The association between physical activity and risk of neurodegenerative diseases is not well established. We therefore aimed to quantify this association using meta-analytical techniques.

We searched Medline, the Cochrane Database of Systematic Reviews and Web of Science databases from 1990 to 2007 for prospective epidemiological studies of physical activity and incident dementia, Alzheimer's and Parkinson's disease. We excluded studies of physical activity and cognitive decline without diagnosis of a neurodegenerative disease. Information on study design, participant characteristics, measurement of exposure and outcome variables, adjustment for potential confounding, and estimates of associations was abstracted independently by the two investigators.

We included 16 prospective studies in the overall analysis, which incorporated 163797 non-demented participants at baseline with 3219 cases at follow-up. We calculated pooled relative risk (RR) using a random effects model. The RR of dementia in the highest physical activity category compared with the lowest was 0.72 [95% confidence interval (CI) 0.60–0.86, p<0.001], for Alzheimer's, 0.55 (95% CI 0.36–0.84, p=0.006), and for Parkinson's 0.82 (95% CI 0.57–1.18, p=0.28).

Our results suggest that physical activity is inversely associated with risk of dementia. Future studies should examine the optimal dose of physical activity to induce protection, which presently remains unclear.

Previous research has shown that adults with intellectual disability (ID) may be more at risk of developing dementia in old age than expected. However, the effect of age and ID severity on dementia prevalence rates has never been reported. We investigated the predictions that older adults with ID should have high prevalence rates of dementia that differ between ID severity groups and that the age-associated risk should be shifted to a younger age relative to the general population.

A two-staged epidemiological survey of 281 adults with ID without Down syndrome (DS) aged ⩾60 years; participants who screened positive with a memory task, informant-reported change in function or with the Dementia Questionnaire for Persons with Mental Retardation (DMR) underwent a detailed assessment. Diagnoses were made by psychiatrists according to international criteria. Prevalence rates were compared with UK prevalence and European consensus rates using standardized morbidity ratios (SMRs).

Dementia was more common in this population (prevalence of 18.3%, SMR 2.77 in those aged ⩾65 years). Prevalence rates did not differ between mild, moderate and severe ID groups. Age was a strong risk factor and was not influenced by sex or ID severity. As predicted, SMRs were higher for younger age groups compared to older age groups, indicating a relative shift in age-associated risk.

Criteria-defined dementia is 2–3 times more common in the ID population, with a shift in risk to younger age groups compared to the general population.

The dual task paradigm (Baddeley et al.1986; Della Sala et al.1995) has been proposed as a sensitive measure of Alzheimer's dementia, early in the disease process.

We investigated this claim by administering the modified dual task paradigm (utilising a pencil-and-paper version of a tracking task) to 33 patients with amnestic mild cognitive impairment (aMCI) and 10 with very early Alzheimer's disease, as well as 21 healthy elderly subjects and 17 controls with depressive symptoms. All groups were closely matched for age and pre-morbid intellectual ability.

There were no group differences in dual task performance, despite poor performance in episodic memory tests of the aMCI and early Alzheimer's disease groups. In contrast, the Alzheimer patients were specifically impaired in the trail-making test B, another commonly used test of divided attention.

The dual task paradigm lacks sensitivity for use in the early differential diagnosis of Alzheimer's disease.

The relationship between mental and physical disorders is well established, but there is less consensus as to the nature of their joint association with disability, in part because additive and interactive models of co-morbidity have not always been clearly differentiated in prior research.

Eighteen general population surveys were carried out among adults as part of the World Mental Health (WMH) Survey Initiative (n=42 697). DSM-IV disorders were assessed using face-to-face interviews with the Composite International Diagnostic Interview (CIDI 3.0). Chronic physical conditions (arthritis, heart disease, respiratory disease, chronic back/neck pain, chronic headache, and diabetes) were ascertained using a standard checklist. Severe disability was defined as on or above the 90th percentile of the WMH version of the World Health Organization Disability Assessment Schedule (WHODAS-II).

The odds of severe disability among those with both mental disorder and each of the physical conditions (with the exception of heart disease) were significantly greater than the sum of the odds of the single conditions. The evidence for synergy was model dependent: it was observed in the additive interaction models but not in models assessing multiplicative interactions. Mental disorders were more likely to be associated with severe disability than were the chronic physical conditions.

This first cross-national study of the joint effect of mental and physical conditions on the probability of severe disability finds that co-morbidity exerts modest synergistic effects. Clinicians need to accord both mental and physical conditions equal priority, in order for co-morbidity to be adequately managed and disability reduced.

Prior research on the nature of the vulnerability of neuroticism to psychopathology suggests biases in information processing towards emotional rather than neutral information. It is unclear to what extent this relationship can be explained by genetic or environmental factors.

The genetic relationship between a neuroticism composite score and free recall of pleasant and unpleasant words and the reaction time on negative probes (dot-probe task) was investigated in 125 female twin pairs. Interaction effects were modelled to test whether the correlation between neuroticism and cognitive measures depended on the level of the neuroticism score.

The only significant correlation was between neuroticism and the proportion of recalled unpleasant words (heritability is 30%), and was only detectable at the higher end of the neuroticism distribution. This interaction effect seems to be due to environmental effects that make people in the same family more similar (e.g. parental discipline style), rather than genetic factors. An interesting sub-finding was that faster reaction times for left versus right visual field probes in the dot-probe task suggest that cognitive processing in the right hemisphere is more sensitive to subliminal (biologically relevant) cues and that this characteristic is under substantial genetic control (49%). Individual differences in reaction times on right visual field probes were due to environmental effects only.

There is no evidence that the predisposition of individuals to focus on negative (emotional) stimuli is a possible underlying genetic mechanism of neuroticism.

Little is known about factors that predict first lifetime episodes of major depression in middle-aged women. It is not known whether health-related factors and life stress pose more or less of a risk to the onset of clinical depression than does the menopausal transition.

The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) was used to assess diagnoses of lifetime, annual and current major depression in a community-based sample of premenopausal or early perimenopausal African American and White women. Menstrual cycle characteristics, psychosocial and health-related factors, and blood samples for assay of reproductive hormones were obtained annually. Two hundred and sixty-six women without a history of major depression at baseline constituted the cohort for the current analyses.

Over 7 years of follow-up, 42 (15.8%) women met criteria for a diagnosis of major depression. Frequent vasomotor symptoms (VMS; hot flashes and/or night sweats) (HR 2.14, p=0.03) were a significant predictor of major depression in univariate analyses. After simultaneous adjustment for multiple predictors in Cox proportional hazards analyses, frequent VMS were no longer significant; lifetime history of an anxiety disorder (HR 2.20, p=0.02) and role limitations due to physical health (HR 1.88, p=0.07) at baseline and a very stressful life event (HR 2.25, p=0.04) prior to depression onset predicted a first episode of major depression.

Both earlier (e.g. history of anxiety disorders) and more proximal factors (e.g. life stress) may be more important than VMS in contributing to a first episode of major depression during midlife.

For more than a decade high-frequency repetitive transcranial magnetic stimulation (rTMS) has been applied to the left dorsolateral prefrontal cortex (DLPFC) in search of an alternative treatment for depression. The aim of this study was to provide an update on its clinical efficacy by performing a meta-analysis involving double-blind sham-controlled studies.

A literature search was conducted in the databases PubMed and Web of Science in the period between January 1980 and November 2007 with the search terms ‘depression’ and ‘transcranial magnetic stimulation’. Thirty double-blind sham-controlled parallel studies with 1164 patients comparing the percentage change in depression scores from baseline to endpoint of active versus sham treatment were included. A random effects meta-analysis was performed to investigate the clinical efficacy of fast-frequency rTMS over the left DLPFC in depression.

The test for heterogeneity was not significant (QT=30.46, p=0.39). A significant overall weighted mean effect size, d=0.39 [95% confidence interval (CI) 0.25–0.54], for active treatment was observed (z=6.52, p<0.0001). Medication resistance and intensity of rTMS did not play a role in the effect size.

These findings show that high-frequency rTMS over the left DLPFC is superior to sham in the treatment of depression. The effect size is robust and comparable to at least a subset of commercially available antidepressant drug agents. Current limitations and future prospects are discussed.

The experience of uncontrollability and helplessness in the face of stressful life events is regarded as an important determinant in the development and maintenance of depression. The inability to successfully deal with stressors might be linked to dysfunctional prefrontal functioning. We assessed cognitive, behavioural and physiological effects of stressor uncontrollability in depressed and healthy individuals. In addition, relationships between altered cortical processing and cognitive vulnerability traits of depression were analysed.

A total of 26 unmedicated depressed patients and 24 matched healthy controls were tested in an expanded forewarned reaction (S1–S2) paradigm. In a factorial design, stressor controllability varied across three consecutive conditions: (a) control, (b) loss of control and (c) restitution of control. Throughout the experiment, error rates, ratings of controllability, arousal, emotional valence and helplessness were assessed together with the post-imperative negative variation (PINV) of the electroencephalogram.

Depressed participants showed an enhanced frontal PINV as an electrophysiological index of altered information processing during both loss of control and restitution of control. They also felt more helpless than controls. Furthermore, frontal PINV magnitudes were associated with habitual rumination in the depressed subsample.

These findings indicate that depressed patients are more susceptible to stressor uncontrollability than healthy subjects. Moreover, the experience of uncontrollability seems to bias subsequent information processing in a situation where control is objectively re-established. Alterations in prefrontal functioning appear to contribute to this vulnerability and are also linked to trait markers of depression.

Previous studies have shown an elevated risk for self-harm in adolescents from ethnic minorities. However, potential contributions to this risk from socio-economic factors have rarely been addressed. The main aim of this article was to investigate any such effects.

A national cohort of 1009 157 children born during 1973–1982 was followed prospectively from 1991 to 2002 in Swedish national registers. Multivariate Cox analyses of proportional hazards were used to estimate the relative risk of hospital admission for self-harm. Parental country/region of birth was used as proxy for ethnicity.

Youth with two parents born outside Sweden (except those from Southern Europe) had higher age- and gender-adjusted hazard ratios (HRs) of self-harm than the majority population (HR 1.6–2.3). The HRs decreased for all immigrant groups when socio-economic factors were accounted for but remained significantly higher for immigrants from Finland and Western countries and for youth with one Swedish-born and one foreign-born parent.

Socio-economic factors explain much of the variation by parental country of birth of hospital admissions for self-harm in youth in Sweden.

Healthy adolescents, and adults who engage in reward-driven, risky behaviours, demonstrate poor decision-making ability. Decision making in deliberate self-harm (DSH), a reward-driven, high-risk behaviour, has received little attention. This study assessed decision making and problem solving in adolescents with current or past SH.

Decision making and problem solving were assessed using the Iowa Gambling Task (IGT) and the Means–Ends Problem-Solving Procedure (MEPS) respectively in 133 adolescents (57 healthy and 22 depressed controls with no SH history and 54 with SH history). A second analysis separated the SH group into current (n=30) and past (n=24) SH.

The collective performance of adolescents with SH history did not differ from depressed or healthy adolescents on the IGT. However, current self-harming adolescents had a trend towards more high-risk choices (p=0.06) than those with previous SH history and were the only group not to significantly improve over time, persisting with high-risk strategy throughout. Those who no longer self-harmed learnt to use a low-risk strategy similar to healthy and depressed controls. Recency of last SH episode correlated with IGT performance. Depressed participants performed well on the IGT but poorly on the MEPS. By contrast, both collective and divided SH groups had comparable MEPS scores to healthy controls, all performing better than depressed participants.

Poor decision making is present in adolescents who currently self-harm but not in those with previous history; improvement in decision-making skills may therefore be linked to cessation of self-harm. Depressed adolescents who do and do not self-harm may have distinct characteristics.

Aetiological studies of eating disorders would benefit from a solution to the problem of instability of eating disorder symptoms. We present an approach to defining an eating disorders phenotype based on the retrospective assessment of lifetime eating disorders symptoms to define a lifetime pattern of illness. We further validate this approach by testing the most common lifetime categories for differences in the prevalence of specific childhood personality traits.

Ninety-seven females participated in this study, 35 with a current diagnosis of restricting anorexia nervosa, 32 with binge/purging subtype of anorexia nervosa and 30 with bulimia nervosa. Subjects were interviewed by a newly developed EATATE Lifetime Diagnostic Interview for a retrospective assessment of the lifetime course of eating disorders symptoms and childhood traits reflecting obsessive–compulsive personality.

The data illustrate the extensive instability of the eating disorders diagnosis. Four most common lifetime diagnostic categories were identified that significantly differ in the prevalence of childhood traits. Perfectionism and rigidity were more common in groups with a longer duration of underweight status, longer episodes of severe food restriction, excessive exercising, and shorter duration of binge eating.

The assessment of lifetime symptoms may produce a more accurate definition of the eating disorders phenotype. Obsessive–compulsive traits in childhood may moderate the course producing longer periods of underweight status. These findings may have important implications for nosology, treatment and future aetiological studies of eating disorders.

Previous studies have shown moderate heritability for female orgasm. So far, however, no study has addressed the pattern of genetic and environmental influences on diverse sexual dysfunctions in women, nor how genetic and environmental factors contribute to the associations between them.

The sample was drawn from the Genetics of Sex and Aggression (GSA) sample and consisted of 6446 female twins (aged 18–43 years) and 1994 female siblings (aged 18–49 years). The participants responded to the Female Sexual Function Index (FSFI), either by post or online.

Model fitting analyses indicated that individual differences on all six subdomains of the FSFI (desire, arousal, lubrication, orgasm, satisfaction, and pain) were primarily due to non-shared (individual-specific) environmental influences. Genetic influences were modest but significant, whereas shared environmental influences were not significant. A correlated factors model including additive and non-additive genetic and non-shared environmental effects proved to have the best fit and suggested that both correlated additive and non-additive genetic factors and unique environmental factors underlie the co-occurrence of the sexual function problems.

The findings suggest that female sexual dysfunctions are separate entities with some shared aetiology. They also indicate that there is a genetic susceptibility for sexual dysfunctions. The unique experiences of each individual are, however, the main factors determining if, and which, dysfunction develops.

Premenstrual dysphoric disorder (PMDD) was included as a provisional diagnostic category in the appendices of Diagnostic and Statistical Manual of Mental Disorders (DSM)-III-R (then called late luteal phase dysphoric disorder) and remained as an appendix in DSM-IV. Our study aimed to determine the prevalence of PMDD using all four DSM-IV research diagnostic criteria in a representative sample of women of reproductive age in the United States.

Data were collected in the homes of women between the ages of 13 and 55 years in two urban and two rural sites using a random sampling procedure developed by the National Opinion Research Center. Women completed daily symptom questionnaires and provided urine specimens each day for two consecutive ovulatory menstrual cycles (ovulation was estimated for women taking oral contraceptives) and were screened for psychiatric disorders by trained interviewers. Symptoms were counted toward a diagnosis of PMDD if they worsened significantly during the late luteal week during two consecutive ovulatory menstrual cycles, occurred on days in which women reported marked interference with functioning, and were not due to another mental disorder.

In the final analysis, 1246 women who had had at least one menstrual cycle and were neither naturally nor surgically menopausal nor pregnant were selected. Of the women in the study, 1.3% met criteria for the diagnosis as defined in DSM-IV.

The prevalence of PMDD is considerably lower than DSM-IV estimates and all but one of the estimates obtained from previous studies when all DSM-IV diagnostic criteria are considered. We suggest a new process for diagnosing PMDD based on our findings.

Little is known about the effects of adult attention deficit hyperactivity disorder (ADHD) on work performance or accidents-injuries.

A survey was administered in 2005 and 2006 to employees of a large manufacturing firm to assess the prevalence and correlates of adult ADHD. Respondents (4140 in 2005, 4423 in 2006, including 2656 in both surveys) represented 35–38% of the workforce. ADHD was assessed with the World Health Organization (WHO) Adult ADHD Self-Report Scale (ASRS), a validated screening scale for DSM-IV adult ADHD. Sickness absence, work performance and workplace accidents-injuries were assessed with the WHO Health and Work Performance Questionnaire (HPQ).

The estimated current prevalence (standard error) of DSM-IV ADHD was 1.9% (0.4). ADHD was associated with a 4–5% reduction in work performance (χ12=9.1, p=0.001), a 2.1 relative-odds of sickness absence (χ12=6.2, p=0.013), and a 2.0 relative-odds of workplace accidents-injuries (χ12=5.1, p=0.024). The human capital value (standard error) of the lost work performance associated with ADHD totaled US$4336 (676) per worker with ADHD in the year before interview. No data were available to monetize other workplace costs of accidents-injuries (e.g. destruction of equipment). Only a small minority of workers with ADHD were in treatment.

Adult ADHD is a significantly impairing condition among workers. Given the low rate of treatment and high human capital costs, in conjunction with evidence from controlled trials that treatment can reduce ADHD-related impairments, ADHD would seem to be a good candidate for workplace trials that evaluate treatment cost-effectiveness from the employer's perspective.

Previous research indicates that alcohol and drug dependence constitute aspects of a general vulnerability to externalizing disorders that accounts for much of the parent-offspring resemblance for these and related disorders. This study examined how adolescent offspring risk for externalizing psychopathology varies with respect to parental alcoholism and illicit drug dependence.

Data from the Minnesota Twin Family Study, a community-based investigation of adolescents (age 17 years, n=1252) and their parents, were used. Lifetime diagnoses of alcohol and drug dependence (among both parents and offspring) and offspring attention deficit hyperactivity disorder, oppositional defiant disorder, conduct disorder, adult antisocial behavior, and nicotine dependence were assessed via structured interviews.

Parental alcohol dependence and parental drug dependence were similarly associated with increased risk for nearly all offspring disorders, with offspring of alcohol and drug-dependent parents having approximately 2–3 times the odds for developing a disorder by late adolescence compared to low-risk offspring. Compared to parental dependence on other illicit drugs, parental cannabis dependence was associated with weaker increased risk for offspring externalizing disorders.

Both parental alcohol and drug dependence are independently associated with an increased risk for a broad range of externalizing psychopathology among late-adolescent offspring.

The ‘gateway’ pattern of drug initiation describes a normative sequence, beginning with alcohol and tobacco use, followed by cannabis, then other illicit drugs. Previous work has suggested that ‘violations’ of this sequence may be predictors of later problems but other determinants were not considered. We have examined the role of pre-existing mental disorders and sociodemographics in explaining the predictive effects of violations using data from the US National Comorbidity Survey Replication (NCS-R).

The NCS-R is a nationally representative face-to-face household survey of 9282 English-speaking respondents aged 18 years and older that used the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI) to assess DSM-IV mental and substance disorders. Drug initiation was estimated using retrospective age-of-onset reports and ‘violations’ defined as inconsistent with the normative initiation order. Predictors of violations were examined using multivariable logistic regressions. Discrete-time survival analysis was used to see whether violations predicted progression to dependence.

Gateway violations were largely unrelated to later dependence risk, with the exception of small increases in risk of alcohol and other illicit drug dependence for those who initiated use of other illicit drugs before cannabis. Early-onset internalizing disorders were predictors of gateway violations, and both internalizing and externalizing disorders increased the risks of dependence among users of all drugs.

Drug use initiation follows a strong normative pattern, deviations from which are not strongly predictive of later problems. By contrast, adolescents who have already developed mental health problems are at risk for deviations from the normative sequence of drug initiation and for the development of dependence.