Both language and music are thought to have evolved from a musical protolanguage that communicated social information, including emotion. Individuals with perceptual music disorders (amusia) show deficits in auditory emotion recognition (AER). Although auditory perceptual deficits have been studied in schizophrenia, their relationship with musical/protolinguistic competence has not previously been assessed.

Musical ability was assessed in 31 schizophrenia/schizo-affective patients and 44 healthy controls using the Montreal Battery for Evaluation of Amusia (MBEA). AER was assessed using a novel battery in which actors provided portrayals of five separate emotions. The Disorganization factor of the Positive and Negative Syndrome Scale (PANSS) was used as a proxy for language/thought disorder and the MATRICS Consensus Cognitive Battery (MCCB) was used to assess cognition.

Highly significant deficits were seen between patients and controls across auditory tasks (p < 0.001). Moreover, significant differences were seen in AER between the amusia and intact music-perceiving groups, which remained significant after controlling for group status and education. Correlations with AER were specific to the melody domain, and correlations between protolanguage (melody domain) and language were independent of overall cognition.

This is the first study to document a specific relationship between amusia, AER and thought disorder, suggesting a shared linguistic/protolinguistic impairment. Once amusia was considered, other cognitive factors were no longer significant predictors of AER, suggesting that musical ability in general and melodic discrimination ability in particular may be crucial targets for treatment development and cognitive remediation in schizophrenia.

The aim of the study was to determinate whether schizophrenia patients with a history of cannabis use have a different prognosis, with regards to readmission and hospital duration, compared with those without a history of cannabis use.

The present investigation was a cohort study of 50 087 Swedish men with data on cannabis use at the ages of 18–20 years. A total of 357 cases of schizophrenia were identified from in-patient care and followed up from 1973 to 2007.

Schizophrenia patients with a history of cannabis use had a higher median duration of first hospital episode (59 days v. 30 days). Patients with a history of cannabis use had a higher median rate of readmission (10 times v. four times). Also, total number of hospital days was higher in patients with a history of cannabis use compared with those without (547 days v. 184 days). Patients with a history of cannabis use had an increased odds of having more than 20 hospital readmissions compared with non-users [3.1, 95% confidence interval (CI) 1.3–7.3] as well as an increased odds of hospital admission lasting more than 2 years (2.4, 95% CI 1.1–7.4) after controlling for diagnosis of personality disorders, family socio-economic position, IQ score, civil status, place of residence, risky use of alcohol and use of other drugs. Patients with a history of cannabis use were less likely to have paranoid schizophrenia compared with never users (8% v. 17%) in the first admission.

Schizophrenia patients with a history of cannabis use had a significantly higher burden of lifetime in-patient care than non-cannabis users. Not only does cannabis increase the risk of schizophrenia, but also our findings indicate that the course and prognosis of schizophrenia may be more severe than schizophrenia cases in general.

A congenital heart defect (CHD) can increase the risk of mental health problems in affected children and their parents. The extent to which risk factors for these problems are shared in families or are specific to the individual family member is unclear.

Prospective data from the Norwegian Mother and Child Cohort Study (MoBa; n = 93 009) were linked with a nationwide CHD registry, and 408 children with CHD were identified. Mothers' reports on child internalizing problems and their own distress were assessed by questionnaires at child ages 6, 18 and 36 months. A structural model was applied to distinguish between familial (shared) factors and individual-specific factors for mental health problems.

CHD was a substantial risk factor for problems in children and their mothers at all time points. CHD contributed on average 31% and 39% to the variance in children's and mothers' problems respectively. Both shared familial and individual-specific factors unique to CHD families contributed to risk for mental health problems. Whereas individual-specific risk factors contributed to the stability of problems in mothers, the effect of these factors lasted only a short time in children. Mutual influences over time were found between the mother's and the child's mental health at 18 and 36 months.

The burden of CHD in a child is shared between family members but is also specific to the individual. This study points to a need for both an individual and a family-based approach to provide psychological support to children with CHD and their parents.

Cardiovascular (CV) co-morbidity is one of the major modifiable risk factors driving the excess mortality in individuals with schizophrenia or bipolar disorder. Population-based studies in this area are sparse.

We used Danish population registers to calculate incidence rate ratios (IRRs) for CV drug use, and mortality rate ratios comparing subjects with schizophrenia or bipolar disorder with subjects with no prior psychiatric hospitalization.

IRRs for CV prescriptions were significantly decreased in patients with schizophrenia or bipolar disorder compared with the general population. Among persons without previous myocardial infarction (MI) or cerebrovascular disease, persons with schizophrenia or bipolar disorder had an up to 6- and 15-fold increased mortality from all causes or unnatural causes, respectively, compared with the general population, being most pronounced among those without CV treatment (16-fold increase). Among those with previous MI or cerebrovascular disease, excess all-cause and unnatural death was lower (up to 3-fold and 7-fold increased, respectively), but was similar in CV-treated and -untreated persons.

The present study shows an apparent under-prescription of most CV drugs among patients with schizophrenia or bipolar disorder compared with the general population in Denmark. The excess of mortality by unnatural deaths in the untreated group suggests that the association between CV treatment and mortality may be confounded by severity of illness. However, our results also suggest that treatment of CV risk factors is neglected in these patients.

The symptoms of major depression (MD) are clinically diverse. Do they form coherent factors that might clarify the underlying nature of this important psychiatric syndrome?

Symptoms at lifetime worst depressive episode were assessed at structured psychiatric interview in 6008 women of Han Chinese descent, age ⩾30 years with recurrent DSM-IV MD. Exploratory factor analysis (EFA) and confirmatoryfactor analysis (CFA) were performed in Mplus in random split-half samples.

The preliminary EFA results were consistently supported by the findings from CFA. Analyses of the nine DSM-IV MD symptomatic A criteria revealed two factors loading on: (i) general depressive symptoms; and (ii) guilt/suicidal ideation. Examining 14 disaggregated DSM-IV criteria revealed three factors reflecting: (i) weight/appetite disturbance; (ii) general depressive symptoms; and (iii) sleep disturbance. Using all symptoms (n = 27), we identified five factors that reflected: (i) weight/appetite symptoms; (ii) general retarded depressive symptoms; (iii) atypical vegetative symptoms; (iv) suicidality/hopelessness; and (v) symptoms of agitation and anxiety.

MD is a clinically complex syndrome with several underlying correlated symptom dimensions. In addition to a general depressive symptom factor, a complete picture must include factors reflecting typical/atypical vegetative symptoms, cognitive symptoms (hopelessness/suicidal ideation), and an agitated symptom factor characterized by anxiety, guilt, helplessness and irritability. Prior cross-cultural studies, factor analyses of MD in Western populations and empirical findings in this sample showing risk factor profiles similar to those seen in Western populations suggest that our results are likely to be broadly representative of the human depressive syndrome.

Maternal stress during pregnancy is associated with a modestly increased risk of fetal growth restriction and pre-eclampsia. Since placental abruption shares similar pathophysiological mechanisms and risk factors with fetal growth restriction and pre-eclampsia, we hypothesized that maternal stress may be implicated in abruption risk. We investigated the association between maternal bereavement during pregnancy and placental abruption.

We studied singleton births in Denmark (1978–2008) and Sweden (1973–2006) (n = 5 103 272). In nationwide registries, we obtained data on death of women's close family members (older children, siblings, parents, and partners), abruption and potential confounders.

A total of 30 312 (6/1000) pregnancies in the cohort were diagnosed with placental abruption. Among normotensive women, death of a child the year before or during pregnancy was associated with a 54% increased odds of abruption [95% confidence interval (CI) 1.30–1.82]; the increased odds were restricted to women who lost a child the year before or during the first trimester in pregnancy. In the group with chronic hypertension, death of a child the year before or in the first trimester of pregnancy was associated with eight-fold increased odds of abruption (odds ratio 8.17, 95% CI 3.17–21.10). Death of other relatives was not associated with abruption risk.

Loss of a child the year before or in the first trimester of pregnancy was associated with an increased risk of abruption, especially among women with chronic hypertension. Studies are needed to investigate the effect of less severe, but more frequent, sources of stress on placental abruption risk.

While many neuroimaging studies have investigated the neurobiological basis of attention deficit hyperactivity disorder (ADHD), few have studied the neurobiology of attention problems in the general population. The ability to pay attention falls along a continuum within the population, with children with ADHD at one extreme of the spectrum and, therefore, a dimensional perspective of evaluating attention problems has an added value to the existing literature. Our goal was to investigate the relationship between cortical thickness and inattention and hyperactivity symptoms in a large population of young children.

This study is embedded within the Generation R Study and includes 6- to 8-year-old children (n = 444) with parent-reported attention and hyperactivity measures and high-resolution structural imaging data. We investigated the relationship between cortical thickness across the entire brain and the Child Behavior Checklist Attention Deficit Hyperactivity Problems score.

We found that greater attention problems and hyperactivity were associated with a thinner right and left postcentral gyrus. When correcting for potential confounding factors and multiple testing, these associations remained significant.

In a large, population-based sample we showed that young (6- to 8-year-old) children who show more attention problems and hyperactivity have a thinner cortex in the region of the right and left postcentral gyrus. The postcentral gyrus, being the primary somatosensory cortex, reaches its peak growth early in development. Therefore, the thinner cortex in this region may reflect either a deviation in cortical maturation or a failure to reach the same peak cortical thickness compared with children without attention or hyperactivity problems.

Healthy first-degree relatives of patients with major depression (rMD+) show brain structure and functional response anomalies and have elevated risk for developing depression, a disorder linked to abnormal serotonergic neurotransmission and reward processing.

In a two-step functional magnetic resonance imaging (fMRI) investigation, we first evaluated whether positive and negative monetary outcomes were differentially processed by rMD+ individuals compared to healthy first-degree relatives of control probands (rMD−). Second, in a double-blinded placebo-controlled randomized trial we investigated whether a 4-week intervention with the selective serotonergic reuptake inhibitor (SSRI) escitalopram had a normalizing effect on behavior and brain responses of the rMD+ individuals.

Negative outcomes increased the probability of risk-averse choices in the subsequent trial in rMD+ but not in rMD− individuals. The orbitofrontal cortex (OFC) displayed a stronger neural response when subjects missed a large reward after a low-risk choice in the rMD+ group compared to the rMD− group. The enhanced orbitofrontal response to negative outcomes was reversed following escitalopram intervention compared to placebo. Conversely, for positive outcomes, the left hippocampus showed attenuated response to high wins in the rMD+ compared to the rMD− group. The SSRI intervention reinforced the hippocampal response to large wins. A subsequent structural analysis revealed that the abnormal neural responses were not accounted for by changes in gray matter density in rMD+ individuals.

Our study in first-degree relatives of depressive patients showed abnormal brain responses to aversive and rewarding outcomes in regions known to be dysfunctional in depression. We further confirmed the reversal of these aberrant activations with SSRI intervention.

Neuroimaging studies have demonstrated an association between lithium (Li) treatment and brain structure in human subjects. A crucial unresolved question is whether this association reflects direct neurochemical effects of Li or indirect effects secondary to treatment or prevention of episodes of bipolar disorder (BD).

To address this knowledge gap, we compared manually traced hippocampal volumes in 37 BD patients with at least 2 years of Li treatment (Li group), 19 BD patients with <3 months of lifetime Li exposure over 2 years ago (non-Li group) and 50 healthy controls. All BD participants were followed prospectively and had at least 10 years of illness and a minimum of five episodes. We established illness course and long-term treatment response to Li using National Institute of Mental Health (NIMH) life charts.

The non-Li group had smaller hippocampal volumes than the controls or the Li group (F2,102 = 4.97, p = 0.009). However, the time spent in a mood episode on the current mood stabilizer was more than three times longer in the Li than in the non-Li group (t51 = 2.00, p = 0.05). Even Li-treated patients with BD episodes while on Li had hippocampal volumes comparable to healthy controls and significantly larger than non-Li patients (t43 = 2.62, corrected p = 0.02).

Our findings support the neuroprotective effects of Li. The association between Li treatment and hippocampal volume seems to be independent of long-term treatment response and occurred even in subjects with episodes of BD while on Li. Consequently, these effects of Li on brain structure may generalize to patients with neuropsychiatric illnesses other than BD.

Our previous work identified deficits in interference processing and learning/memory in past suicide attempters who were currently depressed and medication-free. In this study, we extend this work to an independent sample studied at various stages of illness and treatment (mild symptoms, on average) to determine if these deficits in past suicide attempters are evident during a less severe clinical state.

A total of 80 individuals with a past history of major depression and suicide attempt were compared with 81 individuals with a history of major depression and no lifetime suicide attempts on a battery of neurocognitive measures assessing attention, memory, abstract/contingent learning, working memory, language fluency and impulse control.

Past attempters performed more poorly in attention, memory and working memory domains, but also in an estimate of pre-morbid intelligence. After correction for this estimate, tests that had previously distinguished past attempters – a computerized Stroop task and the Buschke Selective Reminding Test – remained significantly worse in attempters. In a secondary analysis, similar differences were found among those with the lowest levels of depression (Hamilton Depression Rating Scale score <10), suggesting that these deficits may be trait markers independent of current symptomatology.

Deficits in interference processing and learning/memory constitute an enduring defect in information processing that may contribute to poor adaptation, other higher-order cognitive impairments and risk for suicidal behavior.

Post-traumatic stress disorder (PTSD) is a chronic and difficult to treat psychiatric disorder. Objective, performance-based diagnostic markers that uniquely index risk for PTSD above and beyond subjective self-report markers could inform attempts to improve prevention and early intervention. We evaluated the predictive value of threat-related attention bias measured immediately after a potentially traumatic event, as a risk marker for PTSD at a 3-month follow-up. We measured the predictive contribution of attentional threat bias above and beyond that of the more established marker of risk for PTSD, self-reported psychological dissociation.

Dissociation symptoms and threat-related attention bias were measured in 577 motor vehicle accident (MVA) survivors (mean age = 35.02 years, 356 males) within 24 h of admission to an emergency department (ED) of a large urban hospital. PTSD symptoms were assessed at a 3-month follow-up using the Clinician-Administered PTSD Scale (CAPS).

Self-reported dissociation symptoms significantly accounted for 16% of the variance in PTSD at follow-up, and attention bias toward threat significantly accounted for an additional 4% of the variance in PTSD.

Threat-related attention bias can be reliably measured in the context of a hospital ED and significantly predicts risk for later PTSD. Possible mechanisms underlying the association between threat bias following a potentially traumatic event and risk for PTSD are discussed. The potential application of an attention bias modification treatment (ABMT) tailored to reduce risk for PTSD is suggested.

Antidepressants are frequently prescribed but results regarding their efficacy have been equivocal for different spectra of the severity continuum and their side-effects are often burdensome. Non-adherence is a likely consequence. The objective was therefore to examine patients’ trade-offs between the efficacy, side-effects and other drawbacks of antidepressants and whether these trade-offs predicted non-adherence.

Trade-offs from 225 antidepressant users, recruited through community pharmacies, were assessed with an Adaptive Conjoint Analysis (ACA) choice task that was customized to each individual patient. From the estimated utilities, relative importance scores of treatment properties were calculated. Non-adherence was measured through self-report and pharmacy refill data.

Relapse prevention and symptom relief were on average equally important. Side-effects were as important and the side-effect stomach and intestine complaints was on average even slightly more important than relapse prevention and symptom relief. Additional treatment with psychotherapy was preferred by 61% of the patients. A benefit/drawback ratio revealed that 18% of the patients did not consider the efficacy to outweigh the drawbacks. A higher benefit/drawback ratio was associated with a decreased odds of intentional non-adherence [odds ratio (OR) 0.2, 95% confidence interval (CI) 0.07–0.7, Wald = 6.7, p = 0.01).

For nearly one in five patients, the efficacy of antidepressants does not outweigh their drawbacks. Knowing patients’ trade-offs is likely to aid both physicians and patients to identify important treatment preferences, to improve adherence and to make more deliberate decisions on whether or not to continue treatment.

We tested the degree to which longitudinal observations fit two hypotheses of psychiatric co-morbidity in DSM-IV major depressive disorder (MDD) among adult patients: (1) Axis I co-morbidity is dependent on major depressive episode (MDE) course, and (2) Axis I co-morbidity is independent of MDE course.

In the Vantaa Depression Study (VDS), 269 psychiatric secondary-care patients with a DSM-IV MDD were evaluated with the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) at intake and at 6 and 18 months. Three evaluations of co-morbidity were available for 193 out of 259 living patients (75%). A latent curve model (LCM) was used to examine individual-level changes in depressive and anxiety symptoms across time. Outcome of MDD was modeled in terms of categorical DSM-IV diagnosis and Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HAMD) scores, and co-morbidity in terms of categorical DSM-IV anxiety and alcohol use disorder (AUD) diagnoses and Beck Anxiety Inventory (BAI) scores.

Depression and anxiety correlated cross-sectionally at baseline. Longitudinally, changes in depression and anxiety correlated in both the 0–6 and 6–18 months time windows. Higher baseline depression raised the likelihood of an AUD at 6 months, and patients with more depressive symptoms in the 0–6 months time window were more likely to have had an AUD at 6 months, which further linked to less improvement in depression symptoms in the 6–18 months time window.

Longitudinal and individual-level courses of both internalizing and externalizing disorders in adult patients with MDD seem to be dependent, albeit to differing degrees, on the course of depressive symptoms.

More effective prevention of suicide requires a comprehensive understanding of sociodemographic, psychiatric and somatic risk factors. Previous studies have been limited by incomplete ascertainment of these factors. We conducted the first study of this issue using sociodemographic and out-patient and in-patient health data for a national population.

We used data from a national cohort study of 7140589 Swedish adults followed for 8 years for suicide mortality (2001–2008). Sociodemographic factors were identified from national census data, and psychiatric and somatic disorders were identified from all out-patient and in-patient diagnoses nationwide.

There were 8721 (0.12%) deaths from suicide during 2001–2008. All psychiatric disorders were strong risk factors for suicide among both women and men. Depression was the strongest risk factor, with a greater than 15-fold risk among women or men and even higher risks (up to 32-fold) within the first 3 months of diagnosis. Chronic obstructive pulmonary disease (COPD), cancer, spine disorders, asthma and stroke were significant risk factors among both women and men (1.4–2.1-fold risks) whereas diabetes and ischemic heart disease were modest risk factors only among men (1.2–1.4-fold risks). Sociodemographic risk factors included male sex, unmarried status or non-employment; and low education or income among men.

All psychiatric disorders, COPD, cancer, spine disorders, asthma, stroke, diabetes, ischemic heart disease and specific sociodemographic factors were independent risk factors for suicide during 8 years of follow-up. Effective prevention of suicide requires a multifaceted approach in both psychiatric and primary care settings, targeting mental disorders (especially depression), specific somatic disorders and indicators of social support.

Telomere attrition, causing accelerated aging, might be one of the mechanisms through which neuroticism leads to somatic disease and increased all-cause mortality. In the current study we investigated whether neuroticism is prospectively associated with shorter telomere length (TL), a biological marker of aging.

Participants were 3432 adults (mean age 52.9 years, range 32–79). Data were collected at baseline (T1) and at two follow-up visits after 4 years (T2) and 6 years (T3). Neuroticism was assessed using the 12-item neuroticism scale of the Revised Eysenck Personality Questionnaire (EPQ-R) at T2 and T3. TL was measured by a monochrome multiplex quantitative polymerase chain reaction (PCR) assay at T1, T2 and T3. A linear mixed model was used to assess whether neuroticism could predict TL prospectively after adjusting for age, sex, body mass index (BMI), frequency of sports, smoking status, presence of chronic diseases and level of education.

Neuroticism was a significant negative predictor of TL at follow-up (B = −0.004, p = 0.044) after adjusting for sex, age, baseline TL and various biological and lifestyle factors.

High neuroticism is significantly and prospectively associated with telomere attrition independent of lifestyle and other risk factors.

Few studies have examined the latent construct of psychotic symptoms or distinguished between the latent construct and its manifest indicators. The current study aimed to investigate the latent structure of psychotic symptoms using factor mixture modeling (FMM) and to use the best-fitting model to examine its sociodemographic and clinical correlates.

The Singapore Mental Health Study (SMHS) was based on an adult representative sample of the Singapore population. Psychotic symptoms were assessed by using the Psychosis Screen section of the Composite International Diagnostic Interview version 3.0 (CIDI 3.0). FMM analyses were applied to determine the latent construct of psychotic symptoms. Sociodemographic and clinical correlates of the latent structure of psychosis symptoms were examined using multiple linear and logistic regression analyses.

The overall weighted lifetime prevalence of any psychotic experience was 3.8% in the SMHS after excluding subthreshold experiences. The FMM analysis clearly supported the dimensional model of the latent structure of psychotic symptoms. On deriving the total score for ‘psychosis symptoms’ in accordance with the one latent trait model, and correlating it with sociodemographic factors, we found that female gender, vocational education, current and past smokers were positively associated with the ‘psychosis’ total score.

There is a need for an increased understanding of, and research into, this intermediate state of ‘psychosis symptoms’ that do not meet diagnostic criteria for psychosis. It is also important to learn more about the group of individuals in the community who may have preserved functioning to elucidate the protective factors that prevent transition to psychosis.

Postpartum depression (PPD) affects approximately 13% of women and has a negative impact on mother and infant, hence reliable biological tests for early detection of PPD are essential. We aimed to identify robust predictive biomarkers for PPD using peripheral blood gene expression profiles in a hypothesis-free genome-wide study in a high-risk, longitudinal cohort.

We performed a genome-wide association study in a longitudinal discovery cohort comprising 62 women with psychopathology. Gene expression and hormones were measured in the first and third pregnancy trimesters and early postpartum (201 samples). The replication cohort comprised 24 women with third pregnancy trimester gene expression measures. Gene expression was measured on Illumina-Human HT12 v4 microarrays. Plasma estradiol and estriol were measured. Statistical analysis was performed in R.

We identified 116 transcripts differentially expressed between the PPD and euthymic women during the third trimester that allowed prediction of PPD with an accuracy of 88% in both discovery and replication cohorts. Within these transcripts, significant enrichment of transcripts implicated that estrogen signaling was observed and such enrichment was also evident when analysing published gene expression data predicting PPD from a non-risk cohort. While plasma estrogen levels were not different across groups, women with PPD displayed an increased sensitivity to estrogen signaling, confirming the previously proposed hypothesis of increased sex-steroid sensitivity as a susceptibility factor for PPD.

These results suggest that PPD can be robustly predicted in currently euthymic women as early as the third trimester and these findings have implications for predictive testing of high-risk women and prevention and treatment for PPD.

Observing incongruent actions interferes with ongoing action execution. This ‘interference effect’ is larger for observed biological actions than for non-biological actions. The current study used virtual reality to investigate the biological specificity of interference effects of action observation in autism spectrum conditions (ASC).

High-functioning adults with ASC and age- and IQ-matched healthy controls performed horizontal sinusoidal arm movements whilst observing arm movements conducted by a virtual reality agent with either human or robot form, which moved with either biological motion or at a constant velocity. In another condition, participants made the same arm movements while observing a real human. Observed arm movements were either congruent or incongruent with executed arm movements. An interference effect was calculated as the average variance in the incongruent action dimension during observation of incongruent compared with congruent movements.

Control participants exhibited an interference effect when observing real human and virtual human agent incongruent movements but not when observing virtual robot agent movements. Individuals with ASC differed from controls in that they showed no interference effects for real human, virtual human or virtual robot movements.

The current study demonstrates atypical interference effects in ASC.

Mentalizing deficits are a hallmark of the autism spectrum condition (ASC) and a potential endophenotype for atypical social cognition in ASC. Differences in performance and neural activation on the ‘Reading the Mind in the Eyes’ task (the Eyes task) have been identified in individuals with ASC in previous studies.

Performance on the Eyes task along with the associated neural activation was examined in adolescents with ASC (n = 50), their unaffected siblings (n = 40) and typically developing controls (n = 40). Based on prior literature that males and females with ASC display different cognitive and associated neural characteristics, analyses were stratified by sex. Three strategies were applied to test for endophenotypes at the level of neural activation: (1) identifying and locating conjunctions of ASC–control and sibling–control differences; (2) examining whether the sibling group is comparable to the ASC or intermediate between the ASC and control groups; and (3) examining spatial overlaps between ASC–control and sibling–control differences across multiple thresholds.

Impaired behavioural performance on the Eyes task was observed in males with ASC compared to controls, but only at trend level in females; and no difference in performance was identified between sibling and same-sex control groups in both sexes. Neural activation showed a substantial endophenotype effect in the female groups but this was only modest in the male groups.

Behavioural impairment on complex emotion recognition associated with mental state attribution is a phenotypic, rather than an endophenotypic, marker of ASC. However, the neural response during the Eyes task is a potential endophenotypic marker for ASC, particularly in females.

Antidepressants reduce depressive symptoms in patients with coronary heart disease, but they may be associated with increased mortality. This study aimed to examine whether the use of tricyclic antidepressants (TCA) or selective serotonin reuptake inhibitors (SSRI) is associated with mortality in patients with coronary heart disease, and to determine whether this association is mediated by autonomic function.

A total of 956 patients with coronary heart disease were followed for a mean duration of 7.2 years. Autonomic function was assessed as heart rate variability, and plasma and 24-h urinary norepinephrine.

Of 956 patients, 44 (4.6%) used TCA, 89 (9.3%) used SSRI, and 823 (86.1%) did not use antidepressants. At baseline, TCA users exhibited lower heart rate variability and higher norepinephrine levels compared with SSRI users and antidepressant non-users. At the end of the observational period, 52.3% of the TCA users had died compared with 38.2% in the SSRI group and 37.3% in the control group. The adjusted hazard ratio (HR) for TCA use compared with non-use was 1.74 [95% confidence interval (CI) 1.12–2.69, p = 0.01]. Further adjustment for measures of autonomic function reduced the association between TCA use and mortality (HR = 1.27, 95% CI 0.67–2.43, p = 0.47). SSRI use was not associated with mortality (HR = 1.15, 95% CI 0.81–1.64, p = 0.44).

The use of TCA was associated with increased mortality. This association was at least partially mediated by differences in autonomic function. Our findings suggest that TCA should be avoided in patients with coronary heart disease.