The phenotypic variance observed in panic disorder (PD) appears to be best captured by a respiratory and non-respiratory panic subtype. We compared respiratory and non-respiratory panic subtypes across a series of external validators (temporal stability, psychiatric co-morbidity, treatment response) to determine whether subtypes are best conceptualized as differing: (1) only on their symptom profiles with no other differences between them; (2) on a quantitative (i.e. severity) dimension only; or (3) qualitatively from one another.

Data from a large epidemiological survey (National Epidemiologic Survey on Alcohol and Related Conditions) and a clinical trial (Cross-National Collaborative Panic Study) were used. All analytic comparisons were examined within a latent class framework.

High temporal stability of panic subtypes was observed, particularly among females. Respiratory panic was associated with greater odds of lifetime major depression and a range of anxiety disorders as well as increased treatment utilization, but no demographic differences. Treatment outcome data did not suggest that the two PD subtypes were associated with differential response to either imipramine or alprazolam.

These data suggest that respiratory and non-respiratory panic represent valid subtypes along the PD continuum, with the respiratory variant representing a more severe form of the disorder.

Research mostly conducted in the UK and northern Europe has established that there are high rates of first-episode psychosis (FEP) in large cities and immigrant populations; moreover, psychosis has been found to be associated with cannabis use and early trauma. The present study aimed to evaluate the incidence rate of FEP and the distribution of several risk factors (e.g. age, ethnicity, substance abuse) in Bologna, Italy.

The Bologna FEP (BoFEP) study is an 8-year prospective study. All FEP patients, 18–64 years old, consecutively referred to the West Bologna Community Mental Health Centre (CMHC) from 2002 to 2009 were evaluated. Sociodemographic information, migration history and clinical data were collected through an ad-hoc schedule. Psychiatric diagnoses were recorded using the Schedule for Clinical Assessment of Neuropsychiatry (SCAN).

The overall incidence rate (IR) in the BoFEP study was 16.4 per 100 000 person-years [95% confidence interval (CI) 13.9–18.9]. The incidence was higher in young people, men and migrants (MI).

The IR of FEP found by the Bologna study is lower than that found by other European studies. However, as in other studies, the incidence was higher in certain groups. This heterogeneity has implications for policy and mental health service development, and for understanding the aetiology of psychosis.

Alterations in self-monitoring have been reported in patients with psychotic disorders, but it remains unclear to what degree they represent true indicators of familial vulnerability for psychosis.

An error-correction action-monitoring task was used to examine self-monitoring in 42 patients with schizophrenia, 32 of their unaffected siblings and 41 healthy controls.

Significant between-group differences in self-monitoring accuracy were found (χ2=29.3, p<0.0001), patients performing worst and unaffected siblings performing at an intermediate level compared to controls (all between-group differences p<0.05). In the combined group of healthy controls and unaffected siblings, detection accuracy was associated with positive schizotypy as measured by the Structured Interview for Schizotypy – Revised (SIS-R) (β=−0.16, s.e.=0.07, p=0.026), but not with negative schizotypy (β=−0.05, s.e.=0.12, p=0.694). In patients, psychotic symptoms were not robustly associated with detection accuracy (β=−0.01, s.e.=0.01, p=0.094), although stratified analysis revealed suggestive evidence for association in patients not currently using antipsychotic medication (β=−0.03, s.e.=0.01, p=0.052), whereas no association was found in patients on antipsychotic medication (β=−0.01, s.e.=0.01, p=0.426). A similar pattern of associations was found for negative symptoms.

Alterations in self-monitoring may be associated with familial risk and expression of psychosis. The association between psychotic symptoms and self-monitoring in patients may be affected by antipsychotic medication, which may explain previous inconsistencies in the literature.

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.

Depressed mood following an acute coronary syndrome (ACS) is a risk factor for future cardiac morbidity. Hypothalamic–pituitary–adrenal (HPA) axis dysregulation is associated with depression, and may be a process through which depressive symptoms influence later cardiac health. Additionally, a history of depression predicts depressive symptoms in the weeks following ACS. The purpose of this study was to determine whether a history of depression and/or current depression are associated with the HPA axis dysregulation following ACS.

A total of 152 cardiac patients completed a structured diagnostic interview, a standardized depression questionnaire and a cortisol profile over the day, 3 weeks after an ACS. Cortisol was analysed using: the cortisol awakening response (CAR), total cortisol output estimated using the area under the curve method, and the slope of cortisol decline over the day.

Total cortisol output was positively associated with history of depression, after adjustment for age, gender, marital status, ethnicity, smoking status, body mass index (BMI), Global Registry of Acute Cardiac Events (GRACE) risk score, days in hospital, medication with statins and antiplatelet compounds, and current depression score. Men with clinically diagnosed depression after ACS showed a blunted CAR, but the CAR was not related to a history of depression.

Patients with a history of depression showed increased total cortisol output, but this is unlikely to be responsible for associations between depression after ACS and later cardiac morbidity. However, the blunted CAR in patients with severe depression following ACS indicates that HPA dysregulation is present.

Previous studies suggest that alcohol-use disorder severity, defined by the number of criteria met, provides a more informative phenotype than dichotomized DSM-IV diagnostic measures of alcohol use disorders. Therefore, this study examined whether alcohol-use disorder severity predicted first-incident depressive disorders, an association that has never been found for the presence or absence of an alcohol use disorder in the general population.

In a national sample of persons who had never experienced a major depressive disorder (MDD), dysthymia, manic or hypomanic episode (n=27 571), we examined whether a version of DSM-5 alcohol-use disorder severity (a count of three abuse and all seven dependence criteria) linearly predicted first-incident depressive disorders (MDD or dysthymia) after 3-year follow-up. Wald tests were used to assess whether more complicated models defined the relationship more accurately.

First-incidence of depressive disorders varied across alcohol-use disorder severity and was 4.20% in persons meeting no alcohol-use disorder criteria versus 44.47% in persons meeting all 10 criteria. Alcohol-use disorder severity significantly predicted first-incidence of depressive disorders in a linear fashion (odds ratio 1.14, 95% CI 1.06–1.22), even after adjustment for sociodemographics, smoking status and predisposing factors for depressive disorders, such as general vulnerability factors, psychiatric co-morbidity and subthreshold depressive disorders. This linear model explained the relationship just as well as more complicated models.

Alcohol-use disorder severity was a significant linear predictor of first-incident depressive disorders after 3-year follow-up and may be useful in identifying a high-risk group for depressive disorders that could be targeted by prevention strategies.

Depression is associated with alterations of emotional and cognitive processing, and executive control in particular. Previous research has shown that depressed patients are impaired in their ability to shift attention from one emotional category to another, but whether this shifting deficit is more evident on emotional relative to non-emotional cognitive control tasks remains unclear.

The performance of patients with major depressive disorder and matched healthy control participants was compared on neutral and emotional variants of a dynamic cognitive control task that requires participants to shift attention and response from one category to another.

Relative to controls, depressed patients were impaired on both tasks, particularly in terms of performance accuracy. In the neutral go/no-go task, the ability of depressed patients to flexibly shift attention and response from one class of neutral stimuli to the other was unimpaired. This contrasted with findings for the emotional go/no-go task, where responding was slower specifically on blocks of trials that required participants to shift attention and response from one emotional category to the other.

The present data indicate that any depression-related difficulties with cognitive flexibility and control may be particularly evident on matched tasks that require processing of relevant emotional, rather than simply neutral, stimuli. The implications of these findings for our developing understanding of cognitive and emotional control processes in depression are discussed.

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.

Interferon-alpha (IFN-α) treatment for infectious disease and cancer causes high rates of depression and fatigue, and has been used to investigate the impact of inflammatory cytokines on brain and behavior. However, little is known about the transcriptional impact of chronic IFN-α on immune cells in vivo and its relationship to IFN-α-induced behavioral changes.

Genome-wide transcriptional profiling was performed on peripheral blood mononuclear cells (PBMCs) from 21 patients with chronic hepatitis C virus (HCV) either awaiting IFN-α therapy (n=10) or at 12 weeks of IFN-α treatment (n=11).

Significance analysis of microarray data identified 252 up-regulated and 116 down-regulated gene transcripts. Of the up-regulated genes, 2′-5′-oligoadenylate synthetase 2 (OAS2), a gene linked to chronic fatigue syndrome (CFS), was the only gene that was differentially expressed in patients with IFN-α-induced depression/fatigue, and correlated with depression and fatigue scores at 12 weeks (r=0.80, p=0.003 and r=0.70, p=0.017 respectively). Promoter-based bioinformatic analyses linked IFN-α-related transcriptional alterations to transcription factors involved in myeloid differentiation, IFN-α signaling, activator protein-1 (AP1) and cAMP responsive element binding protein/activation transcription factor (CREB/ATF) pathways, which were derived primarily from monocytes and plasmacytoid dendritic cells. IFN-α-treated patients with high depression/fatigue scores demonstrated up-regulation of genes bearing promoter motifs for transcription factors involved in myeloid differentiation, IFN-α and AP1 signaling, and reduced prevalence of motifs for CREB/ATF, which has been implicated in major depression.

Depression and fatigue during chronic IFN-α administration were associated with alterations in the expression (OAS2) and transcriptional control (CREB/ATF) of genes linked to behavioral disorders including CFS and major depression, further supporting an immune contribution to these diseases.

After de-escalation techniques have failed, restraints, seclusion and/or rapid tranquillization may be used for people whose aggression is due to psychosis. Most coercive acts of health care have not been evaluated in trials.

People admitted to the emergency room of Instituto Philippe Pinel, Rio de Janeiro, Brazil, whose aggression/agitation was thought due to psychosis and for whom staff were unsure if best to restrict using physical restraints or a seclusion room, were randomly allocated to one or the other and followed up to 14 days. The primary outcomes were ‘no need to change intervention early – within 1 h’ and ‘not restricted by 4 h’.

A total of 105 people were randomized. Two-thirds of the people secluded were able to be fully managed in this way. Even taking into account the move out of seclusion into restraints, this study provides evidence that embarking on the less restrictive care pathway (seclusion) does not increase overall time in restriction of some sort [not restricted by 4 h: relative risk 1.09, 95% confidence interval 0.75–1.58; mean time to release: restraints 337.6 (s.d.=298.2) min, seclusion room 316.3 (s.d.=264.5) min, p=0.48]. Participants tended to be more satisfied with their care in the seclusion group (17.0% v. 11.1%) but this did not reach conventional levels of statistical significance (p=0.42).

This study should be replicated, but suggests that opting for the least restrictive option in circumstances where there is clinical doubt does not harm or prolong coercion.

Clinical and epidemiological studies suggest an association between cannabis use and psychosis but this relationship remains controversial.

Clinical high-risk (CHR) subjects (age 12–22 years) with attenuated positive symptoms of psychosis (CHR+, n=101) were compared to healthy controls (HC, n=59) on rates of substance use, including cannabis. CHR+ subjects with and without lifetime cannabis use (and abuse) were compared on prodromal symptoms and social/role functioning at baseline. Participants were followed an average of 2.97 years to determine psychosis conversion status and functional outcome.

At baseline, CHR+ subjects had significantly higher rates of lifetime cannabis use than HC. CHR+ lifetime cannabis users (n=35) were older (p=0.015, trend), more likely to be Caucasian (p=0.002), less socially anhedonic (p<0.001) and had higher Global Functioning: Social (GF:Social) scores (p<0.001) than non-users (n=61). CHR+ cannabis users continued to have higher social functioning than non-users at follow-up (p<0.001) but showed no differences in role functioning. A small sample of CHR+ cannabis abusers (n=10) showed similar results in that abusers were older (p=0.008), less socially anhedonic (p=0.017, trend) and had higher baseline GF:Social scores (p=0.006) than non-abusers. Logistic regression analyses revealed that conversion to psychosis in CHR+ subjects (n=15) was not related to lifetime cannabis use or abuse.

The current data do not indicate that low to moderate lifetime cannabis use is a major contributor to psychosis or poor social and role functioning in clinical high-risk youth with attenuated positive symptoms of psychosis.

Understanding individual differences in susceptibility to antidepressant therapy side-effects is essential to optimize the treatment of depression.

We performed genome-wide association studies (GWAS) to search for genetic variation affecting the susceptibility to side-effects. The analysis sample consisted of 1439 depression patients, successfully genotyped for 421K single nucleotide polymorphisms (SNPs), from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Outcomes included four indicators of side-effects: general side-effect burden, sexual side-effects, dizziness and vision/hearing-related side-effects. Our criterion for genome-wide significance was a prespecified threshold ensuring that, on average, only 10% of the significant findings are false discoveries.

Thirty-four SNPs satisfied this criterion. The top finding indicated that 10 SNPs in SACM1L mediated the effects of bupropion on sexual side-effects (p=4.98×10−7, q=0.023). Suggestive findings were also found for SNPs in MAGI2, DTWD1, WDFY4 and CHL1.

Although our findings require replication and functional validation, this study demonstrates the potential of GWAS to discover genes and pathways that could mediate adverse effects of antidepressant medication.

Social anxiety and depression often co-occur. As low self-esteem has been identified as a risk factor for both types of symptoms, it may help to explain their co-morbidity. Current dual process models of psychopathology differentiate between explicit and implicit self-esteem. Explicit self-esteem would reflect deliberate self-evaluative processes whereas implicit self-esteem would reflect simple associations in memory. Previous research suggests that low explicit self-esteem is involved in both social anxiety and depression whereas low implicit self-esteem is only involved in social anxiety. We tested whether the association between symptoms of social phobia and depression can indeed be explained by low explicit self-esteem, whereas low implicit self-esteem is only involved in social anxiety.

Adolescents during the first stage of secondary education (n=1806) completed the Revised Child Anxiety and Depression Scale (RCADS) to measure symptoms of social anxiety and depression, the Rosenberg Self-Esteem Scale (RSES) to index explicit self-esteem and the Implicit Association Test (IAT) to measure implicit self-esteem.

There was a strong association between symptoms of depression and social anxiety that could be largely explained by participants' explicit self-esteem. Only for girls did implicit self-esteem and the interaction between implicit and explicit self-esteem show small cumulative predictive validity for social anxiety, indicating that the association between low implicit self-esteem and social anxiety was most evident for girls with relatively low explicit self-esteem. Implicit self-esteem showed no significant predictive validity for depressive symptoms.

The findings support the view that both shared and differential self-evaluative processes are involved in depression and social anxiety.

Ethnicity has been associated with different incidence rates and different symptom profiles in young patients with psychotic-like disorders. No studies so far have examined the effect of ethnicity on symptoms in people with an At Risk Mental State (ARMS).

In this cross-sectional study, we analysed the relationship between ethnicity and baseline data on the severity of psychopathology scores in 201 help-seeking patients who met the ARMS criteria and agreed to participate in the Dutch Early Detection and Intervention (EDIE-NL) trial. Eighty-seven of these patients had a non-Dutch ethnicity. We explored the possible mediating role of ethnic identity.

Higher rates of negative symptoms, and of anhedonia in particular, were found in the ethnic minority group. This result could be attributed mainly to the Moroccan-Dutch and Turkish-Dutch subgroups, who also presented with more depression symptoms when the groups were examined separately. The ethnic minority group displayed a lower level of ethnic group identity compared to the immigrants of the International Comparative Study of Ethnocultural Youth (ICSEY). Ethnic identity was inversely related to symptoms in the Moroccan-Dutch patient group.

The prevalence of more severe negative symptoms and depression symptoms in ethnic minority groups deserves more attention, as the experience of attenuated positive symptoms when accompanied by negative symptoms or distress has proven to be predictive for transition to a first psychotic episode.

Patients with major depressive disorder (MDD) show deficits in processing of facial emotions that persist beyond recovery and cessation of treatment. Abnormalities in neural areas supporting attentional control and emotion processing in remitted depressed (rMDD) patients suggests that there may be enduring, trait-like abnormalities in key neural circuits at the interface of cognition and emotion, but this issue has not been studied systematically.

Nineteen euthymic, medication-free rMDD patients (mean age 33.6 years; mean duration of illness 34 months) and 20 age- and gender-matched healthy controls (HC; mean age 35.8 years) performed the Emotional Face N-Back (EFNBACK) task, a working memory task with emotional distracter stimuli. We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to measure neural activity in the dorsolateral (DLPFC) and ventrolateral prefrontal cortex (VLPFC), orbitofrontal cortex (OFC), ventral striatum and amygdala, using a region of interest (ROI) approach in SPM2.

rMDD patients exhibited significantly greater activity relative to HC in the left DLPFC [Brodmann area (BA) 9/46] in response to negative emotional distracters during high working memory load. By contrast, rMDD patients exhibited significantly lower activity in the right DLPFC and left VLPFC compared to HC in response to positive emotional distracters during high working memory load. These effects occurred during accurate task performance.

Remitted depressed patients may continue to exhibit attentional biases toward negative emotional information, reflected by greater recruitment of prefrontal regions implicated in attentional control in the context of negative emotional information.

Patients with schizophrenia have excess cardiovascular morbidity and mortality. Previous studies suggest that this may be partly due to inadequate somatic treatment and care, such as non-optimal use of lipid-lowering and antihypertensive pharmacotherapy, but longitudinal studies on such aetiological pathways are scarce.

We investigated the use of lipid-lowering and antihypertensive pharmacotherapy, and the risk of hospitalization for and death from coronary heart disease and stroke among patients with schizophrenia in a birth cohort of 12 939 subjects (Helsinki Birth Cohort Study). This cohort was followed for over 30 adult years by using national databases on cardio- and cerebrovascular hospitalizations and mortality and on reimbursement entitlements and use of drugs for treatment of hypertension, dyslipidaemia, coronary heart disease and diabetes.

Individuals with schizophrenia had a higher risk of hospitalization for coronary heart disease [hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.03–2.57], and mortality from this disease was markedly higher (HR 2.92, 95% CI 1.70–5.00), particularly among women (p=0.001 for women, p=0.008 for men). Women with schizophrenia had also marginally increased stroke mortality (p=0.06). However, patients with schizophrenia used less lipid-lowering (odds ratio 0.47, 95% CI 0.27–0.80) and antihypertensive drug treatment (HR 0.37, 95% CI 0.22–0.61).

In this longitudinal study, coronary heart disease morbidity was increased and coronary heart disease mortality markedly increased in patients, especially in women with schizophrenia. These patients nevertheless received less antihypertensive and lipid-lowering treatment.

In Western countries, a history of major depression (MD) is associated with reports of received parenting that is low in warmth and caring and high in control and authoritarianism. Does a similar pattern exist in women in China?

Received parenting was assessed by a shortened version of the Parental Bonding Instrument (PBI) in two groups of Han Chinese women: 1970 clinically ascertained cases with recurrent MD and 2597 matched controls. MD was assessed at personal interview.

Factor analysis of the PBI revealed three factors for both mothers and fathers: warmth, protectiveness, and authoritarianism. Lower warmth and protectiveness and higher authoritarianism from both mother and father were significantly associated with risk for recurrent MD. Parental warmth was positively correlated with parental protectiveness and negatively correlated with parental authoritarianism. When examined together, paternal warmth was more strongly associated with lowered risk for MD than maternal warmth. Furthermore, paternal protectiveness was negatively and maternal protectiveness positively associated with risk for MD.

Although the structure of received parenting is very similar in China and Western countries, the association with MD is not. High parental protectiveness is generally pathogenic in Western countries but protective in China, especially when received from the father. Our results suggest that cultural factors impact on patterns of parenting and their association with MD.

Although there is substantial evidence for the efficacy of life review therapy as an early treatment of depression in later life, its effectiveness in natural settings has not been studied. The present study evaluates an intervention based on life review and narrative therapy in a large multi-site, pragmatic randomized controlled trial (RCT).

Life review therapy was compared with care as usual. The primary outcome was depressive symptoms; secondary outcomes were anxiety symptoms, positive mental health, quality of life, and current major depressive episode (MDE). To identify groups for whom the intervention was particularly effective, moderator analyses were carried out (on sociodemographic variables, personality traits, reminiscence functions, clinically relevant depressive and anxiety symptoms, and past MDEs).

Compared with care as usual (n=102), life review therapy (n=100) was effective in reducing depressive symptoms, at post-treatment (d=0.60, B=−5.3, p<0.001), at 3-month follow-up (d=0.50, B=−5.0, p<0.001) and for the intervention also at 9-month follow-up (t=5.7, p<0.001). The likelihood of a clinically significant change in depressive symptoms was significantly higher [odds ratio (OR) 3.77, p<0.001 at post-treatment; OR 3.76, p<0.001 at the 3-month follow-up]. Small significant effects were found for symptoms of anxiety and positive mental health. Moderator analyses showed only two significant moderators, the personality trait of extraversion and the reminiscence function of boredom reduction.

This study shows the effectiveness of life review therapy as an early intervention for depression in an ecologically valid context, supporting its applicability to a broad target group. The intervention is also effective in reducing anxiety symptoms and strengthening positive mental health.