Research has pointed to important psychopathological differences between persistent and episodic depressive disorders. Here, we tested the hypothesis that people with persistent rather than episodic depression have difficulty revising established expectations in response to novel positive information. In terms of underlying mechanisms, we predicted that these differences between the two subtypes would be related to the engagement in cognitive immunization (i.e. devaluing expectation-disconfirming positive information).

Prior to their psychotherapeutic treatment, 54 outpatients with persistent depressive disorder and 102 outpatients with episodic major depressive disorder completed an experimental task. In this task, participants watched other patients’ reports of positive effects of psychotherapy. Our primary outcome was change in treatment expectations from before to after watching the positive reports.

Overall, people with persistent depression had lower treatment expectations than people with episodic depression. In addition, they changed their treatment expectations less in response to other patients’ positive reports. This effect was greater for psychotherapy outcome expectations than for role expectations. The lack of expectation change in persistent depression relative to episodic depression was particularly pronounced in a cognitive immunization-promoting experimental condition.

The results indicate that people with persistent depression have difficulty adjusting their treatment expectations in response to positive information on psychotherapy. This may be a risk factor for poor treatment outcome. The results regarding cognitive immunization suggest that for people with persistent depression, slight doubts about the value of information on the positive effects of psychotherapy may be sufficient to prevent them from integrating this information.

Psychological therapy (PT) along with antipsychotic medication is the recommended first line of treatment for first-episode psychosis (FEP). We investigated whether ethnicity, clinical, pathways to care (PtC) characteristics, and access to early intervention service (EIS) influenced the offer, uptake, and type of PT in an FEP sample.

We used data from the Clinical Record Interactive Search-First Episode Psychosis study. Inferential statistics determined associations between ethnicity, clinical, PtC, and PT offer/uptake. Multivariable logistic regression estimated the odds of being offered a PT and type of PT by ethnicity, clinical and PtC characteristics adjusting for confounders.

Of the 558 patients included, 195 (34.6%) were offered a PT, and 193 accepted. Cognitive behavioral therapy (CBT) (n = 165 of 195; 84.1%) was commonly offered than group therapy (n = 30 of 195; 13.3%). Patients who presented via an EIS (adj. OR = 2.24; 95%CI 1.39–3.59) were more likely to be offered a PT compared with those in non-EIS. Among the patients eligible for an EIS, Black African (adj. OR = 0.49; 95%CI = 0.25–0.94), Black Caribbean (adj. OR = 0.45; 95%CI = 0.21–0.97) patients were less likely to be offered CBT compared with their White British counterparts. Patients with a moderate onset of psychosis (adj. OR = 0.34; 95%CI = 0.15–0.73) had a reduced likelihood of receiving CBT compared with an acute onset.

Accessing EIS during FEP increased the likelihood of being offered a PT. However, treatment inequalities remain by ethnicity and clinical characteristics.

Depression runs in families, with both genetic and environmental mechanisms contributing to intergenerational continuity, though these mechanisms have often been studied separately. This study examined the interplay between genetic and environmental influences in the intergenerational continuity of depressive symptoms from parents to offspring.

Using data from the Dutch TRAILS cohort (n = 2201), a prospective, genetically informed, multiple-generation study, we examined the association between parents’ self-reported depressive symptoms (reported at mean age of 41 years) and offspring depressive symptoms, self-reported nearly two decades later, in adulthood (mean age: 29 years). We assessed the role of genetic (polygenic scores for depressive symptoms in parents and offspring) and environmental mechanisms (parental warmth during adolescence) in explaining intergenerational continuity of depressive symptoms in separate and combined models.

Parents’ depressive symptoms, offspring genetic predisposition, and parental warmth were associated with an increased risk of depressive symptoms in offspring. In the combined model, parents’ genetic predisposition was linked to their own depressive symptoms, which were linked to lower parental warmth, which, in turn, was linked to higher depressive symptoms in offspring, after accounting for offspring genetic predisposition, sex, age, and socioeconomic status.

Both genetic and environmental mechanisms contribute to the intergenerational continuity of depressive symptoms independently and in interplay. Despite a significant effect, the influence of parental warmth was modest, suggesting limited covariation between this particular parenting measure and depressive symptoms, at least when assessed with large temporal distance.

After remission of a first-episode psychosis (FEP), antipsychotic discontinuation is associated with an increased risk of relapse compared to maintenance treatment. We studied short and longer-term effects of discontinuation of D2 receptor (D2R) antagonist and partial agonist antipsychotics on striatal dopamine D2/3R availability in FEP patients.

Remitted FEP patients underwent two [11C]raclopride PET scans to measure striatal D2/3R availability: 1 week after antipsychotic discontinuation (n = 16 antagonist users, n = 6 partial agonist users) and after being medication free for 6–8 weeks (n = 8 antagonist users, n = 5 partial agonist users). Fifteen matched healthy controls were scanned once. Psychotic relapse was monitored up to 12 months after discontinuation.

One week after discontinuation, D2R antagonist discontinuers showed higher striatal binding potential (BPND) than partial D2R agonist discontinuers (p < 0.001, CI = 0.749 to 1.681) and controls (p = 0.045, CI = 0.008 to 0.708), while partial agonist discontinuers had significantly lower BPND than controls (p = 0.001, CI = -1.326 to -0.386). 6-8 weeks after discontinuation, former antagonist users showed similar BPND to controls (p > 0.25), whereas former partial agonist users had higher BPND than controls (p = 0.027, CI = 0.069 to 1.085). Participants who discontinued antagonists relapsed more often (81%) than those who discontinued partial agonists (17%)(χ2 = 5.32, p = 0.021).

Discontinuation of partial D2R agonists may affect D2/3R availability differently than discontinuation of antagonists, which might explain the greater relapse risk after tapering antagonists than partial agonist antipsychotics.

This study investigates structural abnormalities in hippocampal subfield volumes and shapes, and their association with plasma CC chemokines in individuals with major depressive disorder (MDD).

A total of 61 patients with MDD and 65 healthy controls (HC) were recruited. All participants underwent high-resolution T1-weighted imaging and provided blood samples for the detection of CC chemokines (CCL2, CCL7, and CCL11). Comparisons of hippocampal subregion volumes, surface shapes, and plasma CC chemokine concentrations were conducted between the MDD and HC groups. Furthermore, partial correlation analysis was performed to assess the relationship between structural abnormalities (hippocampal subfield volume and shape) and plasma CC chemokine levels.

The MDD group exhibited a significant reduction in the volume of the left hippocampal tail compared to the HC group (F = 9.750, Bonferroni-corrected p = 0.026). No significant outward or inward deformation of the hippocampus was detected in MDD patients relative to the HC group (all FWE-corrected p > 0.05). Additionally, plasma CCL11 levels were elevated in the MDD group compared to the HC group (F = 9.982, p = 0.002), with these levels showing a positive correlation with the duration of the illness (r = 0.279, p = 0.029). Partial correlation analysis further revealed a negative correlation between the smaller left hippocampal tail volume and plasma CCL11 levels in MDD patients (r = −0.416, p = 0.001).

Abnormally elevated plasma CCL11 in MDD patients may mediate damage to specific hippocampal substructures.

Return of fear after successful exposure therapy for a phobia is a common clinical challenge. A previous study on mice demonstrated that the persistent attenuation of remote fear memories can be achieved by combining histone deacetylase inhibitors (HDACis) with fear-memory retrieval prior to extinction training.

To evaluate the translational potential of this approach, we conducted a randomized, double-blind, placebo-controlled trial. Forty-eight individuals with DSM-IV spider phobia received either HDACi valproic acid (VPA, 500 mg) or a placebo prior to the retrieval of fear memory, followed by exposure therapy in virtual reality.

No significant group difference was found in terms of behavioral change on the behavioral approach test at 3 months follow-up and baseline (primary outcome). However, the VPA group displayed significantly reduced fear in two self-report questionnaires related to spider phobia (Fear of Spiders Questionnaire; Spider Phobia Beliefs Questionnaire) as compared to the placebo group. No group differences were observed for psychophysiological indicators of fear.

The favorable impact of a single administration of VPA in combination with fear-memory retrieval prior to exposure therapy suggests that it might be an effective way to enhance symptom improvement at the subjective level in the treatment of phobias. Further studies need to investigate the conditions under which an improvement on the psychophysiological and behavioral levels can be achieved as well.

Repetitive negative thinking (RNT) in major depressive disorder (MDD) involves a persistent focus on negative self-related experiences. Resting-state fMRI shows that the functional connectivity (FC) between the anterior insula and the superior temporal sulcus is associated with RNT intensity. This study examines how insular FC patterns differ between resting state and RNT induction in MDD and healthy control (HC) participants.

Forty-one individuals with MDD and 28 HCs (total n = 69) underwent resting-state and RNT-induction fMRI scans. Seed-to-whole brain analysis using insular subregions as seeds was performed.

No diagnosis-by-run interaction effects were observed across insular subregions. MDD participants showed greater FC between the bilateral anterior, middle, and posterior insular regions and the cerebellum (z = 4.31–6.15). During RNT induction, both MDD and HC participants demonstrated increased FC between bilateral anterior/middle insula and prefrontal cortices, parietal lobes, posterior cingulate cortex (PCC), and medial temporal gyrus, encompassing the STS (z = 4.47–8.31). In exploratory correlation analyses, higher trait RNT was associated with increased FC between the right dorsal anterior/middle insula and the PCC, middle temporal gyrus, and orbital frontal gyrus in MDD participants (z = 4.31–6.15). Greater state RNT was linked to increased FC in similar insular regions, as well as the bilateral angular gyrus and right middle temporal gyrus (z = 4.47–8.31).

Hyperconnectivity in insula subregions during active rumination, especially involving the default mode network and salience network, supports theories of heightened self-focused and negative emotional processing in depression. These findings emphasize the neural basis of RNT when actively elicited in MDD.

The months following psychiatric hospitalization are associated with heightened suicide risk among adolescents. Better characterizing predictors of trajectories of suicidal ideation (SI) post-discharge is critical.

We examined trajectories of SI over 18 months post-discharge and emotional processing variables (recognition, reactivity, and regulation) as predictors using a multi-method approach. Participants were 180 adolescents recruited from a pediatric psychiatric inpatient unit, assessed during hospitalization and 3, 6, 12, and 18-months post-discharge. At each time-point, participants reported on SI; at baseline, they completed measures of emotion dysregulation, reactivity, and a behavioral task measuring facial emotion recognition.

A three-group model best fits the data (Chronic SI, Declining SI, and Subthreshold SI groups). The Chronic SI group, compared to the Declining SI group, had greater difficulty identifying children’s sad facial expressions. The Declining SI group compared to the Subthreshold SI group reported greater overall emotion dysregulation and difficulties engaging in goal-directed behavior. No other emotional processing variable was significantly associated with specific SI trajectories.

The findings suggest that difficulties in properly identifying peer emotions may be predictive of resolution of severe SI post-discharge. Furthermore, the results suggest that emotion regulation may be an important target for discharge planning.

Psychiatric disorders are highly heterogeneous. It is clinically valuable to distinguish psychiatric disorders by the presence or absence of a specific comorbid condition.

We employed a novel algorithm (CombGWAS) to decipher the genetic basis of psychiatric disorder combinations using genome-wide association studies summary statistics. We focused on comorbidities and combinations of diseases, such as schizophrenia (SCZ) with and without depression, which can be considered as two ‘subtypes’ of SCZ. We also studied psychiatric disorders comorbid with obesity as disease subtypes.

We compared the genetic architectures of psychiatric disorders with and without specific comorbidities, identifying both shared and unique susceptibility genes/variants across 8 subtype pairs (16 entities). Despite high genetic correlations between subtypes, most subtype pairs exhibited distinct genetic correlations with the same cardiovascular disease (CVD). Some pairs even displayed opposite genetic correlations, especially those involving obesity. For instance, the genetic correlation (rg) between SCZ with obesity and type 2 diabetes (T2DM) was 0.248 (p = 4.42E−28), while the rg between SCZ without obesity and T2DM was −0.154 (p = 6.79E−12). Mendelian randomization analyses revealed that comorbid psychiatric disorders often have stronger causal effects on cardiovascular risks compared to single disorders, but the effects vary across psychiatric subtypes. Notably, obese and nonobese major depressive disorder/SCZ showed opposite causal effects on the risks of T2DM.

Our study provides novel insights into the genetic basis of psychiatric disorder heterogeneity, revealing unique genetic signatures across various disorder combinations. Notably, comorbid psychiatric disorders often showed different causal relationships with CVD compared to single disorders.

Although life stressors are known risk factors for suicide, the specific stressor types that most strongly precipitate suicidal outcomes, and on what timescale, remain poorly understood. Based on existing theory, we investigated whether objectively rated interpersonal stressors, especially social and targeted rejection stressors, are proximally associated with increased likelihood of suicidal ideation and behavior.

Using an objectively rated contextual threat interview to assess stressful life events, and a timeline followback procedure for assessing suicide-related outcomes, we examined how the severity of four types of acute life events (i.e. non-interpersonal, interpersonal without social rejection, social rejection without targeted rejection, and targeted rejection) were temporally associated with the likelihood of same-day and next-day suicidal ideation and behavior over 16 months in 143 young adults (Mage = 25.27, SD = 4.65) with recent suicidal ideation or behavior.

After controlling for prior-day suicidal ideation and non-interpersonal stressors, daily within-person increases in interpersonal stressor severity were related to higher odds of same-day (but not next-day) suicidal ideation. Additionally, greater increases in targeted rejection severity were uniquely related to increased likelihood of both same-day and next-day suicidal behavior after controlling for prior-day suicidal behavior and other types of stressors.

Interpersonal stressors are strong, proximal risk factors for suicidal ideation and behavior, and these effects are particularly strong for targeted rejection life events. Clinicians should thus assess recent interpersonal and, especially, targeted rejection stressors when evaluating acute suicide risk, and may reduce such risk by helping patients stabilize and strengthen their social relationships.

Developmental trauma increases psychosis risk in adulthood and is associated with poor prognosis and treatment response. It has been proposed that developmental trauma may give rise to a distinct psychosis phenotype. Our aim was to explore this by systematically reviewing neuroimaging studies of brain structure and function in adults with psychosis diagnoses, according to whether or not they had survived developmental trauma. We registered our search protocol in PROSPERO (CRD42018105021).

We systematically searched literature databases for relevant studies published before May 2024. We identified 31 imaging studies (n = 1,761 psychosis patients, n = 1,775 healthy controls or healthy siblings).

Developmental trauma was associated with global and regional differences in gray matter; corticolimbic structural dysconnectivity; a potentiated threat detection system; dysfunction in regions associated with mentalization; and elevated striatal dopamine synthesis capacity.

These findings warrant further research to elucidate vulnerability and resilience mechanisms for psychosis in developmental trauma survivors.

Childhood irritability increases the risk of later suicidal behaviors, but the moderators of this association have not been identified. We investigated harsh parenting as a moderator in the association of childhood irritability with adolescent suicide attempt and self-harm, and possible sex differences in these associations.

Data were from 9,480 children from the Millennium Cohort Study. We averaged parent ratings of child irritability and harsh parenting at ages 3, 5, and 7 years (range 1–3). Suicide attempt and self-harm were self-reported at age 17. Logistic regression models were used to estimate associations of irritability with suicide attempt and self-harm, adjusting for confounding factors. Interaction analyses were used to test the moderating role of harsh parenting and sex in these associations.

Children with greater irritability scores were at increased risk to attempt suicide (OR=1.72, 95% CI=1.42–2.08). Interaction analyses suggested that this risk in males was elevated regardless of harsh parenting. However, high levels of harsh parenting interacted with irritability in increasing the risk of suicide attempt in females. Children with high irritability were also more at risk of self-harm (OR = 1.16, 95% CI = 1.03–1.31) but this association was not moderated by harsh parenting in either sex.

Parental behaviors may play an important role in the pathway to suicide attempt of children with irritability, especially for females, who may have a heightened sensitivity to interpersonal stressors. Parenting interventions may be helpful in suicide prevention among females with irritability.

Although perceived threats in a child’s social environment, including in the family, school, and neighborhood, are known to increase risk for adolescent psychopathology, the underlying biological mechanisms remain unclear. To investigate, we examined whether perceived social threats were associated with the functional connectivity of large-scale cortical networks in early adolescence, and whether such connectivity differences mediated the development of subsequent mental health problems in youth.

Structural equation models were used to analyze data from 8,690 youth (50% female, 45% non-White, age 9–10 years) drawn from the large-scale, nationwide Adolescent Brain Cognitive Development study that has 21 clinical and research sites across the United States. Data were collected from 2016 to 2018.

Consistent with Social Safety Theory, perceived social threats were prospectively associated with mental health problems both 6 months (standardized $ \beta =0.27,p<.001 $) and 30 months ($ \beta =0.14,p<.001 $) later. Perceived social threats predicted altered connectivity patterns within and between the default mode (DMN), dorsal attention (DAN), frontoparietal (FPN), and cingulo-opercular (CON) networks. In turn, hypoconnectivity within the DMN and FPN – and higher (i.e., less negative) connectivity between DMN-DAN, DMN-CON, and FPN-CON – mediated the association between perceived social threats and subsequent mental health problems.

Perceiving social threats in various environments may alter neural connectivity and increase the risk of psychopathology in youth. Therefore, parenting, educational, and community-based interventions that bolster social safety may be helpful.

Attachment style is widely recognized as influential in shaping responses to bereavement and prolonged grief disorder (PGD). Although theorized extensively, empirical clarity regarding how attachment styles specifically impact PGD symptoms and therapeutic implications remains limited. This study aimed to identify cognitive-behavioral mechanisms linking attachment styles to PGD symptoms.

Data were collected from a community sample of 695 bereaved adults. Network analysis explored interactions between attachment styles (anxious and avoidant) and various cognitive-behavioral factors associated with PGD, including appraisals, memory characteristics, maladaptive coping strategies, and a sense of social disconnection.

The findings reveal attachment styles as peripheral within the network, suggesting that their direct influence on PGD symptoms may be less central than previously theorized. However, anxious attachment correlated positively with injustice rumination and altered social self, while avoidant attachment was positively associated with perceived loss of future and relationships and preferences for solitude, and negatively associated with proximity-seeking behaviors and fear of losing connection to the deceased. Cognitive-behavioral factors, particularly memory characteristics and social disconnection, held central positions within the network, mediating relationships between attachment styles and PGD.

Attachment styles indirectly influence PGD through cognitive-behavioral pathways rather than exerting strong direct effects. By bridging the gap between attachment theory and cognitive-behavioral approaches to grief, this study offers a more nuanced understanding of its relationship with PGD and points toward potential new avenues for future interventions aimed at addressing attachment-related challenges in bereaved individuals.

Anxiety is a persistent trait that disrupts functioning and increases the risk of severe consequences, while reward processing has garnered attention in anxiety research. Here, we report a critical concern in reward processing among individuals with anxiety: although anxious individuals may show similar reward processing abilities as non-anxious individuals in typical environments, they are more vulnerable to disruptions in positive emotions caused by frustrative non-reward, leading to maladaptive reward processing patterns.

The functional magnetic resonance imaging (fMRI) was used in this study. A total of 66 participants were recruited for the experiment, with 33 in the high anxiety (HA) group and 33 in the low anxiety (LA) group. The simulation of frustrative non-reward was conducted during fMRI scanning.

Under the low frustration condition, the HA group exhibited task accuracy comparable to the LA group and showed greater activation in visual processing regions (inferior occipital gyrus, superior occipital gyrus, angular gyrus) and cognitive control areas (precuneus, precentral gyrus) during attentional reorienting following frustration. However, in the high frustration condition, the HA group displayed significantly lower accuracy, with maladaptive information processing patterns observed in several brain regions associated with the cognitive-emotional control system (cuneus-precuneus, anterior cingulate cortex, precentral gyrus, inferior frontal gyrus, superior frontal gyrus, orbitofrontal cortex, and amygdala).

This demonstration of two contrasting processing patterns deepens the current understanding of reward processing in anxiety. It also holds significance for a broader understanding of the risk factors in cognitive processing among individuals with anxiety.

Little is known regarding the shared genetic architecture underlying the phenotypic associations between depression and preterm birth (PTB). We aim to investigate the genetic overlap and causality of depression with PTB.

Leveraging summary statistics from the largest genome-wide association studies for broad depression (Ntotal = 807,533), major depression (Ntotal = 173,005), bipolar disorder (Ntotal = 414,466), and PTB (Ntotal = 226,330), we conducted a large-scale genome-wide cross-trait analysis to assess global and local genetic correlations, identify pleiotropic loci, and infer potential causal relationships

Positive genetic correlations were observed between PTB and broad depression (rg = 0.242), major depression (rg = 0.236), and bipolar disorder (rg = 0.133) using the linkage disequilibrium score regression, which were further verified by the genetic covariance analyzer. Local genetic correlation was identified at chromosome 11q22.3 (harbors NCAM1-TTC12-ANKK1-DRD2) for PTB with depression. Cross-trait meta-analysis identified two loci shared between PTB and broad depression, two loci shared with major depression, and five loci shared with bipolar disorder, among which three were novel (rs7813444, rs3132948 and rs9273363). Mendelian randomization demonstrated a significantly increased risk of PTB for genetic liability to broad depression (odds ratio [OR]=1.30; 95% confidence interval [CI]: 1.11-1.52) and major depression (OR=1.27; 95%CI: 1.08-1.49), and the estimates remained significant across the sensitivity analyses.

Our findings demonstrate an intrinsic link underlying depression and PTB and shed novel light on the biological mechanisms, highlighting an important role of early screening and effective intervention of depression in PTB prevention, and may provide novel treatment strategies for both diseases.

Strength-based approaches are increasingly common in neurodevelopmental research, but the positive characteristics that may be features of attention-deficit/hyperactivity disorder (ADHD) remain underexplored. The extent to which people with ADHD recognize and use their personal strengths, and whether these play a role in their life outcomes, is also unknown. Tackling these gaps in the literature, we conducted the first study of self-reported strengths, strengths knowledge, and strengths use in ADHD.

Adults with (n = 200) and without (n = 200) ADHD were recruited online and rated their endorsement of 25 putative ADHD-related strengths. Participants also completed self-report measures assessing strengths knowledge, strengths use, subjective wellbeing, quality of life, and mental health. Using both Frequentist and Bayesian methods, we compared the groups and explored the associations of strengths knowledge and use with outcomes across both groups.

The ADHD group endorsed 10 strengths more strongly than the non-ADHD group, including hyperfocus, humor, and creativity, but reported similar endorsement for 14 of the strengths. Adults with and without ADHD did not differ on their strengths knowledge and use but, in both groups, increased strengths knowledge and, to some extent, greater strengths use were associated with better wellbeing, improved quality of life, and fewer mental health symptoms.

We conclude that, while adults with and without ADHD may have both similarities and differences in strengths, interventions that focus on enhancing people’s strength knowledge and promoting the everyday use of their personal strengths could have universal applications to improve wellbeing in adulthood.