This study evaluated the impact of 2015/2016 prescribing guidance on antidepressant prescribing choices in children.

A retrospective e-cohort study of whole population routine electronic healthcare records was conducted. Poisson regression was undertaken to explore trends over time for depression, antidepressant prescribing, indications and secondary care contacts. Time trend analysis was conducted to assess the impact of guidance.

A total of 643 322 primary care patients in Wales UK, aged 6–17 years from 2010–2019 contributed 3 215 584 person-years of follow-up. Adjusted incidence of depression more than doubled (IRR for 2019 = 2.8 [2.5–3.2]) with similar trends seen for antidepressants. Fluoxetine was the most frequently prescribed first-line antidepressant. Citalopram comprised less than 5% of first prescriptions in younger children but 22.9% (95% CI 22.0–23.8; 95% CI 2533) in 16–17-year-olds. Approximately half of new antidepressant prescribing was associated with depression. Segmented regression analysis showed that prescriptions of ‘all’ antidepressants, Fluoxetine and Sertraline were increasing before the guidance. This upward trend flattened for both ‘all’ antidepressants and Fluoxetine and steepened for Sertraline. Citalopram prescribing was decreasing significantly pre guidance being issued with no significant change afterward.

Targeted intervention is needed to address rising rates of depression in children. Practitioners are partially adhering to local and national guidance. The decision-making process behind prescribing choices is likely to be multi-factorial. Activities to support implementation of guidance should be adopted in relation to safety in prescribing of antidepressants in children including timely availability of talking therapies and specialist mental health services.

The lifetime prevalence of suicide is around 5% in patients with schizophrenia. Non-adherence to antipsychotic medication is an important risk factor, but prospective studies investigating joint effects of antipsychotic drugs, antidepressants, and benzodiazepines on suicidality are scarce. We aimed to investigate how use and non-use of psychotropic medications are associated with suicidality in schizophrenia.

An open cohort study followed all patients consecutively admitted to a psychiatric acute unit during a 10-year period with a diagnosis of schizophrenia (n = 696). Cox multiple regression analyses were conducted with use of antipsychotics, antidepressants, and benzodiazepines as time-dependent variables. Adjustments were made for age, gender, depressive mood, agitated behavior, and use of alcohol and illicit substances.

A total of 32 (4.6%) suicide events were registered during follow-up. Of these, 9 (28%) were completed suicides and 23 (72%) were attempted suicides. A total of 59 (8.5%) patients were readmitted with suicidal plans during the follow-up. Compared to non-use, use of antipsychotics was associated with 70% lower risk of attempted or completed suicide (adjusted hazard ratio [AHR] = 0.30, p < 0.01, CI 0.14–0.65) and 69% reduced risk of readmission with suicidal plans (AHR = 0.31, p < 0.01, CI 0.18–0.55). Use of prescribed benzodiazepines was associated with 126% increased risk of readmission with suicidal plans (AHR = 2.26, p = 0.01, CI 1.24–4.13).

Adherence to antipsychotic medication is strongly associated with reduced suicidal risk in schizophrenia. The use of prescribed benzodiazepines was identified as a significant risk factor for being readmitted with suicidal plans.

Pediatric bipolar disorder (PBD) is characterized by abnormal functional connectivity among distributed brain regions. Increasing evidence suggests a role for the limbic network (LN) and the triple network model in the pathophysiology of bipolar disorder (BD). However, the specific relationship between the LN and the triple network in PBD remains unclear. This study aimed to investigate the aberrant causal connections among these four core networks in PBD.

Resting-state functional MRI scans from 92 PBD patients and 40 healthy controls (HCs) were analyzed. Dynamic Causal Modeling (DCM) was employed to assess effective connectivity (EC) among the four core networks. Parametric empirical Bayes (PEB) analysis was conducted to identify ECs associated with group differences, as well as depression and mania severity. Leave-one-out cross-validation (LOOCV) was used to test predictive accuracy.

Compared to HCs, PBD patients exhibited primarily excitatory bottom-up connections from the LN to the salience network (SN) and bidirectional excitatory connections between the default mode network (DMN) and SN. In PBD, top-down connectivity from the triple network to the LN was excitatory in individuals with higher depression severity but inhibitory in those with higher mania severity. LOOCV identified dysconnectivity circuits involving the caudate and hippocampus as being associated with mania and depression severity, respectively.

Disrupted bottom-up connections from the LN to the triple network distinguish PBD patients from healthy controls, while top-down disruptions from the triple network to LN relate to mood state differences. These findings offer insight into the neural mechanisms of PBD.

Adolescence is a critical period for preventing substance use and mental health concerns, often targeted through separate school-based programs. However, co-occurrence is common and is related to worse outcomes. This study explores prevention effects of leading school-based prevention programs on co-occurring alcohol use and psychological distress.

Data from two Australian cluster randomized trials involving 8576 students in 97 schools were harmonized for analysis. Students received either health education (control) or one of five prevention programs (e.g. Climate Schools, PreVenture) with assessments at baseline and 6, 12, 24, and 30 or 36 months (from ages ~13–16). Multilevel multinomial regressions were used to predict the relative risk ratios (RRs) of students reporting co-occurring early alcohol use and psychological distress, alcohol use only, distress only, or neither (reference) across programs.

The combined Climate Schools: Alcohol and Cannabis and Climate Schools: Mental Health courses (CSC) as well as the PreVenture program reduced the risk of adolescents reporting co-occurring alcohol use and psychological distress (36 months RRCSC = 0.37; RRPreVenture = 0.22). Other evaluated programs (excluding Climate Schools: Mental Health) only appeared effective for reducing the risk of alcohol use that occurred without distress.

Evidence-based programs exist that reduce the risk of early alcohol use with and without co-occurring psychological distress, though preventing psychological distress alone requires further exploration. Prevention programs appear to have different effects depending on whether alcohol use and distress present on their own or together, thus suggesting the need for tailored prevention strategies.

There is a lack of large-scale studies exploring labor market marginalization (LMM) among individuals diagnosed with bipolar disorder (BD). We aimed to investigate the association of BD with subsequent LMM in Sweden, and the effect of sex on LMM in BD.

Individuals aged 19–60 years living in Sweden with a first-time BD diagnosis between 2007 and 2016 (n = 25 231) were followed from the date of diagnosis for a maximum of 14 years. Risk of disability pension (DP), long-term sickness absence (SA) (>90 days), and long-term unemployment (>180 days) was compared to a matched comparison group from the general population, matched 1:5 on sex and birth year (n = 126 155), and unaffected full siblings (n = 24 098), using sex-stratified Cox regression analysis, yielding hazard ratios (HRs) with 95% confidence intervals (CIs).

After adjusting for socioeconomic factors, baseline labor market status, and comorbid disorders, individuals with BD had a significantly higher risk of DP compared to the general population (HR = 16.67, 95% CI 15.33–18.13) and their unaffected siblings (HR = 5.54, 95% CI 4.96–6.18). Individuals with BD were also more likely to experience long-term SA compared to the general population (HR = 3.19, 95% CI 3.09–3.30) and their unaffected siblings (HR = 2.83, 95% CI 2.70–2.97). Moreover, individuals diagnosed with BD had an elevated risk of long-term unemployment relative to both comparison groups (HR range: 1.75–1.78). Men with BD had a higher relative risk of SA and unemployment than women. No difference was found in DP.

Individuals with BD face elevated risks of LMM compared to both the general population and unaffected siblings.

Racial, ethnic, and socioeconomic disparities persist in posttraumatic stress disorder (PTSD), which are partly attributed to minoritized women being trauma-exposed, while also contending with harmful contextual stressors. However, few have used analytic strategies that capture the interplay of these experiences and their relation to PTSD. The current study used a person-centered statistical approach to examine heterogeneity in trauma and contextual stress exposure, and their associations with PTSD and underlying symptom dimensions, in a diverse sample of low-income postpartum women.

Using a community-based sample of Black, Hispanic/Latina, and White postpartum women recruited from five U.S. regions (n = 1577), a latent class analysis generated profiles of past-year exposure to traumatic events and contextual stress at one month postpartum. Regression analyses then examined associations between class membership and PTSD symptom severity at six months postpartum as a function of race/ethnicity.

A four-class solution best fit the data, yielding High Contextual Stress, Injury/Illness, Violence Exposure, and Low Trauma/Contextual Stress classes. Compared to the Low Trauma/Contextual Stress class, membership in any of the other classes was associated with greater symptom severity across nearly all PTSD symptom dimensions (all ps < 0.05). Additionally, constellations of exposures were differentially linked to total PTSD symptom severity, reexperiencing, and numbing PTSD symptoms across racial/ethnic groups (ps < 0.05).

A person-centered approach to trauma and contextual stress exposure can capture heterogeneity of experiences in diverse, low-income women. Moreover, racially/ethnically patterned links between traumatic or stressful exposures and PTSD symptom dimensions have implications for screening and intervention in the perinatal period.

Determining whether the incidence of suicidal behavior during the COVID-19 pandemic changed for those with severe mental disorders is essential to ensure the provision of suicide preventive initiatives in the case of future health crises.

Using population-based registers, quarterly cohorts from the first quarter of 2018 (2018Q1) to 2021Q4 were formed including all Swedish-residents >10 years old. Interrupted time series and generalized estimating equations analyses were used to evaluate changes in Incidence Rates (IR) of specialised healthcare use for suicide attempt and death by suicide per 10 000 person-years for individuals with or without specific severe mental disorders (SMDs) during, compared to before the pandemic.

The IR (95% Confidence interval, CI) of suicide in individuals with SMDs decreased from 16.0 (15.0–17.1) in 2018Q1 to 11.6 (10.8–12.5) in 2020Q1 (i.e. the quarter before the start of the pandemic), after which it dropped further to 6.7 (6.3–7.2) in 2021Q2. In contrast, IRs of suicide attempt in SMDs showed more stable trends, as did the trends regarding suicide and suicide attempt for individuals without SMD. These discrepancies were most evident for individuals with substance use disorder and ASD/ADHD. Changes in IRs of suicide v. suicide attempt for one quarter during the pandemic for substance misuse were 11.2% v. 3.6% respectively. These changes for ASD/ADHD were 10.7% v. 3.6%.

The study shows pronounced decreases in suicide rates in individuals with SMDs during the pandemic. Further studies aiming to understand mechanisms behind these trends are warranted to consult future suicide prevention strategies.

Recent stressful life events (SLE) are a risk factor for psychosis, but limited research has explored how SLEs affect individuals at clinical high risk (CHR) for psychosis. The current study investigated the longitudinal effects of SLEs on functioning and symptom severity in CHR individuals, where we hypothesized CHR would report more SLEs than healthy controls (HC), and SLEs would be associated with poorer outcomes.

The study used longitudinal data from the EU-GEI High Risk study. Data from 331 CHR participants were analyzed to examine the effects of SLEs on changes in functioning, positive and negative symptoms over a 2-year follow-up. We compared the prevalence of SLEs between CHR and HCs, and between CHR who did (CHR-T) and did not (CHR-NT) transition to psychosis.

CHR reported 1.44 more SLEs than HC (p < 0.001), but there was no difference in SLEs between CHR-T and CHR-NT at baseline. Recent SLEs were associated with poorer functioning and more severe positive and negative symptoms in CHR individuals (all p < 0.01) but did not reveal a significant interaction with time.

CHR individuals who had experienced recent SLEs exhibited poorer functioning and more severe symptoms. However, as the interaction between SLEs and time was not significant, this suggests SLEs did not contribute to a worsening of symptoms and functioning over the study period. SLEs could be a key risk factor to becoming CHR for psychosis, however further work is required to inform when early intervention strategies mitigating against the effects of stress are most effective.

The mechanisms underlying generalized forms of dissociative (‘psychogenic’) amnesia are poorly understood. One theory suggests that memory retrieval is inhibited via prefrontal control. Findings from cognitive neuroscience offer a candidate mechanism for this proposed retrieval inhibition. By applying predictions based on these experimental findings, we examined the putative role of retrieval suppression in dissociative amnesia.

We analyzed fMRI data from two previously reported cases of dissociative amnesia. Patients had been shown reminders from forgotten and remembered time periods (colleagues and school friends). We examined the neuroanatomical overlap between regions engaged in the unrecognized compared to the recognized condition, and the regions engaged during retrieval suppression in laboratory-based tasks. Effective connectivity analyses were performed to test the hypothesized modulatory relationship between the right anterior dorsolateral prefrontal cortex (raDLPFC) and the hippocampus. Both patients were scanned again following treatment, and analyses were repeated.

We observed substantial functional alignment between the inhibitory regions engaged during laboratory-based retrieval suppression tasks, and those engaged when patients failed to recognize their current colleagues. This included significant activation in the raDLPFC and right ventrolateral prefrontal cortex, and a corresponding deactivation across autobiographical memory regions (hippocampus, medial PFC). Dynamic causal modeling confirmed the hypothesized modulatory relationship between the raDLPFC and the hippocampus. This pattern was no longer evident following memory recovery in the first patient, but persisted in the second patient who remained amnesic.

Findings are consistent with an inhibitory mechanism driving down activity across core memory regions to prevent the recognition of personally relevant stimuli.

Childhood trauma (CT) is related to altered fractional anisotropy (FA) in individuals with schizophrenia (SZ). However, it remains unclear whether CT may influence specific cellular or extracellular compartments of FA in SZ with CT experience. We extended our previous study on FA in SZ (Costello et al., 2023) and examined the impact of CT on hypothesized lower free water-corrected FA (FAT) and higher extracellular free water (FW).

Thirty-seven SZ and 129 healthy controls (HC) were grouped into the ‘none/low’ or ‘high’ CT group. All participants underwent diffusion-weighted magnetic resonance imaging. We performed tract-based spatial statistics to study the main effects of diagnostic group and CT, and the interaction between CT and diagnostic group across FAT and FW.

SZ displayed lower FAT within the corpus callosum and corona radiata compared to HC (p < 0.05, Threshold-Free Cluster Enhancement (TFCE)). Independent of diagnosis, we observed lower FAT (p < 0.05, TFCE) and higher FW (p < 0.05, TFCE) in both SZ and HC with high CT levels compared to SZ and HC with none or low CT levels. Furthermore, we did not identify an interaction between CT and diagnostic group (p > 0.05, TFCE).

These novel findings suggest that the impact of CT on lower FAT may reflect cellular rather than extracellular alterations in established schizophrenia. This highlights the impact of CT on white matter microstructure, regardless of diagnostic status.

Attention-deficit/hyperactivity disorder (ADHD) patients exhibit characteristics of impaired working memory (WM) and diminished sensory processing function. This study aimed to identify the neurophysiologic basis underlying the association between visual WM and auditory processing function in children with ADHD.

The participants included 86 children with ADHD (aged 6–15 years, mean age 9.66 years, 70 boys, and 16 girls) and 90 typically developing (TD) children (aged 7–16 years, mean age 10.30 years, 66 boys, and 24 girls). Electroencephalograms were recorded from all participants while they performed an auditory discrimination task (oddball task). The visual WM capacity and ADHD symptom severity were measured for all participants.

Compared with TD children, children with ADHD presented a poorer visual WM capacity and a smaller mismatch negativity (MMN) amplitude. Notably, the smaller MMN amplitude in children with ADHD predicted a less impaired WM capacity and milder inattention symptom severity. In contrast, the larger MMN amplitude in TD children predicted a better visual WM capacity.

Our results suggest an intimate relationship and potential shared mechanism between visual WM and auditory processing function. We liken this shared mechanism to a total cognitive resource limit that varies between groups of children, which could drive correlated individual differences in auditory processing function and visual WM. Our findings provide a neurophysiological correlate for reports of WM deficits in ADHD patients and indicate potential effective markers for clinical intervention.

Neuroimaging studies have documented brain structural changes in schizophrenia at different stages of the illness, including clinical high-risk (cHR), genetic high-risk (gHR), first-episode schizophrenia (FES), and chronic schizophrenia (ChS). There is growing awareness that neuropathological processes associated with a disease fail to map to a specific brain region but do map to a specific brain network. We sought to investigate brain structural damage networks across different stages of schizophrenia.

We initially identified gray matter alterations in 523 cHR, 855 gHR, 2162 FES, and 2640 ChS individuals relative to 6963 healthy controls. By applying novel functional connectivity network mapping to large-scale discovery and validation resting-state functional magnetic resonance imaging datasets, we mapped these affected brain locations to four specific networks.

Brain structural damage networks of cHR and gHR had limited and non-overlapping spatial distributions, with the former mainly involving the frontoparietal network and the latter principally implicating the subcortical network, indicative of distinct neuropathological mechanisms underlying cHR and gHR. By contrast, brain structural damage networks of FES and ChS manifested as similar patterns of widespread brain areas predominantly involving the somatomotor, ventral attention, and subcortical networks, suggesting an emergence of more prominent brain structural abnormalities with illness onset that have trait-like stability over time.

Our findings may not only provide a refined picture of schizophrenia neuropathology from a network perspective, but also potentially contribute to more targeted and effective intervention strategies for individuals at different schizophrenia stages.

To refine the knowledge on familial transmission, we examined the (shared) familial components among neurodevelopmental problems (i.e. two attention-deficit/hyperactivity–impulsivity disorder [ADHD] and six autism spectrum disorder [ASD] subdomains) and with aggressive behavior, depression, anxiety, and substance use.

Data were obtained from a cross-sectional study encompassing 37 688 participants across three generations from the general population. ADHD subdomains, ASD subdomains, aggressive behavior, depression, anxiety, and substance use were assessed. To evaluate familial (co-)aggregation, recurrence risk ratios (λR) were estimated using Cox proportional hazards models. The (shared) familiality (f2), which is closely related to (shared) heritability, was assessed using residual maximum likelihood-based variance decomposition methods. All analyses were adjusted for sex, age, and age2.

The familial aggregation and familiality of neurodevelopmental problems were moderate (λR = 2.40–4.04; f2 = 0.22–0.39). The familial co-aggregation and shared familiality among neurodevelopmental problems (λR = 1.39–2.56; rF = 0.52–0.94), and with aggressive behavior (λR = 1.79–2.56; rF = 0.60–0.78), depression (λR = 1.45–2.29; rF = 0.43–0.76), and anxiety (λR = 1.44–2.31; rF = 0.62–0.84) were substantial. The familial co-aggregation and shared familiality between all neurodevelopmental problems and all types of substance use were weak (λR = 0.53–1.57; rF = −0.06–0.35).

Neurodevelopmental problems belonging to the same disorder were more akin than cross-disorder problems. That said, there is a clear (shared) familial component to neurodevelopmental problems, in part shared with other psychiatric problems (except for substance use). This suggests that neurodevelopmental disorders, disruptive behavior disorders, and internalizing disorders share genetic and environmental risk factors.

Executive dysfunction, including working memory deficits, is prominent in posttraumatic stress disorder (PTSD) and can impede treatment effectiveness. Intervention approaches that target executive dysfunction alongside standard PTSD treatments could boost clinical response. The current study reports secondary analyses from a randomized controlled trial testing combined PTSD treatment with a computerized training program to improve executive dysfunction. We assessed if pre-treatment neurocognitive substrates of executive functioning predicted clinical response to this novel intervention.

Treatment-seeking veterans with PTSD (N = 60) completed a working memory task during functional magnetic resonance imaging prior to being randomized to six weeks of computerized executive function training (five 30-minute sessions each week) plus twelve 50-minute sessions of cognitive processing therapy (CEFT + CPT) or placebo training plus CPT (PT + CPT). Using linear mixed effects models, we examined the extent to which the neurocognitive substrates of executive functioning predicted PTSD treatment response.

Results indicated that veterans with greater activation of working memory regions (e.g. lateral prefrontal and cingulate cortex) had better PTSD symptom improvement trajectories in CEFT + CPT v. PT + CPT. Those with less neural activation during working memory showed similar trajectories of PTSD symptom change regardless of treatment condition.

Greater activity of frontal regions implicated in working memory may serve as a biomarker of response to a novel treatment in veterans with PTSD. Individuals with greater regional responsiveness benefited more from treatment that targeted cognitive dysfunction than treatment that did not include active cognitive training. Clinically, findings could inform our understanding of treatment mechanisms and may contribute to better personalization of treatment.

The Personalized Advantage Index (PAI) shows promise as a method for identifying the most effective treatment for individual patients. Previous studies have demonstrated its utility in retrospective evaluations across various settings. In this study, we explored the effect of different methodological choices in predictive modelling underlying the PAI.

Our approach involved a two-step procedure. First, we conducted a review of prior studies utilizing the PAI, evaluating each study using the Prediction model study Risk Of Bias Assessment Tool (PROBAST). We specifically assessed whether the studies adhered to two standards of predictive modeling: refraining from using leave-one-out cross-validation (LOO CV) and preventing data leakage. Second, we examined the impact of deviating from these methodological standards in real data. We employed both a traditional approach violating these standards and an advanced approach implementing them in two large-scale datasets, PANIC-net (n = 261) and Protect-AD (n = 614).

The PROBAST-rating revealed a substantial risk of bias across studies, primarily due to inappropriate methodological choices. Most studies did not adhere to the examined prediction modeling standards, employing LOO CV and allowing data leakage. The comparison between the traditional and advanced approach revealed that ignoring these standards could systematically overestimate the utility of the PAI.

Our study cautions that violating standards in predictive modeling may strongly influence the evaluation of the PAI's utility, possibly leading to false positive results. To support an unbiased evaluation, crucial for potential clinical application, we provide a low-bias, openly accessible, and meticulously annotated script implementing the PAI.

Dropout from healthcare interventions can negatively affect patients and healthcare providers through impaired trust in the healthcare system and ineffective use of resources. Research on this topic is still largely missing on refugees and asylum seekers. The current study aimed to characterize predictors for dropout in the Mental Health in Refugees and Asylum Seekers (MEHIRA) study, one of the largest multicentered controlled trials investigating the effectiveness and cost-effectiveness of a nationwide stepped and collaborative care model.

Predictors were multiply imputed and selected for descriptive modelling using backward elimination. The final variable set was entered into logistic regression.

The overall dropout rate was 41,7%. Dropout was higher in participants in group therapy (p = 0.001; OR = 10.7), with larger satisfaction with social relationships (p = 0.017; OR = 1.87), with difficulties in maintaining personal relationships (p = 0.005; OR = 4.27), and with higher depressive symptoms (p = 0.029; OR = 1.05). Participants living in refugee accommodation (p = 0.040; OR = 0.45), with a change in social status (p = 0.008; OR = 0.67) and with conduct (p = 0.020; OR = 0.24) and emotional problems (p = 0.013; OR = 0.31) were significantly less likely to drop out of treatment.

Overall, the outcomes of this study suggest that predictors assessing social relationships, social status, and living conditions should be considered as topics of psychological treatment to increase adherence and as predictors for future research studies (including treatment type).

Schools are central places for adolescent social lives, which is a major factor greatly affecting adolescent mental health; school climate (i.e. quality of the school social environments) can be a proximal social determinant for adolescent mental health. Supportive school environments may serve as a protective factor during crises like COVID-19, which disrupt social lives and worsen adolescent mental health. This is the first study examining whether the pandemic effects differed based on the levels of school climate on depressive symptoms (DS) and psychotic experiences (PEs) among adolescents.

School climate (score range: 0–28), DS (0–26), and PEs (0–5) were self-reported in a population-based cohort (Tokyo Teen Cohort; N = 3171) at four timepoints (10y, 12y, 14y, and 16y) before and during COVID-19. COVID-19 occurred midway through the 16y survey, allowing us to examine its impact and interaction effect with school climate while accounting for within-person changes over time using mixed-effects models.

Significant interaction effects were found on DS (unstandardized coefficient [B] = −0.166, 95% confidence interval [CI] −0.225 to −0.107) and PEs (B = −0.020, 95% CI −0.028 to −0.012). The pandemic effects were not significant for adolescents with high school climate scores (around the 80th percentile or higher), although the pandemic significantly worsened these outcomes among the overall sample.

The negative mental health effects of the pandemic were significantly mitigated among adolescents experiencing a supportive school climate. A positive school climate can protect adolescent mental health during challenging social conditions, such as pandemics.

Psychotic-like experiences (PLEs) are subclinical phenomena that often precede the onset of psychosis and occur in various mental disorders. Social determinants of psychosis and PLEs are important and have been operationalized within the social defeat (SD) hypothesis. The SD hypothesis posits that low social status and exposure to repeated humiliation can lead to imbalanced dopamine neuron activity, and thus increased risk of psychosis. We aimed to assess the role of dynamic interactions between SD components in shaping the occurrence of PLEs using a network analysis.

A total of 2241 non-clinical, young adults were assessed at baseline and invited for reassessment after a 6-month follow-up. Self-reports recording the occurrence of PLEs, aberrant salience (AS), depressive, and anxiety symptoms as well as SD characteristics (socioeconomic status, minority status, humiliation, perceived constraints, and domain control) were administered. Two networks were analyzed (the first one covering all baseline measures and the second one with the baseline SD components and follow-up measures of AS and psychopathology).

The SD components were not directly connected to the measures of PLEs in both networks. However, in both networks, SD components were connected to PLEs through a mediating effect of AS. Among SD components, humiliation had the highest bridge centrality across three predefined communities of variables (SD; depressive and anxiety symptoms; AS, and PLEs).

The findings indicate that SD might make individuals vulnerable to develop PLEs through the mediating effects of AS. Among SD components, humiliation might play the most important role in the development of PLEs.

Late-life depression (LLD) is characterized by repeated recurrent depressive episodes even with maintenance treatment. It is unclear what clinical and cognitive phenotypic characteristics present during remission predict future recurrence.

Participants (135 with remitted LLD and 69 comparison subjects across three institutions) completed baseline phenotyping, including psychiatric, medical, and social history, psychiatric symptom and personality trait assessment, and neuropsychological testing. Participants were clinically assessed every two months for two years while receiving standard antidepressant treatment. Analyses examined group differences in phenotypic measure using general linear models. Concurrent associations between phenotypic measures and diagnostic groups were examined using LASSO logistic regression.

Sixty (44%) LLD participants experienced a relapse over the two-year period. Numerous phenotypic measures across all domains differed between remitted LLD and comparison participants. Only residual depressive symptom severity, rumination, medical comorbidity, and executive dysfunction significantly predicted LLD classification. Fewer measures differed between relapsing and sustained remission LLD subgroups, with the relapsing group exhibiting greater antidepressant treatment intensity, greater fatigue, rumination, and disability, higher systolic blood pressure, greater life stress and lower instrumental social support. Relapsing group classification was informed by antidepressant treatment intensity, lower instrumental social support, and greater life stress.

A wide range of phenotypic factors differed between remitted LLD and comparison groups. Fewer measures differed between relapsing and sustained remission LLD subgroups, with less social support and greater stress informing vulnerability to subsequent relapse. This research suggests potential targets for relapse prevention and emphasizes the need for clinically translatable relapse biomarkers to inform care.