Fear circuitry disorders purportedly include post-traumatic stress disorder (PTSD), panic disorder, agoraphobia, social phobia and specific phobia. It is proposed that these disorders represent a cluster of anxiety disorders triggered by stressful events and lead to fear conditioning. Elevated heart rate (HR) at the time of an aversive event may reflect strength of the unconditioned response, which may contribute to fear circuitry disorders.

This prospective cohort study assessed HR within 48 h of hospital admission in 602 traumatically injured patients, who were assessed during hospital admission and within 1 month of trauma exposure for lifetime psychiatric diagnosis. At 3 months after the initial assessment, 526 patients (87%) were reassessed for PTSD, major depressive disorder, panic disorder, agoraphobia, social phobia, obsessive compulsive disorder and generalized anxiety disorder.

At the 3-month assessment there were 77 (15%) new cases of fear circuitry disorder and 87 new cases of non-fear circuitry disorder (17%). After controlling for gender, age, type of injury and injury severity, patients with elevated HR (defined as ⩾96 beats per min) at the time of injury were more likely to develop PTSD [odds ratio (OR) 5.78, 95% confidence interval (CI) 2.32–14.43], panic disorder (OR 3.46, 95% CI 1.16–10.34), agoraphobia (OR 3.90, 95% CI 1.76–8.61) and social phobia (OR 3.98, 95% CI 1.42–11.14). Elevated HR also predicted new fear circuitry disorders that were not co-morbid with a non-fear circuitry disorder (OR 7.28, 95% CI 2.14–24.79).

These data provide tentative evidence of a common mechanism underpinning the onset of fear circuitry disorders.

The current study examined the pattern of neurocognitive impairments in a community-recruited sample of clinical high-risk (CHR) participants and established relationships with psychosocial functioning.

CHR-participants (n = 108), participants who did not fulfil CHR-criteria (CHR-negatives) (n = 42) as well as a group of healthy controls (HCs) (n = 55) were recruited. CHR-status was assessed using the Comprehensive Assessment of At-Risk Mental States (CAARMS) and the Schizophrenia Proneness Instrument, Adult Version (SPI-A). The Brief Assessment of Cognition in Schizophrenia Battery (BACS) as well as tests for emotion recognition, working memory and attention were administered. In addition, role and social functioning as well as premorbid adjustment were assessed.

CHR-participants were significantly impaired on the Symbol-Coding and Token-Motor task and showed a reduction in total BACS-scores. Moreover, CHR-participants were characterised by prolonged response times (RTs) in emotion recognition as well as by reductions in both social and role functioning, GAF and premorbid adjustments compared with HCs. Neurocognitive impairments in emotion recognition accuracy, emotion recognition RT, processing speed and motor speed were associated with several aspects of functioning explaining between 4% and 12% of the variance.

The current data obtained from a community sample of CHR-participants highlight the importance of dysfunctions in motor and processing speed and emotion recognition RT. Moreover, these deficits were found to be related to global, social and role functioning, suggesting that neurocognitive impairments are an important aspect of sub-threshold psychotic experiences and a possible target for therapeutic interventions.

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.

Attainment of remission is viewed as the optimal outcome of acute antidepressant treatment. However, some patients experience subsyndromal symptoms after they achieve remission. This study examines the prognostic significance of subsyndromal symptoms occurring during the first 6 months after remission of late-life depression.

Older (age 60–89 years) in-patients and out-patients with unipolar major depression were followed until remission (asymptomatic or almost asymptomatic for 3 consecutive weeks). Two hundred and forty-two achieved remission after uncontrolled antidepressant treatment. This analysis focused on remitted patients who had follow-up data over a 2.5-year period (n = 185).

Approximately 18% of patients relapsed. Of the remainder (n = 152), 42.8% had subsyndromal depressive symptoms during the 6 months following remission. Cox's proportional survival analysis demonstrated that longer duration of subsyndromal symptoms [number of weeks with the Longitudinal Follow-up Examination (LIFE) Psychiatric Status Rating Scale (PSR) score of 3 or 4] in the first 6 months after remission was significantly associated with shorter time to recurrence and higher recurrence rate [hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.08–1.24]. Based on our analysis, patients with 0, 4, 8 and 12 weeks of subsyndromal symptoms in the first 6 months after remission have estimated recurrence rates of 28, 45, 66 and 86% respectively during the ensuing 2 years.

These findings highlight the clinical importance of subsyndromal symptoms occurring after remission in late-life depression. They also argue that studies of geriatric depression may complement the definition of remission with information on subsyndromal symptoms occurring after the initial asymptomatic period.

Subanesthetic ketamine infusion therapy can produce fast-acting antidepressant effects in patients with major depression. How single and repeated ketamine treatment modulates the whole-brain functional connectome to affect clinical outcomes remains uncharacterized.

Data-driven whole brain functional connectivity (FC) analysis was used to identify the functional connections modified by ketamine treatment in patients with major depressive disorder (MDD). MDD patients (N = 61, mean age = 38, 19 women) completed baseline resting-state (RS) functional magnetic resonance imaging and depression symptom scales. Of these patients, n = 48 and n = 51, completed the same assessments 24 h after receiving one and four 0.5 mg/kg intravenous ketamine infusions. Healthy controls (HC) (n = 40, 24 women) completed baseline assessments with no intervention. Analysis of RS FC addressed effects of diagnosis, time, and remitter status.

Significant differences (p < 0.05, corrected) in RS FC were observed between HC and MDD at baseline in the somatomotor network and between association and default mode networks. These disruptions in FC in MDD patients trended toward control patterns with ketamine treatment. Furthermore, following serial ketamine infusions, significant decreases in FC were observed between the cerebellum and salience network (SN) (p < 0.05, corrected). Patient remitters showed increased FC between the cerebellum and the striatum prior to treatment that decreased following treatment, whereas non-remitters showed the opposite pattern.

Results support that ketamine treatment leads to neurofunctional plasticity between distinct neural networks that are shown as disrupted in MDD patients. Cortico-striatal-cerebellar loops that encompass the SN could be a potential biomarker for ketamine treatment.

While risk for alcohol use disorder (AUD) is correlated in twins, siblings and parent-offspring pairs, we know little of how this syndrome is transmitted across three generations.

We examined 685 172 individuals born in Sweden from 1980 to 1990 with four grandparents, and both parents alive in 1980. AUD was assessed in all these individuals from nationwide medical, criminal and pharmacy registries.

AUD was stably transmitted across three generations. Parent-child and grandparent-grandchild tetrachoric correlations equaled +0.25 and +0.12, respectively. Grandchild AUD risk did not vary as a function of the sex of the parent or grandparent. However, from grandparents and parents, transmission to grandchildren was stronger in same-sex than opposite-sex pairs. Compared with a grandchild with unaffected parents and grandparents, risk for AUD with a grandparent but no parent affected, a parent but no grandparent affected or both affected increased approximately 70% and 3 and 4-fold, respectively. Grandchildren with ⩾2 grandparents affected had a 40% greater AUD risk than those with only one affected. Tetrachoric correlations for AUD between offspring and great-aunts/uncles, and aunts/uncles equaled +0.06 and +0.13, respectively.

The transmission of AUD in Sweden across three generations is relatively stable. An orderly pattern of resemblance is seen with correlations declining by approximately 50% between first and second, and second and third-degree relatives. While the transmission of risk from affected male and female relatives does not differ, we find consistent evidence for greater resemblance in same-sex v. opposite-sex across generational pairs of relatives.

Functional somatic disorders (FSD) feature medical symptoms of unclear etiology. Attempts to clarify their origin have been hampered by a lack of rigorous research designs. We sought to clarify the etiology of the FSD by examining the genetic risk patterns for FSD and other related disorders.

This study was performed in 5 829 186 individuals from Swedish national registers. We quantified familial genetic risk for FSD, internalizing disorders, and somatic disorders in cases of chronic fatigue syndrome (CFS), fibromyalgia (FM), and irritable bowel syndrome (IBS), using a novel method based on aggregate risk in first to fifth degree relatives, adjusting for cohabitation. We compared these profiles with those of a prototypic internalizing psychiatric – major depression (MD) – and a somatic/autoimmune disorder: rheumatoid arthritis (RA).

Patients with FM carry substantial genetic risks not only for FM, but also for pain syndromes and internalizing, autoimmune and sleep disorders. The genetic risk profiles for IBS and CFS are also widely distributed although with lower average risks. By contrast, genetic risk profiles of MD and RA are much more restricted to related conditions.

Patients with FM have a relatively unique family genetic risk score profile with elevated genetic risk across a range of disorders that differs markedly from the profiles of a classic autoimmune disorder (RA) and internalizing disorder (MD). A similar less marked pattern of genetic risks was seen for IBS and CFS. FSD arise from a distinctive pattern of genetic liability for a diversity of psychiatric, autoimmune, pain, sleep, and functional somatic disorders.

Callous-unemotional (CU) traits are critical to developmental, diagnostic, and clinical models of antisocial behaviors (AB). However, assessments of CU traits within large-scale longitudinal and neurobiologically focused investigations remain remarkably sparse. We sought to develop a brief measure of CU traits using items from widely administered instruments that could be linked to neuroimaging, genetic, and environmental data within already existing datasets and future studies.

Data came from a large and diverse sample (n = 4525) of youth (ages~9–11) taking part in the Adolescent Brain and Cognitive Development (ABCD) Study. Moderated nonlinear factor analysis was used to assess measurement invariance across sex, race, and age. We explored whether CU traits were distinct from other indicators of AB, investigated unique links with theoretically-relevant outcomes, and replicated findings in an independent sample.

The brief CU traits measure demonstrated strong psychometric properties and evidence of measurement invariance across sex, race, and age. On average, boys endorsed higher levels of CU traits than girls and CU traits were related to, yet distinguishable from other indicators of AB. The CU traits construct also exhibited expected associations with theoretically important outcomes. Study findings were also replicated across an independent sample of youth.

In a large, multi-site study, a brief measure of CU traits can be measured distinctly from other dimensions of AB. This measure provides the scientific community with a method to assess CU traits in the ABCD sample, as well as in other studies that may benefit from a brief assessment of CU.

Observing another person performing a complex action accelerates the observer's acquisition of the same action and limits the time-consuming process of learning by trial and error. Learning by observation requires specific skills such as attending, imitating and understanding contingencies. Individuals with autism spectrum disorder (ASD) exhibit deficits in these skills.

The performance of 20 ASD children was compared with that of a group of typically developing (TD) children matched for chronological age (CA), IQ and gender on tasks of learning of a visuomotor sequence by observation or by trial and error. Acquiring the correct sequence involved three phases: a detection phase (DP), in which participants discovered the correct sequence and learned how to perform the task; an exercise phase (EP), in which they reproduced the sequence until performance was error free; and an automatization phase (AP), in which by repeating the error-free sequence they became accurate and speedy.

In the DP, ASD children were impaired in detecting a sequence by trial and error only when the task was proposed as first, whereas they were as efficient as TD children in detecting a sequence by observation. In the EP, ASD children were as efficient as TD children. In the AP, ASD children were impaired in automatizing the sequence. Although the positive effect of learning by observation was evident, ASD children made a high number of imitative errors, indicating marked tendencies to hyperimitate.

These findings demonstrate the imitative abilities of ASD children although the presence of imitative errors indicates an impairment in the control of imitative behaviours.

The clinical course of psychotic disorders is highly variable. Typically, researchers have captured different course types using broad pre-defined categories. However, whether these adequately capture symptom trajectories of psychotic disorders has not been fully assessed. Using data from AESOP-10, we sought to identify classes of individuals with specific symptom trajectories over a 10-year follow-up using a data-driven approach.

AESOP-10 is a follow-up, at 10 years, of 532 incident cases with a first episode of psychosis initially identified in south-east London and Nottingham, UK. Using extensive information on fluctuations in the presence of psychotic symptoms, we fitted growth mixture models to identify latent trajectory classes that accounted for heterogeneity in the patterns of change in psychotic symptoms over time.

We had sufficient data on psychotic symptoms during the follow-up on 326 incident patients. A four-class quadratic growth mixture model identified four trajectories of psychotic symptoms: (1) remitting-improving (58.5%); (2) late decline (5.6%); (3) late improvement (5.4%); (4) persistent (30.6%). A persistent trajectory, compared with remitting-improving, was associated with gender (more men), black Caribbean ethnicity, low baseline education and high disadvantage, low premorbid IQ, a baseline diagnosis of non-affective psychosis and long DUP. Numbers were small, but there were indications that those with a late decline trajectory more closely resembled those with a persistent trajectory.

Our current approach to categorising the course of psychotic disorders may misclassify patients. This may confound efforts to elucidate the predictors of long-term course and related biomarkers.

Mild cognitive impairment (MCI), as a stage in the cognitive continuum between normal ageing and dementia, is mainly characterized by memory impairment. The aims of this study were to examine CANTAB measures of temporal changes of visual memory in MCI and to evaluate the usefulness of the baseline scores for predicting changes in cognitive status.

The study included 201 participants aged over 50 years with subjective cognitive complaints. Visual memory was assessed with four CANTAB tests [paired associates learning (PAL), delayed matching to sample (DMS), pattern recognition memory (PRM) and spatial span (SSP)] administered at baseline and on two further occasions, with a follow-up interval of 18–24 months. Participants were divided into three groups according to the change in their cognitive status: participants with subjective cognitive complaints who remained stable, MCI participants who remained stable (MCI-Stable) and MCI participants whose cognitive deterioration continued (MCI-Worsened). Linear mixed models were used to model longitudinal changes, with evaluation time as a fixed variable, and multinomial regression models were used to predict changes in cognitive status.

Isolated significant effects were obtained for age and group with all CANTAB tests used. Interactions between evaluation time and group were identified in the PAL and DMS tests, indicating different temporal patterns depending on the changes in cognitive status. Regression models also indicated that CANTAB scores were good predictors of changes in cognitive status.

Decline in visual memory measured by PAL and DMS tests can successfully distinguish different types of MCI, and considered together PAL, DMS, PRM and SSP can predict changes in cognitive status.

Anhedonia is apparent in different mental disorders and is suggested to be related to dysfunctions in the reward system and/or affect regulation. It may hence be a common underlying feature associated with symptom severity of mental disorders.

We constructed a cross-sectional graphical Least Absolute Shrinkage and Selection Operator (LASSO) network and a relative importance network to estimate the relationships between anhedonia severity and the severity of symptom clusters of major depressive disorder (MDD), anxiety sensitivity (AS), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) in a sample of Dutch adult psychiatric patients (N = 557).

Both these networks revealed anhedonia severity and depression symptom severity as central to the network. Results suggest that anhedonia severity may be predictive of the severity of symptom clusters of MDD, AS, ADHD, and ASD. MDD symptom severity may be predictive of AS and ADHD symptom severity.

The results suggest that anhedonia may serve as a common underlying transdiagnostic psychopathology feature, predictive of the severity of symptom clusters of depression, AS, ADHD, and ASD. Thus, anhedonia may be associated with the high comorbidity between these symptom clusters and disorders. If our results will be replicated in future studies, it is recommended for clinicians to be more vigilant about screening for anhedonia and/or depression severity in individuals diagnosed with an anxiety disorder, ADHD and/or ASD.

This study investigated whether higher maternal choline levels mitigate effects of marijuana on fetal brain development. Choline transported into the amniotic fluid from the mother activates α7-nicotinic acetylcholine receptors on fetal cerebro-cortical inhibitory neurons, whose development is impeded by cannabis blockade of their cannabinoid-1(CB1) receptors.

Marijuana use was assessed during pregnancy from women who later brought their newborns for study. Mothers were informed about choline and other nutrients, but not specifically for marijuana use. Maternal serum choline was measured at 16 weeks gestation.

Marijuana use for the first 10 weeks gestation or more by 15% of mothers decreased newborns' inhibition of evoked potentials to repeated sounds (d’ = 0.55, p < 0.05). This effect was ameliorated if women had higher gestational choline (rs = −0.50, p = 0.011). At 3 months of age, children whose mothers continued marijuana use through their 10th gestational week or more had poorer self-regulation (d’ = −0.79, p < 0.05). This effect was also ameliorated if mothers had higher gestational choline (rs = 0.54, p = 0.013). Maternal choline levels correlated with the children's improved duration of attention, cuddliness, and bonding with parents.

Prenatal marijuana use adversely affects fetal brain development and subsequent behavioral self-regulation, a precursor to later, more serious problems in childhood. Stopping marijuana use before 10 weeks gestational age prevented these effects. Many mothers refuse to cease use because of familiarity with marijuana and belief in its safety. Higher maternal choline mitigates some of marijuana's adverse effects on the fetus.