Faculty Bibliography

BACKGROUND:Children born very preterm (VPT) are at high risk for attention problems. This study's purpose was to describe the Conners Kiddie Continuous Performance Test (K-CPT) assessment in children born VPT, including rates of clinically elevated scores, change over time, and associations between K-CPT scores and parent reported attention problems. METHODS:We studied 305 children from a multi-site study of children born VPT who completed at least one K-CPT assessment at age 5, 6, and/or 7 years. Parent-reported ADHD symptoms and diagnosis were also collected. We calculated K-CPT completion rates, mean scores, and rates of clinically elevated scores at each timepoint. Linear mixed models examined change over time in K-CPT scores. Correlations and generalized linear models investigated associations between K-CPT scores and ADHD symptoms and diagnoses. RESULTS:K-CPT scores showed expected age-related improvements from age 5-7, with significant intra- and inter-individual variability. Up to 1/3 of children had clinically elevated attention problems and another 1/3 had subclinical elevations. K-CPT scores were modestly correlated with parent-rated ADHD symptoms and children with a parent-reported ADHD diagnosis performed worse on nearly all K-CPT metrics. CONCLUSION/CONCLUSIONS:Performance-based measures like the K-CPT can be useful for research and clinical practice in VPT populations. IMPACT/CONCLUSIONS:Attention problems are a specific area of weakness for children born very preterm. Performance-based tests of attention have benefits and drawbacks compared to parent report measures yet are understudied in this population. We examined one performance-based measure (the Conners Kiddie Continuous Performance Test [K-CPT]) in 305 children born very preterm. We observed improving task scores from age 5-7 years with significant intra- and inter-individual variability, a sizable proportion of children with clinically and subclinically elevated scores, and modest associations between K-CPT scores and parent reported attention problems. The K-CPT could be a useful clinical and research tool in this population.

Dialectical thinking represents a cognitive style emphasizing change, contradiction, and holism. Cross-cultural studies reveal a stark contrast of dialectical thinking between East Asian and Western cultures, highlighting East Asians' superior ability to embrace contradictions and foresee transformation, fostering psychological resilience through emotional complexity and tolerance for contradictions. Despite its importance, the neural basis of dialectical thinking remains underexplored. This review synthesizes current neuroscientific findings and introduces the dialectical-integration network (DIN) hypothesis, which identifies key brain regions such as the dorsal anterior cingulate cortex (dACC), medial prefrontal cortex (mPFC), dorsal lateral prefrontal cortex (DLPFC), nucleus accumbens, basal ganglia, and amygdala. These regions, along with networks like the default mode network (DMN) and frontoparietal network (FPN), facilitate holistic reasoning, conflict resolution, and sensory-emotional integration. The psychological benefits of dialectical thinking include enhanced cognitive flexibility, reduced emotional extremes, and improved conflict resolution. This review emphasizes the need for cross-cultural and neuroscientific research to explore the principle of change, a core aspect of dialectical cognition. By bridging cultural psychology and cognitive neuroscience, this work offers theoretical and methodological insights into culturally shaped cognitive styles, with practical applications in education, mental health, and intercultural communication. The DIN model provides a framework for future research on dynamic neural interactions supporting dialectical thinking.

Monosodium glutamate (MSG) has become one of the most widely used food additives in the global food supply. Although it has been classified for decades as a food ingredient that is generally recognized as safe, concerns about the health impacts of chronic MSG use, especially its potential effect on weight, are still ongoing. This comprehensive review summarizes the available human and animal evidence, highlighting potential mechanisms linking MSG use to weight gain or obesity, and discusses challenges and future research directions. Because of MSG intake worldwide as well as hidden MSG in food labeling, there is a pressing need for a mechanistic understanding of the health impacts of MSG use especially on weight. To generate robust scientific evidence and to clarify public concerns, rigorous mechanistic studies and randomized controlled clinical trials are warranted.

BACKGROUND/UNASSIGNED:Essential tremor (ET) is characterized by often disabling action tremors. No pharmacological agent has been developed specifically for symptomatic treatment. Anecdotal reports describe tremor improvement with cannabis, but no evidence exists to support these claims. We conducted a phase Ib/II double-blind, placebo-controlled, crossover pilot trial in participants with ET to investigate tolerability, safety, and efficacy of Tilray TN-CT120 LM, an oral pharmaceutical-grade formulation containing tetrahydrocannabinol (THC) 5 mg and cannabidiol (CBD) 100 mg. Our objectives were to determine if short-term THC/CBD exposure improved tremor amplitude and was tolerated. METHODS/UNASSIGNED:Participants with ET were randomized (1:1) to receive either TN-CT120 LM or placebo. Dose titration, driven by tolerability, was attempted every 2-3 days to three capsules daily maximum. Participants remained on the highest tolerated dose for two weeks before returning to complete assessments. After completing the first arm, participants titrated off the agent, underwent a three-week washout, and then returned for the same procedures with the alternate compound. The primary endpoint was tremor amplitude change from baseline using digital spiral assessment. Secondary endpoints explored safety and tolerability. RESULTS/UNASSIGNED:Among thirteen participants screened, seven were eligible and enrolled. Five completed all visits; one withdrew following a serious adverse event, and another did not tolerate the lowest dose. Intent-to-treat analyses performed for six participants did not reveal significant effects on primary or secondary endpoints. CONCLUSIONS/UNASSIGNED:This pilot trial did not detect any signals of efficacy of THC/CBD in ET. Although preliminary due to the small sample size, our data do not support anecdotal reports of cannabinoid effectiveness for ET. HIGHLIGHTS/UNASSIGNED:This double-blind, randomized, placebo-controlled efficacy and tolerability pilot trial did not detect any signals of efficacy of oral cannabidiol and tetrahydrocannabinol in reducing essential tremor amplitude using either digital outcome measures or clinical rating scales. The oral cannabinoids were well-tolerated by most (five out of seven) participants.

Professor Alessandro Zuddas, from the University of Cagliari (Italy), passed away prematurely in July 2022. As a prominent figure in child and adolescent neuropsychiatry, he substantially influenced the fields of neurodevelopmental disorders and neuropsychopharmacology both nationally and internationally. Professor Zuddas was a renowned expert in basic and clinical research in child and adolescent psychopharmacology, an enlightened and stimulating educator, and a mentor to many students, residents, and senior colleagues. With his enthusiasm and unique ability to network, he contributed enormously to trace a path in the field that we continue to follow. His name will remain in the textbooks and articles he authored. Here, as colleagues and friends who had the honor to work with him, we provide our personal views of Alessandro's impact and legacy, which go far beyond his publications.

BACKGROUND:Spontaneous thought is a universal, complex, and heterogeneous cognitive activity that significantly impacts mental activity and strongly correlates with mental disorders. METHODS:Utilizing the think-aloud method, we captured spontaneous thoughts during rest from 38 diagnosed with depression, alongside 36 healthy controls and 137 healthy individuals. Through a comprehensive assessment of various dimensions of thought content, we compared thought content between individuals with depression and healthy controls, and between healthy women and men. Finally, we employed natural language processing (NLP) to develop regression models for multidimensional content assessment and a classification model to differentiate between individuals with and without depression. RESULTS:Compared to healthy controls, individuals with depression had more internally oriented and less externally oriented spontaneous thoughts. They focused more on themselves and negative things, and less on positive things, experiencing higher levels of negative emotions and lower levels of positive emotions. Besides, we found that compared to healthy men, healthy women's spontaneous thoughts focus more on interoception, the self, past events, and negative events, and they experience higher levels of negative emotions. Meanwhile, we identified the potential application of the think-aloud method to collect spontaneous thoughts and integrate NLP in the field of depression. CONCLUSIONS:This study offers direct insights into the stream of thought during individuals' resting state, revealing differences between individuals with depression and healthy controls, as well as sex differences in the content of spontaneous thoughts. It enhances our understanding of spontaneous thought and offers a new perspective for preventing, diagnosing, and treating depression.

BACKGROUND:Children born preterm are at heightened risk for neurodevelopmental impairment, including specific deficits in attention. Few studies have investigated change over time in attention problems prior to school entry. The current study aims to describe trajectories of attention problems from age 2 through 5 years in a cohort of children born <30 weeks of gestational age (GA), identify sociodemographic, medical, and neurobehavioral characteristics associated with attention trajectories, and test whether attention problem trajectories predict the risk of a reported attention-deficit/hyperactivity disorder (ADHD) diagnosis. METHODS:We studied 608 infants from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study, a prospective, multisite study of infants born <30 weeks of GA. Parents reported on child attention problems at ages 2, 3, 4, and 5 years using the Child Behavior Checklist and the Behavior Assessment System for Children. Sociodemographic and medical characteristics were assessed via maternal interview and medical record review. Neurobehavioral characteristics were determined using neonatal and 2-year assessments. Parent report of child ADHD diagnosis was obtained. We used latent growth curve (LGC) modeling to test our study aims. RESULTS:A linear LGC model provided the best fit to the data. The average trajectory of attention problems evidenced low initial levels of symptoms and little change over time, yet there was significant heterogeneity in both initial levels and change over time. Individual differences in trajectory parameters were associated with sociodemographic, medical, environmental, and neurobehavioral characteristics. Children with higher initial levels of attention problems as well as steeper increases in attention problems over time were more likely to have a reported ADHD diagnosis. CONCLUSIONS:There is significant heterogeneity in trajectories of attention problems from age 2 to 5 in children born <30 weeks of GA and these differences have clinical relevance. These data could inform follow-up guidelines for preterm infants.

Approaching the 30th anniversary of the discovery of resting state functional magnetic resonance imaging (rsfMRI) functional connectivity, we reflect on the impact of this neuroimaging breakthrough on the field of child and adolescent psychiatry. The study of intrinsic functional brain architecture that rsfMRI affords across a wide range of ages and abilities has yielded numerous key insights. For example, we now know that many neurodevelopmental conditions are associated with more widespread circuit alterations across multiple large-scale brain networks than previously suspected. The emergence of population neuroscience and effective data-sharing initiatives have made large rsfMRI datasets publicly available, providing sufficient power to begin to identify brain-based subtypes within heterogeneous clinical conditions. Nevertheless, several methodological and theoretical challenges must still be addressed to fulfill the promises of personalized child and adolescent psychiatry. In particular, incomplete understanding of the physiological mechanisms driving developmental changes in intrinsic functional connectivity remains an obstacle to further progress. Future directions include cross-species and multimodal neuroimaging investigations to illuminate such mechanisms. Data collection and harmonization efforts that span multiple countries and diverse cohorts are urgently needed. Finally, incorporating naturalistic fMRI paradigms such as movie watching should be a priority for future research efforts.

Both cortical and cerebellar developmental differences have been implicated in attention-deficit/hyperactivity disorder (ADHD). Recently accumulating neuroimaging studies have highlighted hierarchies as a fundamental principle of brain organization, suggesting the importance of assessing hierarchy abnormalities in ADHD. A novel gradient-based resting-state functional connectivity analysis was applied to investigate the cerebro-cerebellar disturbed hierarchy in children and adolescents with ADHD. We found that the interaction of functional gradient between diagnosis and age was concentrated in default mode network (DMN) and visual network (VN). At the same time, we also found that the opposite gradient changes of DMN and VN caused the compression of the cortical main gradient in ADHD patients, implicating the co-occurrence of both low- (visual processing) and high-order (self-related thought) cognitive dysfunction manifesting in abnormal cerebro-cerebellar organizational hierarchy in ADHD. Our study provides a neurobiological framework to better understand the co-occurrence and interaction of both low-level and high-level functional abnormalities in the cortex and cerebellum in ADHD.