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Article ; Online: Recreational Marijuana Use, Adolescent Cognitive Development, and Schizophrenia Susceptibility.

Ho, Beng-Choon / Barry, Amy B / Koeppel, Julie A / Macleod, John / Boyd, Andy / David, Anthony / O'Leary, Daniel S

Biological psychiatry global open science

2022 Volume 3, Issue 2, Page(s) 222–232

Abstract: Background: We investigated how low marijuana (MJ) use levels, the typical use pattern in most adolescent users, affect cognitive maturation and schizophrenia risk.: Methods: In two complementary adolescent samples where the majority reported minimal ...

Abstract	Background: We investigated how low marijuana (MJ) use levels, the typical use pattern in most adolescent users, affect cognitive maturation and schizophrenia risk. Methods: In two complementary adolescent samples where the majority reported minimal MJ use, we compared cognitive performances before and after MJ use initiation. The Iowa sample (40 first-degree relatives and 54 second-degree relatives of patients with schizophrenia and 117 control subjects with no schizophrenia family history) underwent a battery of standardized neuropsychological tests at 0, 18, and 36 months. Based on self-administered Timeline Followback interviews, 26.5% of adolescents had emergent MJ use (eMJ) during follow-up. The second sample ( Results: In the Iowa sample, longitudinal changes in 5 of 8 cognitive domains were significantly associated with eMJ. On sustained attention, visuospatial working memory, and executive sequencing, adolescents with eMJ showed less age-expected improved performance. In addition, first-degree relatives with eMJ were less improved on processing speed and executive reasoning than first-degree relatives without eMJ. In the birth cohort, greater intraindividual variability in reaction times (indicative of poorer sustained attention) was significantly associated with more frequent MJ use and with recreational use levels. Conclusions: Nonheavy MJ use disrupts normal adolescent maturation and compounds aberrant adolescent maturation associated with familial schizophrenia risk. These findings underscore the importance of reducing adolescent MJ access in the context of increased availability to high-potency MJ.
Language	English
Publishing date	2022-02-08
Publishing country	United States
Document type	Journal Article
ISSN	2667-1743
ISSN (online)	2667-1743
DOI	10.1016/j.bpsgos.2022.01.008
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Article ; Online: Impact of binge drinking during college on resting state functional connectivity.

Tong, Tien T / Vaidya, Jatin G / Kramer, John R / Kuperman, Samuel / Langbehn, Douglas R / O'Leary, Daniel S

Drug and alcohol dependence

2021 Volume 227, Page(s) 108935

Abstract: Aim: The current study examined the longitudinal effects of standard binge drinking (4+/5+ drinks for females/males in 2 hours) and extreme binge drinking (8+/10+ drinks for females/males in 2 hours) on resting-state functional connectivity.: Method: ...

Abstract	Aim: The current study examined the longitudinal effects of standard binge drinking (4+/5+ drinks for females/males in 2 hours) and extreme binge drinking (8+/10+ drinks for females/males in 2 hours) on resting-state functional connectivity. Method: 119 college students (61 males) were recruited in groups of distinct bingeing patterns at baseline: non-bingeing controls, standard and extreme bingers. Resting-state scans were first obtained when participants were freshmen/sophomores and again approximately two years later. Associations between longitudinal bingeing (reported during this two-year gap) and network connectivity were examined. Network connectivity was calculated by aggregating all edges affiliated with the same network (an edge is a functional connection between two brain regions). The relationship between longitudinal bingeing and connectivity edges was also studied using connectome-based predictive modeling (CPM). Results: Greater standard bingeing was negatively associated with change in connectivity between Default Mode Network and Ventral Attention Network (DMN-VAN; False Discovery Rate corrected), controlling for initial binge groups, longitudinal network changes, motions, scanner, SES, sex, and age. The correlations between change in DMN-VAN connectivity and change in cognitive performance (Stroop, Digit Span, Letter Fluency, and Trail Making) were also tested, but the results were not significant. Lastly, CPM failed to identify a generalizable predictive model of longitudinal bingeing from change in connectivity edges. Conclusions: Binge drinking is associated with abnormality in networks implicated in attention and self-focused processes, which, in turn, have been implicated in rumination, craving, and relapse. More extensive alterations in functional connectivity might be observed with heavier or longer binge drinking pattern.
MeSH term(s)	Binge Drinking/diagnostic imaging ; Brain/diagnostic imaging ; Connectome ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Nerve Net ; Universities
Language	English
Publishing date	2021-07-31
Publishing country	Ireland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	519918-9
ISSN	1879-0046 ; 0376-8716
ISSN (online)	1879-0046
ISSN	0376-8716
DOI	10.1016/j.drugalcdep.2021.108935
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Article ; Online: Behavioral inhibition and reward processing in college binge drinkers with and without marijuana use.

Tong, Tien T / Vaidya, Jatin G / Kramer, John R / Kuperman, Samuel / Langbehn, Douglas R / O'Leary, Daniel S

Drug and alcohol dependence

2020 Volume 213, Page(s) 108119

Abstract: Aim: Binge drinking is common during college, and studies have shown that many college students drink in quantities that far exceed the standard binge drinking threshold. Previous research has noted personality differences in individuals who engage in ... ...

Abstract	Aim: Binge drinking is common during college, and studies have shown that many college students drink in quantities that far exceed the standard binge drinking threshold. Previous research has noted personality differences in individuals who engage in binge drinking, but few studies have examined neurobiological differences in both standard bingers (4/5 drinks in two hours for females/males; sBinge) and extreme binge drinkers (8+/10+ drinks in two hours for females/males; eBinge). Method: The current study of 221 college students used functional magnetic resonance imaging (fMRI) to study neural activation on a stop signal task (SST) to assess behavioral inhibition and a monetary incentive delay (MID) task to assess activation to rewards and losses. Non-bingeing controls, sBinge, and eBinge freshmen and sophomores were recruited. In addition, because binge/extreme binge drinking is often associated with marijuana (MJ) use, MJ + sBinge and MJ + eBinge groups were also included. Results: All five groups showed strong activation in expected key cortical and striatal regions on both the SST and the MID. However, there were no significant differences between groups either at the whole-brain level or in specific regions of interest. Behavioral performance on the fMRI tasks also did not differ between groups. Conclusions: These results suggest that our sample of individuals who engage in binge or extreme binge drinking with or without MJ co-use do not differ in brain activity on reward and inhibitory tasks. Neural differences may be present on other cognitive tasks or may emerge later after more sustained use of alcohol, MJ, and other drugs.
Language	English
Publishing date	2020-06-12
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	519918-9
ISSN	1879-0046 ; 0376-8716
ISSN (online)	1879-0046
ISSN	0376-8716
DOI	10.1016/j.drugalcdep.2020.108119
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Article ; Online: Association Between Age and Familial Risk for Alcoholism on Functional Connectivity in Adolescence.

Vaidya, Jatin G / Elmore, Alexis L / Wallace, Alexander L / Langbehn, Douglas R / Kramer, John R / Kuperman, Samuel / O'Leary, Daniel S

Journal of the American Academy of Child and Adolescent Psychiatry

2019 Volume 58, Issue 7, Page(s) 692–701

Abstract: Objective: Youth with a family history of alcohol use disorder (family history positive [FHP]) are at increased risk for developing maladaptive substance use relative to family history negative (FHN) peers. Building on earlier studies demonstrating ... ...

Abstract	Objective: Youth with a family history of alcohol use disorder (family history positive [FHP]) are at increased risk for developing maladaptive substance use relative to family history negative (FHN) peers. Building on earlier studies demonstrating morphological differences and distinct patterns of neural activation in FHP, the purpose of the present study was to investigate differential intrinsic functional connectivity among brain networks indexing premorbid risk of developing alcohol use disorder (AUD). Method: The current study examined intrinsic functional connectivity using resting state functional magnetic resonance imaging in 191 adolescents 13 to 18 years of age with and without family history of AUD via independent component analysis, a method enabling data-driven investigation of internetwork and intranetwork connectivity among brain regions at rest. Results: Analyses revealed significantly lower intranetwork connectivity in FHP compared to FHN participants between the dorsal premotor cortex and other sensorimotor network regions. Reduced intranetwork connectivity in this region was further correlated with the number of biological family members with AUD and mood disorders. Robust differences were also evident in internetwork connectivity as a function of age. However, there was no evidence for family history by age interactions. Conclusion: Intra- but not internetwork connectivity appears to differentiate FHP and FHN adolescents, whereas age differences within adolescence are marked by differences in internetwork connectivity.
MeSH term(s)	Adolescent ; Age Factors ; Alcoholism/complications ; Alcoholism/physiopathology ; Alcoholism/psychology ; Brain Mapping ; Depression/complications ; Depression/physiopathology ; Depression/psychology ; Executive Function ; Family Health ; Female ; Humans ; Inhibition, Psychological ; Magnetic Resonance Imaging ; Male ; Memory, Short-Term ; Neural Pathways/physiopathology ; Reward ; Risk Factors
Language	English
Publishing date	2019-02-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	392535-3
ISSN	1527-5418 ; 0890-8567
ISSN (online)	1527-5418
ISSN	0890-8567
DOI	10.1016/j.jaac.2018.12.008
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Article ; Online: Personality traits and negative consequences associated with binge drinking and marijuana use in college students.

O'Leary, Daniel S / Langbehn, Douglas R / Kramer, John R / Kuperman, Samuel / Fuhrmeister, Lindsey A / Vaidya, Jatin G

The American journal of drug and alcohol abuse

2019 Volume 45, Issue 4, Page(s) 400–409

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Adolescent ; Alcohol Drinking in College/psychology ; Binge Drinking/psychology ; Case-Control Studies ; Female ; Humans ; Impulsive Behavior ; Iowa ; Male ; Marijuana Use/psychology ; Personality ; Personality Assessment ; Psychiatric Status Rating Scales ; Risk-Taking ; Students/psychology ; Universities ; Young Adult
Language	English
Publishing date	2019-05-01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	193086-2
ISSN	1097-9891 ; 0095-2990
ISSN (online)	1097-9891
ISSN	0095-2990
DOI	10.1080/00952990.2019.1601200
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Article ; Online: Determination of ∆-9-Tetrahydrocannabinol (THC), 11-hydroxy-THC, 11-nor-9-carboxy-THC and Cannabidiol in Human Plasma using Gas Chromatography-Tandem Mass Spectrometry.

Andrenyak, David M / Moody, David E / Slawson, Matthew H / O'Leary, Daniel S / Haney, Margaret

Journal of analytical toxicology

2017 Volume 41, Issue 4, Page(s) 277–288

Abstract: Two marijuana compounds of particular medical interest are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). A gas chromatography-tandem mass spectrometry (GC-MS-MS) method was developed to test for CBD, THC, hydroxy-THC (OH-THC) and carboxy-THC ( ...

Abstract	Two marijuana compounds of particular medical interest are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). A gas chromatography-tandem mass spectrometry (GC-MS-MS) method was developed to test for CBD, THC, hydroxy-THC (OH-THC) and carboxy-THC (COOH-THC) in human plasma. Calibrators (THC and OH-THC, 0.1 to 100; CBD, 0.25 to 100; COOH-THC, 0.5-500 ng/mL) and controls (0.3, 5 and 80 ng/mL, except COOH-THC at 1.5, 25 and 400 ng/mL) were prepared in blank matrix. Deuterated (d3) internal standards were added to 1-mL samples. Preparation involved acetonitrile precipitation, liquid-liquid extraction (hexane:ethyl acetate, 9:1), and MSTFA derivatization. An Agilent 7890 A GC was interfaced with an Agilent 7000 MS Triple Quadrupole. Selected reaction monitoring was employed. Blood samples were provided from a marijuana smoking study (two participants) and a CBD ingestion study (eight participants). Three analytes with the same transitions (THC, OH-THC and COOH-THC) were chromatographically separated. Matrix selectivity studies showed endogenous chromatographic peak area ratios (PAR) at the analyte retention times were <20% of the analyte limit of quantitation PAR. The intra-assay accuracy ranged from 83.5% to 118% of target and the intra-run imprecision ranged from 2.0% to 19.1%. The inter-assay accuracy ranged from 90.3% to 104% of target and the inter-run imprecision ranged from 6.5% to 12.0%. Stability was established for 25 hours at room temperature, 207 days at -20°C, after three freeze-thaw cycles and for 26 days for rederivatized processed samples. After smoking marijuana predictable concentrations of THC, OH-THC and COOH-THC were seen; low concentrations of CBD were detected at early time points. In moderate users who had not smoked for at least 9 hours before ingesting an 800 mg oral dose of CBD, the method was sensitive enough to follow residual concentrations of THC and OH-THC; sustained COOH-THC concentrations over 50 ng/mL validated its higher analytical range.
MeSH term(s)	Calibration ; Cannabidiol/blood ; Cannabinoids/blood ; Dronabinol/blood ; Gas Chromatography-Mass Spectrometry ; Humans ; Marijuana Smoking ; Street Drugs/blood ; Substance Abuse Detection/methods
Chemical Substances	Cannabinoids ; Street Drugs ; Cannabidiol (19GBJ60SN5) ; Dronabinol (7J8897W37S)
Language	English
Publishing date	2017-05-01
Publishing country	England
Document type	Journal Article
ZDB-ID	752391-9
ISSN	1945-2403 ; 0146-4760
ISSN (online)	1945-2403
ISSN	0146-4760
DOI	10.1093/jat/bkw136
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Article ; Online: Auditory oddball hypoactivation in schizophrenia.

Nakahara, Soichiro / Male, Alie G / Turner, Jessica A / Calhoun, Vince D / Lim, Kelvin O / Mueller, Bryon A / Bustillo, Juan R / O'Leary, Daniel S / Voyvodic, James / Belger, Aysenil / Preda, Adrian / Mathalon, Daniel H / Ford, Judith M / Guffanti, Guia / Macciardi, Fabio / Potkin, Steven G / Van Erp, Theo G M

Psychiatry research. Neuroimaging

2023 Volume 335, Page(s) 111710

Abstract: Individuals with schizophrenia (SZ) show aberrant activations, assessed via functional magnetic resonance imaging (fMRI), during auditory oddball tasks. However, associations with cognitive performance and genetic contributions remain unknown. This study ...

Abstract	Individuals with schizophrenia (SZ) show aberrant activations, assessed via functional magnetic resonance imaging (fMRI), during auditory oddball tasks. However, associations with cognitive performance and genetic contributions remain unknown. This study compares individuals with SZ to healthy volunteers (HVs) using two cross-sectional data sets from multi-center brain imaging studies. It examines brain activation to auditory oddball targets, and their associations with cognitive domain performance, schizophrenia polygenic risk scores (PRS), and genetic variation (loci). Both sample 1 (137 SZ vs. 147 HV) and sample 2 (91 SZ vs. 98 HV), showed hypoactivation in SZ in the left-frontal pole, and right frontal orbital, frontal pole, paracingulate, intracalcarine, precuneus, supramarginal and hippocampal cortices, and right thalamus. In SZ, precuneus activity was positively related to cognitive performance. Schizophrenia PRS showed a negative correlation with brain activity in the right-supramarginal cortex. GWA analyses revealed significant single-nucleotide polymorphisms associated with right-supramarginal gyrus activity. RPL36 also predicted right-supramarginal gyrus activity. In addition to replicating hypoactivation for oddball targets in SZ, this study identifies novel relationships between regional activity, cognitive performance, and genetic loci that warrant replication, emphasizing the need for continued data sharing and collaborative efforts.
MeSH term(s)	Humans ; Schizophrenia/diagnostic imaging ; Schizophrenia/genetics ; Schizophrenia/complications ; Cross-Sectional Studies ; Brain ; Cerebral Cortex ; Frontal Lobe
Language	English
Publishing date	2023-08-28
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	445361-x
ISSN	1872-7506 ; 1872-7123 ; 0925-4927 ; 0165-1781
ISSN (online)	1872-7506 ; 1872-7123
ISSN	0925-4927 ; 0165-1781
DOI	10.1016/j.pscychresns.2023.111710
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Article ; Online: Sparse deep neural networks on imaging genetics for schizophrenia case-control classification.

Chen, Jiayu / Li, Xiang / Calhoun, Vince D / Turner, Jessica A / van Erp, Theo G M / Wang, Lei / Andreassen, Ole A / Agartz, Ingrid / Westlye, Lars T / Jönsson, Erik / Ford, Judith M / Mathalon, Daniel H / Macciardi, Fabio / O'Leary, Daniel S / Liu, Jingyu / Ji, Shihao

Human brain mapping

2021 Volume 42, Issue 8, Page(s) 2556–2568

Abstract: Deep learning methods hold strong promise for identifying biomarkers for clinical application. However, current approaches for psychiatric classification or prediction do not allow direct interpretation of original features. In the present study, we ... ...

Abstract	Deep learning methods hold strong promise for identifying biomarkers for clinical application. However, current approaches for psychiatric classification or prediction do not allow direct interpretation of original features. In the present study, we introduce a sparse deep neural network (DNN) approach to identify sparse and interpretable features for schizophrenia (SZ) case-control classification. An L
MeSH term(s)	Adult ; Case-Control Studies ; Cerebral Cortex/diagnostic imaging ; Cerebral Cortex/pathology ; Deep Learning ; Gray Matter/diagnostic imaging ; Gray Matter/pathology ; Humans ; Magnetic Resonance Imaging ; Neuroimaging/methods ; Polymorphism, Single Nucleotide ; Schizophrenia/classification ; Schizophrenia/diagnostic imaging ; Schizophrenia/genetics ; Schizophrenia/pathology ; Support Vector Machine
Language	English
Publishing date	2021-03-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1197207-5
ISSN	1097-0193 ; 1065-9471
ISSN (online)	1097-0193
ISSN	1065-9471
DOI	10.1002/hbm.25387
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Article ; Online: Cortical Thickness in Adolescents with a Family History of Alcohol Use Disorder.

Henderson, Kate E / Vaidya, Jatin G / Kramer, John R / Kuperman, Samuel / Langbehn, Douglas R / O'Leary, Daniel S

Alcoholism, clinical and experimental research

2017 Volume 42, Issue 1, Page(s) 89–99

Abstract: Background: Individuals with a family history (FH+) of alcohol use disorder (AUD) have a higher risk for developing an AUD than those with no family history (FH-) of AUD. In addition, FH+ individuals tend to perform worse on neuropsychological measures ... ...

Abstract	Background: Individuals with a family history (FH+) of alcohol use disorder (AUD) have a higher risk for developing an AUD than those with no family history (FH-) of AUD. In addition, FH+ individuals tend to perform worse on neuropsychological measures and show heightened impulsivity, which may be due to underlying differences in brain structure such as cortical thickness. The primary aim of this study was to investigate differences in cortical thickness in FH+ compared to FH- adolescents. Secondary aims were to (i) investigate differences in executive functioning and impulsivity, and (ii) examine associations between brain structure and behavior. Methods: Brain scans of 95 FH- and 93 FH+ subjects aged 13 to 18 were obtained using magnetic resonance imaging. FH+ subjects were required to have at least 1 biological parent with a history of an AUD. FH+ and FH- individuals had limited or no past alcohol use, thereby minimizing potential effects of alcohol. Subjects were evaluated on impulsivity and executive functioning tasks. Thicknesses of cortical lobes and subregions were analyzed using FreeSurfer. Regions showing group differences were examined for group-by-age interactions and correlations with neuropsychological and personality measures. Results: FH+ adolescents had thinner cortices in frontal and parietal lobes, notably in the medial orbitofrontal, lateral orbitofrontal, and superior parietal cortices. The difference in cortical thickness between family history groups was strongest among the youngest subjects. FH+ subjects were also more impulsive and had poorer performance on a spatial memory task. Conclusions: These findings demonstrate frontal and parietal structural differences in FH+ adolescents that might underlie cognitive and behavioral characteristics associated with AUD risk.
MeSH term(s)	Adolescent ; Adolescent Behavior/physiology ; Adolescent Behavior/psychology ; Alcoholism/diagnostic imaging ; Alcoholism/genetics ; Alcoholism/psychology ; Cerebral Cortex/diagnostic imaging ; Female ; Humans ; Impulsive Behavior/physiology ; Magnetic Resonance Imaging/methods ; Male ; Organ Size
Language	English
Publishing date	2017-12-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	428999-7
ISSN	1530-0277 ; 0145-6008
ISSN (online)	1530-0277
ISSN	0145-6008
DOI	10.1111/acer.13543
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Article ; Online: Neural sensitivity to absolute and relative anticipated reward in adolescents.

Vaidya, Jatin G / Knutson, Brian / O'Leary, Daniel S / Block, Robert I / Magnotta, Vincent

PloS one

2013 Volume 8, Issue 3, Page(s) e58708

Abstract: Adolescence is associated with a dramatic increase in risky and impulsive behaviors that have been attributed to developmental differences in neural processing of rewards. In the present study, we sought to identify age differences in anticipation of ... ...

Abstract	Adolescence is associated with a dramatic increase in risky and impulsive behaviors that have been attributed to developmental differences in neural processing of rewards. In the present study, we sought to identify age differences in anticipation of absolute and relative rewards. To do so, we modified a commonly used monetary incentive delay (MID) task in order to examine brain activity to relative anticipated reward value (neural sensitivity to the value of a reward as a function of other available rewards). This design also made it possible to examine developmental differences in brain activation to absolute anticipated reward magnitude (the degree to which neural activity increases with increasing reward magnitude). While undergoing fMRI, 18 adolescents and 18 adult participants were presented with cues associated with different reward magnitudes. After the cue, participants responded to a target to win money on that trial. Presentation of cues was blocked such that two reward cues associated with $.20, $1.00, or $5.00 were in play on a given block. Thus, the relative value of the $1.00 reward varied depending on whether it was paired with a smaller or larger reward. Reflecting age differences in neural responses to relative anticipated reward (i.e., reference dependent processing), adults, but not adolescents, demonstrated greater activity to a $1 reward when it was the larger of the two available rewards. Adults also demonstrated a more linear increase in ventral striatal activity as a function of increasing absolute reward magnitude compared to adolescents. Additionally, reduced ventral striatal sensitivity to absolute anticipated reward (i.e., the difference in activity to medium versus small rewards) correlated with higher levels of trait Impulsivity. Thus, ventral striatal activity in anticipation of absolute and relative rewards develops with age. Absolute reward processing is also linked to individual differences in Impulsivity.
MeSH term(s)	Adolescent ; Adult ; Anticipation, Psychological ; Basal Ganglia/physiopathology ; Brain Mapping ; Child ; Female ; Humans ; Impulsive Behavior/physiopathology ; Male ; Motivation ; Nervous System/physiopathology ; Prefrontal Cortex/physiopathology ; Reward ; Task Performance and Analysis
Language	English
Publishing date	2013-03-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0058708
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