms when applied to illicit drugs.

This study utilizes data on abuse/dependence criteria for cannabis, cocaine, stimulants, sedatives, tranquilizers, opiates, hallucinogens and inhalants from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC, n=43 093). Analyses included factor analysis to explore the dimensionality of illicit drug abuse and dependence criteria, calculation of item difficulty and discrimination within an item response framework and a descriptive analysis of ‘diagnostic orphans’: individuals meeting criteria for 1–2 dependence symptoms but not abuse. Rates of psychiatric disorders were compared across groups.

Results favor a uni-dimensional construct for abuse/dependence on each of the eight drug classes. Factor loadings, item difficulty and discrimination were remarkably consistent across drug categories. For each drug category, between 29% and 51% of all individuals meeting criteria for at least one symptom did not receive a formal diagnosis of either abuse or dependence and were therefore classified as ‘orphans’. Mean rates of disorder in these individuals suggested that illicit drug use disorders may be more adequately described along a spectrum of severity.

While there were remarkable similarities across categories of illicit drugs, consideration of item difficulty suggested that some alterations to DSM regarding the relevant severity of specific abuse and dependence criteria may be warranted.

We investigated the genetic and environmental contributions to covariation between smoking age-at-onset, cigarette consumption and smoking persistence.

Multivariate biometrical modelling methods were applied to questionnaire data from Australian twins and their siblings (14 472 individuals from 6247 families). The contributions of genetic and environmental factors to covariation between the three traits were estimated, allowing for sex differences in both trait prevalence and the magnitude of genetic and environmental effects.

All traits were moderately heritable in males and females (estimates between 0·40 and 0·62), but there were sex differences in the extent to which additive genetic influences were shared across traits. Twin-specific environmental factors accounted for a substantial proportion of the variance in smoking age-at-onset in females (0·19) and males (0·12), but had little influence (<0·08) on other traits. Unique environmental factors were estimated to have a moderate influence on smoking age-at-onset (0·17 for females, 0·19 for males), but a stronger influence on other traits (between 0·39 and 0·49).

These results provide some insight into observed sex differences in smoking behaviour, and suggest that searching for pleiotropic genes may prove fruitful. However, further work on phenotypic definitions of smoking behaviour, particularly persistence, is warranted.