Renata Cupertino

University of California, San Diego | UCSD · Department of Psychiatry

Background and Aims Recently, we demonstrated that a distinct pattern of structural covariance networks (SCN) from magnetic resonance imaging (MRI)‐derived measurements of brain cortical thickness characterized young adults with alcohol use disorder (AUD) and predicted current and future problematic drinking in adolescents relative to controls. Her...

Leveraging ~10 years of prospective longitudinal data on 704 participants, we examined the effects of adolescent versus young adult cannabis initiation on MRI-assessed cortical thickness development and behavior. Data were obtained from the IMAGEN study conducted across eight European sites. We identified IMAGEN participants who reported being cann...

Introduction: Fetal alcohol spectrum disorder (FASD), a life-long condition resulting from prenatal alcohol exposure (PAE), is associated with structural brain anomalies and neurobehavioral differences. Evidence from longitudinal neuroimaging suggest trajectories of white matter microstructure maturation are atypical in PAE. We aimed to further ch...

Several GWAS reported Myocyte Enhancer Factor 2 C (MEF2C) gene associations with white matter microstructure and psychiatric disorders, and MEF2C involvement in pathways related to neuronal development suggests a common biological factor underlying these phenotypes. We aim to refine the MEF2C effects in the brain relying on an integrated analysis o...

The course of ADHD from childhood up to young adulthood has been characterized in several studies. However, little is known about the course of symptoms into middle age and beyond. This study aims to evaluate predictors of ADHD trajectories in midlife based on three assessments. The follow-up sample comprised 323 adults with ADHD, evaluated at base...

Introduction: Genome Wide Association Studies (GWAS) revealed the highly polygenic architecture of Attention-Deficit/Hyperactivity Disorder (ADHD) and highlighted the contribution of common variants related to brain development and function. In parallel, several imaging studies attempted to discover disorder-related brain structures, with some sign...

The neurobiological bases of the association between development and psychopathology remain poorly understood. Here, we identify a shared spatial pattern of cortical thickness (CT) in normative development and several psychiatric and neurological disorders. Principal component analysis (PCA) was applied to CT of 68 regions in the Desikan-Killiany a...

Importance: Past studies have identified associations between brain macrostructure and alcohol use behaviors. However, identifying directional associations between these phenotypes is difficult due to the limitations of observational studies. Objective: To use mendelian randomization (MR) to identify directional associations between brain struct...

While there is substantial evidence that cannabis use is associated with differences in human brain development, most of this evidence is correlational in nature. Bayesian causal network (BCN) modeling attempts to identify probable causal relationships in correlational data using conditional probabilities to estimate directional associations betwee...

One of the main challenges in investigating the neurobiology of ADHD is our limited capacity to study its neurochemistry in vivo. Magnetic resonance spectroscopy (MRS) estimates metabolite concentrations within the brain, but approaches and findings have been heterogeneous. To assess differences in brain metabolites between patients with ADHD and h...

The Forkhead box P2 (FOXP2) encodes for a transcription factor with a broad role in embryonic development. It is especially represented among GWAS hits for neurodevelopmental disorders and related traits, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, neuroticism, and risk-taking behaviors. While several functi...

Background Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/peri-natal period may be reflected in individual variations in cortical surface area. Methods Inter-regional profiles of grou...

Background and aims Graph theoretic analysis of structural covariance networks (SCN) provides an assessment of brain organization that has not yet been applied to alcohol dependence (AD). We estimated whether SCN differences are present in adults with AD and heavy drinking adolescents at age 19 and age 14, prior to substantial exposure to alcohol....

The Synaptotagmin-1 encoding gene ( SYT1 ) is a key regulator of neurotransmitter release and is associated with cognitive and psychiatric phenotypes in GWAS, and with ADHD in single-gene studies, raising the need for dissecting possible cross-trait effects on clinical and brain phenotypes. Inferences about white matter microstructure can be made b...

ADHD is associated with smaller subcortical brain volumes and cortical surface area, with greater effects observed in children than adults. It is also associated with dysregulation of the HPA axis. Considering the effects of the glucocorticoid receptor (NR3C1) in neurophysiology, we hypothesize that the blurred relationships between brain structure...

Mixed findings exist in studies comparing brain responses to reward in adolescents and adults. Here we examined the trajectories of brain response, functional connectivity and task-modulated network properties during reward processing with a large-sample longitudinal design. Participants from the IMAGEN study performed a Monetary Incentive Delay ta...

Background Nicotine and illicit stimulants are very addictive substances. Although associations between grey matter and dependence on stimulants have been frequently reported, white matter correlates have received less attention. Methods Eleven international sites ascribed to the ENIGMA-Addiction consortium contributed data from individuals with d...

White matter (WM) abnormalities in patients with cocaine use disorder (CUD) have been studied; however, the reported effects on the human brain are heterogenous and most results have been obtained from male participants. In addition, biological data supporting the imaging findings and revealing possible mechanisms underlying the neurotoxic effects...

Objective: Some studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium. Methods: We analyzed...

Despite major advances in the study of the brain, investigations on neurochemistry in vivo still lack the solid ground of more established methods, such as structural and functional magnetic resonance imaging. Proton magnetic resonance spectroscopy (MRS) is a technique that might potentially fill in this gap. Nevertheless, studies using this approa...

Brain asymmetry reflects left‐right hemispheric differentiation, which is a quantitative brain phenotype that develops with age and can vary with psychiatric diagnoses. Previous studies have shown that substance dependence is associated with altered brain structure and function. However, it is unknown whether structural brain asymmetries are differ...

Importance Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood. Objective To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: atten...

Attention-Deficit/Hyperactivity Disorder (ADHD) has been associated with altered brain anatomy in neuroimaging studies. However, small and heterogeneous study samples, and the use of region-of-interest and tissue-specific analyses have limited the consistency and replicability of these effects. We used a data-driven multivariate approach to investi...

Abstract Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder in children and adults. Neuroanatomic heterogeneity limits our understanding of the etiology of ADHD. This study aimed to parse neuroanatomic heterogeneity of ADHD, and to determine whether subgroups could be discerned in patients based...

Daylight is the strongest synchronizer of human circadian rhythms. The circadian pathway hypothesis posits that synchrony between daylight and the circadian system relates to (in)attention. The dopamine neurotransmitter system is implicated in regulating the circadian system as well as in (attention)-deficit hyperactivity disorder [ADHD]. We studie...

Objective Neuroimaging studies have associated Attention-Deficit/Hyperactivity Disorder (ADHD) with altered brain anatomy. However, small and heterogeneous study samples, and the use of region-of-interest and tissue-specific analyses have limited the consistency and replicability of these effects. The present study uses a fully data-driven multivar...

The SNP rs2251214 of the SYT1 gene was recently associated with externalizing phenotypes, including ADHD and cocaine use disorder (CUD). Here, we investigated whether SYT1-rs2251214 could also be implicated with cognitive performance variations among women with CUD. Results showed that G homozygous (n = 146) have lower cognitive performance in the...

Synaptotagmin-1 is an essential regulator of synaptic vesicle exocytosis, and its encoding gene (SYT1) is a genome and transcriptome-wide association hit in cognitive performance, personality and cocaine use disorder (CUD) studies. Additionally, in candidate gene studies the specific variant rs2251214 has been associated with attention-deficit/hype...

There is evidence that dopamine receptors D2 (DRD2) and D4 (DRD4) polymorphisms may influence substance use disorders (SUD) susceptibility both individually and through their influence in the formation of DRD2–DRD4 heteromers. The dopaminergic role on the vulnerability to addiction appears to be influenced by sex. A cross-sectional study with 307 c...

Background ADHD is a common neuropsychiatric disorder, it is highly heritable and polygenic, with a great number of combinations of variants, each with small effects, involved in its underlying molecular processes. However, the identification of the specific genetic factors associated to ADHD is still a great challenge, and genome-wide significant...

Background Synaptotagmin 1 is expressed in synaptic vesicles and plays an important role on neuroexocytosis. A variant in its encoding gene (SYT1-rs2251214) has been associated with ADHD susceptibility and with other externalizing behaviors and comorbidities. Recently, it was also shown to influence response variability to Methylphenidate (MPH) in...

Background Attention-Deficit Hyperactivity Disorder (ADHD) is highly heritable and has been associated with several genes in different reports. The serotonergic genes are among the most consistently associated with ADHD and related phenotypes, according to meta-analyses. Therefore, the aim of this study was to investigate associations between serot...

Background Substantial interindividual variability is observed in treatment response to Methylphenidate (MPH), which is considered the first-line pharmacological treatment for adults with ADHD. In addition to its main known mechanism of action involving the blockade of the dopamine transporter, experimental studies have also indicated an ability of...

Objective: This study evaluated the hypothesis that methylphenidate immediate release (MPH-IR) treatment would improve Default Mode Network (DMN) within-connectivity. Method: Resting-state functional connectivity of the main nodes of DMN was evaluated in a highly homogeneous sample of 18 drug-naive male adult participants with ADHD. Results: Compar...

Background: A history of childhood maltreatment (HCM) has been associated with detrimental psychiatric outcomes. This is particularly true for transgender, for whom there is initial evidence that HCM may be associated with psychiatric morbidity. Our study aimed to further characterize the relationship between HCM and the development of mental disor...

Attention-deficit/hyperactivity disorder (ADHD) is a very common psychiatric disorder across the life cycle and frequently presents comorbidities. Since ADHD is highly heritable, several studies have focused in the underlying genetic factors involved in its etiology. One of the major challenges in this search is the phenotypic heterogeneity, which...

Attention-deficit/hyperactivity disorder (ADHD) is highly heritable and has been associated with multiple variants within serotonergic genes. Therefore, the aim of this study was to investigate associations between serotonergic pathway genes and ADHD, through both gene-based and gene-set approaches. The sample comprised 417 subjects with ADHD and 4...

Attention-Deficit/Hyperactivity Disorder (ADHD) is a common and highly heritable neuropsychiatric disorder. Despite the high heritability, the unraveling of specific genetic factors related to ADHD is hampered by its considerable genetic complexity. Recent evidence suggests that gene-gene interactions can explain part of this complexity. We examine...

Experimental studies have demonstrated that methylphenidate (MPH) modulates the synaptic vesicle trafficking and synaptotagmin-1 (SytI) mRNA levels. SytI is a regulatory protein of the SNARE complex, a neurotransmitter exocytosis mediator. Despite this evidence, most SNARE complex-related genes have never been evaluated in attention-deficit/hyperac...

Attention-Deficit/Hyperactivity Disorder (ADHD) is a common psychiatric disorder, affecting both children and adults. The Soluble N-ethylmaleimide sensitive factor Attachment REceptors (SNARE) complex has been implicated in ADHD pathophysiology since it is a key component of neurotransmitter release events and neurodevelopment processes, and SNPs i...

The serotonin system is associated with mood disorders and impulsivity. The serotonin transporter is encoded by SLC6A4 gene and may influence alcohol intake. Along this gene, STin2 is described as a functional VNTR polymorphism of 17bp, in intron 2, with three main alleles (9, 10 and 12 repeats); 9 repeats is the less frequent among these (<1%). Th...

Multiple biological processes throughout development require intracellular vesicular trafficking, where the SNARE (soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptors) complex plays a major role. The core proteins forming the SNARE complex are SNAP-25 (synaptosomal-associated protein 25), VAMP (vesicle-associated mem...

Background: The corticotropin-releasing hormone receptor 1 (CRHR1) gene has been repeatedly implicated in Major Depressive Disorder (MDD) in humans and animal models; however, the findings are not absolutely convergent. Since recent evidence from genome-wide association studies suggests that narrowing the phenotypic heterogeneity may be crucial in...

Several investigations documented that Attention-Deficit/Hyperactivity Disorder (ADHD) is better conceptualized as a dimensional disorder. At the same time, the disorder seems to have different neurobiological underpinnings and phenotypic presentation in children compared to adults. Neurodevelopmental genes could explain, at least partly these diff...

A number of studies have demonstrated that stress is involved in all aspects of smoking behavior, including initiation, maintenance and relapse. The mineralocorticoid (MR) and glucocorticoid (GR) receptors are expressed in several brain areas and play a key role in negative feedback of the hypothalamic-pituitary-adrenal (HPA) axis. As nicotine incr...