Late-life depression (LLD) in the elderly was reported to present with emotion dysregulation accompanied by high perceived loneliness. Previous research has suggested that LLD is a disorder of connectivity and is associated with aberrant network properties. On the other hand, perceived loneliness is found to adversely affect the brain, but little is known about its neurobiological basis in LLD. The current study investigated the relationships between the structural connectivity, functional connectivity during affective processing, and perceived loneliness in LLD.

The current study included 54 participants aged >60 years of whom 31 were diagnosed with LLD. Diffusion tensor imaging (DTI) data and task-based functional magnetic resonance imaging (fMRI) data of an affective processing task were collected. Network-based statistics and graph theory techniques were applied, and the participants’ perceived loneliness and depression level were measured. The affective processing task included viewing affective stimuli.

Structurally, a loneliness-related sub-network was identified across all subjects. Functionally, perceived loneliness was related to connectivity differently in LLD than that in controls when they were processing negative stimuli, with aberrant networking in subcortical area.

Perceived loneliness was identified to have a unique role in relation to the negative affective processing in LLD at the functional brain connectional and network levels. The findings increas our understanding of LLD and provide initial evidence of the neurobiological mechanisms of loneliness in LLD. Loneliness might be a potential intervention target in depressive patients.

Deficits in gamma aminobutyric acid (GABA) neuron-related markers, including the GABA-synthesizing enzyme GAD67, the calcium-binding protein parvalbumin, the neuropeptide somatostatin, and the transcription factor Lhx6, are most pronounced in a subset of schizophrenia subjects identified as having a ‘low GABA marker’ (LGM) molecular phenotype. Furthermore, schizophrenia shares degrees of genetic liability, clinical features and cortical circuitry abnormalities with schizoaffective disorder and bipolar disorder. Therefore, we determined the extent to which a similar LGM molecular phenotype may also exist in subjects with these disorders.

Transcript levels for GAD67, parvalbumin, somatostatin, and Lhx6 were quantified using quantitative PCR in prefrontal cortex area 9 of 184 subjects with a diagnosis of schizophrenia (n = 39), schizoaffective disorder (n = 23) or bipolar disorder (n = 35), or with a confirmed absence of any psychiatric diagnoses (n = 87). A blinded clustering approach was employed to determine the presence of a LGM molecular phenotype across all subjects.

Approximately 49% of the subjects with schizophrenia, 48% of the subjects with schizoaffective disorder, and 29% of the subjects with bipolar disorder, but only 5% of unaffected subjects, clustered in the cortical LGM molecular phenotype.

These findings support the characterization of psychotic and bipolar disorders by cortical molecular phenotype which may help elucidate more pathophysiologically informed and personalized medications.

Relatively few studies have investigated whether relatives of patients with bipolar disorder show brain functional changes, and these have focused on activation changes. Failure of de-activation during cognitive task performance is also seen in the disorder and may have trait-like characteristics since it has been found in euthymia.

A total of 20 euthymic patients with bipolar disorder, 20 of their unaffected siblings and 40 healthy controls underwent functional magnetic resonance imaging during performance of the n-back working memory task. An analysis of variance (ANOVA) was fitted to individual whole-brain maps from each set of patient–relative–matched pair of controls. Clusters of significant difference among the groups were used as regions of interest to compare mean activations/de-activations between them.

A single cluster of significant difference among the three groups was found in the whole-brain ANOVA. This was located in the medial prefrontal cortex, a region of task-related de-activation in the healthy controls. Both the patients and their siblings showed significantly reduced de-activation compared with the healthy controls in this region, but the failure was less marked in the relatives.

Failure to de-activate the medial prefrontal cortex in both euthymic bipolar patients and their unaffected siblings adds to evidence for default mode network dysfunction in the disorder, and suggests that it may act as a trait marker.

Intrusive memories of traumatic events are a core feature of post-traumatic stress disorder but little is known about the neurobiological formation of intrusions. The aim of this study was to determine whether the activity of the noradrenergic system during an intrusion-inducing stressor would influence subsequent intrusive memories.

We conducted an experimental, double-blind, placebo-controlled study in 118 healthy women. Participants received a single dose of either 10 mg yohimbine, stimulating noradrenergic activity, or 0.15 mg clonidine, inhibiting noradrenergic activity, or placebo. Subsequently, they watched an established trauma film which induced intrusions. The number of consecutive intrusions resulting from the trauma film, the vividness of the intrusions, and the degree of distress evoked by the intrusions were assessed during the following 4 days. Salivary cortisol and α-amylase were collected before and after the trauma film.

A significant time × treatment interaction for the number of intrusions and the vividness of intrusions indicated a different time course of intrusions depending on treatment. Post-hoc tests revealed a delayed decrease of intrusions and a delayed decrease of intrusion vividness after the trauma film in the yohimbine group compared with the clonidine and placebo groups. Furthermore, after yohimbine administration, a significant increase in salivary cortisol levels was observed during the trauma film.

Our findings indicate that pharmacological activation of the noradrenergic system during an emotionally negative event makes an impact on consecutive intrusive memories and their vividness in healthy women. The noradrenergic system seems to be involved in the formation of intrusive memories.

Healthy lifestyles prevent cardiovascular disease and are increasingly recognized in relation to mental health but longitudinal studies are limited. We examined bi-directional associations between mood disorders and healthy lifestyles in a cohort followed for 5 years.

Participants were aged 26–36 years at baseline (2004–2006) and 31–41 years at follow-up (2009–2011). At follow-up, lifetime mood disorders (depression or dysthymia) were retrospectively diagnosed with the Composite International Diagnostic Interview. A five-item lifestyle score (comprising body mass index, non-smoking, alcohol consumption, leisure time physical activity and healthy diet) was measured at both time points. Linear and log multinomial regression determined if mood disorder before baseline predicted changes in lifestyle (n = 1041). Log binomial regression estimated whether lifestyle at baseline predicted new episodes of mood disorder (n = 1233). Covariates included age, sex, socio-economic position, parental and marital status, social support, major life events, cardiovascular disease history, and self-rated physical and mental health.

A history of mood disorder before baseline predicted unfavourable trajectories of lifestyle over follow-up, including somewhat lower risk of improvement [relative risk (RR) 0.76, 95% confidence interval (CI) 0.56–1.03] and greater risk of worsening (RR 1.46, 95% CI 0.99–2.15) of lifestyle independent of confounding factors. Higher lifestyle scores at baseline were associated with a 22% (RR 0.76, 95% CI 0.61–0.95) reduced risk of first episodes of mood disorder, independent of confounding factors.

Healthy lifestyles and mood disorders are closely related. Our results suggest that healthy lifestyles may not only reduce cardiovascular disease but also promote mental health.

It remains unclear whether the topological deficits of the white matter network documented in cross-sectional studies of chronic schizophrenia patients are due to chronic illness or to other factors such as antipsychotic treatment effects. To answer this question, we evaluated the white matter network in medication-naive first-episode schizophrenia patients (FESP) before and after a course of treatment.

We performed a longitudinal diffusion tensor imaging study in 42 drug-naive FESP at baseline and then after 8 weeks of risperidone monotherapy, and compared them with 38 healthy volunteers. Graph theory was utilized to calculate the topological characteristics of brain anatomical network. Patients’ clinical state was evaluated using the Positive and Negative Syndrome Scale (PANSS) before and after treatment.

Pretreatment, patients had relatively intact overall topological organizations, and deficient nodal topological properties primarily in prefrontal gyrus and limbic system components such as the bilateral anterior and posterior cingulate. Treatment with risperidone normalized topological parameters in the limbic system, and the enhancement positively correlated with the reduction in PANSS-positive symptoms. Prefrontal topological impairments persisted following treatment and negative symptoms did not improve.

During the early phase of antipsychotic medication treatment there are region-specific alterations in white matter topological measures. Limbic white matter topological dysfunction improves with positive symptom reduction. Prefrontal deficits and negative symptoms are unresponsive to medication intervention, and prefrontal deficits are potential trait biomarkers and targets for negative symptom treatment development.

Little is known about time perception, its putative role as cognitive endophenotype, and its neuroanatomical underpinnings in adults with attention deficit hyperactivity disorder (ADHD).

Twenty adults with ADHD, 20 unaffected first-degree relatives and 20 typically developing controls matched for age and gender undertook structural magnetic resonance imaging scans. Voxel-based morphometry with DARTEL was performed to obtain regional grey-matter volumes. Temporal processing was investigated as a putative cognitive endophenotype using a temporal reproduction paradigm. General linear modelling was employed to examine the relationship between temporal reproduction performances and grey-matter volumes.

ADHD participants were impaired in temporal reproduction and unaffected first-degree relatives performed in between their ADHD probands and typically developing controls. Increased grey-matter volume in the cerebellum was associated with poorer temporal reproduction performance.

Adults with ADHD are impaired in time reproduction. Performances of the unaffected first-degree relatives are in between ADHD relatives and controls, suggesting that time reproduction might be a cognitive endophenotype for adult ADHD. The cerebellum is involved in time reproduction and might play a role in driving time performances.

It is unclear which potentially modifiable risk factors best predict post-trauma psychiatric disorders. We aimed to identify pre-trauma risk factors for post-traumatic stress disorder (PTSD) or major depression (MD) that could be targeted with resilience interventions.

Newly recruited paramedics (n = 453) were assessed for history of mental disorders with structured clinical interviews within the first week of their paramedic training and completed self-report measures to assess hypothesized predictors. Participants were assessed every 4 months for 2 years to identify any episodes of PTSD and MD; 386 paramedics (85.2%) participated in the follow-up interviews.

In all, 32 participants (8.3%) developed an episode of PTSD and 41 (10.6%) an episode of MD during follow-up. In all but nine cases (2.3%), episodes had remitted by the next assessment 4 months later. At 2 years, those with episodes of PTSD or MD during follow-up reported more days off work, poorer sleep, poorer quality of life, greater burn-out; and greater weight-gain for those with PTSD. In line with theories of PTSD and depression, analyses controlling for psychiatric and trauma history identified several pre-trauma predictors (cognitive styles, coping styles and psychological traits). Logistic regressions showed that rumination about memories of stressful events at the start of training uniquely predicted an episode of PTSD. Perceived resilience uniquely predicted an episode of MD.

Participants at risk of developing episodes of PTSD or depression could be identified within the first week of paramedic training. Cognitive predictors of episodes of PTSD and MD are promising targets for resilience interventions.

Previous research indicates a high prevalence of post-traumatic stress disorder (PTSD) and depression among refugees. Eye movement desensitization and reprocessing (EMDR) is an effective treatment for PTSD for victims of natural disasters, car accidents or other traumatic events. The current study examined the effect of EMDR on symptoms of PTSD and depression by comparing the treatment with a wait-list control condition in Syrian refugees.

Adult refugees located in Kilis Refugee Camp at the Turkish–Syrian border with a PTSD diagnosis were randomly allocated to either EMDR (n = 37) or wait-list control (n = 33) conditions. All participants were assessed with the Mini-International Neuropsychiatric Interview Plus at pre-intervention, at 1 week after finishing the intervention and at 5 weeks after finishing the intervention. The main outcome measures were the Harvard Trauma Questionnaire (HTQ) and the Impact of Event Scale-Revised. The Beck Depression Inventory and the Hopkins Symptoms Checklist-25 were included as secondary outcome measures. The Trial Registration no. is NCT01847742.

Mixed-model analyses adjusted for the baseline scores indicated a significant effect of group at post-treatment indicating that the EMDR therapy group showed a significantly larger reduction of PTSD symptoms as assessed with the HTQ. Similar findings were found on the other outcome measures. There was no effect of time or group × time interaction on any measure, showing that the difference between the groups at the post-treatment was maintained to the 5-week follow-up.

EMDR may be effective in reducing PTSD and depression symptoms among Syrian refugees with PTSD located in a refugee camp.

Many adults with autism spectrum disorder (ASD) remain undiagnosed. Specialist assessment clinics enable the detection of these cases, but such services are often overstretched. It has been proposed that unnecessary referrals to these services could be reduced by prioritizing individuals who score highly on the Autism-Spectrum Quotient (AQ), a self-report questionnaire measure of autistic traits. However, the ability of the AQ to predict who will go on to receive a diagnosis of ASD in adults is unclear.

We studied 476 adults, seen consecutively at a national ASD diagnostic referral service for suspected ASD. We tested AQ scores as predictors of ASD diagnosis made by expert clinicians according to International Classification of Diseases (ICD)-10 criteria, informed by the Autism Diagnostic Observation Schedule-Generic (ADOS-G) and Autism Diagnostic Interview-Revised (ADI-R) assessments.

Of the participants, 73% received a clinical diagnosis of ASD. Self-report AQ scores did not significantly predict receipt of a diagnosis. While AQ scores provided high sensitivity of 0.77 [95% confidence interval (CI) 0.72–0.82] and positive predictive value of 0.76 (95% CI 0.70–0.80), the specificity of 0.29 (95% CI 0.20–0.38) and negative predictive value of 0.36 (95% CI 0.22–0.40) were low. Thus, 64% of those who scored below the AQ cut-off were ‘false negatives’ who did in fact have ASD. Co-morbidity data revealed that generalized anxiety disorder may ‘mimic’ ASD and inflate AQ scores, leading to false positives.

The AQ's utility for screening referrals was limited in this sample. Recommendations supporting the AQ's role in the assessment of adult ASD, e.g. UK NICE guidelines, may need to be reconsidered.

Language use is of increasing interest in the study of mental illness. Analytical approaches range from phenomenological and qualitative to formal computational quantitative methods. Practically, the approach may have utility in predicting clinical outcomes. We harnessed a real-world sample (blog entries) from groups with psychosis, strong beliefs, odd beliefs, illness, mental illness and/or social isolation to validate and extend laboratory findings about lexical differences between psychosis and control subjects.

We describe the results of two experiments using Linguistic Inquiry and Word Count software to assess word category frequencies. In experiment 1, we compared word use in psychosis and control subjects in the laboratory (23 per group), and related results to subject symptoms. In experiment 2, we examined lexical patterns in blog entries written by people with psychosis and eight comparison groups. In addition to between-group comparisons, we used factor analysis followed by clustering to discern the contributions of strong belief, odd belief and illness identity to lexical patterns.

Consistent with others’ work, we found that first-person pronouns, biological process words and negative emotion words were more frequent in psychosis language. We tested lexical differences between bloggers with psychosis and multiple relevant comparison groups. Clustering analysis revealed that word use frequencies did not group individuals with strong or odd beliefs, but instead grouped individuals with any illness (mental or physical).

Pairing of laboratory and real-world samples reveals that lexical markers previously identified as specific language changes in depression and psychosis are probably markers of illness in general.

Psychological models of conversion disorder (CD) traditionally assume that psychosocial stressors are identifiable around symptom onset. In the face of limited supportive evidence such models are being challenged.

Forty-three motor CD patients, 28 depression patients and 28 healthy controls were assessed using the Life Events and Difficulties Schedule in the year before symptom onset. A novel ‘escape’ rating for events was developed to test the Freudian theory that physical symptoms of CD could provide escape from stressors, a form of ‘secondary gain’.

CD patients had significantly more severe life events and ‘escape’ events than controls. In the month before symptom onset at least one severe event was identified in 56% of CD patients – significantly more than 21% of depression patients [odds ratio (OR) 4.63, 95% confidence interval (CI) 1.56–13.70] and healthy controls (OR 5.81, 95% CI 1.86–18.2). In the same time period 53% of CD patients had at least one ‘high escape’ event – again significantly higher than 14% in depression patients (OR 6.90, 95% CI 2.05–23.6) and 0% in healthy controls. Previous sexual abuse was more commonly reported in CD than controls, and in one third of female patients was contextually relevant to life events at symptom onset. The majority (88%) of life events of potential aetiological relevance were not identified by routine clinical assessments. Nine per cent of CD patients had no identifiable severe life events.

Evidence was found supporting the psychological model of CD, the Freudian notion of escape and the potential aetiological relevance of childhood traumas in some patients. Uncovering stressors of potential aetiological relevance requires thorough psychosocial evaluation.

Efficacy of pre-trauma prevention for post-traumatic stress disorder (PTSD) has not yet been established in a randomized controlled trial. Attention bias modification training (ABMT), a computerized intervention, is thought to mitigate stress-related symptoms by targeting disruptions in threat monitoring. We examined the efficacy of ABMT delivered before combat in mitigating risk for PTSD following combat.

We conducted a double-blind, four-arm randomized controlled trial of 719 infantry soldiers to compare the efficacy of eight sessions of ABMT (n = 179), four sessions of ABMT (n = 184), four sessions of attention control training (ACT; n = 180), or no-training control (n = 176). Outcome symptoms were measured at baseline, 6-month follow-up, 10 days following combat exposure, and 4 months following combat. Primary outcome was PTSD prevalence 4 months post-combat determined in a clinical interview using the Clinician-Administered PTSD Scale. Secondary outcomes were self-reported PTSD and depression symptoms, collected at all four assessments.

PTSD prevalence 4 months post-combat was 7.8% in the no-training control group, 6.7% with eight-session ABMT, 2.6% with four-session ABMT, and 5% with ACT. Four sessions of ABMT reduced risk for PTSD relative to the no-training condition (odds ratio 3.13, 95% confidence interval 1.01–9.22, p < 0.05, number needed to treat = 19.2). No other between-group differences were found. The results were consistent across a variety of analytic techniques and data imputation approaches.

Four sessions of ABMT, delivered prior to combat deployment, mitigated PTSD risk following combat exposure. Given its low cost and high scalability potential, and observed number needed to treat, research into larger-scale applications is warranted. The ClinicalTrials.gov identifier is NCT01723215.

Childhood maltreatment (CM) has been associated with increased risk of attention deficit hyperactivity disorder (ADHD) in children and adults. It is, however, unclear whether this association is causal or due to familial confounding.

Data from 18 168 adult twins, aged 20–46 years, were drawn from the population-based Swedish twin registry. Retrospective self-ratings of CM (emotional and physical neglect, physical and sexual abuse and witnessing family violence), and self-ratings for DSM-IV ADHD symptoms in adulthood were analysed. Possible familial confounding was investigated using a within twin-pair design based on monozygotic (MZ) and dizygotic (DZ) twins.

CM was significantly associated with increased levels of ADHD symptom scores in adults [regression coefficient: 0.40 standard deviations, 95% confidence interval (CI) 0.37–0.43]. Within twin-pair analyses showed attenuated but significant estimates within DZ (0.29, 95% CI 0.21–0.36) and MZ (0.18, 95% CI 0.10–0.25) twin pairs. Similar results emerged for hyperactive/impulsive and inattentive ADHD symptom scores separately in association with CM. We conducted sensitivity analyses for early maltreatment, before age 7, and for abuse and neglect separately, and found similarly reduced estimates in DZ and MZ pairs. Re-traumatization after age 7 did not significantly influence results.

CM was significantly associated with increased ADHD symptoms in adults. Associations were partly due to familial confounding, but also consistent with a causal interpretation. Our findings support cognitive neuroscience studies investigating neural pathways through which exposure to CM may influence ADHD. Clinicians treating adults with ADHD should be aware of the association with maltreatment.

Tests requiring the pronunciation of irregular words are used to estimate premorbid cognitive ability in patients with clinical diagnoses, and prior cognitive ability in normal ageing. However, scores on these word-reading tests correlate with scores on the Mini-Mental State Examination (MMSE), a widely used screening test for possible cognitive pathology. This study aimed to test whether the word-reading tests’ correlations with MMSE scores in healthy older people are explained by childhood IQ or education.

Wechsler Test of Adult Reading (WTAR), National Adult Reading Test (NART), MMSE scores and information about education were obtained from 1024 70-year-olds, for whom childhood intelligence test scores were available.

WTAR and NART were positively correlated with the MMSE (r ≈ 0.40, p < 0.001). The shared variance of WTAR and NART with MMSE was significantly attenuated by ~70% after controlling for childhood intelligence test scores. Education explained little additional variance in the association between the reading tests and the MMSE.

MMSE, which is often used to index cognitive impairment, is associated with prior cognitive ability. MMSE score is related to scores on WTAR and NART largely due to their shared association with prior ability. Obtained MMSE scores should be interpreted in the context of prior ability (or WTAR/NART score as its proxy).

Studies on whether the co-occurrence of psychotic experiences (PEs) and depression confers a more pronounced decrement in health status and function compared with depression alone are scarce in the general adult population.

Data on 195 479 adults aged ⩾18 years from the World Health Survey were analysed. Using the World Mental Health Survey version of the Composite International Diagnostic Interview (CIDI), depression in the past 12 months was categorized into four groups: depressive episode, brief depressive episode, subsyndromal depression, and no depression. Past 12-month psychotic symptoms were assessed using four questions on positive symptoms from the CIDI. Health status across seven domains (cognition, interpersonal activities, sleep/energy, self-care, mobility, pain/discomfort, vision) and interviewer-rated presence of a mental health problem were assessed. Multivariable logistic and linear regression analyses were performed to assess the associations.

When compared with those with no depression, individuals with depression had higher odds of reporting at least one PE, and this was seen across all levels of depression severity: subsyndromal depression [odds ratio (OR) 2.38, 95% confidence interval (CI) 2.02–2.81], brief depressive episode (OR 3.84, 95% CI 3.31–4.46) and depressive episode (OR 3.75, 95% CI 3.24–4.33). Having coexisting PEs and depression was associated with a higher risk for observable illness behavior and a significant decline in health status in the cognition, interpersonal activities and sleep/energy domains, compared with those with depression alone.

This coexistence of depression and PEs is associated with more severe social, cognitive and sleep disturbances, and more outwardly apparent illness behavior. Detecting this co-occurrence may be important for treatment planning.

Traditional approaches for the classification of eating disorders (EDs) attribute symptoms to an underlying, latent disease entity. The network approach is an alternative model in which mental disorders are represented as networks of interacting, self-reinforcing symptoms. This project was the first to use network analysis to identify interconnected systems of ED symptoms.

Adult participants (n = 143; 77.6% women) with a Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) ED were recruited from the community to take part in a larger ongoing longitudinal study. The Structured Clinical Interview for DSM Disorders (SCID-I) was used to establish diagnoses. An undirected network of ED symptoms was created using items from the Eating Pathology Symptoms Inventory (EPSI) and the R package qgraph.

Body checking emerged as the strongest and most important single symptom in the entire network by having the shortest average distance to other symptoms in the network, and by being the most frequent symptom on the path between any two other symptoms. Feeling the need to exercise every day and two symptoms assessing dietary restraint/restricting emerged as ‘key players’, such that their removal from the network resulted in maximal fracturing of the network into smaller components.

Although cognitive–behavioral therapy for EDs focuses on reducing body checking to promote recovery, our data indicate that amplified efforts to address body checking may produce stronger (and more enduring) effects. Finally, results of the ‘key players analysis’ suggested that targeting interventions at these key nodes might prevent or slow the cascade of symptoms through the ‘network’ of ED psychopathology.