Neurocognitive and psychiatric outcomes associated with postacute COVID-19 infection without severe medical complication: a meta-analysis.

BACKGROUND: Cognitive symptoms are often reported by those with a history of COVID-19 infection. No comprehensive meta-analysis of neurocognitive outcomes related to COVID-19 exists despite the influx of studies after the COVID-19 pandemic. This study meta-analysed observational research comparing cross-sectional neurocognitive outcomes in adults with COVID-19 (without severe medical/psychiatric comorbidity) to healthy controls (HCs) or norm-referenced data. METHODS: Data were extracted from 54 studies published between January 2020 and June 2023. Hedges' g was used to index effect sizes, which were pooled using random-effects modelling. Moderating variables were investigated using meta-regression and subgroup analyses. RESULTS: Omnibus meta-analysis of 696 effect sizes extracted across 54 studies (COVID-19 n=6676, HC/norm-reference n=12 986; average time since infection=~6 months) yielded a small but significant effect indicating patients with COVID-19 performed slightly worse than HCs on cognitive measures (g=-0.36; 95% CI=-0.45 to -0.28), with high heterogeneity (Q=242.30, p<0.001, τ=0.26). Significant within-domain effects was yielded by cognitive screener (g=-0.55; 95% CI=-0.75 to -0.36), processing speed (g=-0.44; 95% CI=-0.57 to -0.32), global cognition (g=-0.40; 95% CI=-0.71 to -0.09), simple/complex attention (g=-0.38; 95% CI=-0.46 to -0.29), learning/memory (g=-0.34; 95% CI=-0.46 to -0.22), language (g=-0.34; 95% CI=-0.45 to -0.24) and executive function (g=-0.32; 95% CI=-0.43 to -0.21); but not motor (g=-0.40; 95% CI=-0.89 to 0.10), visuospatial/construction (g=-0.09; 95% CI=-0.23 to 0.05) and orientation (g=-0.02; 95% CI=-0.17 to 0.14). COVID-19 samples with elevated depression, anxiety, fatigue and disease severity yielded larger effects. CONCLUSION: Mild cognitive deficits are associated with COVID-19 infection, especially as detected by cognitive screeners and processing speed tasks. We failed to observe clinically meaningful cognitive impairments (as measured by standard neuropsychological instruments) in people with COVID-19 without severe medical or psychiatric comorbidities.

Compassion Versus Accuracy: Lenient Scoring of the Spatial Orientation Items on the Mini-mental State Exam Lowers Sensitivity.

The Mini-mental State Examination (MMSE) is a commonly used screening tool for cognitive impairment. Lenient scoring of spatial orientation errors (SOEs) on the MMSE is common and negatively affects its diagnostic utility. We examined the effect of lenient SOE scoring on MMSE classification accuracy in a consecutive case series of 103 older adults (age 60 or above) clinically referred for neuropsychological evaluation. Lenient scoring of SOEs on the MMSE occurred in 53 (51.4%) patients and lowered the sensitivity by 7% to 18%, with variable gains in specificity (0% to 11%) to psychometrically operationalized cognitive impairment. Results are consistent with previous reports that lenient scoring is widespread and attenuates the sensitivity of the MMSE. Given the higher clinical priority of correctly detecting early cognitive decline over specificity, a warning against lenient scoring of SOEs (on the MMSE and other screening tools) during medical education and in clinical practice is warranted.

Accelerated long-term forgetting of recall and recognition memory in people with epilepsy.

PURPOSE: Persons with epilepsy (PWE) report memory deficits as one of the most distressing aspects of their disorder. Recently, a long-term memory deficit known as Accelerated Long-Term Forgetting (ALF) has been described in PWE. ALF is characterized by the initial retention of learned information, followed by an accelerated rate of memory decay. However, the rate of ALF varies widely across literature and it is unclear how it impacts different memory retrieval types. The current study aimed to capture the time course of ALF on both free recall and recognition memory using a movie-based task in PWE. METHODS: A sample of 30 PWE and 30 healthy comparison (HC) subjects watched a nature documentary and were tested on their recall and recognition of the film's content immediately after viewing and at delays of 24 hours, 48 hours, and 72 hours. Participants also rated the confidence they had in their recognition memory trial responses. RESULTS: For recall, PWE exhibit ALF at 72 hours (ß = -19.840, SE = 3.743, z(226) = -5.301, p < 0.001). For recognition, PWE had decreased performance compared to controls at the 24-hour (ß = -10.165, SE = 4.174, z(224) = -3.166, p = 0.004), 48-hour (ß = -8.113, SE = 3.701, z(224) = -2.195, p = 0.044), and 72-hour (ß = -10.794, SE = 3.017, z(224) = -3.295, p = 0.003) delays. The PWE group showed positive correlations (tau = 0.165, p < 0.001) between confidence ratings and accuracy, with higher confidence reflecting successful recognition. PWE were 49% less likely to answer either retrieval type correctly at 72 hours (OR 0.51, 95% CI [0.35, 0.74], p < 0.001). Left hemispheric seizure onset decreased the odds of successful retrieval by 88% (OR 0.12, 95% CI [0.01, 0.42], p = 0.019). CONCLUSIONS: These findings provide evidence of ALF in PWE, with a differential impact on recall and recognition memory. This further supports the call to include ALF assessments in standard memory evaluations in PWE. Additionally, identifying the neural correlates of ALF in the future will be important in developing targeted therapies to alleviate the burden of memory impairment for PWE.

Cardio-ankle vascular index of increased arterial wall stiffness is associated with neurocognitive impairment in well-controlled HIV.

OBJECTIVES: HIV-associated neurocognitive disorders (HAND) remain prevalent in people living with HIV (PLWH) despite widespread use of combined antiretroviral therapy (ART). Vascular disease contributes to the pathogenesis of HAND, but traditional vascular risk factors do not fully explain the relation between vascular disease and HAND. A more direct measure of vascular dysfunction is needed. This cross-sectional study tested whether the cardio-ankle vascular index (CAVI), a novel method to assess arterial stiffness, is associated with HAND among PLWH. METHODS: Participants included 75 non-diabetic adults with well-controlled HIV from an outpatient HIV clinic. We assessed the relation between CAVI and neurocognitive impairment (NCI). The latter was primarily characterized by the Frascati criteria and secondarily (post hoc) using the Global Deficit Score (GDS). Logistic regression models tested whether high CAVI (≥ 8) was independently associated with NCI when controlling for potential confounders. RESULTS: Participants (Mage  = 45.6 ± 8.3 years; 30.1% male) had few traditional cardiovascular disease (CVD) risk factors (hypertension, n = 7; dyslipidaemia, n = 34; body mass index ≥ 25 kg/m2 , n = 12; smoking history, n = 13; 2.2% mean 10-year risk of CVD or stroke). Twelve (16%) participants had high CAVI, which was independently associated with meeting Frascati criteria for NCI [n = 39, odds ratio (OR) = 7.6, p = 0.04], accounting for age, education, gender, income, CD4 nadir, recent CD4 and traditional CVD risk factors. High CAVI was also associated with NCI as reflected by higher GDS (OR = 17.4, p = 0.02). CONCLUSIONS: Cardio-ankle vascular index is a promising measure of vascular dysfunction that may be independently associated with NCI in relatively healthy PLWH. Larger studies should test the utility of CAVI in predicting NCI/decline in PLWH.

Psychometric utility of the international HIV dementia scale and Montreal Cognitive Assessment in HIV-associated asymptomatic neurocognitive impairment.

There is a growing need for brief screening measures for HIV Associated Neurocognitive Disorders (HAND). We compared two commonly used measures (the Montreal Cognitive Assessment [MoCA] and the International HIV Dementia Scale [IHDS]) in their ability to identify asymptomatic HAND (i.e., asymptomatic neurocognitive impairment [ANI]). Participants included 74 Thai PLWH: 38 met Frascati criteria for ANI and 36 were cognitively normal (CN). Participants completed Thai language versions of the MoCA (MoCA-T) and IHDS, and a validated neurocognitive battery. We examined between-group differences for MoCA-T and IHDS total scores, and scale subcomponents. We also conducted receiver operating characteristic (ROC) analyses to determine the ability of the MoCA-T and IHDS to discriminate between CN and ANI groups, and compared their area under the curve (AUC) values. Results revealed lower MoCA-T total score, as well as the Visuospatial/Executive and Delayed Recall subtask scores, in the ANI relative to CN group. Groups did not differ on the IHDS. For ROC analyses, the MoCA-T, but not the IHDS, significantly differentiated the ANI from CN group, and there was a significant difference in AUC values between the MoCA-T (AUC = .71) and IHDS (AUC = .56). Sensitivity and specificity statistics were poor for both screening measures. These data indicate while the MoCA-T functions better than the IHDS in detecting Thai PLWH with ANI, the mildest form of HAND, neither cognitive screener, showed strong utility. Our findings reflect the limited efficacy of common screening measures in detecting subtler cognitive deficits among Thai PLWH, and highlight the need for better screening tools.

Self-rated executive dysfunction in adults with epilepsy and effects of a cognitive-behavioral intervention (HOBSCOTCH).

RATIONALE: Cognitive problems are common in adults with epilepsy and significantly affect their quality of life. HOBSCOTCH (HOme Based Self-management and COgnitive Training CHanges lives) was developed to teach problem-solving and compensatory memory strategies to these individuals. This study examined whether HOBSCOTCH is associated with improvement in specific aspects of subjective executive functions. METHODS: Fifty-one adults, age 18-65, with epilepsy and subjective cognitive concerns were randomized to receive HOBSCOTCH (n = 31) or a care-as-usual control sample (n = 20). Participants completed the Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A), as well as the Patient Health Questionnaire-9 (PHQ-9) to assess depression. Rates of elevated (i.e., T ≥ 65, impaired) BRIEF-A scores at baseline, as well as pre-post score changes for the BRIEF-A clinical scales were evaluated. Significance was set at α = 0.05, one-tailed, given our directional hypothesis. RESULTS: At baseline, a considerable percentage of patients in the overall sample endorsed executive dysfunction on BRIEF-A scales: Inhibit = 28%, Shift = 51%, Emotional Control = 45%, Self-Monitor = 33%, Initiate = 35%, Working Memory = 88%, Plan/Organize = 45%, Task Monitor = 47%, Organization of Materials = 28%. Significant improvement was seen in mean T-scores for Inhibit, Shift, Initiate, and Working Memory in the treatment group, but only Working Memory improved in the control group. The control group endorsed worse task monitoring and organization of materials at baseline and follow-up. Change in depression was not observed for either group, and there was no association between changes in depression and BRIEF-A scores. CONCLUSIONS: A sizeable subset of adults with epilepsy reported experiencing executive dysfunction in their everyday lives, especially for working memory. HOBSCOTCH resulted in amelioration of subjective executive functioning independent of changes in mood.

Antiepileptic drug effects on subjective and objective cognition.

RATIONALE: Cognitive impairment is one of the most common complaints for persons with epilepsy (PWE). These impairments are not only associated with seizures, but are also regularly reported as adverse effects of antiepileptic drugs (AEDs). Previous studies have examined cognitive effects of both AED monotherapy and polytherapy, yet there is limited research on these differences with respect to both subjective and objective cognition. The current study uses data from previous research conducted by the Centers for Disease Control and Prevention (CDC)-sponsored Managing Epilepsy Well (MEW) Network collaborative. We used three distinct archival datasets from the following: (1) the HOBSCOTCH efficacy trial at Dartmouth-Hitchcock Medical Center (HOB-1), (2) the multisite replication trial (HOB-2), and (3) epilepsy self-management research conducted at the NYU School of Medicine. METHODS: This retrospective analysis combined baseline data from three datasets to determine how the number of AEDs and the type of AEDs were associated with subjective (patient-reported) and objective (examiner-assessed) cognition. Subjective cognition was captured using the cognitive subscale of the Quality of Life in Epilepsy Inventory (QOLIE-31) in all three datasets (n = 224), while objective cognition was measured using the Repeated Battery for the Assessment of Neuropsychological Status (RBANS) in the HOB-1 dataset (n = 65) and the Brief Test of Adult Cognition by Telephone (BTACT) in the HOB-2 dataset (n = 91). Multivariable linear regression was utilized for our initial assessments, followed by propensity score matching to provide stronger control of covariates. Matching was based on significantly different covariates, such as education, depression, and history of prior epilepsy surgery. Nonparametric statistical tests were utilized to compare these matched subjects. RESULTS: Subjective cognitive impairment was significantly worse among individuals on polytherapy (2 + AEDs) compared with those on monotherapy (1 AED) (adjusted p  =  0.041). These findings were consistent with our propensity score matched comparison of monotherapy and polytherapy, which indicated that polytherapy was associated with worse overall subjective cognition (adjusted p = 0.01), in addition to impairments on the RBANS (Total score p = 0.05) and specific subdomains of the BTACT (Episodic Verbal Memory p < 0.01, Working Memory p < 0.01, Processing Speed p < 0.01). Interestingly, older generation AEDs were associated with better language performance than newer generation and combined generation AED therapy (RBANS Language p = 0.03). These language-specific findings remained significant after controlling for the effects of topiramate and zonisamide (p = 0.04). CONCLUSIONS: A greater number of AEDs is significantly and negatively associated with subjective and objective cognition in PWE, and is in line with previous research. Antiepileptic drug type did not, in itself, appear to be associated with subjective cognition. Our findings suggest that ineffective AEDs should be replaced, rather than introducing additional AEDs to a treatment regimen. Further, while subjective and objective cognition assessments were both sensitive at detecting differences based on AED status, the neuropsychological objective subdomains offer additional and specific insights into how cognition is impaired with AEDs.

Effects of Left Versus Right Dorsolateral Prefrontal Cortex Repetitive Transcranial Magnetic Stimulation on Affective Flexibility in Healthy Women: A Pilot Study.

OBJECTIVE: To determine the antidepressant mechanism of action for repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (DLPFC) in healthy women. Our primary hypothesis was that a single session of left DLPFC rTMS, compared with a session of right DLPFC rTMS, would result in better (reduced) negative nonaffective switch costs in healthy women. BACKGROUND: The antidepressant mechanism of action for rTMS is not clear. It is possible that rTMS to the DLPFC improves emotion regulation, which could be a part of its antidepressant mechanism. METHODS: Twenty-five healthy women were randomized to receive left high-frequency (HF) rTMS versus right HF rTMS in one session and then contralateral stimulation during a second session. Emotion regulation was assessed via switch costs for reappraisal of negatively valenced information on an affective flexibility task. RESULTS: For negative nonaffective switch costs, the interaction effect in the two-way ANOVA was not significant (F1,19=3.053, P=0.097). Given that left HF rTMS is the approved treatment for depression, post hoc t tests were completed with particular interest in the left-side findings. These tests confirmed that negative nonaffective switch costs significantly improved immediately after left rTMS (t1,19=2.664, P=0.015) but not right rTMS. CONCLUSIONS: These findings suggest that left DLPFC HF rTMS may lead to antidepressant effects by improving the regulation of emotion.

Subjective rating of executive functions in mild Alzheimer's disease.

OBJECTIVES: Subjective cognitive decline is considered to be a core feature of pre-Alzheimer's disease (AD) conditions, the vast majority of literature having focused on memory concerns. Neuropsychological studies have implicated executive dysfunction on objective performance measures in AD, but no research has evaluated whether individuals with AD have concerns about their executive functions and whether it differs from their caregiver's concerns. In the present study, we sought to evaluate self- and informant ratings of executive functioning in patients with mild AD. METHOD: Participants were 23 patients with mild AD and 32 healthy elderly controls (HC) and their informants who completed the Behavior Rating Inventory of Executive Function - Adult version. RESULTS: Patients with AD and their informants reported greater executive dysfunction than the HC group and their informants, respectively, and patients reported greater difficulty than their informants. The largest effect size for both self- and informant ratings was obtained for the Working Memory scale. CONCLUSIONS: These findings indicate that subjective cognitive concerns in mild AD extend beyond the memory domain to executive functions. That greater difficulty was endorsed by patients than their informants suggests that at least in the mild stage of AD some awareness of executive dysfunction may be maintained in some patients. Implications for clinical care are discussed.

Effects of Transcranial Magnetic Stimulation on the Cognitive Control of Emotion: Potential Antidepressant Mechanisms.

Depression negatively impacts quality of life and is associated with high mortality rates. Recent research has demonstrated that improvement in depression symptoms with transcranial magnetic stimulation (TMS) to the dorsolateral prefrontal cortex (DLPFC) may involve changes in the cognitive control network, a regulatory system modulating the function of cognitive and emotional systems, composed of the DLPFC, dorsal anterior cingulate, and posterior parietal cortices. Transcranial magnetic stimulation to the DLPFC node of the cognitive control network may have antidepressant efficacy via direct effects on cognitive control processes involved in emotion regulation. This review provides a review of the impact of TMS on cognitive control processes, especially those related to emotion regulation, and posits that these effects are critical to the mechanism of action of TMS for depression. Treatment implications and future directions for study are discussed.

Investigating social cognition in epilepsy using a naturalistic task.

OBJECTIVE: The primary objective for this study was to assess social cognition in patients with focal epilepsy using a naturalistic task, which accurately models complex real-world social interaction. METHODS: We conducted an observational study of social cognition in 43 patients with focal epilepsy and in 22 controls. Patients and controls completed The Awareness of Social Inference Test, which measures both basic and advanced social cognition in a realistic video-based format. Patient and controls also completed standard measures of cognitive functioning and measures of depression. RESULTS: Compared to controls, we found that patients with epilepsy (PWEs) had no difficulty identifying positively valenced emotional states (happiness) yet had difficulty identifying most negatively valenced emotional states (anger, fear, and disgust). In addition, PWEs were able to identify sincere exchanges correctly but could not identify sarcastic and insincere exchanges. We found that basic social cognition significantly correlated with standard generalized cognitive measures, whereas advanced social cognition did not. Finally, age at onset had significant impact on social cognition, whereas other epilepsy characteristics did not. SIGNIFICANCE: PWEs have deficits in social cognition when measured using a naturalistic video-based task. Advanced social cognition may be an independent cognitive domain in PWEs that is not adequately measured using standard psychometric instruments. Problems with social cognition may arise as a consequence of epilepsy during the periods of robust social development in childhood and adolescence.

CVLT-II Forced Choice Recognition Trial as an Embedded Validity Indicator: A Systematic Review of the Evidence.

OBJECTIVES: The Forced Choice Recognition (FCR) trial of the California Verbal Learning Test, 2nd edition, was designed as an embedded performance validity test (PVT). To our knowledge, this is the first systematic review of classification accuracy against reference PVTs. METHODS: Results from peer-reviewed studies with FCR data published since 2002 encompassing a variety of clinical, research, and forensic samples were summarized, including 37 studies with FCR failure rates (N=7575) and 17 with concordance rates with established PVTs (N=4432). RESULTS: All healthy controls scored >14 on FCR. On average, 16.9% of the entire sample scored ≤14, while 25.9% failed reference PVTs. Presence or absence of external incentives to appear impaired (as identified by researchers) resulted in different failure rates (13.6% vs. 3.5%), as did failing or passing reference PVTs (49.0% vs. 6.4%). FCR ≤14 produced an overall classification accuracy of 72%, demonstrating higher specificity (.93) than sensitivity (.50) to invalid performance. Failure rates increased with the severity of cognitive impairment. CONCLUSIONS: In the absence of serious neurocognitive disorder, FCR ≤14 is highly specific, but only moderately sensitive to invalid responding. Passing FCR does not rule out a non-credible presentation, but failing FCR rules it in with high accuracy. The heterogeneity in sample characteristics and reference PVTs, as well as the quality of the criterion measure across studies, is a major limitation of this review and the basic methodology of PVT research in general. (JINS, 2016, 22, 851-858).

Apathy Is Associated With Ventral Striatum Volume in Schizophrenia Spectrum Disorder.

Apathy is prevalent in schizophrenia, but its etiology has received little investigation. The ventral striatum (VS), a key brain region involved in motivated behavior, has been implicated in studies of apathy. We therefore evaluated whether apathy is associated with volume of the VS on MRI in 23 patients with schizophrenia using voxel-based morphometry. Results indicated that greater self-reported apathy severity was associated with smaller volume of the right VS even when controlling for age, gender, depression, and total gray matter volume. The finding suggests that apathy is related to abnormality of brain circuitry subserving motivated behavior in patients with schizophrenia.

A cognitive behavioral intervention (HOBSCOTCH) improves quality of life and attention in epilepsy.

OBJECTIVE: Cognitive difficulties in epilepsy are common and add to disability beyond seizures alone. A self-management intervention targeting cognitive dysfunction was developed and assessed for whether it improves quality of life, objective memory, and mood in adults with epilepsy. METHODS: The HOme Based Self-management and COgnitive Training CHanges lives (HOBSCOTCH) program was developed to incorporate (1) psychoeducation, (2) self-awareness training, (3) compensatory strategies, and (4) application of these strategies in day-to-day life using problem solving therapy. Adults aged 18-65 years with epilepsy (n=66) were randomized into 3 groups, to receive 8 weeks of HOBSCOTCH, with (H+) or without (H) additional working memory training on a commercial gaming device, or to a waitlisted control group. The primary outcome was quality of life (Quality of Life in Epilepsy scale, QOLIE-31) with secondary outcomes of objective cognition measured with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and depression (as measured by PHQ9 and NDDIE). RESULTS: Both intervention arms showed a significant improvement in quality of life, as compared with controls who demonstrated a decline in QOLIE-31 scores. There was significant improvement in objective cognitive performance among the intervention groups, most notably in attention, compared with the waitlisted controls. There was no significant change in depression scores. SIGNIFICANCE: The HOBSCOTCH program significantly improved quality of life and appeared to be an effective intervention to address cognitive dysfunction in adults with epilepsy. Further studies are needed to assess the generalizability and cost-effectiveness of this intervention.

Design and feasibility of a memory intervention with focus on self-management for cognitive impairment in epilepsy.

The aim of this study was to assess the feasibility of a self-management intervention targeting cognitive dysfunction to improve quality of life and reduce memory-related disability in adults with epilepsy. The intervention incorporates (1) education on cognitive function in epilepsy, (2) self-awareness training, (3) compensatory strategies, and (4) application of these strategies in day-to-day life using problem-solving therapy. In addition to the behavioral modification, formal working memory training was conducted by utilizing a commercially available program in a subgroup of patients. Our findings suggest that a self-management intervention targeting cognitive dysfunction was feasible for delivery to a rural population with epilepsy, with 13 of 16 enrolled participants completing the 8-session program. Qualitative data indicate high satisfaction and subjective improvement in cognitive functioning in day-to-day life. These findings provide support for further evaluation of the efficacy of this intervention through a randomized controlled trial.

Replicating the classification accuracy of the Verbal Paired Associates and Visual Reproduction recognition trials as embedded performance validity tests.

OBJECTIVE: This study was designed to replicate previous research on the clinical utility of the Verbal Paired Associates (VPA) and Visual Reproduction (VR) subtests of the WMS-IV as embedded performance validity tests (PVTs) and perform a critical item (CR) analysis within the VPA recognition trial. METHOD: Archival data were collected from a mixed clinical sample of 119 adults (MAge = 42.5, MEducation = 13.9). Classification accuracy was computed against psychometrically defined criterion groups based on the outcome of various free-standing and embedded PVTs. RESULTS: Age-corrected scaled scores ≤ 6 were specific (.89-.98) but had variable sensitivity (.36-.64). A VPA recognition cutoff of ≤ 34 produced a good combination of sensitivity (.46-.56) and specificity (.92-.93), as did a VR recognition cutoff of ≤ 4 (.48-.53 sensitivity at .86-.94 specificity). Critical item analysis expanded the VPA's sensitivity by 3.5%-7.0% and specificity by 5%-8%. Negative learning curves (declining output on subsequent encoding trials) were rare but highly specific (.99-1.00) to noncredible responding. CONCLUSIONS: Results largely support previous reports on the clinical utility of the VPA and VR as embedded PVTs. Sample-specific fluctuations in their classification accuracy warrant further research into the generalizability of the findings. Critical item analysis offers a cost-effective method for increasing confidence in the interpretation of the VPA recognition trial as a PVT. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Randomized Laboratory Study of Single-Dose Cannabis, Dronabinol, and Placebo in Patients With Schizophrenia and Cannabis Use Disorder.

BACKGROUND AND HYPOTHESIS: Up to 43% of people with schizophrenia have a lifetime cannabis use disorder (CUD). Tetrahydrocannabinol (THC) has been shown to exacerbate psychosis in a dose-dependent manner, but little research has assessed its effects on schizophrenia and co-occurring CUD (SCZ-CUD). In this double-dummy, placebo-controlled trial (total n = 130), we hypothesized that a modest dose of THC would worsen cognitive function but not psychosis. STUDY DESIGN: Effects of single-dose oral THC (15 mg dronabinol) or smoked 3.5% THC cigarettes vs placebo in SCZ-CUD or CUD-only on positive and negative symptoms of schizophrenia (only for SCZ-CUD), cognition, and drug experiences assessed several hours after drug administration. SCZ-only and healthy control participants were also assessed. STUDY RESULTS: Drug liking was higher in THC groups vs placebo. Neither smoked THC nor oral dronabinol predicted positive or negative symptom subscale scores 2 and 5 h, respectively, after drug exposure in SCZ-CUD participants. The oral dronabinol SCZ-CUD group, but not smoked THC SCZ-CUD group, performed worse than placebo on verbal learning (B = -9.89; 95% CI: -16.06, -3.18; P = .004) and attention (B = -0.61; 95% CI: -1.00, -0.23; P = .002). Every 10-point increment in serum THC + THCC ng/ml was associated with increased negative symptoms (0.40 points; 95% CI: 0.15, 0.65; P = .001; subscale ranges 7-49) and trends were observed for worse positive symptoms and performance in verbal learning, delayed recall, and working memory. CONCLUSIONS: In people with SCZ-CUD, a modest single dose of oral THC was associated with worse cognitive functioning without symptom exacerbation several hours after administration, and a THC dose-response effect was seen for negative symptoms.

Do executive functions differentiate Iranian children with attention-deficit/hyperactivity disorder with and without comorbid obesity?

OBJECTIVE: To compare multiple dimensions of executive function between children with attention-deficit/hyperactivity disorder (ADHD) with and without comorbid obesity. METHOD: Participants were 90 Iranian children (ages 8-13, 50% female) who were equally dispersed across three study groups: typically developing (TD), ADHD with obesity (ADHD+O), and ADHD without obesity (ADHD-O). Study participants were administered a comprehensive battery of Iranian-adapted "cool" executive function tasks including Digit Span from the Wechsler Intelligence Scale for Children-Fifth Edition (WISC-V), Victoria Stroop Test (VST), Wisconsin Card Sorting Test (WCST), Tower of London, and dot-probe task (i.e., a task of attentional bias). Parents completed the Children's Scale for Future Thinking Questionnaire, which assesses future-oriented cognition (e.g., saving, planning, episodic foresight, delay of gratification), aligning more with "hot" executive functions. Groups were compared using multivariate and post-hoc univariate general linear models. RESULTS: Significant group effects were observed for all executive function variables, broadly with the gradient pattern of TD > ADHD-O > ADHD+O. ADHD+O had poorer performances than ADHD-O for WISC-V Digit Span (d = -0.84), WCST Categories Completed (d = -0.55) and Perseverative Responses (d = 1.15), VST Interference Errors (d = 0.83) and Interference Time (d = 1.38), and Dot-Probe Task (d = 0.84). Relative to the ADHD-O group, ADHD+O had also poorer parent-reported Prospective Memory (d = -0.62), Episodic Foresight (d = -0.63), and Delay of Gratification (d = -0.54). CONCLUSIONS: Children with ADHD-O have poorer executive functioning than those without obesity. We observed stronger effects for "cool" rather than "hot" domains of executive function, though this could be due to the former being performance-based and the latter parent-reported.

Replicating a Meta-Analysis: The Search for the Optimal Word Choice Test Cutoff Continues.

This study was designed to expand on a recent meta-analysis that identified ≤42 as the optimal cutoff on the Word Choice Test (WCT). We examined the base rate of failure and the classification accuracy of various WCT cutoffs in four independent clinical samples (N = 252) against various psychometrically defined criterion groups. WCT ≤ 47 achieved acceptable combinations of specificity (.86-.89) at .49 to .54 sensitivity. Lowering the cutoff to ≤45 improved specificity (.91-.98) at a reasonable cost to sensitivity (.39-.50). Making the cutoff even more conservative (≤42) disproportionately sacrificed sensitivity (.30-.38) for specificity (.98-1.00), while still classifying 26.7% of patients with genuine and severe deficits as non-credible. Critical item (.23-.45 sensitivity at .89-1.00 specificity) and time-to-completion cutoffs (.48-.71 sensitivity at .87-.96 specificity) were effective alternative/complementary detection methods. Although WCT ≤ 45 produced the best overall classification accuracy, scores in the 43 to 47 range provide comparable objective psychometric evidence of non-credible responding. Results question the need for designating a single cutoff as "optimal," given the heterogeneity of signal detection environments in which individual assessors operate. As meta-analyses often fail to replicate, ongoing research is needed on the classification accuracy of various WCT cutoffs.

Univariate and Multivariate Base Rates of Score Elevations, Reliable Change, and Inter-Rater Discrepancies in the BRIEF-A Standardization Samples.

The Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) is a standardized rating scale of subjective executive functioning. We provide univariate and multivariate base rates (BRs) for scale/index scores in the clinical range (T scores ≥65), reliable change, and inter-rater information not included in the Professional Manual. Participants were adults (ages = 18-90 years) from the BRIEF-A self-report (N = 1,050) and informant report (N = 1,200) standardization samples, as well as test-retest (n = 50 for self, n = 44 for informant) and inter-rater (n = 180) samples. Univariate BRs of elevated T scores were low (self-report = 3.3%-15.4%, informant report = 4.5%-16.3%). Multivariate BRs revealed the common occurrence of obtaining at least one elevated T-score across scales (self-report = 26.5%-37.3%, informant report = 22.7%-30.3%), whereas virtually none had elevated scores on all scales. Test-retest scores were highly correlated (self = .82-.94; informant = .91-.96). Inter-rater correlations ranged from .44 to .68. Significant (p < .05) test-retest T-score differences ranged from 7 to 12 for self-report, from 6 to 8 for informant report, and from 16 to 21 points for inter-rater T-score differences. Applications of these findings are discussed.