Biomedical subjects

Nelly Alia-Klein

Publications and source records attributed to Nelly Alia-Klein.

7 recordsLinked to original sources

PubMed2026

Dynamic Alterations in the Blood Transcriptome Characterize Drug Use Behavior and Co-Morbidities in Cocaine Use Disorder: A Preliminary Study.

Individuals with cocaine use disorder (CUD) who attempt abstinence experience craving and relapse that can benefit from multimodal treatment monitoring. Longitudinal studies linking behavioral manifestations in CUD to the blood transcriptome are not only limited but also computationally complex. Therefore, we developed an analytical pipeline to investigate the connection between drug use behaviors during abstinence and change in the blood transcriptome. We conducted a longitudinal study with CUD (n = 12 subjects) and collected behavioral metrics and blood RNA-seq at baseline, 3, 6, and 9 months. Our analytical pipeline of the high-dimensional data encompasses hierarchical k-means clustering to classify subjects to responder groups based on behavioral scores and abstinence duration, in silico cell deconvolution, differential analysis with correlated multivariate testing over time, gene set enrichment analysis, and gene co-expression with time splines and RNA-seq data. The pipeline captured dynamic changes in behavioral scores and abstinence duration in responder groups. Genes showing differential transcript-level expression were enriched in substance use and cardiovascular disease-associated genetic risk loci in responder groups. Lastly, time-dependent gene co-expression revealed dynamic changes related to immune processes, cell cycle, RNA-protein synthesis, and second messenger signaling for days of abstinence. This is a preliminary investigation, providing an innovative and scalable pipeline for blood-based longitudinal RNA-seq studies in CUD, potentially applicable to other substance use disorders. It outlines a data-driven approach for analyzing composite longitudinal drug use behavioral phenotypes with blood-based transcriptomics. We also demonstrate changes in drug use behaviors and the blood transcriptome during drug abstinence.

Humans↗

PubMed2007

Is decreased prefrontal cortical sensitivity to monetary reward associated with impaired motivation and self-control in cocaine addiction?

OBJECTIVE: This study attempted to examine the brain's sensitivity to monetary rewards of different magnitudes in cocaine abusers and to study its association with motivation and self-control. METHOD: Sixteen cocaine abusers and 13 matched healthy comparison subjects performed a forced-choice task under three monetary value conditions while brain activation was measured with functional magnetic resonance imaging. Objective measures of state motivation were assessed by reaction time and accuracy, and subjective measures were assessed by self-reports of task engagement. Measures of trait motivation and self-control were assessed with the Multidimensional Personality Questionnaire. RESULTS: The cocaine abusers demonstrated an overall reduced regional brain responsivity to differences between the monetary value conditions. Also, in comparison subjects but not in cocaine abusers, reward-induced improvements in performance were associated with self-reports of task engagement, and money-induced activations in the lateral prefrontal cortex were associated with parallel activations in the orbitofrontal cortex. For cocaine abusers, prefrontal cortex sensitivity to money was instead associated with motivation and self-control. CONCLUSIONS: These findings suggest that in cocaine addiction 1) activation of the corticolimbic reward circuit to gradations of money is altered; 2) the lack of a correlation between objective and subjective measures of state motivation may be indicative of disrupted perception of motivational drive, which could contribute to impairments in self-control; and 3) the lateral prefrontal cortex modulates trait motivation and deficits in self-control, and a possible underlying mechanism may encompass a breakdown in prefrontal-orbitofrontal cortical communication.

Adult↗

PubMed2006

Evidence that brain MAO A activity does not correspond to MAO A genotype in healthy male subjects.

BACKGROUND: A functional polymorphism in the promoter region of the monoamine oxidase A (MAO A) gene has two common alleles that are referred to as the high and low MAO A genotypes. We report the first in vivo human study to determine whether there is an association between MAO A genotype and brain MAO A activity in healthy male subjects. METHODS: Brain MAO A activity was measured with positron emission tomography and [(11)C]clorgyline in 38 healthy adult male nonsmokers genotyped for MAO A polymorphism. RESULTS: There was no significant difference in brain MAO A activity between the high (n = 26) and low (n = 12) MAO A genotypes. CONCLUSIONS: The lack of an association between the high and low MAO A genotype and brain MAO A activity suggests that this polymorphism by itself does not contribute to differences in brain MAO A activity in healthy adult male subjects.

Adult↗

PubMed2006

Subjective sensitivity to monetary gradients is associated with frontolimbic activation to reward in cocaine abusers.

Drug addiction is characterized by marked disruptions in the ability to process reward. Here we evaluated in cocaine addicted and healthy control participants the subjective sensitivity to reward gradients and its association with neural responses to sustained reward. A self-report questionnaire was used to assess the former. A functional magnetic resonance imaging task that utilized monetary reward as feedback in a blocked design was used to assess the latter. Results revealed that whereas control subjects valued high money more than low money, over half of the cocaine addicted subjects valued all monetary amounts equally. This compromised subjective sensitivity to gradients in reward value was significantly correlated with higher activations to money in the lateral orbitofrontal cortex/inferior frontal gyrus (BA 47) and amygdala, and lower activations in the middle frontal gyrus (BA 6), which together explained 85% of the variability on this rating scale in the cocaine abusers only. These results provide for the first time evidence of restricted subjective sensitivity to gradients of reward in cocaine addiction and of the involvement of frontolimbic brain regions (including the orbitofrontal cortex) in this deficit.

Cocaine-Related Disorders↗

PubMed2005

Anger and depression in cocaine addiction: association with the orbitofrontal cortex.

The high prevalence of anger, impulsivity and violence in cocaine addiction implicates chronic cocaine use in the compromise of higher-order inhibitory control neurocognitive processes. We used the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) anger content scale as a personality measure of inhibitory control and examined its association with glucose metabolism in the lateral orbitofrontal gyrus (LOFG) at rest as measured by positron emission tomography with 2-deoxy-2[(18)F]fluoro-D-glucose (PET (18)FDG) in 17 recently abstinent cocaine-dependent subjects and 16 comparison subjects. Three additional variables--the MMPI-2 depression content scale, metabolism in the medial orbitofrontal gyrus (MOFG) and the anterior cingulate (AC) gyrus--were inspected. When level of education was statistically controlled for, the LOFG was significantly associated with anger within the cocaine group. No other region was associated with anger within the cocaine-dependent group, and the LOFG did not correlate with depression within any of the study groups. The present study confirms earlier reports in demonstrating a positive association between relative metabolism at rest in the LOFG and cognitive-behavioral and personality measures of inhibitory control in drug addiction: the higher the metabolism, the better the inhibitory control.

Adult↗

PubMed2005

Exploiting temporal information in functional magnetic resonance imaging brain data.

Functional Magnetic Resonance Imaging(fMRI) has enabled scientists to look into the active human brain, leading to a flood of new data, thus encouraging the development of new data analysis methods. In this paper, we contribute a comprehensive framework for spatial and temporal exploration of fMRI data, and apply it to a challenging case study: separating drug addicted subjects from healthy non-drug-using controls. To our knowledge, this is the first time that learning on fMRI data is performed explicitly on temporal information for classification in such applications. Experimental results demonstrate that, by selecting discriminative features, group classification can be successfully performed on our case study although training data are exceptionally high dimensional, sparse and noisy fMRI sequences. The classification performance can be significantly improved by incorporating temporal information into machine learning. Both statistical and neuroscientific validation of the method's generalization ability are provided. We demonstrate that incorporation of computer science principles into functional neuroimaging clinical studies, facilitates deduction about the behavioral probes from the brain activation data, thus providing a valid tool that incorporates objective brain imaging data into clinical classification of psychopathologies and identification of genetic vulnerabilities.

Algorithms↗

PubMed2002

Schizophrenia risk and paternal age: a potential role for de novo mutations in schizophrenia vulnerability genes.

How schizophrenia (SZ) is maintained at roughly 1% of the population despite diminished reproduction is one puzzle currently facing researchers. De novo mutations were first proposed over half a century ago as a source for new SZ genes. Current evidence linking advancing paternal age to SZ risk makes revisiting this hypothesis important. Advancing paternal age is the major source of new mutations in the human population. This article will examine potential mechanisms whereby parental age may impact new mutations, as well as review recent data supporting such a hypothesis.

Journal Article↗