Papers by Christine Cloak
Magnetic Resonance in Medicine, Dec 2, 2023
NeuroImage, Nov 1, 2009
Methamphetamine (METH) is a neurotoxic drug. This study aimed to evaluate brain metabolite levels... more Methamphetamine (METH) is a neurotoxic drug. This study aimed to evaluate brain metabolite levels and cognitive function in young children with prenatal METH-exposure. 101 children ages 3-4 years were evaluated with neuropsychological tests and underwent proton magnetic resonance spectroscopy (1 H-MRS) without sedation. Complete datasets from 49 METH-exposed and 49 controls who completed the neuropsychological test battery, and 38 METH-exposed and 37 controls with high-quality MR spectra are reported here. Despite similar physical characteristics (including head circumference), global cognitive function (on Stanford-Binet), parental education, intelligence, mood, and socioeconomic status, METH-exposed children had higher total creatine (tCr: +7%, p=0.003), N-acetyl compounds (NA: +4.3%, p=0.004) and glutamate+glutamine (GLX: +9.6%, p=0.02) concentrations in the frontal white matter, but lower myoinositol (MI:-7%, p=0.01) and MI/tCr (-7.5%, p=0.03) in the thalamus, than control children. The higher frontal white matter NA in the METH exposed children were due to the higher NA in the METH-exposed girls (+10.2%, p=0.0027), but not the boys (+0.8%) compared to sex-matched controls. Furthermore, the METH-exposed children had poorer performance on a visual motor integration (VMI) task, which correlated with lower MI in the thalamus (r=0.26, p=0.03). The higher NA, tCr and GLX concentrations suggest higher neuronal density or cellular compactness in the white matter, especially in the girls, whereas the lower MI suggests lower glial content in the thalamus of these METH-expose children. These findings combined with their poorer performance on VMI also suggest accelerated but aberrant neuronal and glial development in these brain regions.
Objectives: To evaluate whether prenatal tobacco exposure (PTE) is related to poorer cognitive pe... more Objectives: To evaluate whether prenatal tobacco exposure (PTE) is related to poorer cognitive performance, abnormal brain morphometry, and whether poor cognitive performance is mediated by PTE-related structural brain differences. Methods: The Adolescent Brain Cognitive Development study dataset was used to compare structural MRI data and neurocognitive (NIH Toolbox ®) scores in 9-to-10-yearold children with (n=620) and without PTE (n=10,989). We also evaluated whether PTE effects on brain morphometry mediated PTE effects on neurocognitive scores. Group effects were evaluated using Linear Mixed Models, covaried for socio-demographics and prenatal exposures to alcohol and/or marijuana, and corrected for multiple comparisons using the false-discovery rate (FDR). Results: Compared to unexposed children, those with PTE had poorer performance (all p-values <0.05) on executive function, working memory, episodic memory, reading decoding, crystallized intelligence, fluid intelligence
Journal of Neuroimmune Pharmacology, Oct 12, 2010
Opiate abuse increases the risk for human immunodeficiency virus (HIV) infection, while both opia... more Opiate abuse increases the risk for human immunodeficiency virus (HIV) infection, while both opiates and HIV may impact the immune and nervous systems. To model potential interactions between opiate drugs and HIV on the brain, neurometabolite levels were evaluated in simian immunodeficiency virus (SIV)-infected macaques with or without chronic morphine administration. Over the course of the study, 58% of these SIV-infected animals progressed to acquired immune deficiency syndrome (AIDS). Brain extracts from four brain regions were evaluated with proton magnetic resonance spectroscopy. Animals with AIDS had lower N-acetylaspartate in all four brain regions (p≤0.05) as well as lower frontal gray matter total creatine (p=0.03), lower frontal white matter (p= 0.003) and caudate (p=0.002) glutamate, and higher frontal white matter myo-inositol (p=0.05) than the healthier non-AIDS macaques. Morphinedependent animals had higher levels of myo-inositol in the putamen (p=0.003), especially those with AIDS. In the animals with AIDS, those with morphine dependence had higher total creatine in the frontal white matter (p=0.04) than those treated with saline, which in turn had lower creatine than saline-injected animals without AIDS (p=0.04), leading to an interaction between the effects of morphine and AIDS on total creatine in this brain region (ANOVA p=0.02). The majority of these brain metabolites correlated with viral counts indicating more severe metabolite abnormalities in animals with higher viral loads or set points. Collectively, these findings suggest
JAMA Psychiatry, Dec 1, 2016
IMPORTANCE-Methamphetamine is a common illicit drug used worldwide. Methamphetamine and/or tobacc... more IMPORTANCE-Methamphetamine is a common illicit drug used worldwide. Methamphetamine and/or tobacco use by pregnant women remains prevalent. However, little is known about the effect of comorbid methamphetamine and tobacco use on human fetal brain development. OBJECTIVE-To investigate whether microstructural brain abnormalities reported in children with prenatal methamphetamine and/or tobacco exposure are present at birth before childhood environmental influences. DESIGN, SETTING, AND PARTICIPANTS-A prospective, longitudinal study was conducted between September 17, 2008, and February 28, 2015, at an ambulatory academic medical center. A total of 752 infant-mother dyads were screened and 139 of 195 qualified neonates were evaluated (36 methamphetamine/tobacco exposed, 32 tobacco exposed, and 71 unexposed controls). They were recruited consecutively from the community. EXPOSURES-Prenatal methamphetamine and/or tobacco exposure. MAIN OUTCOMES AND MEASURES-Quantitative neurologic examination and diffusion tensor imaging performed 1 to 3 times through age 4 months; diffusivities and fractional anisotropy (FA) assessed in 7 white matter tracts and 4 subcortical brain regions using an automated atlas-based method. RESULTS-Of the 139 infants evaluated, 72 were female (51.8%); the mean (SE) postmenstrual age at baseline was 41.5 (0.27) weeks. Methamphetamine/tobacco-exposed infants showed delayed developmental trajectories on active muscle tone (group × age, P < .001) and total neurologic scores (group × age, P = .01) that normalized by ages 3 to 4 months. Only methamphetamine/tobacco-exposed boys had lower FA (group × age, P = .02) and higher Chang et al.
Prenatal tobacco exposure (PTE) can affect the offspring cognitive and brain development outcomes... more Prenatal tobacco exposure (PTE) can affect the offspring cognitive and brain development outcomes. Our study evaluated children who had PTE in the Adolescent Brain and Cognitive Development (ABCD) study and found poorer overall cognitive scores, especially working memory scores, lower cortical surface areas and subcortical volumes, with smaller surface areas in the posterior cingulate (PCC) and entorhinal cortices, the lingual and inferior parietal gyri, and abnormally smaller volumes in the thalamus and nucleus accumbens. Furthermore, we found that only PTE-girls had significantly smaller surface areas in the postcentral gyrus, while only PTE-boys had smaller volumes in the posterior corpus callosum.
Few studies identified brain morphometric changes associated with peer-victimization (“being bull... more Few studies identified brain morphometric changes associated with peer-victimization (“being bullied”), and no study examined how these changes can mediate the relationship between bullying and cognition. Using T1-weighted MRI scans and cognitive test scores from the Adolescent Brain Cognitive Development longitudinal dataset, we found that bullying is associated with reduced cognitive performance over time. Bullied children had smaller putamen volumes and right insula surface areas, thinner left precentral and banks of superior temporal sulcus cortices, but larger left entorhinal and right pars orbitalis surface areas. Importantly, these altered brain measures partially mediated the relationship between bullying and cognitive scores.
PubMed, 2003
Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous sy... more Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system and is integral to managing brain excitability. GABA concentrations vary according to age, gender, and brain region. Magnetic resonance spectroscopy (MRS), with editing or with localized 2-dimensional chemical shift methods, can measure GABA levels in vivo, ex vivo, or in vitro, particularly at ultra-high magnetic field strengths. Proton ((1)H) MRS studies have found reduced or abnormal GABA concentrations in several neuropsychiatric disorders, including epilepsy, anxiety disorders, major depression, and drug addiction. Disorders with low GABA levels may be treated by augmentation of GABAergic function, such as by medications that block the degradation or reuptake of GABA. Examples of such a rational therapeutic approach include anticonvulsants that elevate brain GABA levels and are effective for the treatment of epilepsy and anxiety disorder.
Brain Imaging and Behavior, Sep 29, 2013
Human brain development has been studied intensively with neuroimaging. However, little is known ... more Human brain development has been studied intensively with neuroimaging. However, little is known about how genes influence developmental brain trajectories, even though a significant number of genes (about 10,000, or approximately one-third) in the human genome are expressed primarily in the brain and during brain development. Interestingly, in addition to showing differential expression among tissues, many genes are differentially expressed across the ages (e.g., antagonistic pleiotropy). Age-specific gene expression plays an important role in several critical events in brain development, including neuronal cell migration, synaptogenesis and neurotransmitter receptor specificity, as well as in aging and neurodegenerative disorders (e.g., Alzheimer disease or amyotrophic lateral sclerosis). In addition, the majority of psychiatric and mental disorders are polygenic, and many have onsets during childhood and adolescence. In this review, we summarize the major findings from neuroimaging studies that link genetics with brain development, from infancy to young adulthood. Specifically, we focus on the heritability of brain structures across the ages, age-related genetic influences on brain development and sex-specific developmental trajectories.
Psychiatry Research: Neuroimaging, Oct 1, 2009
Methamphetamine (METH) users showed structural and chemical abnormalities on magnetic resonance (... more Methamphetamine (METH) users showed structural and chemical abnormalities on magnetic resonance (MRI) studies, particularly in the frontal and basal ganglia brain regions. Diffusion tensor imaging (DTI) may provide further insights regarding the microstructural changes in METH users. We investigated diffusion tensor measures in frontal white matter and basal ganglia of 30 adult METH users and 30 control subjects using a 3 T MR scanner. Compared with healthy control subjects, METH users showed lower fractional anisotropy (FA) in right frontal white matter, and higher apparent diffusion coefficient (ADC) in left caudate and bilateral putamen. Higher left putamen ADC was associated with earlier initiation of METH use, greater daily amounts, and a higher cumulative lifetime dose. Similarly, higher right putamen ADC was associated with greater daily amounts and a higher cumulative lifetime dose. The lower FA in the right frontal white matter suggests axonal injury in these METH users. The higher ADC in the basal ganglia suggests greater inflammation or less myelination in these brain regions of those with younger age of first METH use and greater METH usage.
Journal of Traumatic Stress, Feb 8, 2022
The current cross‐sectional study aimed to extend the literature on childhood adversity by examin... more The current cross‐sectional study aimed to extend the literature on childhood adversity by examining the unique associations between potentially traumatic events (PTEs) and a range of mental health concerns, including domain‐specific versus comorbid concerns. Participants were 11,877 preadolescents (47.8% female, 15.0% Black, 20.3% Hispanic/Latinx, Mage = 9.5 years) taking part in the Adolescent Brain and Cognitive Development (ABCD) Study®. The Kiddie Schedule for Affective Disorders and Schizophrenia was used to measure PTEs and caregiver‐ and child‐reported mental health concerns. Adjusted odds ratios (aORs) were used for the outcomes of interest. Overall, PTEs were consistently associated with increased odds of experiencing comorbid posttraumatic stress disorder (PTSD), internalizing disorders, and externalizing disorders, significant AORs = 1.34–4.30, after accounting for children's experiences of other PTEs and polyvictimization. In contrast, PTEs were generally not associated with meeting the criteria for diagnoses within only one domain (i.e., internalizing‐only or externalizing‐only diagnoses). We also found PTEs to be differentially related to the various mental health outcomes. In particular, witnessing domestic violence was consistently associated with children's psychopathology. Other PTEs, such as witnessing community violence, were not associated with children's psychopathology in the final model. Associations between PTEs and mental health concerns did not differ as a function of sex. Overall, the results support the notion that PTEs are associated with comorbid concerns rather than individual disorders. These findings have important implications for the screening of PTEs, continued research on the conceptualization of traumatic stress, and the importance of accounting for comorbidities across mental health domains.
Pediatric Research, Apr 1, 1999
Journal of Neuroimmune Pharmacology, Sep 13, 2011
Many pregnant women smoke cigarettes during pregnancy, but the effect of nicotine on the developi... more Many pregnant women smoke cigarettes during pregnancy, but the effect of nicotine on the developing human brain is not well understood, especially in young children. This study aims to determine the effects of prenatal nicotine exposure (PNE) on brain metabolite levels in young (3-4 years old) children, using proton magnetic resonance spectroscopy (1 H MRS). Twenty-six children with PNE and 24 nicotine-unexposed children (controls) were evaluated with a structured examination, a battery of neuropsychological tests, and MRI/ 1 H MRS (without sedation). Concentrations of N-acetyl compounds (NA), total creatine (tCR), choline-containing compounds (CHO), myo-inositol (MI), and glutamate+glutamine (GLX) were measured in four brain regions.
JAMA otolaryngology-- head & neck surgery, May 1, 2021
ImportancePrevious studies have identified an association between habitual snoring and lower cogn... more ImportancePrevious studies have identified an association between habitual snoring and lower cognitive performance in children. However, whether and to what extent this association is confounded by pertinent demographic, anthropometric, and socioeconomic characteristics is unknown.ObjectiveTo assess the extent to which potential confounding factors modify the association between parent-reported habitual snoring and cognitive outcomes among a large and diverse sample of typically developing preadolescent children.Design, Setting, and ParticipantsThis cross-sectional analysis used a baseline data set (version 2.0.1) from children enrolled in the ongoing Adolescent Brain Cognitive Development study between September 1, 2016, and October 15, 2018. Children aged 9 to 10 years without serious psychiatric or neurological comorbidities were recruited at 21 research sites in the US. Study recruitment was designed to approximate the racial and socioeconomic diversity of the US population. Data were analyzed from February 1 to March 31, 2020.ExposuresParent-reported habitual snoring in children that occurs 3 or more nights per week.Main Outcomes and MeasuresAssociations between habitual snoring and cognitive performance were assessed using the Sleep Disturbance Scale for Children and the National Institutes of Health Toolbox Cognition Battery, which includes 7 domain-specific and 3 composite (total cognitive function, fluid cognition, and crystallized cognition) standard scores that are uncorrected for covariates. Cognitive performance was examined before and after adjustment for covariates, which included age, sex, body mass index percentile, annual household income before taxes, and highest educational level of caregiver. The extent of confounding was assessed by the effect size, represented by Cohen d, before and after inclusion of covariates using linear mixed-effects models.ResultsA total of 11 873 children aged 9 to 10 years (6187 boys [52.1%]; 6174 White [52.0%]) with available data were included in the study. Of those, habitual snoring (≥3 nights per week) was reported in 810 children (6.8%), and nonhabitual snoring (1-2 nights per week) was reported in 4058 children (34.2%). In the unadjusted models, the total cognitive function composite score among children who habitually snored was significantly lower compared with children who never snored (Cohen d, 0.35; 95% CI, 0.28-0.42). Differences were also identified in the crystallized cognition (Cohen d, 0.34; 95% CI, 0.26-0.41) and fluid cognition (Cohen d, 0.28; 95% CI, 0.21-0.35) composite scores. The association between habitual snoring and cognitive performance was substantially attenuated after adjustment for covariates (Cohen d, 0.16 [95% CI, 0.09 to 0.24] for total cognitive function, 0.14 [95% CI, 0.07 to 0.21] for crystallized cognition, and 0.13 [95% CI, 0.06 to 0.21] for fluid cognition). Similar mitigation was also observed for all domain-specific scores.ConclusionsIn this cross-sectional study, when adjusted for baseline demographic, anthropometric, and socioeconomic characteristics, the association between parent-reported habitual snoring and cognitive performance was substantially attenuated among children aged 9 to 10 years.
American Journal on Addictions, 2008
This study examined the differences in psychiatric symptoms between adult methamphetamine users (... more This study examined the differences in psychiatric symptoms between adult methamphetamine users (n = 46) and control subjects (n = 31), the relationship between psychiatric symptoms and the intensity of methamphetamine craving, and whether psychiatric symptoms were correlated to methamphetamine drug-usage variables (ie, length of abstinence, frequency, duration, and lifetime grams). We found that depressive symptoms on the Center for Epidemiology Studies-Depression (CES-D) and many other psychiatric symptoms on the Symptom Checklist-90 (SCL-90) significantly correlated with craving methamphetamine on the visual analog scale (VAS) for craving. Methamphetamine users had significantly more depressive symptoms (on CES-D) and psychotic symptoms (on SCL-90) compared to controls. There were no significant correlations between psychiatric symptoms and methamphetamine-usage variables. This study provides the first evidence to suggest that depressive symptoms (on CES-D) and psychiatric symptoms (on SCL-90) are strongly associated with the intensity of craving (on VAS) for the drug in methamphetamine users. However, the methamphetamine usage variables had no relationship with psychiatric symptoms. Therefore, methamphetamine users, regardless of their usage patterns, may benefit from treatment of their psychiatric symptoms in order to minimize craving and subsequent relapse to drug use.
Oxford University Press eBooks, Jul 1, 2013
Even though anomalies on brain metabolites have been found in schizophrenia, researches about sub... more Even though anomalies on brain metabolites have been found in schizophrenia, researches about subjects with high risk (HR) show heterogeneous results. Thus, this meta-analysis aims to characterize the metabolic profile of HR subjects, first, compared to controls (HC) and then compared to people with schizophrenia. Methods: After a systematic database search, means and standard deviations were extracted to calculate standardized mean differences (SMD). Cerebral metabolites levels were compared between HR subjects and HC or patients with schizophrenia in all regions of interest investigated in included studies. Meta-regressions were performed to explore the influence of demographic and clinical variables on metabolites level's SMDs. Results: Thirty-nine studies were included in this meta-analysis. A higher level of glutamine + glutamate (Glx) was found in the medial prefrontal cortex (mPFC) (p < 0.01) and potentially in the basal ganglia (p = 0,05) as well as a higher level of myo-inositol (mI) in the dorsolateral prefrontal cortex (DLPFC) (p = 0.04) in HR subjects compared to HC. A higher level of choline (Cho) was found in people with schizophrenia compared to HR subjects in the DLPFC (p < 0.001) and the medial temporal lobe (p = 0.02). Meta-regression analyses showed negative associations between SMD for Cho concentration, the percentage of females or the age (p = 0.01). Conclusions: The present meta-analysis provides evidence that some brain metabolites concentrations are disrupted before the transition to psychosis and could be considered like a vulnerability.
Drug and Alcohol Dependence, Dec 1, 2011
Background-Methamphetamine can be neurotoxic to the adult brain; however, many individuals first ... more Background-Methamphetamine can be neurotoxic to the adult brain; however, many individuals first use methamphetamine during adolescence, and the drug's impact on this period of brain development is unknown. Therefore, we evaluated young methamphetamine users for possible abnormalities in brain metabolite concentrations. Methods-Anterior cingulate cortex (ACC), frontal white matter (FWM), basal ganglia, and thalamus were studied with localized proton magnetic resonance spectroscopy in 54 periadolescent (ages 13-23 years) methamphetamine users and 53 comparison subjects. The concentrations of major brain metabolites and their associations with age, sex and cognition were assessed. Results-FWM total-creatine correlated with age in methamphetamine-using males and comparison females, but not comparison males or methamphetamine-using females, leading to a drug by sex by age interaction (p=0.003) and ACC choline-containing compounds (CHO) correlated with age only in comparison males leading to a drug by sex by age interaction (p=0.03). Higher ACC CHO was associated with faster performance on the Stroop Interference task in the control males. Male methamphetamine users had slowest performance on the Stroop Interference task and did not show showed age-appropriate levels of ACC CHO. Conclusions-The altered age-appropriate levels of ACC CHO and poorer executive function in male methamphetamine users suggest methamphetamine abuse may interfere with brain maturation. These periadolescents did not have the abnormal neuronal markers previously reported in adult methamphetamine users, suggesting that neuronal abnormalities may be the result of longterm use or interference in normal cortical maturation, emphasizing the need for early intervention for young methamphetamine users.
Developmental Cognitive Neuroscience, Jun 1, 2023
Drug and Alcohol Dependence, 2015
Drug and Alcohol Dependence, 2015
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Papers by Christine Cloak