Cross-sectional studies support an association between depression and inflammatory markers. However, little is known of their relationship in the context of antidepressant treatment. Our aim was to explore via meta-analysis whether antidepressant treatment is associated with a reduction in three inflammatory markers associated with depression.

A computerized search of EMBASE, Medline, PsycINFO and Cochrane Library databases was completed using subject headings for depression and either interleukin-6, C-reactive protein or interleukin-10, selecting studies which reported circulating levels of inflammatory markers before and after antidepressant treatment for people with depression. Outcome and moderator variables were coded for analysis, including inflammatory marker change, depression severity change, age, gender ratio, assay brand, treatment response and weight change.

Pooled effect sizes showed a significant decrease in interleukin-6 (n=14, d=−0.42, p=0.02), marginally significant decrease in C-reactive protein (n=8, d=−0.57, p=0.05) and a non-significant decrease in interleukin-10 (n=3, d=−0.45, p=0.14) after treatment. High levels of heterogeneity were observed, which may be associated with clinical variations between the studies such as weight gain, anxiety, incomplete remission and other individual differences and co-morbidities.

The findings of this meta-analysis indicate that there may be a normalization of overactive inflammatory processes following antidepressant treatment.

It has been proposed that non-steroidal anti-inflammatory drugs (NSAIDs) may interfere with the efficacy of antidepressants and contribute to treatment resistance in major depressive disorder (MDD). This effect requires replication and a test of whether it is specific to serotonin-reuptake inhibiting (SRI) antidepressants.

We tested the effect of concomitant medication with NSAIDs on the efficacy of escitalopram, a SRI antidepressant, and nortriptyline, a tricyclic antidepressant, among 811 subjects with MDD treated for up to 12 weeks in the GENDEP study. Effects of NSAIDs on improvement of depressive symptoms were tested in mixed-effect linear models. Effects on remission were tested in logistic regression. Age, sex, baseline severity and centre of recruitment were considered as potential confounding factors.

Ten percent (n=78) of subjects were taking NSAIDs during the antidepressant treatment. Older subjects were significantly more likely to take NSAIDs. After controlling for age, sex, centre of recruitment and baseline severity, concomitant medication with NSAIDs did not significantly influence the efficacy of escitalopram [β=0.035, 95% confidence interval (CI) −0.145 to 0.215, p=0.704] or nortriptyline (β=0.075, 95% CI −0.131 to 0.281, p=0.476). Although slightly fewer subjects who took NSAIDs reached remission [odds ratio (OR) 0.80, 95% CI 0.49–1.31, p=0.383], this non-significant effect was reversed after controlling for age, sex, baseline severity and recruitment centre effects (OR 1.04, 95% CI 0.61–1.77, p=0.882).

NSAIDs are unlikely to affect the efficacy of SRI or other antidepressants. Concurrent use of NSAIDs and antidepressants does not need to be avoided.

Older adults have the lowest prevalence and incidence of major depressive disorder, although it has been hypothesized that this finding is due in part to differences in expression of psychopathology in later life. The aim of this study was to examine variation in depressive symptomatology in the general population across the lifespan.

Data came from three sites of the Epidemiologic Catchment Area (ECA) Project (n=10 529). Depressive symptoms during the past 6 months were assessed using the Diagnostic Interview Schedule (DIS). Latent class analysis (LCA) was used to identify homogeneous groups of depressive symptomatology based on 16 individual symptoms, and to examine variation in the prevalence and composition of depression classes across age groups.

The DIS symptoms fit a four-class model composed of non-depressed (83.2%), mild depression (11.6%), severe depression (1.9%), and despondent (3.2%) groups. Relative to the non-depressed class, older age was inversely associated with being in the mild or severe depression class. The profile of the latent classes was similar across age groups with the exception of the despondent class, which was not well differentiated among the youngest adults and was not inversely associated with age.

The symptom profiles of depression are similar across age with the exception of the despondent class, which is more differentiated from severe depression among older adults. The findings demonstrate the benefit of examining individual symptoms rather than broad symptom groups for understanding the natural history of depression over the lifespan.

The National Psychiatric Morbidity Survey (NPMS) programme was partly designed to monitor trends in mental disorders, including depression, with comparable data spanning 1993 to 2007. Findings already published from this programme suggest that concerns about increasing prevalence of common mental disorders (CMDs) may be unfounded. This article focuses on depression and tests the hypothesis that successive birth cohorts experience the same prevalence of depression as they age.

We carried out a pseudo-cohort analysis of a sequence of three cross-sectional surveys of the English household population using identical diagnostic instruments. The main outcome was ICD-10 depressive episode or disorder. Secondary outcomes were the depression subscales of the Clinical Interview Schedule – Revised (CIS-R).

There were 8670, 6977 and 6815 participants in 1993, 2000 and 2007 respectively. In men, the prevalence of depression increased between cohorts born in 1943–1949 and 1950–1956 [odds ratio (OR) 2.5, 95% confidence interval (CI) 1.4–4.2], then remained relatively stable across subsequent cohorts. In women, there was limited evidence of change in prevalence of depression. Women born in 1957–1963, surveyed aged 44–50 years in 2007, had exceptionally high prevalence. It is not clear whether this represents a trend or a quirk of sampling.

There is no evidence of an increase in the prevalence of depression in male cohorts born since 1950. In women, there is limited evidence of increased prevalence. Demand for mental health services may stabilize or even fall for men.

Cross-sectional surveys of older people commonly find associations between higher levels of depressive symptoms and poorer cognitive performance, but the direction of effect is unclear. We examined whether there was a bidirectional relationship between depressive symptoms and general cognitive ability in non-demented older people, and explored the role of physical health, smoking, exercise, social class and education as potential confounders of this association and as possible determinants of the rate of change of cognitive decline and depressive symptoms.

The English Longitudinal Study of Ageing consists of people aged 50 years and over. Cognitive function and self-reported depressive symptoms were measured in 2002–2003, 2004–2005, 2006–2007 and 2008–2009. We fitted linear piecewise models with fixed knot positions to allow different slopes for different age groups. Analyses are based on 8611 people.

Mean cognitive function declined with age; there was no trend in the trajectory of depressive symptoms. Better cognitive function was associated with less depression up to the age of 80 years. Greater depression was associated with a slightly faster rate of cognitive decline but only in people aged 60–80 years. There were no consistent associations across age groups between sex, smoking, education, social class, exercise or number of chronic physical illnesses and the rate of change of cognitive decline or depressive symptoms.

In this longitudinal study of older people, there was no consistent evidence that being more depressed led to an acceleration in cognitive decline and no support for the hypothesis that there might be reciprocal dynamic influences between cognitive ability and depressive symptoms.

Depression has been associated with functional alterations in several areas of the cingulate cortex. In this study we have taken a systematic approach to examining how alterations in functional connectivity vary across the functionally diverse subregions of the rostral cingulate cortex.

Eighteen patients with major depressive disorder, aged 15 to 24 years, were matched with 20 healthy control participants. Using resting-state functional connectivity magnetic resonance imaging (fcMRI), we systematically investigated the functional connectivity of four subregions of the rostral cingulate cortex. Voxelwise statistical maps of each subregion's connectivity with other brain areas were compared between the patient and control groups.

The depressed participants showed altered patterns of connectivity with ventral cingulate subregions. They showed increased connectivity between subgenual anterior cingulate cortex (ACC) and dorsomedial frontal cortex, with connectivity strength showing positive correlation with illness severity. Depressed participants also showed increased connectivity between pregenual ACC and left dorsolateral frontal cortex, and decreased connectivity between pregenual ACC and the caudate nucleus bilaterally.

The results reinforce the importance of subgenual ACC for depression, and show a close link between brain regions that support self-related processes and affective visceromotor function. The pregenual ACC also has an important role, with its increased connectivity with dorsolateral frontal cortex suggesting heightened cognitive regulation of affect; and reduced connectivity with the caudate nucleus potentially underlying symptoms such as anhedonia, reduced motivation and psychomotor dysfunction.

Identifying depressive subtypes is an important tool in reducing the heterogeneity of major depressive disorder. However, few studies have examined the stability of putative subtypes of depression over time.

The sample included 488 persons from the Netherlands Study of Depression and Anxiety (NESDA) who had major depressive disorder at baseline and at the 2-year follow-up assessment. A latent transition analysis (LTA) was applied to examine the stability of depressive subtypes across time-points. Differences in demographic, clinical, psychosocial and health correlates between subtypes were evaluated in a subsample of persons with stable subtypes.

Three subtypes were identified at each time-point: a moderate subtype (prevalence T0 39%, T1 42%), a severe typical subtype (T0 30%, T1 25%), and a severe atypical subtype (T0 31%, T1 34%). The LTA showed 76% stability across the 2-year follow-up, with the greatest stability in the severe atypical class (79%). Analyses of correlates in the stable subtypes showed a predominance of women and more overweight and obesity in the severe atypical subtype, and a greater number of negative life events and higher neuroticism and functioning scores in the severe typical subtype.

Subtypes of major depressive disorder were found to be stable across a 2-year follow-up and to have distinct determinants, supporting the notion that the identified subtypes are clinically meaningful.

Depression is a leading cause of worldwide disability. Adolescence represents a key developmental window in which rates of this disorder increase markedly. Children with an anxiety disorder show a particular risk of developing depression during adolescence.

We present and review evidence for a developmental model that considers the intersection of two vulnerabilities relevant to the trajectory from anxiety to depression: difficulties in response to potential social evaluation and changes in reward processing at puberty.

Evidence suggests that these vulnerabilities (a) have been associated with depression, (b) are likely to be problematic in many, but not all, anxious youth, and (c) may be exacerbated by maturational processes that occur around pubertal development in ways that can create a negative spiral into a depressive disorder.

We discuss the possibility that early intervention strategies targeting key aspects of these vulnerabilities could alter the trajectory away from depression for many anxious youth.

Suicide rates increase following periods of war; however, the mechanism through which this occurs is not known. The aim of this paper is to shed some light on the associations of war exposure, mental disorders, and subsequent suicidal behavior.

A national sample of Lebanese adults was administered the Composite International Diagnostic Interview to collect data on lifetime prevalence and age of onset of suicide ideation, plan, and attempt, and mental disorders, in addition to information about exposure to stressors associated with the 1975–1989 Lebanon war.

The onset of suicide ideation, plan, and attempt was associated with female gender, younger age, post-war period, major depression, impulse-control disorders, and social phobia. The effect of post-war period on each type of suicide outcome was largely explained by the post-war onset of mental disorders. Finally, the conjunction of having a prior impulse-control disorder and either being a civilian in a terror region or witnessing war-related stressors was associated with especially high risk of suicide attempt.

The association of war with increased risk of suicidality appears to be partially explained by the emergence of mental disorders in the context of war. Exposure to war may exacerbate disinhibition among those who have prior impulse-control disorders, thus magnifying the association of mental disorders with suicidality.

Post-traumatic stress disorder (PTSD) that develops after military personnel have been discharged may lead to severe impairment. We investigated whether personnel who develop PTSD after discharge can be identified by independent evidence of internalizing signs such as depression or of externalizing signs such as disciplinary offences while still serving.

Veterans in receipt of a war pension who only developed PTSD post-discharge were compared with matched veterans who developed PTSD in service or never suffered from PTSD. Contemporaneous medical and personnel records were searched for objective evidence of internalizing and externalizing disorder.

Service personnel who developed PTSD post-discharge were indistinguishable from controls with no PTSD on their psychiatric presentation in service. Those with post-discharge PTSD had significantly more disciplinary offences, specifically absence without leave, disobedience, and dishonesty, than the no-PTSD group, and this excess of offences was present before any exposure to trauma.

This is the first study to find objective evidence independent of self-report for the claimed link between externalizing disorder and vulnerability to PTSD. Early signs of externalizing disorders may play an important role in helping to identify service personnel at risk of PTSD after military discharge.

Deficits in memory and executive performance are well-established features of bipolar disorder and schizophrenia. By contrast, data on cognitive impairment in schizoaffective disorder are scarce and the findings are conflicting.

We used the Wechsler Memory Scale (WMS-III) and the Behavioural Assessment of the Dysexecutive Syndrome (BADS) to test memory and executive function in 45 schizophrenic patients, 26 schizomanic patients and 51 manic bipolar patients in comparison to 65 healthy controls. The patients were tested when acutely ill.

All three patient groups performed significantly more poorly than the controls on global measures of memory and executive functioning, but there were no differences among the patient groups. There were few differences in memory and executive function subtest scores within the patient groups. There were no differences in any test scores between manic patients with and without psychotic symptoms.

Schizophrenic, schizomanic and manic patients show a broadly similar degree of executive and memory deficits in the acute phase of illness. Our results do not support a categorical differentiation across different psychotic categories with regard to neuropsychological deficits.

The aim of this study was to extend an earlier retrospective cohort study of schizophrenia via a prospective study to a follow-up of 34 years, with an emphasis on describing the life-course of the illness.

Subjects were 128 first-ever admissions for schizophrenia in 1963 to either of two mental hospital in Alberta, Canada. Follow-up continued until death or 1997. A symptom severity scale, with scores ranging from 0 (no symptoms) to 3 (hospitalized), was used to collect time-series data on each subject and create life-course curves. Indices were constructed to summarize the information in each curve. Information on social functioning was also collected.

Results were similar for men and women. The life-course curves showed marked variability of symptom severity across subjects and over time. The average score over the entire period of follow-up for the cohort indicated ‘moderate’ symptoms, and the change in average score from beginning to end of follow-up demonstrated a slight worsening of symptoms. The measures of social functioning indicated that only about one quarter of the patients had a good to excellent outcome.

The long-term course in schizophrenia is one of varying symptom severity, and for many patients, there is a poor overall outcome.

The prevailing standard of care in the field involves background assumptions about the importance of prolonged use of antipsychotic medications for all schizophrenia (SZ) patients. However, do all SZ patients need antipsychotics indefinitely? Are there factors that help to identify which SZ patients can enter into prolonged periods of recovery without antipsychotics? This 20-year longitudinal research studied these issues.

A total of 139 early young psychotic patients from the Chicago Follow-up Study, including 70 patients with SZ syndromes and 69 with mood disorders, were assessed, prospectively, at the acute phase and then followed up six times over the next 20 years. Patients were assessed with standardized instruments for major symptoms, psychosocial functioning, personality, attitudinal variables, neurocognition and treatment.

At each follow-up, 30–40% of SZ patients were no longer on antipsychotics. Starting at the 4.5-year follow-ups and continuing thereafter, SZ patients not on antipsychotics for prolonged periods were significantly less likely to be psychotic and experienced more periods of recovery; they also had more favorable risk and protective factors. SZ patients off antipsychotics for prolonged periods did not relapse more frequently.

The data indicate that not all SZ patients need treatment with antipsychotics continuously throughout their lives. SZ patients not on antipsychotics for prolonged periods are a self-selected group with better internal resources associated with greater resiliency. They have better prognostic factors, better pre-morbid developmental achievements, less vulnerability to anxiety, better neurocognitive skills, less vulnerability to psychosis and experience more periods of recovery.

Psychotic symptoms, also termed psychotic-like experiences (PLEs) in the absence of psychotic disorder, are common in adolescents and are associated with increased risk of schizophrenia-spectrum illness in adulthood. At the same time, schizophrenia is associated with deficits in social cognition, with deficits particularly documented in facial emotion recognition (FER). However, little is known about the relationship between PLEs and FER abilities, with only one previous prospective study examining the association between these abilities in childhood and reported PLEs in adolescence. The current study was a cross-sectional investigation of the association between PLEs and FER in a sample of Irish adolescents.

The Adolescent Psychotic-Like Symptom Screener (APSS), a self-report measure of PLEs, and the Penn Emotion Recognition-40 Test (Penn ER-40), a measure of facial emotion recognition, were completed by 793 children aged 10–13 years.

Children who reported PLEs performed significantly more poorly on FER (β=−0.03, p=0.035). Recognition of sad faces was the major driver of effects, with children performing particularly poorly when identifying this expression (β=−0.08, p=0.032).

The current findings show that PLEs are associated with poorer FER. Further work is needed to elucidate causal relationships with implications for the design of future interventions for those at risk of developing psychosis.

Patients with schizophrenia consistently demonstrate information processing abnormalities assessed with visual masking (VM) tasks, and these deficits have been linked to clinical and functional severity. It has been suggested that VM impairments may be a vulnerability marker in individuals at risk for developing psychosis.

Forward and backward VM performance was assessed in 72 first-episode (FE) psychosis patients, 98 subjects at risk (AR) for psychosis and 98 healthy controls (HC) using two identification tasks (with either a high- or low-energy mask) and a location task. VM was examined for stability in a subgroup (FE, n=15; AR, n=35; HC, n=21) and assessed relative to clinical and functional measures.

In the identification tasks, backward VM deficits were observed in both FE and AR relative to HC whereas forward VM deficits were only present in FE patients compared to HC. In the location task, AR subjects demonstrated superior performance in forward VM relative to HC. VM performance was stable over time, and VM deficits were associated with baseline functional measures and predicted future negative symptom severity in AR subjects.

Visual information processing deficits, as indexed by backward VM, are present before and after the onset of frank psychosis, and probably represent a stable vulnerability marker that is associated with negative symptoms and functional decline. Additionally, the paradoxically better performance of AR subjects in select forward tasks suggests that early compensatory changes may characterize an emerging psychotic state.

Emotion dysregulation, characterized by heightened emotional arousal and increased emotional sensitivity, is a core feature of borderline personality disorder (BPD). Although current theories emphasize the disruptive potential of negative emotions on cognitive functioning in BPD, behavioral and neurobiological data on this relationship are still lacking.

Using functional magnetic resonance imaging (fMRI), neural activity was investigated in 22 unmedicated BPD patients and 22 healthy participants (matched for age, education and intelligence) performing an adapted Sternberg working memory task, while being distracted by emotional (negatively arousing) and neutral pictures from the International Affective Picture System (IAPS).

Emotional distraction was associated with significantly higher activation in the amygdala and decreased activation in the dorsolateral prefrontal cortex (DLPFC), extending findings of previous studies in healthy individuals. Patients with BPD showed significantly longer reaction times (RTs) along with significantly higher activation in the amygdala and insula during emotional distraction compared to healthy participants, suggesting that they were more distracted by emotional pictures during the working memory task. Moreover, in the group of BPD patients, a significant negative correlation was found between activation in limbic brain regions and self-reports of current dissociative states.

Our findings suggest hyper-responsiveness to emotionally distracting pictures in BPD patients that negatively affects working memory performance. This stresses the importance of emotion dysregulation in the context of cognitive functioning. Moreover, our findings suggest that dissociative states have a dampening effect on neural reactivity during emotional challenge in BPD.

Cognitive behaviour therapy (CBT) is an effective treatment for obsessive–compulsive disorder (OCD) but access to CBT is limited. Internet-based CBT (ICBT) with therapist support is potentially a more accessible treatment. There are no randomized controlled trials testing ICBT for OCD. The aim of this study was to investigate the efficacy of ICBT for OCD in a randomized controlled trial.

Participants (n=101) diagnosed with OCD were randomized to either 10 weeks of ICBT or to an attention control condition, consisting of online supportive therapy. The primary outcome measure was the Yale–Brown Obsessive Compulsive Scale (YBOCS) administered by blinded assessors.

Both treatments lead to significant improvements in OCD symptoms, but ICBT resulted in larger improvements than the control condition on the YBOCS, with a significant between-group effect size (Cohen's d) of 1.12 (95% CI 0.69–1.53) at post-treatment. The proportion of participants showing clinically significant improvement was 60% (95% CI 46–72) in the ICBT group compared to 6% (95% CI 1–17) in the control condition. The results were sustained at follow-up.

ICBT is an efficacious treatment for OCD that could substantially increase access to CBT for OCD patients. Replication studies are warranted.

Cognitive behaviour therapy (CBT) for chronic fatigue syndrome (CFS) is an effective but intensive treatment, requiring trained therapists. A minimal intervention based on CBT for CFS, guided self-instruction, was shown to be an effective treatment when delivered in a tertiary treatment centre. Implementing this intervention in a community-based mental health centre (MHC) will increase the treatment capacity for CFS patients. This study evaluated the effectiveness of guided self-instruction for CFS implemented in an MHC, delivered by nurses.

One hundred and twenty-three patients were randomly assigned to either guided self-instruction (n=62) or a waiting list (n=61). Randomization was computer generated, with allocation by numbered sealed envelopes. Group allocation was open to all those involved. Patients fulfilled US Centers for Disease Control and Prevention (CDC) criteria for CFS. Primary outcome variables were fatigue severity and physical and social functioning, measured with the Checklist Individual Strength (CIS) and the Medical Outcomes Survey Short Form-36 (SF-36) respectively.

After 6 months, patients who followed guided self-instruction reported a significantly larger decrease in fatigue compared to the waiting list [mean difference –8.1, 95% confidence interval (CI) −3.8 to −12.4, controlled effect size 0.70]. There was no significant difference in physical and social functioning. However, post-hoc analyses showed a significant decrease in fatigue and physical disabilities following the intervention in a subgroup of patients with physical disabilities at baseline (SF-36 physical functioning ⩽70).

Implementation of guided self-instruction in a community-based MHC was partially successful. The minimal intervention can be effectively implemented for CFS patients with physical impairments.

To evaluate the effectiveness of graded exercise therapy (GET), counselling (COUNS) and usual care plus a cognitive behaviour therapy (CBT) booklet (BUC) for people presenting with chronic fatigue in primary care.

A randomized controlled trial in general practice. The main outcome measure was the change in the Chalder fatigue score between baseline and 6 months. Secondary outcomes included a measure of global outcome, including anxiety and depression, functional impairment and satisfaction.

The reduction in mean Chalder fatigue score at 6 months was 8.1 [95% confidence interval (CI) 6.6–10.4] for BUC, 10.1 (95% CI 7.5–12.6) for GET and 8.6 (95% CI 6.5–10.8) for COUNS. There were no significant differences in change scores between the three groups at the 6- or 12-month assessment. Dissatisfaction with care was high. In relation to the BUC group, the odds of dissatisfaction at the 12-month assessment were less for the GET [odds ratio (OR) 0.11, 95% CI 0.02–0.54, p=0.01] and COUNS groups (OR 0.13, 95% CI 0.03–0.53, p=0.004).

Our evidence suggests that fatigue presented to general practitioners (GPs) tends to remit over 6 months to a greater extent than found previously. Compared to BUC, those treated with graded exercise or counselling therapies were not significantly better with respect to the primary fatigue outcome, although they were less dissatisfied at 1 year. This evidence is generalizable nationally and internationally. We suggest that GPs ask patients to return at 6 months if their fatigue does not remit, when therapy options can be discussed further.