This economic evaluation supplements a pragmatic randomized controlled trial conducted in community care settings, which showed superior improvement in the symptoms of adults with anxiety disorders who received 12 sessions of transdiagnostic cognitive-behavioural group therapy in addition to treatment as usual (tCBT + TAU) compared to TAU alone.

This study evaluates the cost-utility and cost-effectiveness of tCBT + TAU over an 8-month time horizon. For the reference case, quality-adjusted life years (QALYs) obtained using the EQ-5D-5L, and the health system perspective were chosen. Alternatively, anxiety-free days (AFDs), derived from the Beck Anxiety Inventory, and the limited societal perspective were considered. Unadjusted incremental cost-effectiveness/utility ratios were calculated. Net-benefit regressions were done for a willingness-to-pay (WTP) thresholds range to build cost-effectiveness acceptability curves (CEAC). Sensitivity analyses were included.

Compared to TAU (n = 114), tCBT + TAU (n = 117) generated additional QALYs, AFDs, and higher mental health care costs from the health system perspective. From the health system and the limited societal perspectives, at a WTP of Can$ 50 000/QALY, the CEACs showed that the probability of tCBT + TAU v. TAU being cost-effective was 97 and 89%. Promising cost-effectiveness results using AFDs are also presented. The participation of therapists from the public health sector could increase cost-effectiveness.

From the limited societal and health system perspectives, this first economic evaluation of tCBT shows favourable cost-effectiveness results at a WTP threshold of Can$ 50 000/QALY. Future research is needed to replicate findings in longer follow-up studies and different health system contexts to better inform decision-makers for a full-scale implementation.

Cluster analyses have become popular tools for data-driven classification in biological psychiatric research. However, these analyses are known to be sensitive to the chosen methods and/or modelling options, which may hamper generalizability and replicability of findings. To gain more insight into this problem, we used Specification-Curve Analysis (SCA) to investigate the influence of methodological variation on biomarker-based cluster-analysis results.

Proteomics data (31 biomarkers) were used from patients (n = 688) and healthy controls (n = 426) in the Netherlands Study of Depression and Anxiety. In SCAs, consistency of results was evaluated across 1200 k-means and hierarchical clustering analyses, each with a unique combination of the clustering algorithm, fit-index, and distance metric. Next, SCAs were run in simulated datasets with varying cluster numbers and noise/outlier levels to evaluate the effect of data properties on SCA outcomes.

The real data SCA showed no robust patterns of biological clustering in either the MDD or a combined MDD/healthy dataset. The simulation results showed that the correct number of clusters could be identified quite consistently across the 1200 model specifications, but that correct cluster identification became harder when the number of clusters and noise levels increased.

SCA can provide useful insights into the presence of clusters in biomarker data. However, SCA is likely to show inconsistent results in real-world biomarker datasets that are complex and contain considerable levels of noise. Here, the number and nature of the observed clusters may depend strongly on the chosen model-specification, precluding conclusions about the existence of biological clusters among psychiatric patients.

There are few theoretical proposals that attempt to account for the variation in affective processing across different affective states of bipolar disorder (BD). The Interacting Cognitive Subsystems (ICS) framework has been recently extended to account for manic states. Within the framework, positive mood state is hypothesized to tap into an implicational level of processing, which is proposed to be more extreme in states of mania.

Thirty individuals with BD and 30 individuals with no history of affective disorder were tested in euthymic mood state and then in induced positive mood state using the Question–Answer task to examine the mode of processing of schemas. The task was designed to test whether individuals would detect discrepancies within the prevailing schemas of the sentences.

Although the present study did not support the hypothesis that the groups differ in their ability to detect discrepancies within schemas, we did find that the BD group was significantly more likely than the control group to answer questions that were consistent with the prevailing schemas, both before and after mood induction.

These results may reflect a general cognitive bias, that individuals with BD have a tendency to operate at a more abstract level of representation. This may leave an individual prone to affective disturbance, although further research is required to replicate this finding.

The transition to adolescence implicates heightened vulnerability alongside increased opportunities for resilience. Contexts of early life stress (ELS) exacerbate risk; still, little research addressed biobehavioral mediators of risk and resilience across the adolescent transition following ELS. Utilizing a unique cohort, we tested biosocial moderators of chronicity in adolescents’ internalizing disorders v. resilience.

Families exposed to chronic war-related trauma, v. controls, were followed. We utilized data from three time-points framing the adolescent transition: late childhood (N = 177, Mage = 9.3 years ± 1.41), early adolescence (N = 111, Mage = 11 0.66 years ± 1.23), and late adolescence (N = 138, Mage = 15.65 years ± 1.31). In late childhood and late adolescence children's internalizing disorders were diagnosed. At early adolescence maternal and child's hair cortisol concentrations (HCC), maternal sensitivity, and mothers’ post-traumatic symptoms evaluated.

War-exposed children exhibited more internalizing disorders of chronic trajectory and mothers were less sensitive and more symptomatic. Three pathways elucidated the continuity of psychopathology: (a) maternal sensitivity moderated the risk of chronic psychopathology, (b) maternal post-traumatic symptoms mediated continuity of risk, (c) trauma exposure moderated the association between child internalizing disorders at late childhood and maternal HCC, which linked with child HCC. Child HCC linked with maternal post-traumatic symptoms, which were associated with child disorders in late adolescence.

Results demonstrate the complex interplay of maternal and child's biosocial factors as mediators and moderators of risk chronicity across the adolescent transition following trauma. Findings are first to utilize maternal and child's HCC as biomarkers of chronic stress v. resilience during adolescence, a period of neural reorganization and personal growth that shapes the individual's lifetime adaptation.

Problems in learning that sights, sounds, or situations that were once associated with danger have become safe (extinction learning) may explain why some individuals suffer prolonged psychological distress following traumatic experiences. Although simple learning models have been unable to provide a convincing account of why this learning fails, it has recently been proposed that this may be explained by individual differences in beliefs about the causal structure of the environment.

Here, we tested two competing hypotheses as to how differences in causal inference might be related to trauma-related psychopathology, using extinction learning data collected from clinically well-characterised individuals with varying degrees of post-traumatic stress (N = 56). Model parameters describing individual differences in causal inference were related to multiple post-traumatic stress disorder (PTSD) and depression symptom dimensions via network analysis.

Individuals with more severe PTSD were more likely to assign observations from conditioning and extinction stages to a single underlying cause. Specifically, greater re-experiencing symptom severity was associated with a lower likelihood of inferring that multiple causes were active in the environment.

We interpret these results as providing evidence of a primary deficit in discriminative learning in participants with more severe PTSD. Specifically, a tendency to attribute a greater diversity of stimulus configurations to the same underlying cause resulted in greater uncertainty about stimulus-outcome associations, impeding learning both that certain stimuli were safe, and that certain stimuli were no longer dangerous. In the future, better understanding of the role of causal inference in trauma-related psychopathology may help refine cognitive therapies for these disorders.

Maternal Rheumatoid Arthritis (RA) is suggested to increase the risk of Autism Spectrum Disorder (ASD) in the offspring, mainly through inflammation/autoimmunity, but the association is unclear. A prospective population-based cohort study was implemented to examine the association between maternal RA and offspring ASD.

We included all children born alive in Sweden from 1995 to 2015, followed up through 2017. Diagnoses of ASD and RA were clinically ascertained from National Patient Register. We quantified the association by hazard ratios (HR) and two-sided 95% confidence intervals (CI), from Cox regression after detailed adjustment for potential confounders. We examined RA serostatus, etiological subgroups and the timing of exposure. To closer examine the underlying mechanism for the association, we included a negative control group for RA, arthralgia, with similar symptomology as RA but free from inflammation/autoimmunity.

Of 3629 children born to mothers with RA, 70 (1.94%) were diagnosed with ASD, compared to 28 892 (1.92%) of 1 503 908 children born to mothers without RA. Maternal RA before delivery was associated with an increased risk of offspring ASD (HR = 1.43, 95% CI 1.11–1.84), especially for seronegative RA (HR = 1.61, 95% CI 1.12–2.30). No similar association was observed for paternal RA, maternal sisters with RA, or RA diagnosed after delivery. Maternal arthralgia displayed as high risks for offspring ASD as did maternal RA (HR = 1.41, 95% CI 1.24–1.60).

In Sweden, maternal RA before delivery was associated with an increased risk of offspring ASD. The comparable association between maternal arthralgia and ASD risk suggests other pathways of risk than autoimmunity/inflammation, acting jointly or independently of RA.

Prior studies suggest parental and perinatal risk factors are associated with later offending. It remains uncertain, however, if such risk factors are similarly related to sexual offending.

We linked socio-demographic, family relations, and perinatal (obtained at birth) data from the nationwide Swedish registers from 1973 to 2009 with information on criminal convictions of cases and control subjects. Male sex offenders (n = 13 773) were matched 1:5 on birth year and county of birth in Sweden to male controls without sexual or non-sexual violent convictions. To examine risk-factor specificity for sexual offending, we also compared male violent, non-sexual offenders (n = 135 953) to controls without sexual or non-sexual violent convictions. Predictors included parental (young maternal or paternal age at son's birth, educational attainment, violent crime, psychiatric disorder, substance misuse, suicide attempt) and perinatal (number of older brothers, low Apgar score, low birth weight, being small for gestational age, congenital malformations, small head size) variables.

Conditional logistic regression models found consistent patterns of statistically significant, small to moderate independent associations of parental risk factors with sons’ sexual offending and non-sexual violent offending. For perinatal risk factors, patterns varied more; small for gestational age and small head size exhibited similar risk effects for both offence types whereas a higher number of older biological brothers and any congenital malformation were small, independent risk factors only for non-sexual violence.

This nationwide study suggests substantial commonalities in parental and perinatal risk factors for the onset of sexual and non-sexual violent offending.

Preliminary evidence shows that discordance in stress experience, expression, and physiology (EEP) in adolescents is linked to depression, suicidal ideation (SI), non-suicidal self-injury (NSSI), and brain functioning. This study employs person-centered analysis to probe the relationship between stress responses, psychopathology, and neural patterns in female adolescents who are oversampled for engagement in NSSI.

Adolescent females (N = 109, ages 12–17) underwent a social stress test from which self-report measures of stress experience, observer ratings of stress expression, and physiological metrics of stress (via salivary cortisol) were obtained. Multi-trajectory modeling was employed to identify concordant and discordant stress EEP groups. Depressive symptoms, SI and attempt, NSSI engagement, frontal and limbic activation to emotional stimuli, and resting state fronto-limbic connectivity were examined in the EEP groups derived from the multi-trajectory models.

Four groups were identified, three of which demonstrated relatively concordant EEP and one which demonstrated discordant EEP (High Experience-High Expression-Low Physiology). Further, replicating past research, the High Experience-High Expression-Low Physiology discordant group exhibited higher depressive symptoms, SI, suicide attempt, and NSSI episodes (only for sensitivity analyses based on past year) relative to other EEP groups. No significant group differences in brain functioning emerged.

Results indicate that within-person, multi-level patterns in stress responding capture risk for dysfunction including depression and self-injurious thoughts and behaviors. Further interrogating of system-level stress functioning may better inform assessment and intervention efforts.

Research is needed to identify the factors that explain the link between prior and future suicidality. This study evaluated possible mediators of the relationship between: (1) the severity of prior suicidality and (2) suicidal ideation severity at 3-month follow-up among a sample of high-risk military personnel.

US military service members referred to or seeking care for suicide risk (N = 624) completed self-report psychiatric domain measures and a clinician interview assessing prior suicidality severity at baseline. Three months later, participants completed a self-report measure of suicidal ideation severity. Three separate percentile bootstrap mediation models were used to examine psychiatric factors (i.e. alcohol abuse, anxiety sensitivity, hopelessness, insomnia, posttraumatic stress symptoms, suicidal ideation, and thwarted belongingness) as parallel mediators of the relationship between prior suicidality severity (specifically, suicidal ideation, suicide attempt, and overall suicidality – i.e. ideation/attempt severity combined) at baseline and suicidal ideation severity at follow-up.

Hopelessness, specifically, and the total effect of all mediators, each significantly accounted for the relationship between prior suicidality severity and subsequent ideation severity across models. In the models with attempt severity and overall suicidality severity as predictors, thwarted belongingness was also a significant mediator.

Hopelessness, thwarted belongingness, and overall severity of psychiatric indices may explain the relationship between prior suicidality severity and future suicidal ideation severity among service members at elevated suicide risk. Research is needed to replicate these findings and examine other possible mediators.

Amnestic mild cognitive impairment (aMCI) is characterized by delayed P300 latency and reduced grey matter (GM) volume, respectively. The relationship between the features in aMCI is unclear. This study was to investigate the relationship between the altered P300 latency and the GM volume in aMCI.

Thirty-four aMCI and 34 well-matched normal controls (NC) were studied using electroencephalogram during a visual oddball task and scanned with MRI. Both tests were finished in the same day.

As compared with the NC group, the aMCI group exhibited delayed P300 latency in parietal cortex and reduced GM volumes in bilateral temporal pole and left hippocampus/parahippocampal gyrus. A remarkable negative correlation was found between delayed P300 latency and reduced left hippocampal volume only in the aMCI group. Interestingly, the mediating analysis found P300 latency significantly mediated the association between right supramarginal gyrus volume and information processing speed indicated by Stroop Color and Word Test A scores.

The association between delayed P300 latency and reduced left hippocampal volume in aMCI subjects suggests that reduced left hippocampal volume may be the potential structural basis of delayed P300 latency.

There is evidence for a polygenic contribution to psychosis. One targetable mechanism through which polygenic variation may impact on individuals and interact with the social environment is stress sensitization, characterized by elevated reactivity to minor stressors in daily life. The current study aimed to investigate whether stress reactivity is modified by polygenic risk score for schizophrenia (PRS) in cases with enduring non-affective psychotic disorder, first-degree relatives of cases, and controls.

We used the experience sampling method to assess minor stressors, negative affect, positive affect and psychotic experiences in 96 cases, 79 first-degree relatives, i.e. siblings, and 73 controls at wave 3 of the Dutch Genetic Risk and Outcome of Psychosis (GROUP) study. Genome-wide data were collected at baseline to calculate PRS.

We found that associations of momentary stress with psychotic experiences, but not with negative and positive affect, were modified by PRS and group (all pFWE<0.001). In contrast to our hypotheses, siblings with high PRS reported less intense psychotic experiences in response to momentary stress compared to siblings with low PRS. No differences in magnitude of these associations were observed in cases with high v. low level of PRS. By contrast, controls with high PRS showed more intense psychotic experiences in response to stress compared to those with low PRS.

This tentatively suggests that polygenic risk may operate in different ways than previously assumed and amplify reactivity to stress in unaffected individuals but operate as a resilience factor in relatives by attenuating their stress reactivity.