Chiang-shan Ray Li

Yale University | YU · Department of Psychiatry

Background and Hypothesis Sensory gating deficit is considered a pathophysiological feature of schizophrenia, which has been linked to N-methyl-d-aspartate receptor (NMDAR) hypofunction as one of the potential underlying mechanisms. Here, we hypothesize that higher levels of NMDAR antibody (Ab) may contribute to the sensory gating deficits in schiz...

Background The hypothalamus is a key hub of the neural circuits of motivated behavior. Alcohol misuse may lead to hypothalamic dysfunction. Here, we investigated how resting-state hypothalamic functional connectivities are altered in association with the severity of drinking and clinical comorbidities and how men and women differ in this associatio...

Physical pain and negative emotions represent two distinct drinking motives that contribute to harmful alcohol use. Proactive avoidance, in contrast, can reduce consumption in response to these motives but appears to be impaired in those with problem drinking. Despite such evidence, proactive avoidance and its underlying neural deficits have not be...

The interplay between emotion and attention has long been intensely scrutinized, with competing theories proposing divergent mechanisms. Building on our previous work, here we present evidence that refines these perspectives, revealing a nuanced, temporally dynamic relationship between emotional stimuli and attentional focus. Using a modified Flank...

Introduction Older adults experience less anxiety. We examined how memory of negative emotional images varied with age and may reflect age-related differences in anxiety. Methods Fifty-one adults, age 22-80 years, underwent imaging with a memory task where negative and neutral images were displayed pseudo-randomly. They were queried post-scan abou...

Background Increasing evidence suggested that immune abnormalities involved in the pathophysiology of schizophrenia. However, the relationship between immunity and clinical features has not been clarified. The aim of this study was to measure the plasma levels of tumor necrosis factor alpha (TNF-α) and soluble TNF-α receptor 1 (sTNF-α R1) and to in...

Background Working memory refers to a process of temporary storage and manipulation of information to support planning, decision-making, and action. Frequently comorbid alcohol misuse and sleep deficiency have both been associated with working memory deficits. However, how alcohol misuse and sleep deficiency interact to impact working memory remain...

Alcohol misuse is associated with altered punishment and reward processing. Here, we investigated neural network responses to reward and punishment and the molecular profiles of the connectivity features predicting alcohol use severity in young adults. We curated the Human Connectome Project data and employed connectome-based predictive modeling (C...

Background Premature ovarian insufficiency (POI) seriously affects the reproductive health of women. Several studies have been conducted to show that POI appears to be associated with psychological and psychosocial problems, but whether POI increases the risk of mental health problems has not been identified. Therefore, this meta-analysis provides...

Introduction Short sleep duration and inconsistent timing have been linked to poor glycemic target achievement and greater comorbidities in individuals with type 1 diabetes (T1D), particularly adults aged 18-26 years who achieve glycemic targets at the lowest rates (only 14%). Preliminary evidence supports cognitive behavioral sleep interventions (...

Background Many studies showed disrupted tryptophan metabolism in patients with affective disorders. The aims of this study were to explore the differences in the metabolites of tryptophan pathway (TP) and the relationships between TP metabolites and clinical symptoms, therapeutic effect in patients with bipolar disorder with acute manic episode (B...

Background: Many studies showed disrupted tryptophan metabolism in patients with affective disorders. The aims of this study were to explore the differences in the metabolites of tryptophan pathway (TP) and the relationships between TP metabolites and clinical symptoms, therapeutic effect in patients with bipolar disorder with acute manic episode (...

Background: Many studies showed disrupted tryptophan metabolism in patients with affective disorders. The aims of this study were to explore the differences in the metabolites of tryptophan pathway (TP) and the relationships between TP metabolites and clinical symptoms, therapeutic effect in patients with bipolar disorder with acute manic episode (...

Background: Many studies showed disrupted tryptophan metabolism in patients with affective disorders. The aims of this study were to explore the differences in the metabolites of tryptophan pathway (TP) and the relationships between TP metabolites and clinical symptoms, therapeutic effect in patients with bipolar disorder with acute manic episode (...

Background: Many studies showed disrupted tryptophan metabolism in patients with affective disorders. The aims of this study were to explore the differences in the metabolites of tryptophan pathway (TP) and the relationships between TP metabolites and clinical symptoms, therapeutic effect in patients with bipolar disorder with acute manic episode (...

Background: Males and females who consume cannabis can experience different mental health and cognitive problems. Neuroscientific theories of addiction postulate that dependence is underscored by neuroadaptations, but do not account for the contribution of distinct sexes. Further, there is little evidence for sex differences in the neurobiology of...

Men with prostate cancer are at increased risk of developing cognitive decline by the use of second‐generation androgen signaling inhibitors. To date, reliable and sensitive biomarkers that could distinguish men at high risk of cognitive dysfunction under androgen deprivation therapy (ADT) have not been characterized. We used high‐throughput transc...

Background Deficient sleep is implicated in nicotine dependence as well as depressive and anxiety disorders. The hypothalamus regulates the sleep-wake cycle and supports motivated behavior, and hypothalamic dysfunction may underpin comorbid nicotine dependence, depression and anxiety. We aimed to investigate whether and how the resting state functi...

Genetic variants may confer risks for depression by modulating brain structure and function. Prior evidence has underscored a key role of the subgenual anterior cingulate cortex (sgACC) in depression. Here, we built on the literature and examined how the resting state functional connectivity (rsFC) of the sgACC was associated with polygenic risks f...

Organisms learn to gain reward and avoid punishment through action–outcome associations. Reinforcement learning (RL) offers a critical framework to understand individual differences in this associative learning by assessing learning rate, action bias, pavlovian factor (i.e., the extent to which action values are influenced by stimulus values), and...

Background Men and women are known to show differences in the incidence and clinical manifestations of mood and anxiety disorders. Many imaging studies have investigated the neural correlates of sex differences in emotion processing. However, it remains unclear how anxiety might impact emotion processing differently in men and women. Method We rec...

White matter pathways, typically studied with diffusion tensor imaging (DTI), have been implicated in the neurobiology of obsessive-compulsive disorder (OCD). However, due to limited sample sizes and the predominance of single-site studies, the generalizability of OCD classification based on diffusion white matter estimates remains unclear. Here, w...

Background: Alcohol misuse is associated with altered punishment and reward processing. Here, we investigated neural network responses to reward and punishment and the molecular profiles of the connectivity features predicting alcohol use severity in young adults. Methods: We curated the Human Connectome Project data and employed connectome-based p...

Physical pain and negative emotions represent two distinct drinking motives that contribute to harmful alcohol use. Proactive avoidance which can reduce problem drinking in response to these motives appears to be impaired in problem drinkers. However, proactive avoidance and its underlying neural deficits have not been assessed experimentally. How...

The COVID-19 pandemic has profoundly impacted the mental health and education of college students. This study examined the interrelationships among loneliness, resilience, and COVID-19 fear among college students in Northern Michigan, a region of the United States severely affected by the pandemic. Data were collected from two student cohorts (n=25...

Introduction There are growing concerns about commonly inflated effect sizes in small neuroimaging studies, yet no study has addressed recalibrating effect size estimates for small samples. To tackle this issue, we propose a hierarchical Bayesian model to adjust the magnitude of single-study effect sizes while incorporating a tailored estimation of...

Alcohol dependence is a disorder with a high recurrence rate that leads to a considerable public health burden. The risk of relapse appears to be related to a complex interplay of multiple factors. Herein, we aimed to explore the potential neural predictors of relapse in Chinese male patients with alcohol dependence. This study enrolled 58 male pat...

Background Men and women are known to show differences in the incidence and clinical manifestations of mood and anxiety disorders. Many imaging studies have investigated the neural correlates of sex differences in emotion processing. However, it remains unclear how anxiety might impact emotion processing differently in men and women. Method We recr...

Schizophrenia patients have been reported to have impairments in attention. In this study, we investigated their selective attention and tested whether they have difficulties in segmenting cues from the context. Twenty-one patients with schizophrenia and twenty-one healthy controls performed an arrow Flanker task, in which a potential cue was prese...

Several studies have reported compromised white matter integrity, and that some inflammatory mediators may underlie this functional dysconnectivity in the brain of patients with schizophrenia. The immune-inflammatory response system and compensatory immune-regulatory reflex system (IRS/CIRS) are novel biomarkers for exploring the role of immune imb...

Over the last decades, theoretical perspectives in the interdisciplinary field of the affective sciences have proliferated rather than converged due to differing assumptions about what human affective phenomena are and how they work. These metaphysical and mechanistic assumptions, shaped by academic context and values, have dictated affective const...

Background The basal nucleus of Meynert (BNM), a primary source of cholinergic projections to the cortex, plays key roles in regulating sleep-wake cycle and attention. Sleep deficit is associated with impairment in cognitive and emotional functions. However, whether or how cholinergic circuit, sleep, cognitive/emotional dysfunction are inter-relate...

Introduction Transcranial alternating current stimulation (tACS) at 5-Hz to the right hemisphere can alleviate anxiety symptoms. This study aimed to explore the connectivity changes following the treatment. Methods We collected electroencephalography (EEG) data from 24 participants with anxiety disorders before and after the tACS treatment during a...

Background: Magnetic resonance imaging provides noninvasive tools to investigate alcohol and nicotine use disorders (AUD/NUD) and neural phenotypes for genetic studies. A data-driven transdiagnostic approach could provide a new perspective on the neurobiology of AUD and NUD. Methods: Using samples of individuals with AUD (N=140), NUD (N=249), an...

Background: Previous studies have focused on both ventral striatum (VS) and dorsal striatum (DS) in characterizing dopaminergic deficits in addiction. Animal studies suggest VS and DS dysfunction each in association with impulsive and compulsive cocaine use during early and later stages of addiction. However, few human studies have aimed to distin...

Background and hypothesis: Low-grade neural and peripheral inflammation are among the proposed pathophysiological mechanisms of schizophrenia. White matter impairment is one of the more consistent findings in schizophrenia but the underlying mechanism remains obscure. Many cerebral white matter components are sensitive to neuroinflammatory conditi...

Background: The hypothalamus plays a crucial role in regulating sleep-wake cycle and motivated behavior. Sleep disturbance is associated with impairment in cognitive and affective functions. However, how hypothalamic dysfunction may contribute to inter-related sleep, cognitive, and emotional deficits remain unclear. Methods: We curated the Human...

Background Numerous studies characterized how resting-state functional connectivities (rsFCs) of the amygdala were disrupted in emotional disorders and varied with emotional traits, including anxiety. With trait anxiety known to diminish with age, a critical issue concerns disambiguating the effects of age and anxiety on amygdala rsFCs in studying...

Emerging evidence suggests distinct neurobiological correlates of alcohol use disorder (AUD) between sexes, which however remain largely unexplored. This work from ENIGMA Addiction Working Group aimed to characterize the sex differences in gray matter (GM) and white matter (WM) correlates of AUD using a whole-brain, voxel-based, multi-tissue mega-a...

Objective Accumulating evidence suggested that immune system activation might be involved in the pathophysiology of schizophrenia. The neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), platelet/lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) can measure inflammation. This study aimed to investigate the inflamma...

Previous research reported an age‐related decline in brain norepinephrine transporter (NET) using (S, S)‐[11C]O‐methylreboxetine ([11C]MRB) as a radiotracer. Studies with the same tracer have been mixed in regard to differences related to body mass index (BMI). Here, we investigated potential age‐, BMI‐, and gender‐related differences in brain NET...

Trait anxiety diminishes with age, which may result from age-related decline in registering salient emotional stimuli and/or enhancement in emotion regulation. We tested the hypotheses in 88 adults 21 to 85 years of age and studied with fMRI of the Hariri task. Age-related decline in stimulus registration would manifest in delayed reaction time (RT...

Background Personality traits contribute to the risks of smoking. The striatum has been implicated in nicotine addiction and nicotine deprivation is associated with alterations in resting state functional connectivity (rsFC) of the ventral (VS) and dorsal (DS) striatum. However, it remains unclear how striatal rsFC may change following overnight ab...

Current knowledge about functional connectivity in obsessive-compulsive disorder (OCD) is based on small-scale studies, limiting the generalizability of results. Moreover, the majority of studies have focused only on predefined regions or functional networks rather than connectivity throughout the entire brain. Here, we investigated differences in...

Aging is associated with reduction in the severity of alcohol misuse. However, the psychological and neural mechanisms underlying the age-related changes remain unclear. Here, we tested the hypothesis that age-related diminution of positive alcohol expectancy (AE) mediated the effects of age on problem drinking and investigated the neural correlate...

Treatment-resistant schizophrenia (TRS) patient respond poorly to antipsychotics. Inflammatory imbalance involving pro- and anti-inflammatory cytokines may play an important role in the mechanism of antipsychotic-medication response. This study aimed to investigate immune imbalance and how the latter relates to clinical manifestations in patients w...

Craving reflects the subjective urge to use drugs and can be triggered by both positive and negative emotional states. No studies have systematically investigated the relative roles of these mechanisms in the pathophysiology of substance misuse. Here, we performed meta-analyses of drug cue-elicited reactivity and win and loss processing in the mone...

Ventral striatum (VS) processes rewarding and punishing stimuli. Women and men vary in externalizing and internalizing traits, which may influence neural responses to reward and punishment. To investigate sex differences in how individual traits influence VS responses to reward and punishment, we curated the data of the Human Connectome Project and...

Background Alcohol dependence (AD) is a disorder with a high recurrence rate that leads to a considerable public health burden. The risk of relapse appears to be related to a complex interplay of multiple factors. Herein, we aimed to explore the potential neural predictors of relapse in Chinese male patients with AD. Methods This study enrolled 58...

The purpose of this study was to explore perceptions of the first dose of a cognitive behavioral sleep self-management intervention (CB-sleep) among young adults aged 18 to 25 years with type 1 diabetes (T1D). We used a qualitative descriptive approach to conduct in-depth semi-structured focused interviews with a purposive sample of 16 young adults...

Abstract Attention deficit hyperactivity disorder (ADHD) is associated with reduction of cortical and subcortical gray matter volumes (GMVs). The kinectin 1 gene (KTN1) has recently been reported to significantly regulate GMVs and ADHD risk. In this study, we aimed to identify sex-specific, replicable risk KTN1 alleles for ADHD and to explore their...

Depression and alcohol misuse, frequently comorbid, are associated with altered reward processing. However, no study has examined whether and how the neural markers of reward processing are shared between depression and alcohol misuse. We studied 43 otherwise-healthy drinking adults in a monetary incentive delay task (MIDT) during fMRI. All partici...

Background: Studies have shown sensory gating deficits and severe childhood trauma in patients with schizophrenia; however, their relationship with this condition remains unclear. Here, we hypothesized that sensory gating deficits mediate the effects of childhood trauma on schizophrenia onset. Methods: We recruited 79 patients with first-episode...

Ventral striatum (VS) processes rewarding and punishing stimuli. Women and men vary in externalizing and internalizing traits, which may influence neural responses to reward and punishment. To investigate sex differences in how individual traits influence VS responses to reward and punishment, we curated the data of the Human Connectome Project and...

The neurobiological bases of the association between development and psychopathology remain poorly understood. Here, we identify a shared spatial pattern of cortical thickness (CT) in normative development and several psychiatric and neurological disorders. Principal component analysis (PCA) was applied to CT of 68 regions in the Desikan-Killiany a...

Accumulating evidence suggests that hypothalamic-pituitary-adrenal axis dysfunction might play an important role in the pathophysiology of schizophrenia. The aim of this study was to explore the cortisol response to psychological stress in patients with schizophrenia. In this study, patients with schizophrenia (n = 104) and healthy volunteers (n =...

Reward and punishment motivate decision making and behavioral changes. Numerous studies have examined regional activities during anticipation and outcome of win and loss in the monetary incentive delay task (MIDT). However, the great majority of studies reported findings of anticipation or outcome and of win or loss alone. It remains unclear how th...

Background: Earlier studies have described the neural markers of apathy in Alzheimer's disease (AD) and mild cognitive impairment (MCI), but few focused on the motivation circuits. Here, we targeted hypothalamus, a hub of the motivation circuit. Objective: To examine hypothalamic resting state functional connectivity (rsFC) in relation to apathy...

Objective Our study aimed to investigate the associations between the serum level of kynurenine pathway (KP) metabolites and P50 auditory gating in non-smoking patients with first-episode schizophrenia (FES). Materials and methods In this study, 82 non-smoking patients with FES and 73 healthy controls (HC). P50 auditory gating was measured using a...

Studies have associated chemotherapy-elicited changes in cognitive function with impaired white matter integrity in cancer patients. Androgen deprivation therapy (ADT) may lead to cognitive deficits in prostate cancer patients; however, whether ADT influences white matter integrity has never been investigated. In a prospective study, 15 men with no...

Background Childhood trauma influences the clinical features of schizophrenia. In this study, we examined how childhood trauma and perceived stress are associated with clinical manifestations and subcortical gray matter volumes (GMVs) in patients with schizophrenia. Methods We recruited 127 patients with schizophrenia and 83 healthy controls for a...

Background: Previous studies have characterized the impact of substance use on cerebral structure and function in adolescents. Yet, the great majority of prior studies employed a small sample, presented cross-sectional findings, and omitted potential sex differences. Methods: Using data based on 724 adolescents (370 females) curated from the NCA...

Objective Previous studies have implicated intricate interactions between innate immunity and the brain in schizophrenia. Monocytic Toll-like receptor (TLR) 4 signaling, a crucial “sensor” of innate immunity, was reported to be over-activated in link with cognitive impairment in schizophrenia. As TLR4 is predominantly expressed on gliocytes prior t...