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PubMed2026

Recall-by-genotype of neurodevelopmental disorder copy number variants in a multi-ancestry, healthcare-system biobank.

Clinical biobanks linking electronic health records (EHRs) with genotype data enable the study of genomic risk factors in real-world populations. However, recall-by-genotype (RbG) of psychiatric risk variants in diverse healthcare-system biobanks remains scarce. Leveraging BioMe, a multi-ancestry biobank within the Mount Sinai Health System, we recalled carriers of rare copy number variants (CNVs) that confer increased risk for neurodevelopmental disorders (NDDs) to establish empirical benchmarks for RbG implementation. We recontacted 892 participants: 335 NDD CNV carriers, 217 individuals with schizophrenia without NDD CNVs, and 340 neurotypical controls without NDD CNVs. Participants completed clinical and cognitive assessments. Overall, 18% of recontacted participants responded to recruitment, and 8% completed the study: 30 NDD CNV carriers, 20 individuals with schizophrenia, and 23 controls. The mean age was 48.8 years, 66% were female, and self-reported ancestry was 37% African, 34% Hispanic, and 26% European. Seventy percent of NDD CNV carriers had at least one neuropsychiatric or developmental condition, including mood or anxiety disorders (40%). Among 22 NDD CNV carriers at loci implicated in impaired cognition, performance was lower than controls on Digit Span Backward (β = -1.76, FDR = 0.04) and Digit Span Sequencing (β = -2.01, FDR = 0.04). NDD CNV carriers also outperformed the schizophrenia group on verbal learning (β = 4.5, FDR = 0.05). Recall of individuals-including those with psychiatric illness-yielded phenotypes not captured in EHRs and provides empirical benchmarks relevant to RbG implementation and precision psychiatry in diverse healthcare systems.

Journal Article↗
PubMed1989

A controlled study of neuropsychological deficits in acute spinal cord injury patients.

According to a number of studies, between 40% and 60% of acute traumatic spinal cord injury (SCI) patients demonstrate cognitive dysfunction resulting from various forms of cerebral damage, including concurrent or premorbid closed head injury, chronic alcohol or substance abuse, and other causes. However, applicability of findings from these reports has been limited due to the use of inadequate neuropsychological testing techniques and the lack of control data. In a collaborative investigation, 81 acute SCI patients and 61 non-injured control subjects between 18 and 55 years of age completed a comprehensive motor-free neuropsychological test battery, including: Halstead Category Test (HCT), Vocabulary Subtest (VOCAB) of the Wechsler Adult Intelligence Scale - Revised; Mental Control (MC) Subtest, and Initial and Recall trials of Logical Memory (LM) and Paired Associates (PA) Subtests of the Wechsler Memory Scale; and the 8 trials of the Rey Auditory Verbal Learning Test (RAVLT). Percentages of retained information on the LM and PA were also calculated. Impairment levels for each test were defined as values which exceeded two standard deviations (one-tailed) from the control mean. Based on this definition, the prevalence of neuropsychological abnormality on each test ranged between 10% and 40%. Mean performance levels of patients were significantly more impaired than those of control subjects for all tests except for the Interference trial of the RAVLT and for the percentages of retained information on the LM and PA subtests. Comparison of test results of SCI patients with those of control subjects demonstrates that poor attention span and limited initial learning ability are frequent problems among SCI patients. Other common neuropsychological deficits among these patients include poor concentration ability, impaired memory function, and altered problem solving ability. These deficits may interfere with rehabilitation following SCI.

Adolescent↗
PubMed2006

Enhanced sensitivity to the euphoric effects of alcohol in schizophrenia.

The purpose of this study was to determine whether schizophrenia was associated with alterations in alcohol response that might explain the elevated risk for AUDs in this population. In a randomized, double-blind, placebo-controlled, counter-balanced 3 test day laboratory study, the effects of alcohol were compared in 23 subjects with schizophrenia (without any previous alcohol use disorder (AUD) but with some alcohol exposure) and in 14 healthy subjects matched for age, gender, education, and lifetime exposure to alcohol. Standard alcohol drinks in a scheduled design were administered to produce blood alcohol levels of 0, 0.02-0.04 mg%, or 0.06-0.08 mg%. Schizophrenia symptoms, perceptual alterations, stimulant and depressant subjective effects of alcohol, and 'high' were measured before alcohol administration and at several post-drug time points. Verbal learning and recall, vigilance and distractibility, and motor function were assessed once per test day. Relative to healthy subjects, subjects with schizophrenia reported greater euphoria and stimulatory effects in response to alcohol. Alcohol produced small transient increases in positive psychotic symptoms and perceptual alterations without affecting negative symptoms. Alcohol also impaired several aspects of immediate and delayed recall, and vigilance, and distractibility. Schizophrenia patients showed increased euphoric and stimulatory responses to alcohol. These exaggerated positive responses to alcohol doses may contribute to the increased risk for AUDs associated with schizophrenia. The absence of 'beneficial' effects of alcohol does not support a self-medication hypothesis of alcohol use in schizophrenia.

Adolescent↗
PubMed1975

The conditioning of language in a nonverbal child conducted in a special education classroom.

The purpose of this study was twofold: first, to assess the feasibility of conducting speech conditioning sessions within a preschool classroom, and second, to examine the process of transfer of learned verbalizations from those sessions to classroom free time. The results indicated that the former was not only feasible but effective. A nonverbal boy, enrolled in a special education preschool, was taught to imitate reliably six words in 46 15-minute sessions. Furthermore, the child's use of spontaneous whole words during the rest of the classroom day seemed to be responsive to the contingencies of the speech sessions.

Behavior Therapy↗
PubMed1999

Network analysis in episodic encoding and retrieval of word-pair associates: a PET study.

The involvement of distributed brain regions in declarative memory has been hypothesized based on studies with verbal memory tasks. To characterize episodic declarative memory function further, 14 right-handed volunteers performed a visual verbal learning task using paired word associates. The volunteers underwent positron emission tomography. 15O-butanol was used as a tracer of regional cerebral blood flow (rCBF). Inter-regional functional interactions were assessed based on within-task, across-subject inter-regional rCBF correlations. Anatomical connections between brain areas were based on known anatomy. Structural equation modelling was used to calculate the path coefficients representing the magnitudes of the functional influences of each area on the ones to which it is connected by anatomical pathways. The encoding and the retrieval network elicit similarities in a general manner but also differences. Strong functional linkages involving visual integration areas, parahippocampal regions, left precuneus and cingulate gyrus were found in both encoding and retrieval; the functional linkages between posterior regions and prefrontal regions were more closely linked during encoding, whereas functional linkages between the left parahippocampal region and posterior cingulate as well as extrastriate areas and posterior cingulate gyrus were stronger during retrieval. In conclusion, these findings support the idea of a global bihemispheric, asymmetric encoding/retrieval network subserving episodic declarative memory. Our results further underline the role of the precuneus in episodic memory, not only during retrieval but also during encoding.

Adult↗
PubMed1999

A 24-month, double-blind, placebo-controlled multicentre pilot study of the efficacy and safety of nicergoline 60 mg per day in elderly hypertensive patients with leukoaraiosis.

In this pilot study, 72 non-demented and non-depressive elderly hypertensive patients with evidence of leukoaraiosis on cerebral computed tomography scan (Rezek score: > 16) were randomly assigned to receive either nicergoline 30 mg b.i.d. (n = 36) or a placebo (n = 36) for 24 months. All patients received antihypertensives and their hypertension was controlled under treatment. They were evaluated by nine neuropsychological tests exploring memory, concentration, verbal and motor performances, administered at baseline and at every six-month interval during the study period. At baseline, the two groups were comparable for all demographic and clinical characteristics, including cognitive functions, except for the delayed recall of the Auditory Verbal Learning Test (AVLT), which was better in the placebo group (P = 0.04). Changes in scores over time were compared between the two groups. At the last visit, patients on nicergoline (n = 31) were found to have deteriorated less or to have improved more on test scores than the patients on placebo (n = 30). Significant differences were observed for memory function (AVLT short term recall, P = 0.026; AVLT delayed recall, P = 0.013; and, Benton Visual Retention Test, P = 0.002) and attention and concentration (Letter Cancellation Test, P = 0.043; and, WAIS-R Digit Symbol subtest, P = 0.006). The Rezek score remained unchanged in the two groups. Tolerance of nicergoline was similar to that of placebo. In conclusion, this study shows that nicergoline 30 mg b.i. d. administered over a 24-month period attenuates the deterioration in cognitive functions in elderly hypertensive patients with leukoaraiosis. Whether these effects were specific for this type of white matter changes could not be determined in the context of this pilot study.

Aged↗
PubMed2001

Open-label study of donepezil in traumatic brain injury.

OBJECTIVE: To determine preliminarily whether donepezil will improve memory, behavior, and global function after chronic traumatic brain injury (TBI). DESIGN: Sixteen-week open-label study. SETTING: Outpatient TBI rehabilitation program. PATIENTS: Four patients with chronic, severe TBI. INTERVENTIONS: Donepezil 5mg daily for 8 weeks followed by 10mg daily for 4 weeks. MAIN OUTCOME MEASURES: Memory measures included the Rey Auditory Verbal Learning Test (RAVLT), the Complex Figure Test (CFT), items from the Rivermead Behavioural Memory Test (RBMT), and a semantic fluency task. The Neuropsychiatric Inventory (NPI) evaluated behavior and affect. Function was assessed by using the FIM instrument and a clinical global impression of change. RESULTS: On the RAVLT, the mean scores for learning and short- and long-term recall improved by 0.4, 1.04, and.83 standard deviations (SDs) above baseline, respectively. On the CFT, the mean scores for short-term recall and long-term recall improved by 1.56 and 1.38 SDs above baseline, respectively. A positive trend was observed on the RBMT and on the NPI subscales. CONCLUSIONS: Donepezil may improve some aspects of memory and behavior in persons with chronic TBI. Randomized clinical trials are required to support these preliminary findings.

Adult↗
PubMed2003

Cognitive dysfunction and health-related quality of life in long-term liver transplant survivors.

Although several studies have investigated short-term effects of liver transplantation on cognitive function and health-related quality of life, there have been no studies looking at long-term effects. Patients who received a single liver transplant at St James's University Hospital (Leeds, UK) before October 1, 1991, were invited to participate in this cross-sectional study. Cognitive function was assessed using the Mini-Mental State Examination, the Rey Auditory Verbal Learning Test, trail-making tests, the Stroop test, and the Benton Visual Retention Test. Anxiety and depression were documented using the Hospital Anxiety and Depression Scale. Health-related quality of life was assessed using the EuroQol. Twenty-five healthy volunteers acted as controls. Thirty-six patients had undergone transplantation before October 1, 1991. Thirteen patients (36%) had died, 6 patients had received more than one transplant, 2 patients did not speak English, and 3 patients did not want to participate, leaving 12 patients included in the study. Patients scored significantly lower on measures of health-related quality of life than healthy controls, but there were no differences in levels of anxiety or depression. Patients scored significantly lower than controls across a wide range of cognitive functions, suggesting global cognitive impairment. We show that patients who survive for more than 10 years after liver transplantation have significant cognitive dysfunction and poor health-related quality of life. Whether these patients never return to normal after transplantation or whether they experience an increased rate of decline in cognitive function and health-related quality of life is uncertain and requires further study.

Aged↗