Biological psychiatry. Cognitive neuroscience and neuroimaging最新文献

Background: Cannabis use among young adults has reached the highest levels ever recorded. Evidence indicates that acute Δ⁹-tetrahydrocannabinol (THC) disrupts brain connectivity. Few studies have examined this on a whole-brain level. We examined the effects of a single moderate dose of THC on resting-state functional brain networks among young adult cannabis users.

Methods: In a within-subject, double-blind, randomized study, 33 healthy occasional cannabis users received THC (7.5 mg, oral) and placebo before completing resting-state functional magnetic resonance imaging (rs-fMRI) during peak intoxication. Group-information-guided independent component analysis was performed on resting-state brain data to identify whole-brain networks associated with each scan. Within-samples t tests assessed for differences in intrinsic network functional connectivity and between-network functional connectivity after THC versus placebo. Additional linear models examined relationships between brain connectivity, subjective drug effects, and past-month cannabis use.

Results: THC reduced within-network intrinsic connectivity in corticostriatal circuits and other networks associated with sensory systems, interoceptive experiences, and spatial reasoning. THC reduced connectivity between 2 networks characterized by the anterior cingulate cortex and dorsal insula regions as well as the ventral insula and lingual gyrus, respectively. Network connectivity during THC (vs. placebo) was not related to subjective measures of drug effect or recent cannabis use.

Conclusions: Our findings add to a growing literature showing that THC decreases rs-fMRI throughout the brain, impacting networks linked to the many behavioral and perceptual changes associated with THC. Future work is needed to extend these findings to clinical samples and to assess the extent to which these networks are associated with negative outcomes of chronic THC use.

Background: Advances in neuroimaging of bipolar disorder (BD) have highlighted key structural and functional abnormalities in prefrontal-limbic circuits. Youth with a family history of BD often experience early onset of mood symptoms that may increase their risk for developing BD. However, the etiologic mechanisms underlying this risk remain poorly understood. We aimed to identify white matter connectivity abnormalities by comparing regional microstructure in high-risk youth and healthy control (HC) participants.

Methods: Youths with depression and/or anxiety (n = 108, mean age [SD] = 14.9 [1.6] years) with a family history of BD but no prior antidepressant exposure and matched HC youths (n = 45, age = 14.8 [1.6] years) were recruited at 2 sites. Automated fiber quantification using diffusion tensor imaging was used to calculate the diffusion properties of fiber tracks and identify microstructural abnormalities. Correlations between clinical ratings and diffusion properties that differed between groups were examined in high-risk youths.

Results: The high-risk group showed higher fractional anisotropy in anterior thalamic radiation and corticospinal, higher axial diffusivity in anterior thalamic radiation, lower mean diffusivity in corticospinal, and lower radial diffusivity in corticospinal and callosum forceps minor compared with the HC group (familywise error-corrected p < .05). Significant positive correlations between regional microstructural metrics and both the Pediatric Anxiety Rating Scale and the Children's Global Assessment Scale were observed in high-risk youths (false discovery rate-corrected p < .05).

Conclusions: Compared with the HC group, youths at risk for BD had altered integrity in the white matter of the callosum forceps minor, anterior thalamic radiation, and corticospinal tracts. Damage to these tracts may be a structural basis for impaired emotional regulation in high-risk youth and a potential target for early intervention.

Background: The glymphatic system (GS) plays a central role in eliminating metabolic waste from the human brain. Diffusion tensor image analysis along the perivascular space (ALPS) has emerged as a noninvasive biomarker for evaluating GS function. While decreased ALPS is consistently linked to impaired GS in various central nervous system pathologies, the genetic architectures and neural mechanisms underlying ALPS and its role in maintaining brain health remain unknown.

Methods: A genome-wide association study (GWAS) of ALPS was conducted in 31,579 participants from the UK Biobank. Genetic associations were identified using positional, expression quantitative trait loci, and chromatin mapping strategies. Gene-set enrichment analysis and Mendelian randomization (MR) were performed to characterize biological pathways and causal relationships between ALPS, brain phenotypes, and neurological disorders.

Results: The GWAS identified 6 unique loci and 175 genes associated with ALPS. Gene enrichment analyses identified significant associations with brain morphogenesis, along with implications for GS function and neurodegenerative pathways. Genetic and individual-level correlations linked ALPS to brain volume, cerebrospinal fluid-related imaging phenotypes, and cognitive metrics. MR demonstrated that genetically predicted lower ALPS increased the risk of multiple sclerosis and Alzheimer's disease.

Conclusions: This study elucidates the genetic architecture of ALPS, a biomarker that reflects GS function, and its association with brain health. The findings highlight decreased ALPS as a potential risk factor for neuroinflammatory and neurodegenerative disorders, emphasizing the importance of GS integrity in maintaining neurological health.

Background: American Indians (AIs) experience chronic stressors that may be associated with disproportionate prevalence rates of major depressive disorder (MDD). Stress affects mental health through increased inflammatory processes and has been associated with increased risk of MDD and disruptions to reward processing. In this study, we investigated the role of inflammation in reward-processing disruptions among AI individuals with lifetime MDD, a population at heightened risk due to chronic stressors.

Methods: Participants (N = 73) completed a monetary incentive delay task during simultaneous electroencephalography and functional magnetic resonance imaging. Blood samples were analyzed for proinflammatory (tumor necrosis factor [TNF], interleukin 6 [IL-6], C-reactive protein [CRP]) and anti-inflammatory (IL-10) biomarkers. Depression severity was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Depression scale. Covariates were included and assessed using self-report measures.

Results: Regression analyses revealed that elevated TNF concentrations and sex were associated with reduced activation across subregions of the basal ganglia during gain anticipation. Similarly, TNF and CRP concentrations, as well as medication, were associated with reduced activation within basal ganglia subregions across loss anticipation. IL-10, IL-6, and P300 showed limited predictive value for neural responses.

Conclusions: These findings suggest that inflammation may contribute to reward-processing disruptions by impairing striatal function in a sample with lifetime MDD. The observed associations underscore the importance of inflammation's potential role in and association with the pathophysiology of MDD, particularly in contexts of chronic stress. This study highlights the need to address the disproportionate mental health burden in AI communities through a biopsychosocial approach.

Background: Recent epidemiological evidence links early-life obesity and metabolic dysregulation to adult psychosis vulnerability, though a causal relationship remains unclear. Establishing causality in highly heritable psychotic disorders requires 1) demonstrating that early-life metabolic factors mediate between genetic vulnerability and psychosis trajectory, 2) dissecting mechanisms leading to early-life obesity in genetically vulnerable individuals, and 3) clarifying downstream neurodevelopmental pathways linking early-life obesity to psychosis symptoms.

Methods: Here we investigated bidirectional pathways linking behavioral, body mass index (BMI), and neurodevelopmental trajectories in a unique longitudinal cohort of 184 individuals at high genetic risk for psychosis, due to 22q11.2 deletion syndrome (22q11DS), and 182 neurotypical control individuals, followed-up since childhood. We combined repeated BMI measurements with clinical/neurocognitive phenotyping and neuroimaging. We investigated the relationship between BMI trajectories with risk of psychosis and tested whether altered cortical or cerebellar development could underlie this association.

Results: Childhood behavioral impulsivity predicted early and progressive deviations in BMI trajectories, mediating the effects of 22q11DS vulnerability to early-life obesity. Chronic BMI increases manifesting during childhood predicted the subsequent emergence of psychosis during late adolescence/early adulthood, mediating the effects of behavioral impulsivity. A dose-effect relationship linked duration of increased BMI status to worsening of motor and cognitive disorganization, a key schizophrenia symptom domain, which was mediated by progressive gray matter volume reductions in posterior-inferior cerebellum.

Conclusions: These findings suggest that metabolic dysregulation associated with obesity may link childhood behavioral impulsivity to psychosis vulnerability in 22q11DS by influencing cerebellar maturation. These findings might support preventive interventions targeting early-life metabolic trajectories in individuals at risk of psychosis.

Background: Internet gaming disorder (IGD) is a clinically heterogeneous condition, yet the underlying neurobiological subtypes remain to be elucidated. Investigating subpatterns of spontaneous neural activity and state switching from individual to group patterns may provide deeper insights into the etiology of IGD.

Methods: Resting-state functional magnetic resonance imaging data were collected from 519 participants (257 with IGD, 262 recreational game users [RGUs]). The fractional amplitude of low-frequency fluctuations was computed to assess spontaneous neural activity. Nonnegative matrix factorization was used to extract features that were predictive of addiction severity. Network control theory (NCT) was utilized to quantify the energy required for brain state transitions.

Results: Compared with RGUs, participants with IGD exhibited heightened activity in brain patterns (involving the basal ganglia and thalamic regions) associated with reward processing. The individual weight of this pattern was positively associated with addiction severity, and the spatial intensity was negatively correlated with the density of serotonin 1A (5-HT_1A) receptors. Furthermore, NCT analysis demonstrated that transitioning to a high-craving state required less control energy than transitioning to other states.

Conclusions: Although neural activity varies among individuals with IGD, the homogeneity can be embedded in reward processing-related brain areas. Reduction in 5-HT_1A receptor density may be a substrate for this pattern. Individuals with IGD transition more readily to high-craving states than to other states. These results elucidate neural mechanisms underlying IGD and highlight the importance of individualized approaches to treating the disorder.

Background: The interthalamic adhesion (IA) is a midline structure connecting the left and right thalamus that typically develops during the second trimester of pregnancy. Missing and smaller IA have been linked to neurodevelopmental disorders, including schizophrenia, and subtle deficits in cognition. However, the findings are inconsistent, and the association between IA and other anatomical variants linked to atypical brain development in schizophrenia, including incomplete hippocampal inversion (IHI), is unclear.

Methods: The presence/absence and morphology of IA were ascertained on structural T1-weighted magnetic resonance images obtained at 3T in individuals with schizophrenia spectrum disorders (SSDs) (n = 223) and healthy individuals (n = 194) and compared between groups. Associations between IA morphology, cognitive function, and IHI were assessed.

Results: The prevalence of missing IA was 1.7% and did not differ between groups. IA was significantly smaller in the SSD group (p < .001). However, follow-up analyses revealed that smaller IA size in SSD was due to a significant diagnosis × age interaction characterized by a stronger negative age effect in SSD. IHI was significantly more common in individuals with missing IA. Neurocognition was not correlated with IA size when controlling for age and diagnosis.

Conclusions: Stronger effects of age on IA size in SSDs suggests that abnormal IA size measured during adulthood may not be a reliable static indicator of atypical neurodevelopment but may reflect disease progression or accelerated aging. Missing IA was rare in our sample. Conversely, missing IA was associated with IHI, suggesting a shared neurodevelopmental disruption during the second trimester.

Background: Childhood trauma is a risk factor for adolescent psychopathology, including posttraumatic stress disorder (PTSD). Most research has relied on caregiver (i.e., parent or legal guardian) reports of child trauma. In this study, we investigated the impact of reporter (child vs. caregiver) in assessing neurobiological correlates of trauma and PTSD in children.

Methods: Two independent samples of youths (original sample: N = 76, 47% female, mean [SD] age = 9.39 [0.492] years; replication sample: N = 98, 51% female, mean [SD] age = 9.38 [0.089]) and their caregivers were interviewed regarding the children's trauma exposure and PTSD severity. Youths in the original sample were assessed for fear-potentiated startle (FPS) during fear conditioning and bilateral amygdala reactivity during an emotional faces functional magnetic resonance imaging task. To assess reporter effects, effect sizes and directions of associations between interview measures and neurobiological correlates were compared using multiple linear regression analysis.

Results: Children's self-reported trauma exposure was associated with children's self-reported PTSD severity (original sample: β = 0.55, p < .001; replication sample: β = 0.37, p < .01), while caregivers' reports of child's trauma exposure were not associated with children's self-reported PTSD severity (original sample: β = -0.01, p = .99; replication sample: β = 0.07, p = .57). Children's self-report of PTSD severity was positively associated with FPS (original sample: β = 0.29, p < .05) and amygdala reactivity (original sample: β = 0.39, p < .05), while caregivers' reports of their children's PTSD were not (ps > .05).

Conclusions: These findings suggest that the reporter's perspective may influence associations between trauma, PTSD, and their neurobiological correlates. Child report rather than caregiver report may better align with the child's perceived experience and therefore better predict underlying neurobiology. These findings support the inclusion of children's self-reports of trauma and PTSD when investigating candidate biomarkers of PTSD vulnerability in trauma-exposed youth.

Background: Posttraumatic stress disorder (PTSD) can be characterized as a disorder of fear learning and memory in which there is a failure to retain memory for the extinction of conditioned fear. Sleep has been implicated in successful extinction retention. The coupling of sleep spindles to slow oscillations (SOs) during non-rapid eye movement sleep has been shown to broadly underpin sleep's beneficial effect on memory consolidation. However, the role of this oscillatory coupling in the retention of extinction memories is unknown.

Methods: In a large sample of 124 trauma-exposed individuals, we investigated SO-spindle coupling in relation to fear extinction memory.

Results: We found that participants with a PTSD diagnosis, relative to trauma-exposed control participants, showed significantly altered SO-spindle timing, such that participants with PTSD exhibited spindle coupling farther away from the peak of the SO. Across participants, the amount of coupling significantly predicted extinction retention, with coupled spindles uniquely predicting successful extinction retention compared with uncoupled spindles.

Conclusions: These results suggest that SO-spindle coupling is critical for successful retention of extinguished fear and that SO-spindle coupling dynamics are altered in PTSD. These alterations in the mechanics of sleep may have substantial clinical implications, meriting further investigation.

Background: Aberrant decision making is a hallmark of substance use disorders (SUDs), often impeding recovery. While uncertainty, which comprises risk and ambiguity, is central to real-world choices, its distinct effects in SUDs remain underexplored. In this study, we disentangle risk and ambiguity to identify context-specific impairments in methamphetamine use disorder (MUD) and alcohol use disorder (AUD).

Methods: We used a Choice under Risk and Ambiguity task to examine uncertainty decision making (UDM) in 101 individuals with MUD, 56 individuals with AUD, and their respective healthy control participant (HC) groups (n = 45 and n = 75). Group-level analyses applied a modified psychometric function to estimate decision parameters, while individual-level UDM indicators were derived using custom computational methods and subjective value models.

Results: Individuals with MUD exhibited heightened reward sensitivity and a stronger preference for large rewards under high uncertainty, with flexible shifts across ambiguity levels. In addition, reward sensitivity under high ambiguity was linked to symptom severity. In contrast, individuals with AUD showed no evident decision-making impairments across conditions, and like HCs, they adopted conservative strategies under ambiguity. Direct comparisons confirmed more pronounced UDM impairments in MUD than in AUD.

Conclusions: These findings underscore the heterogeneity of decision-making patterns across SUDs, validating the need for precision in therapeutic strategies.