Many patients with major depressive disorder (MDD) who experience full symptomatic remission after antidepressant treatment still have residual depressive symptoms. We describe the types and frequency of residual depressive symptoms and their relationship to subsequent depressive relapse after treatment with citalopram in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial.

Participants in primary (n=18) and psychiatric (n=23) practice settings were openly treated with citalopram using measurement-based care for up to 14 weeks and follow-up for up to 1 year. We assessed 943 (32.8% of 2876) participants who met criteria for remission to determine the proportions with individual residual symptoms and any of the nine DSM-IV criterion symptom domains to define a major depressive episode. At each visit, the 16-item Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR16) and the self-report Frequency, Intensity, and Burden of Side Effects Rating (FIBSER) scale were used to assessed depressive symptoms and side-effects respectively.

More than 90% of remitters had at least one residual depressive symptom (median=3). The most common were weight increase (71.3%) and mid-nocturnal insomnia (54.9%). The most common residual symptom domains were sleep disturbance (71.7%) and appetite/weight disturbance (35.9%). Those who remitted before 6 weeks had fewer residual symptoms at study exit than did later remitters. Residual sleep disturbance did not predict relapse during follow-up. Having a greater number of residual symptom domains was associated with a higher probability of relapse.

Patients with remission of MDD after treatment with citalopram continue to experience selected residual depressive symptoms, which increase the risk of relapse.

It has become widely accepted that cognitive deficits in schizophrenia are related to functional outcome. However, it remains to be seen whether these associations are relevant for predicting which cases will have a global functional recovery. In this study, we attempt to determine whether global functional recovery (integrating social and occupational outcomes) after first-episode schizophrenia (FES) can be predicted by cognitive variables.

A total of 131 FES patients with functional deficits (n=97) and functional recovery (n=34) as determined at 1-year follow-up were examined. Neuropsychological, sociodemographic, pre-morbid and clinical data at baseline were analysed using independent groups comparisons and a logistic regression method.

Sustained attention and negative symptoms emerged as significant predictors of good global functional outcome. Although the model revealed a high accuracy (91%) in the classification of patients with functional deficits, it was unacceptably low (26%) in the classification of patients with global functional recovery.

The limitations found in the prediction of a favourable global functional outcome may well be an indication for a need to address the role of other factors not commonly included in longitudinal studies of long-term outcomes in schizophrenia.

Encoding and maintenance of information in working memory, followed by internal manipulation of that information for planning adaptive behavior, are two key components of working-memory systems. Both processes have been reported to be impaired in schizophrenia, but few studies have directly compared the relative severity of these abnormalities, or the degree to which manipulation deficits might be secondary to alterations in maintenance processes.

Clinically stable schizophrenia patients (n=25) and a demographically similar healthy comparison group (n=24) were administered a verbal span task with three levels of working-memory load. Maintenance was assessed using sequential position questions. Manipulation processes were assessed by requiring comparison of the relative sequential position of test items, which entailed simultaneous serial search strategies regarding item order.

Both groups showed reduced accuracy and increased reaction time for manipulation compared with maintenance processing. There were significant patient impairments across working-memory loads. There was no differential deficit in manipulation processing, and effect sizes of relative deficit in the patient group were higher for maintenance than manipulation processing.

The strong correlation for maintenance and manipulation deficits suggest that impairments in the ability to internally manipulate information stored in working-memory systems are not greater than alterations in the encoding and maintaining of information in working memory and that disturbances in maintenance processing may contribute to deficits in higher-order working-memory operations.

In countries where legal abortion is restricted, many unwanted pregnancies are carried to term. Attempting an unsuccessful abortion may influence women's mental health. This study investigated the common mental disorders (CMDs) of depression and anxiety in the third trimester of pregnancy in women who wanted or had attempted an abortion in a poor region of Brazil.

CMDs were assessed by using the 20-item Self-Reporting Questionnaire (SRQ-20) in all pregnant women aged 18–49 years who were registered with publicly funded primary health care in Recife, Northeast Brazil.

The study achieved a high response rate and 1121 (98.9%) women completed the interview. The prevalence of CMDs for the sample was 43.1% [95% confidence interval (CI) 40.2–46.1], and 63.6% (95% CI 55.4–71.2) among the 13.7% of women who attempted an abortion. The association between CMDs and attempted an abortion [odds ratio (OR) 2.05, 95% CI 1.3–3.1] remained after adjustment for confounders.

This study found that attempting an abortion in the current pregnancy was associated with CMDs. Good access to family planning programs, including access to contraceptive methods and safe abortion, should help to improve the mental health of women.

The effects of cannabis use on neuropsychological indices that show characteristic disturbances in schizophrenia are unclear. The effect of cannabis use on these cognitive functions is of particular interest given the hypothesized association between cannabis use and schizophrenia. Therefore, this study aimed to examine the effects of cannabis use on attentional control, working memory and executive functioning, in both healthy individuals and patients with schizophrenia.

Neuropsychological performance was assessed in 36 cannabis users who were otherwise healthy, 35 healthy non-users, 22 cannabis-using patients with schizophrenia, and 49 non-using patients with schizophrenia. Participants were administered the Stroop task, the letter–number sequencing and spatial span subtests of the Wechsler Memory Scale, and the Wisconsin Card Sorting Test (WCST).

Patients with schizophrenia (both cannabis users and non-users) showed significantly poorer performance across all neuropsychological tasks, relative to controls; however, there were no significant differences between schizophrenic cannabis users and schizophrenic non-users on any measures, with the exception of increased non-perseverative errors on the WCST in cannabis-using patients. Similarly, healthy cannabis users showed no significant differences from healthy non-users in any of the cognitive domains, with the exception of a schizophrenic-like increase in perseveration on the WCST.

Amongst both healthy individuals and patients with schizophrenia there appears to be little difference in cognitive performance between cannabis users and non-users, suggesting that cannabis use has only subtle effects on the neurocognitive performance indices assessed here, which have been well established to be disturbed in schizophrenia.

To examine the role of psychological distress, negative life events, social support and lack of fitness (using breathlessness on exertion as a proxy) in the development of new onset fatigue in a primary care population.

Adults between the ages of 18 and 45 years who were registered with five general practices in South East England were asked to complete a fatigue questionnaire and the 12-item General Health Questionnaire. Between 1 and 12 months later, subjects who visited the general practitioner (GP) with a suspected viral infection were recruited to the study and asked to complete measures of fatigue, psychological distress, life events, social support and allergies (stage 2). The next person to present to the GP with a complaint other than a viral illness was recruited as a control. Factors assessed at stage 2 that were associated with the development of fatigue were examined with stepwise logistic regression.

Acute fatigue was not associated with a viral illness. Negative life events and breathlessness on exertion (interpreted as lack of fitness) were associated with incident cases of fatigue. However, when controlling for concurrent psychological distress, the independent association of negative life events disappeared.

Psychological distress was strongly associated with new onset fatigue and hence emphasizes the significance of psychological distress as a concomitant complaint in fatigue. Further, the salient association between breathlessness and fatigue may indicate the need to recommend exercise as a therapeutic strategy to improve physical fitness in the primary care setting.

Slow-frequency repetitive transcranial magnetic stimulation (rTMS) to the frontal cortex has been suggested as a safer and better tolerable alternative to fast-frequency rTMS in the treatment of major depressive disorder (MDD). The aim of the present study was to examine the efficacy of slow-frequency rTMS to the frontal cortex in MDD.

A literature search was carried out in the databases PubMed and Web of Science in the period between January 1994 and July 2009 with the search terms ‘depression’ and ‘transcranial magnetic stimulation’. Nine double-blind sham-controlled parallel intention-to-treat studies (252 patients) fulfilled inclusion criteria and were entered in a random-effects meta-analysis.

The test for heterogeneity was not significant (QT=9.63, p=0.38). An overall weighted moderate mean effect size (d=0.63, 95% confidence interval=0.03–1.24) for active treatment was observed.

The findings suggest that slow-frequency rTMS to the frontal cortex is more effective than sham treatment and may be equally effective as fast-frequency rTMS in the treatment of MDD.

Patterns of suicide rates in China differ in many ways from those in the West. This study aimed to identify the risk factors characteristic for young rural Chinese suicides.

This was a case-control psychological autopsy (PA) study. The samples were suicides and living controls (both aged 15–34 years) from 16 rural counties of China. We interviewed two informants for each suicide and each control with pretested and validated instruments to estimate psychosocial, psychiatric and other risk factors for suicides.

The prevalence of mental disorders was higher among the young Chinese who died by suicide than among the living controls, but was lower than among suicides in the West. Marriage was not a protecting factor for suicide among young rural Chinese women, and never-married women who were involved in relationships were about three times more likely to commit suicide than single women who were unattached. Religion/religiosity was not a protecting factor in Chinese suicide, as it tended to be stronger for suicides than for controls. Impulsivity was significantly higher for suicides than for controls. Psychological strain, resulting from conflicting social values between communist gender equalitarianism and Confucian gender discrimination, was associated significantly with suicide in young rural Chinese women, even after accounting for the role of psychiatric illness.

Risk factors for suicide in rural China are different from those in the West. Psychological strain plays a role in suicide. Suicide prevention programs in China should incorporate culture-specific considerations.

The psychosocial vulnerability model of hostility posits that hostile individuals, given their oppositional attitudes and behaviours, are more likely to have increased interpersonal conflicts, lower social support, more stressful life events (SL-E) and higher likelihood of depression. However, little research has tested this hypothesis using large-scale prospective samples. The present study aims to assess the predictive value of hostility for depressive mood.

Data are from 3399 participants in the Whitehall II cohort study, aged 35–55 years at baseline (phase 1 1985–1988). Cynical hostility was measured at phase 1. Depressive mood was assessed at phase 7 (2002–2004). Sociodemographic characteristics, health-related behaviours, common mental disorders and antidepressant medication intake were assessed at phase 1. SL-E and confiding/emotional support were measured at phases 1, 2 (1989–1990) and 5 (1997–1999).

Compared with participants in the lowest quartile of cynical hostility, those in the highest quartiles were more likely to have depressive mood [second quartile: odds ratio (OR) 1.58, 95% confidence interval (CI) 1.14–2.20; third quartile: OR 2.78, 95% CI 2.03–3.77; fourth quartile: OR 4.66, 95% CI 3.41–6.36] in analysis adjusted for sociodemographic characteristics. This graded association was somewhat attenuated (⩽18%) but remained robust to adjustments for the covariates measured at baseline and follow-up. The association was also evident in participants free of mental health difficulties at baseline.

Cynical hostility is a strong and robust predictor of depressive mood. Consideration of personality characteristics may be crucial to the understanding and management of depression.

Although depression appears to decrease in late life, this could be due to misattribution of depressive symptom to physical disorders that increase in late life.

We studied age differences in major depressive episodes (MDE) in the National Comorbidity Survey Replication, a national survey of the US household population. DSM-IV MDE was defined without organic exclusions or diagnostic hierarchy rules to facilitate analysis of co-morbidity. Physical disorders were assessed with a standard chronic conditions checklist and mental disorders with the WHO Composite International Diagnostic Interview (CIDI) version 3.0.

Lifetime and recent DSM-IV/CIDI MDE were significantly less prevalent among respondents aged ⩾65 years than among younger adults. Recent episode severity, but not duration, was also lower among the elderly. Despite prevalence of mental disorders decreasing with age, co-morbidity of hierarchy-free MDE with these disorders was either highest among the elderly or unrelated to age. Co-morbidity of MDE with physical disorders, in comparison, generally decreased with age despite prevalence of co-morbid physical disorders usually increasing. Somewhat more than half of respondents with 12-month MDE received past-year treatment, but the percentage in treatment was lowest and most concentrated in the general medical sector among the elderly.

Given that physical disorders increase with age independent of depression, their lower associations with MDE in old age argue that causal effects of physical disorders on MDE weaken in old age. This result argues against the suggestion that the low estimated prevalence of MDE among the elderly is due to increased confounding with physical disorders.

Large community-based epidemiological surveys have consistently identified high co-morbidity between major depressive episode (MDE) and generalized anxiety disorder (GAD). Some have suggested that this co-morbidity may be artificial and the product of the current diagnostic system. Because of the added direct and indirect costs associated with co-morbidity, it is important to investigate whether methods of diagnostic classification are artificially increasing the level of observed co-morbidity.

The item response theory (IRT) log-likelihood ratio procedure was used to test for differential item functioning (DIF) of MDE symptoms between respondents with and without a diagnosis of GAD in the 2001–2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC).

The presence of GAD significantly increased the chances of reporting any symptom of MDE, with odds ratios ranging from 2.54 to 5.36. However, there was no indication of significant DIF of MDE symptoms in respondents with and without GAD.

The lack of any significant DIF indicates that cases with GAD do not present with a distinct MDE symptom profile, one that is consistent with the endorsement of symptoms that are conceptually similar in nature between the two disorders, compared to cases without GAD. This does not support the hypothesis that co-morbidity between MDE and GAD is artificially inflated because of the similar symptom criteria required by the current diagnostic system. Instead, MDE and GAD may be thought of as two distinct diagnostic entities that frequently co-occur because of a shared underlying trait.

The attribution of self-generated speech to others could explain the experience of verbal hallucinations. To test this hypothesis, we developed a task to simultaneously evaluate (A) operations of self-other distinction and (B) operations that have the same cognitive demands as in A apart from self-other distinction. By adjusting A to B, operations of self-other distinction were specifically evaluated.

Thirty-nine schizophrenia patients and 26 matched healthy controls were required to distinguish between self-generated, other-generated and non-generated (self or other) sentences. The sentences were in the first, second or third person and were read in a male or female voice in equal proportions. Mixed multi-level logistic regression models were used to investigate the effect of group, sentence source, pronoun and gender of the heard sentences on response accuracy.

Patients differed from controls in the recognition of self-generated and other-generated sentences but not in general recognition ability. Pronoun was a significant predictor of response accuracy but without any significant interaction with group. Differences in the gender of heard sentences were not significant. Misattribution bias differentiated groups only in the self-other direction.

These data support the theory that misattribution of self-generated speech to others could result in verbal hallucinations. The syntactic (pronoun) factor could impact self-other distinction in subtypes of verbal hallucinations that are phenomenologically defined whereas the acoustic factor (gender of heard speech) is unlikely to affect self-other distinction.

Cognitive deficits persist despite clinical recovery in subjects with late-life depression, but more needs to be known about their longer-term outcome and factors affecting their course. To investigate this, we followed the pattern of cognitive impairments over time and examined the effects of current mood, remission status, age of depression onset and antidepressant (AD) treatment on these deficits.

Sixty-seven subjects aged ⩾60 years with DSM-IV major depressive disorder and 36 healthy comparison subjects underwent tests of global cognition, memory, executive functioning and processing speed at baseline, 6 and 18 months, with some subjects tested again after 4 years. z scores were compared between groups, with analyses of clinical factors that may have influenced cognitive performance in depressed subjects.

Half of the patients exhibited a generalized cognitive impairment (GCI) that persisted after 18 months. Patients performed worse across all cognitive domains at all time points, without substantial variability due to current mood, remission status or AD treatment. Late age of onset was associated significantly with decline in memory and executive functioning. Impaired processing speed may be a partial mediator of some deficits, but was insufficient to explain differences between patients and controls. Four-year follow-up data suggest impairments persist, but do not further decline.

Cognitive deficits in late-life depression persist up to 4 years, affect multiple domains and are related to trait rather than state effects. Differences in severity and course between early and late onset depression suggest different pathogenic processes.

Several theories have posited a common internalizing factor to help account for the relationship between mood and anxiety disorders. These disorders are often co-morbid and strongly covary. Other theories and data suggest that personality traits may account, at least in part, for co-morbidity between depression and anxiety. The present study examined the relationship between neuroticism and an internalizing dimension common to mood and anxiety disorders.

A sample of ethnically diverse adolescents (n=621) completed self-report and peer-report measures of neuroticism. Participants also completed the Structured Clinical Interview for DSM-IV (SCID).

Structural equation modeling showed that a single internalizing factor was common to lifetime diagnosis of mood and anxiety disorders, and this internalizing factor was strongly correlated with neuroticism. Neuroticism had a stronger correlation with an internalizing factor (r=0.98) than with a substance use factor (r=0.29). Therefore, neuroticism showed both convergent and discriminant validity.

These results provide further evidence that neuroticism is a necessary factor in structural theories of mood and anxiety disorders. In this study, the correlation between internalizing psychopathology and neuroticism approached 1.0, suggesting that neuroticism may be the core of internalizing psychopathology. Future studies are needed to examine this possibility in other populations, and to replicate our findings.

The mildly learning disabled population has a three-fold elevated risk for schizophrenia. It has been proposed that in some individuals this cognitive limitation is a pre-psychotic manifestation of early onset schizophrenia. We examined clinical and neuroanatomical measures of a putative extended phenotype of schizophrenia in an adolescent population receiving special educational assistance. We predicted that people with intellectual impairment and schizotypal features would exhibit amygdala volume reduction as one of the neuroanatomical abnormalities associated with schizophrenia.

Assessment by clinical interview, neuropsychological assessment and magnetic resonance imaging scanning was carried out in 28 intellectually impaired individuals identified as being at elevated risk of schizophrenia due to the presence of schizotypal traits, 39 intellectually impaired controls and 29 non-intellectually impaired controls. Amygdala volume was compared in these three groups and the relationship between symptomatology and amygdala volume investigated.

Right amygdala volume was significantly increased in the elevated risk group compared with the intellectually impaired controls (p=0.05). A significant negative correlation was seen between left amygdala volume and severity of negative symptoms within this group (p<0.05), but not in either control group.

Intellectually impaired subjects judged to be at elevated risk of schizophrenia on the basis of clinical assessment exhibit structural imaging findings which distinguish them from the generality of learning disabled subjects. Within this population reduced amygdala volume may be associated with negative-type symptoms and be part of an extended phenotype that reflects particularly elevated risk and/or early manifestations of the development of psychosis.

Major depressive disorder (MDD) co-occurs frequently with personality disorders (PDs). The extent to which this results from shared genetic or environmental risk factors remains uncertain.

Young adult twins (n=2801) from the population-based Norwegian Institute of Public Health Twin Panel were assessed at personal interview for DSM-IV lifetime MDD and the 10 Axis II PDs. The relationship between MDD and dimensional representations of all PDs was explored by stepwise logistic regression. Multivariate Cholesky twin models were fitted using the Mx program, and genetic and environmental correlations were estimated.

Dimensional representations of borderline (BPD), avoidant (AVPD) and paranoid personality disorder (PPD) were independently and significantly associated with increased risk for MDD. Multivariate twin modeling indicated that one latent factor accounted for the genetic covariance between MDD and the three PDs. The genetic correlations between MDD and dimensional representations of BPD, AVPD and PPD were +0.56, +0.22 and +0.40 respectively. No sex differences or shared environmental effects were found. The structure of the individual-specific environmental factors influencing MDD and the three PDs were similar to the genetic factors but the environmental correlations were lower: +0.39, +0.23 and +0.27 respectively.

There is substantial overlap between liability factors for MDD and BPD from cluster B, PPD from cluster A and AVPD from cluster C. The vulnerability to general PD pathology and MDD seem to be closely related. The patterns of co-morbidity observed between diverse psychiatric disorders might result from just a few liability factors.

Childhood adversity (CA) is associated with adult mental disorders, but the mechanisms underlying this association remain inadequately understood. Stress sensitization, whereby CA increases vulnerability to mental disorders following adult stressful life events, has been proposed as a potential mechanism. We provide a test of the stress sensitization hypothesis in a national sample.

We investigated whether the association between past-year stressful life events and the 12-month prevalence of major depression, post-traumatic stress disorder (PTSD), other anxiety disorders, and perceived stress varies according to exposure to CA. We used data from the National Epidemiological Survey of Alcohol and Related Conditions (NESARC) (n=34 653).

Past-year stressful life events were associated with an increased risk of major depression, PTSD, anxiety disorders, and perceived stress. However, the magnitude of the increased risk varied according to respondents' history of CA. For example, past-year major stressors were associated with a 27.3% increase in the 12-month risk of depression among individuals with ⩾3 CAs and a 14.8% increased risk among individuals without CAs. Stress sensitization effects were present for depression, PTSD, and other anxiety disorders in women and men, although gender differences were found in the threshold of past-year stress needed to trigger such effects. Stress sensitization was most evident among individuals with ⩾3 CAs.

CA is associated with increased vulnerability to the deleterious mental health effects of adult stressors in both men and women. High levels of CA may represent a general diathesis for multiple types of psychopathology that persists throughout the life course.

This study examined whether there were associations between individual measures of socio-economic status (SES) and the 12-month prevalence of major depressive disorder (MDD) in representative samples of Blacks, Latinos, Asians and Whites in the USA.

The data used were from the Collaborative Psychiatric Epidemiology Studies (CPES).

There was an association between household income and MDD among Whites. However, the association was not statistically significant. Statistically significant associations were present between educational attainment and MDD among Whites. Among both Whites and Latinos, being out of the labor force was significantly associated with MDD. In analyses by nativity, being out of the labor force was significantly associated with MDD among US-born and foreign-born Latinos.

Significant associations between various measures of SES and MDD were consistently observed among White and, in some cases, Latino populations. Future studies should continue to examine sociopsychological factors related to SES that increase the risk of MDD among people from racial-ethnic communities.

Painful physical symptoms (PPS) are both common and reduce the likelihood of remission in major depressive disorder (MDD), based upon results of clinical trials in selected populations. Whether PPS significantly contribute to poorer treatment outcome overall in primary or specialty psychiatric care settings remains unclear.

Out-patients (n=2876) with MDD were treated in the first step of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial with citalopram up to 60 mg/day for up to 14 weeks. Presence of painful symptoms, as well as severity of depression, physical illness, and demographic and treatment factors were examined. Time to and overall rates of remission were analysed in relation to the presence of PPS.

Of the participants, 80% complained of PPS. These patients, both in primary and specialty psychiatric settings, had significantly lower remission rates and took longer to remit. Increasing severity of PPS was associated with greater physical illness burden, lower socio-economic status, absence of private insurance and being female, African-American or Hispanic. After adjustment for these factors, patients with PPS no longer had significantly poorer treatment outcomes.

Presence and severity of PPS is an indicator of MDD that may have poorer treatment outcome with an initial selective serotonin reuptake inhibitor. These poorer treatment outcomes are multifactorial, however, and are not explained by the presence and severity of pain per se.