Biological psychiatry. Cognitive neuroscience and neuroimaging最新文献

Background: It is important to unveil factors that differentiate persistent and distressing psychosis-like experiences (PLEs) in youth from more normative transient, nondistressing PLEs, as the former have been associated with greater symptom, cognitive, and functional impairment and psychopathology risk, including risk for psychosis. In this study, we examined 1) whether certain baseline latent profiles can differentiate PLE groups (persistent/transient, distressing/nondistressing) and 2) whether baseline profile membership predicts psychopathology symptoms and academic/social functioning at follow-up.

Methods: Latent profile analyses were conducted on the ABCD (Adolescent Brain Cognitive Development) Study baseline sample (N = 11,724; mean age = 9.91; 47.8% female) using biological, cognitive, clinical, and sociodemographic indicators. Generalized mixed-effects models predicted PLE group, grades, several mental health symptoms, mental health treatment seeking, and social problems at follow-up.

Results: From the final 6-profile solution, 2 profiles emerged as potentially pertinent to the emergence of clinically relevant PLEs. Both profiles were characterized by higher externalizing symptoms, goal-motivated behavior, and likelihood of psychosis family history, but one profile had broader psychopathology elevations including affective dysregulation, while the other profile had low neurocognitive scores, brain patterns more like those found in schizophrenia, and greater socioeconomic disadvantage. At follow-up, both profiles were linked to more persistent distressing PLEs than the other profiles and showed shared and differential associations with outcomes.

Conclusions: The 2 profiles most predictive of persistent distressing PLEs may represent youth at risk for psychosis through different pathways, a neurodevelopmental pathway linked to cognitive and environmental vulnerability and an affective pathway associated with genetic risk, stress reactivity, and emotion dysregulation.

Background: Previous investigations of whole thalamus and thalamic nuclei volumes in posttrauma psychopathology have been sparse and limited in scope and have yielded inconsistent results. To address this, volumetric estimates of whole thalamus and thalamic nuclei were obtained from structural brain magnetic resonance imaging scans from 2058 participants across 20 worldwide sites in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Posttraumatic Stress Disorder (PTSD) working group.

Methods: Thalamic volumes were compared in trauma-exposed participants with PTSD (n = 238), major depressive disorder (MDD) (n = 184), and comorbid PTSD+MDD (n = 618) and in trauma-exposed control participants (n = 1018). PTSD and MDD symptom severity, PTSD symptom clusters, and childhood trauma were similarly examined for associations with thalamic volume.

Results: Participants with PTSD had smaller sensorimotor thalamic nuclei, while participants with MDD or comorbid PTSD+MDD had smaller mediodorsal (MD) thalamus volumes relative to control participants. Severity of PTSD and MDD symptoms negatively correlated with MD volume. A significant interaction between PTSD and MDD severity was found, such that MDD severity was positively associated with whole thalamus volume only among individuals with high PTSD severity. We observed both positive and negative volumetric associations for specific PTSD symptom clusters and childhood trauma subtypes.

Conclusions: Whole thalamus volume and volumes of the sensorimotor and limbic thalamus may play an important role in the development of PTSD and MDD in the aftermath of trauma exposure. The interaction between PTSD and MDD symptoms and contrasting effects across PTSD symptom clusters and types of childhood adversity suggest that multiple neurobiological mechanisms are involved in shaping thalamic volume posttrauma.

Background: Although glutamatergic genetic variation, reduced amygdala volume, and impaired fear recognition have been linked to callous-unemotional (CU) traits and aggression, the pathways connecting these constructs remain unclear. Therefore, we examined associations between genetic proxies for glutamine/glutamate blood levels and CU traits; reactive and proactive aggression; and the mediating role of amygdala morphology and fear recognition.

Methods: Our pooled case-control sample consisted of 278 youths (8-18 years, n_male = 203) with (n = 177) and without (n = 101) clinically significant aggressive behavior and/or disruptive behavior disorders who participated in a European multicenter study. We used continuous scores for CU traits and aggression, polygenic scores (PGSs) for blood levels of glutamine/glutamate, and T1-weighted magnetic resonance images for calculating amygdala volume and vertexwise shape analyses. We applied path analysis to test direct and total associations and mediation effects.

Results: Glutamine PGS was negatively associated with CU traits. Glutamate PGS was positively associated with amygdala volume and fear recognition, which in turn were negatively associated with CU traits and proactive aggression; fear recognition was also associated with reactive aggression. The total path between glutamate PGS and CU traits was also significant and was mediated by fear recognition.

Conclusions: Our results suggest that glutamatergic genetic variation 1) is associated with CU traits; 2) is associated with amygdala volume and fear recognition; and 3) is indirectly associated with CU traits through fear recognition. Overall, we provide support for an etiological pathway underlying CU traits encompassing glutaminergic/glutamatergic genetic variation, amygdala volume, and fear recognition and the relevance of using PGSs for glutamate/glutamine blood metabolites.

Background: The cognitive effects of transcranial direct current stimulation (tDCS) show substantial interindividual variability, emphasizing the need to identify moderators of responsiveness, with negative affectivity as a potential factor influencing both cognitive performance and tDCS outcomes. Here, we examine whether and how negative affectivity (depressiveness, anxiety, and stress level), conceptualized as both transient states and stable traits, moderates the effects of tDCS on working memory (WM) and associative memory (AM).

Methods: We pooled data from 6 sham-controlled experiments involving 144 healthy young adults (351 tDCS sessions) using within-subject crossover designs. Participants completed WM and AM tasks following active anodal tDCS or sham, as well as the 21-item Depression Anxiety Stress Scale (DASS-21) before each session.

Results: Trait-level, but not state-level, negative affectivity moderated WM. Individuals with higher levels of depression, anxiety, or stress demonstrated greater tDCS-induced WM gains. tDCS-induced AM benefits were consistent and unaffected by affective traits or states.

Conclusions: Negative affectivity may shape individual susceptibility to tDCS, increasing the potential for stimulation-induced improvement on tasks requiring significant executive control.

Background: Agency is the awareness of being the originator of one's own thoughts and actions. Patients with schizophrenia (SZ) show deficits in agency that contribute to distortions in reality monitoring (RM) (distinguishing self-generated from externally produced information) and psychotic symptoms. Agency is also critical for speech monitoring (SM) (monitoring what we hear ourselves say while speaking). For example, disruptions in agency that manifest as hallucinations are thought to result from the misattribution of the source of patients' inner thoughts/speech as external voices.

Methods: We used magnetoencephalography (MEG) to assess agency during RM and SM tasks. In healthy control participants (HCs) during SM, the auditory cortical (A1) response is smaller while speaking (speak condition) compared with listening to the same speech (listen condition). This is known as the speaking-induced suppression (SIS) M100 response, which is measured using MEG 100 ms after speech onset.

Results: During RM, patients with SZ (N = 30) showed impairments in both self-agency (identification of self-generated information) and external agency (identification of externally produced information) compared with HCs (N = 30). During SM, patients with SZ failed to enhance M100 responses during the listen condition, resulting in weakened SIS-that is, smaller M100 listen minus speak differences. Weakened SIS predicted worsening hallucination severity.

Conclusions: Patients with SZ showed degraded neural M100 responses in A1 during the listen condition, which drove impaired SIS (i.e., smaller M100 listen minus speak differences). Impaired SIS indicated degraded auditory sensory predictions, making it more likely for patients with SZ to misattribute the source of inner thoughts/speech as externally derived, giving rise to disruptions in agency during RM and more severe hallucinations.

Background: Neuroimaging studies of functional neurological disorder (FND), a core neuropsychiatric condition, often rely on discrete connections or parcellations that may obscure the brain's functional network architecture. In this study, we applied a gradient-based approach to examine macroscale cortical organization in FND.

Methods: We analyzed resting-state functional magnetic resonance imaging data from 64 patients with mixed FND (FND-mixed), 61 age- and sex-matched healthy control participants (HCs), and 62 psychiatric control participants (PCs) matched on age, sex, depression, anxiety, and posttraumatic stress disorder (PTSD) severity. Functional connectivity gradients were computed to capture dominant axes of cortical organization. Between-group comparisons were conducted for the top 3 gradients, and associations with symptom severity were investigated. Subtype-specific patterns in functional motor disorder (n = 49) and functional seizure (n = 24) were also examined. Analyses controlled for age, sex, antidepressant use, and head motion and were post hoc adjusted for depression, anxiety, and PTSD severity, as well as for childhood maltreatment.

Results: The FND-mixed group showed alterations across all 3 gradients compared with HCs and PCs. Gradient 1 revealed increased values in sensorimotor regions, reflecting a shift toward more association-like connectivity. Gradient 2 showed altered differentiation between sensory systems. Gradient 3 exhibited reduced functional separation between representational and modulatory regions, with prominent shifts in the anterior cingulate cortex. Several regions displaying between-group differences also showed correlations with FND and somatic symptom severity. Exploratory analyses revealed overlapping and distinct patterns across subtypes versus control groups.

Conclusions: We provide novel evidence of atypical hierarchical brain organization in FND, highlighting gradient-based approaches for identifying mechanistically relevant altered functional brain organization.

Background: Earlier timing and faster tempo of puberty have been associated with altered brain development and increased mental health problems in adolescents, particularly females. However, the role of estradiol (E2) in these associations is unclear.

Methods: Using longitudinal data from the U.S.-based ABCD (Adolescent Brain Cognitive Development) Study, we investigated whether, in females (n ∼3000), E2 timing (at age 10) and tempo (rate of change from ages 10-12 years) were prospectively associated with mental health problems at age 13 via structural brain development from ages 10 to 12. Linear mixed-effects models and Bayesian mediation models were fitted to investigate the aims of the study.

Results: Findings showed that E2 timing was not associated with mental health problems. However, earlier E2 timing was associated with a greater reduction in total cortical volume, total surface area, and surface area in the superior and middle temporal cortices over time. Furthermore, a faster E2 tempo was associated with an increase in mental health problems, and this association was mediated by a faster reduction in total cortical volume and total surface area over time.

Conclusions: Findings suggest that earlier E2 timing and faster E2 tempo contribute to accelerated development of gray matter structure in adolescent females, and for E2 tempo, such associated brain changes may partly contribute to increased mental illness risk.

Background: Diminished use of goal-directed (model-based) decision making is a hallmark of transdiagnostic compulsivity, promoting an overreliance on inflexible and habitual behaviors. However, the origin of this impairment remains unclear. Here, we tested the hypothesis that these impairments arise due to uncertainty within the internal world model that subserves goal-directed decision making.

Methods: We adapted a validated gamified decision-making task to characterize how individuals build an internal model of an environment, pairing these data with computational modeling to uncover the exact mechanisms underpinning behavior and quantify individual differences. Two samples of participants (a discovery sample and a preregistered replication sample, n = 551 and 1322, respectively) performed the task, and we also acquired longitudinal data over 2-week and 3-month periods to assess task reliability and stability of behavior over time.

Results: In the discovery and replication samples, we found that individuals higher in compulsivity and intrusive thought learned more slowly and formed a less certain representation of the task's structure. This uncertainty mediated the link between compulsive symptoms and use of goal-directed behavior. Behavior in the task was relatively stable over a 3-month (n = 385) and 1-year (n = 326) period and did not predict changes in symptoms.

Conclusions: Our results suggest that reliance on habitual behaviors seen in individuals with high levels of compulsive symptoms result from a tendency to form less certain internal models of the external world. Given the stability of this behavior and its links to symptoms, this may represent a trait-level vulnerability for this symptom dimension.

Background: Late-life depression (LLD) is a risk factor for age-related cognitive decline. Postmortem studies have highlighted pathological changes in the locus coeruleus (LC) and its projections as potential early cognitive vulnerability markers. Here, we used a novel individualized multimodal magnetic resonance imaging (MRI) approach to characterize the cognitive correlates of LC microstructure and connectivity in participants with LLD and age-matched never-depressed (ND) control participants.

Methods: Diffusion-weighted and LC-sensitive MRI were acquired for 52 participants (LLD: n = 26, 19 female, age 67.8 ± 5.48 years; ND: n = 26, 12 female, age 69.8 ± 7.62 years). Using LC-sensitive MRI to localize the LC in each participant's native space, we computed diffusion metrics (fractional anisotropy [FA] and mean diffusivity [MD]) for the LC and its projections to the hippocampus (Hp), reconstructed with constrained spherical deconvolution tractography. Associations of FA and MD with diagnosis and cognitive performance were evaluated with analyses of covariance and Pearson correlations, respectively, adjusted for demographic/disease covariates and multiple testing (Bonferroni-corrected p < .05).

Results: Higher MD (F_1,45 = 10.07, p = .003) was observed in the LC of individuals with LLD relative to ND control participants. Conversely, no group differences emerged in the LC-Hp pathway. In the combined LLD-ND sample, accounting for LLD diagnosis, lower FA in the LC and its hippocampal projections were associated with worse processing speed (LC: word reading r = -0.47; LC-medial temporal lobe [MTL]: word reading r = -0.46, color naming r = -0.49; all ps ≤ .0007) and executive functions (LC-MTL: inhibition r = -0.50, inhibition/switching r = -0.45, number/letter sequencing r = -0.40; all ps ≤ .0033).

Conclusions: Neuronal injury of the LC may be a marker for LLD. Alternatively, the microstructural status of LC-Hp projections may be a biomarker more specific to age-related cognitive deterioration, irrespective of depression diagnosis.

Background: It is unknown whether brain-based predictive models derived from sleep features are useful for the clinical diagnosis of major depressive disorder (MDD).

Methods: Using resting-state functional magnetic resonance imaging data from the curated ABCD (Adolescent Brain Cognitive Development) Study Data Release 3.0, we trained a connectome-based predictive model (CPM) on 35,778 pairwise connections (Pearson's r) from 2349 (237 participants with at least 1 psychiatric disorder and 2112 control participants) participants ages 11 to 12 to predict sleep duration (measured from a Fitbit tracker). Linear regression models were used to compare the predicted values from these CPMs with self-reported sleep duration and diagnostic group status in an independent cohort of 78 participants (57 participants with MDD and 21 control participants) ages 14 to 18.

Results: The ABCD-based CPM predicted self-reported sleep duration in the independent cohort of participants with MDD (partial r = 0.332, p = .009). Even though self-reported sleep duration did not significantly differ between diagnostic groups (t₇₅ = 0.13, p = .90), the ABCD-based CPM successfully distinguished between diagnostic groups (partial r = 0.334, p < .001), and CPM-predicted sleep durations correlated with depression symptom severity (partial r = 0.294, p < .001). These diagnostic group differences were driven primarily by patterns of hypoconnectivity between various resting-state networks (including the default mode, frontoparietal, motor, subcortical, and visual associative networks).

Conclusions: CPMs trained to predict objective sleep duration are robust and generalizable. Intrinsic functional connectivity differences between clinically depressed and psychiatrically healthy adolescents are detectable by CPMs optimized for sleep prediction, underscoring the shared neural bases between sleep health and depression. Future work will test whether sleep-based CPMs are predictive of clinical course and if they generalize to other disorders beyond depression.