Neurobiological Profiles Research Articles

228. Polygenic Pleiotropy and Potential Causal Relationships between Neurobiological Profile for Psychosis, Higher Cognitive Ability, and Positive Psychotic Symptoms

228. Polygenic Pleiotropy and Potential Causal Relationships between Neurobiological Profile for Psychosis, Higher Cognitive Ability, and Positive Psychotic Symptoms

Adolescent cocaine exposure enhances goal-tracking behavior and impairs hippocampal cell genesis selectively in adult bred low-responder rats.

Environmental challenges during adolescence, such as drug exposure, can cause enduring behavioral and molecular changes that contribute to life-long maladaptive behaviors, including addiction. Selectively bred high-responder (bHR) and low-responder (bLR) rats represent a unique model for assessing the long-term impact of adolescent environmental manipulations, as they inherently differ on a number of addiction-related traits. bHR rats are considered "addiction-prone," whereas bLR rats are "addiction-resilient," at least under baseline conditions. Moreover, relative to bLRs, bHR rats are more likely to attribute incentive motivational value to reward cues, or to "sign-track." We utilized bHR and bLR rats to determine whether adolescent cocaine exposure can alter their inborn behavioral and neurobiological profiles, with a specific focus on Pavlovian conditioned approach behavior (i.e., sign- vs. goal-tracking) and hippocampal neurogenesis. bHR and bLR rats were administered cocaine (15mg/kg) or saline for 7days during adolescence (postnatal day, PND 33-39) and subsequently tested for Pavlovian conditioned approach behavior in adulthood (PND 62-75), wherein an illuminated lever (conditioned stimulus) was followed by the response-independent delivery of a food pellet (unconditioned stimulus). Behaviors directed toward the lever and the food cup were recorded as sign- and goal-tracking, respectively. Hippocampal cell genesis was evaluated on PND 77 by immunohistochemistry. Adolescent cocaine exposure impaired hippocampal cell genesis (proliferation and survival) and enhanced the inherent propensity to goal-track in adult bLR, but not bHR, rats. Adolescent cocaine exposure elicits long-lasting changes in stimulus-reward learning and enduring deficits in hippocampal neurogenesis selectively in adult bLR rats.

Impulse Control and Related Disorders in Parkinson's Disease.

Impulse control disorders (ICDs), such as compulsive gambling, buying, sexual, and eating behaviors, are a serious and increasingly recognized complication in Parkinson's disease (PD), occurring in up to 20% of PD patients over the course of their illness. Related behaviors include punding (stereotyped, repetitive, purposeless behaviors), dopamine dysregulation syndrome (DDS) (compulsive medication overuse), and hobbyism (e.g., compulsive internet use, artistic endeavors, and writing). These disorders have a significant impact on quality of life and function, strain interpersonal relationships, and worsen caregiver burden, and are associated with significant psychiatric comorbidity. ICDs have been most closely related to the use of dopamine agonists (DAs), while DDS is primarily associated with shorter acting, higher potency dopamine replacement therapy (DRT), such as levodopa. However, in preliminary research ICDs have also been reported to occur with monoamine oxidase inhibitor-B and amantadine treatment, and after deep brain stimulation (DBS) surgery. Other risk factors for ICDs may include sex (e.g., male sex for compulsive sexual behavior, and female sex for compulsive buying behavior); younger age overall at PD onset; a pre-PD history of an ICD; personal or family history of substance abuse, bipolar disorder, or gambling problems; and impulsive personality traits. Dysregulation of the mesocorticolimbic dopamine system is thought to be the major neurobiological substrate for ICDs in PD, but there is preliminary evidence for alterations in opiate and serotonin systems too. The primary treatment of ICDs in PD is discontinuation of the offending treatment, but not all patients can tolerate this due to worsening motor symptoms or DA withdrawal syndrome. While psychiatric medications and psychosocial treatments are frequently used to treat ICDs in the general population, there is limited empirical evidence for their use in PD, so it is critical for patients to be monitored closely for ICDs from disease onset and routine throughout its course. In the future, it may be possible to use a precision medicine approach to decrease the incidence of ICDs in PD by avoiding DA use in patients determined to be at highest risk based on their clinical and neurobiological (e.g., motor presentation, behavioral measures of medication response, genetics, dopamine transporter neuroimaging) profile. Additionally, as empirically validated treatments for ICDs and similar disorders (e.g., substance use disorders) emerge, it will also be important to examine their efficacy and tolerability in individuals with comorbid PD.

Oxytocin system dysfunction as a common mechanism underlying metabolic syndrome and psychiatric symptoms in schizophrenia and bipolar disorders.

There is growing interest in using intranasal oxytocin (OT) to treat social dysfunction in schizophrenia and bipolar disorders (i.e., psychotic disorders). While OT treatment results have been mixed, emerging evidence suggests that OT system dysfunction may also play a role in the etiology of metabolic syndrome (MetS), which appears in one-third of individuals with psychotic disorders and associated with increased mortality. Here we examine the evidence for a potential role of the OT system in the shared risk for MetS and psychotic disorders, and its prospects for ameliorating MetS. Using several studies to demonstrate the overlapping neurobiological profiles of metabolic risk factors and psychiatric symptoms, we show that OT system dysfunction may be one common mechanism underlying MetS and psychotic disorders. Given the critical need to better understand metabolic dysregulation in these disorders, future OT trials assessing behavioural and cognitive outcomes should additionally include metabolic risk factor parameters.

Salivary Cortisol Levels in Abused Children with Attention Deficit Hyperactivity Disorder

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is the most common neurobehavioral disorder during childhood. Family violence is a psychosocial factor that has been recently introduced in the literature about ADHD, with indications that parents of hyperactive children are more likely to use physical methods to their discipline. Cortisol as the primary stress hormone and as an index of the hypothalamic-pituitary-adrenal axis regulation has been used to study the neurobiological profile of ADHD patients. Methods: This study was conducted on 50 ADHD children & 30 matched controls, severity was assessed using the Conners’ Parent Rating Scales-Revised long version, children IQ and exposure to abuse was measured; salivary cortisol levels was measured using enzyme- linked immunosorbent assay in two samples (ELISA). Aim of the study was to measure prevalence and impact of abuse on ADHD children and correlate results with salivary cortisol level Results: Results showed significant higher exposure of ADHD children to parental abuse than control group. Executive function showed to be impaired in abused ADHD children, lower bedtime cortisol level in abused ADHD children compared to control. There was a negative correlation between cortisol level and child abuse. In addition, there was a negative correlation between different types of abuse and components of WCST. While no correlation between both cortisol samples and components of WCST. Conclusion: We concluded that children with ADHD displayed higher exposure to parental abuse, lower cognitive function and this was linked to their lower levels of cortisol level.

Magnetic Resonance Imaging Studies of Postpartum Depression: An Overview.

Postpartum depression is a frequent and disabling condition whose pathophysiology is still unclear. In recent years, the study of the neural correlates of mental disorders has been increasingly approached using magnetic resonance techniques. In this review we synthesize the results from studies on postpartum depression in the context of structural, functional, and spectroscopic magnetic resonance studies of major depression as a whole. Compared to the relative wealth of data available for major depression, magnetic resonance studies of postpartum depression are limited in number and design. A systematic literature search yielded only eleven studies conducted on about one hundred mothers with postpartum depression overall. Brain magnetic resonance findings in postpartum depression appear to replicate those obtained in major depression, with minor deviations that are not sufficient to delineate a distinct neurobiological profile for this condition, due to the small samples used and the lack of direct comparisons with subjects with major depression. However, it seems reasonable to expect that studies conducted in larger populations, and using a larger variety of brain magnetic resonance techniques than has been done so far, might allow for the identification of neuroimaging signatures for postpartum depression.

From the Multifactorial Nature of Alzheimer`s Disease to Multitarget Therapy: The Contribution of the Translational Approach

The drug discovery for disease-modifying agents in Alzheimer disease (AD) is facing a failure of clinical trials with drugs based on two driving hypotheses, i.e. the cholinergic and amyloidogenic hypotheses. In this article we recapitulate the main aspects of AD pathology, focusing on possible mechanisms for synaptic dysfunction, neurodegeneration and inflammation. We then present the pharmacological and neurobiological profile of a novel compound (CHF5074) showing both anti-inflammatory and gamma-secretase modulatory activities, discussing the possible time-window for effective treatment in an AD transgenic mouse model. Finally, the concept of cognitive reserve is introduced as possible target for preventive therapies.

Not All Reading Disabilities Are Dyslexia: Distinct Neurobiology of Specific Comprehension Deficits

Although an extensive literature exists on the neurobiological correlates of dyslexia (DYS), to date, no studies have examined the neurobiological profile of those who exhibit poor reading comprehension despite intact word-level abilities (specific reading comprehension deficits [S-RCD]). Here we investigated the word-level abilities of S-RCD as compared to typically developing readers (TD) and those with DYS by examining the blood oxygenation-level dependent response to words varying on frequency. Understanding whether S-RCD process words in the same manner as TD, or show alternate pathways to achieve normal word-reading abilities, may provide insights into the origin of this disorder. Results showed that as compared to TD, DYS showed abnormal covariance during word processing with right-hemisphere homologs of the left-hemisphere reading network in conjunction with left occipitotemporal underactivation. In contrast, S-RCD showed an intact neurobiological response to word stimuli in occipitotemporal regions (associated with fast and efficient word processing); however, inferior frontal gyrus (IFG) abnormalities were observed. Specifically, TD showed a higher-percent signal change within right IFG for low-versus-high frequency words as compared to both S-RCD and DYS. Using psychophysiological interaction analyses, a coupling-by-reading group interaction was found in right IFG for DYS, as indicated by a widespread greater covariance between right IFG and right occipitotemporal cortex/visual word-form areas, as well as bilateral medial frontal gyrus, as compared to TD. For S-RCD, the context-dependent functional interaction anomaly was most prominently seen in left IFG, which covaried to a greater extent with hippocampal, parahippocampal, and prefrontal areas than for TD for low- as compared to high-frequency words. Given the greater lexical access demands of low frequency as compared to high-frequency words, these results may suggest specific weaknesses in accessing lexical-semantic representations during word recognition. These novel findings provide foundational insights into the nature of S-RCD, and set the stage for future investigations of this common, but understudied, reading disorder.

Pre-existing brain function predicts subsequent practice of mindfulness and compassion meditation

While a variety of meditation techniques are increasingly employed as health interventions, the fact that meditation requires a significant commitment of time and effort may limit its potential widespread utility. In the current study, we ask whether baseline subjective reports or brain activity in response to a "Pain for Self and Others" paradigm predicts subsequent engagement in mindfulness and compassion meditation. The study also investigated whether compassion training would impact neural responses when compared to an active health education control group. Prior to training, activation of the left and right anterior insula, an area thought to be important for empathy, in response to the Other pain task was positively related to engagement with compassion meditation as measured by practice time (n=13). On the other hand, activity in the left amygdala during the Self pain task was negatively correlated with mindfulness practice time. Following the study intervention, there was no difference between the compassion group (n=13), and the control group (n=8), in brain responses to either the Self or Other task. These results are the first to indicate that baseline neural responses may predict engagement with meditation training and suggest that pre-existing neurobiological profiles differentially predispose individuals to engage with disparate meditation techniques.

The Translation of Substance Dependence Criteria to Food-Related Behaviors: Different Views and Interpretations

The Translation of Substance Dependence Criteria to Food-Related Behaviors: Different Views and Interpretations

Alcoholism and Diabetes Mellitus

Chronic use of alcohol is considered to be a potential risk factor for the incidence of type 2 diabetes mellitus (T2DM), which causes insulin resistance and pancreatic β-cell dysfunction that is a prerequisite for the development of diabetes. However, alcohol consumption in diabetes has been controversial and more detailed information on the diabetogenic impact of alcohol seems warranted. Diabetes, especially T2DM, causes dysregulation of various metabolic processes, which includes a defect in the insulin-mediated glucose function of adipocytes, and an impaired insulin action in the liver. In addition, neurobiological profiles of alcoholism are linked to the effects of a disruption of glucose homeostasis and of insulin resistance, which are affected by altered appetite that regulates the peptides and neurotrophic factors. Since conditions, which precede the onset of diabetes that are associated with alcoholism is one of the crucial public problems, researches in efforts to prevent and treat diabetes with alcohol dependence, receives special clinical interest. Therefore, the purpose of this mini-review is to provide the recent progress and current theories in the interplay between alcoholism and diabetes. Further, the purpose of this study also includes summarizing the pathophysiological mechanisms in the neurobiology of alcoholism.

Cortisol reactivity in boys with attention-deficit/hyperactivity disorder and disruptive behavior problems: The impact of callous unemotional traits

There is a body of literature demonstrating an association between altered hypothalamic pituitary adrenal (HPA) axis reactivity and aggressive behavior. Aggressive and disruptive behavior also is highly prevalent in children with attention deficit/hyperactivity disorder (ADHD). Findings on HPA-axis reactivity in ADHD, however, are rather inconsistent. Specific temperamental risk factors previously were associated with a specific subtype of severe disruptive behavior. These traits might also be characterized by a distinct neurobiological profile across ADHD and disruptive behavior disorders. In this study we focus on psychopathic traits, notably callous unemotional (CU) traits. The main objective of the present study was to investigate whether two groups of ADHD patients with high or low CU traits differed in cortisol reactivity. Subjects were 36 boys with ADHD and disruptive behavior symptoms aged 8 to 14years. Salivary cortisol probes were taken before and repeatedly after an experimental standardized stress test. Patients scoring high on CU traits showed a blunted HPA axis reactivity to the experimentally induced stress. Results underscore the need to consider specific personality traits in investigating neurobiological correlates in ADHD with disruptive behavior problems.

Fingolimod is a potential novel therapy for multiple sclerosis

Fingolimod (also known as FTY720) is an orally available sphingosine-1-phosphate (S1P) receptor modulator that has unique and potent immunoregulatory properties. Mechanistic studies indicate that on phosphorylation fingolimod can bind with high affinity to S1P(1) receptors. Persistent modulation of lymphocyte S1P(1) receptors by fingolimod and the subsequent internalization of these receptors inhibits lymphocyte egress from the lymph nodes, and prevents these cells from infiltrating inflammatory lesions in the CNS. Results of two phase III studies--FREEDOMS and TRANSFORMS--support previous phase II trial observations indicating that fingolimod exerts powerful anti-inflammatory effects in relapsing-remitting multiple sclerosis (MS). Fingolimod might, therefore, be one of the first orally active drug therapies available for the treatment of relapsing-remitting MS. Moreover, results from preclinical studies suggest that fingolimod might promote neural repair in vivo. In this article, we review the background to these findings, present the proposed immunological and neurobiological profile of fingolimod, discuss the data from the FREEDOMS and TRANSFORMS trials, and provide an expert opinion regarding the future of next-generation S1P receptor modulators for MS therapy.

Cortical thickness and subcortical gray matter reductions in neuropsychiatric systemic lupus erythematosus.

Within systemic lupus erythematosus (SLE) patients can be divided into groups with and without central nervous system involvement, the latter being subcategorized as neuropsychiatric systemic lupus erythematosus (NPSLE). While a number of research groups have investigated NPSLE, there remains a lack of consistent application of this diagnostic criteria within neuroimaging studies. Previous neuroimaging research suggests that SLE patients have reduced subcortical and regional gray matter volumes when compared to controls, and that these group differences may be driven by SLE patients with neuropsychiatric symptoms. The current study sought to compare measures of cortical thickness and subcortical structure volume between NPSLE, SLE, and healthy controls. We hypothesized that patients with NPSLE (N = 21) would have thinner cortex and reduced subcortical gray matter volumes when compared to SLE (N = 16) and control subjects (N = 21). All subjects underwent MRI examinations on a 1.5 Tesla Siemens Sonata scanner. Anatomical reconstruction and segmentation were performed using the FreeSurfer image analysis suite. Cortical and subcortical volumes were extracted from FreeSurfer and analyzed for group differences, controlling for age. The NPSLE group exhibited decreased cortical thickness in clusters of the left frontal and parietal lobes as well as in the right parietal and occipital lobes compared to control subjects. Compared to the SLE group, the NPSLE group exhibited comparable thinning in clusters of the frontal and temporal lobes. Controlling for age, we found that between group effects for subcortical gray matter structures were significant for the thalamus (F = 3.06, p = .04), caudate nucleus (F = 3.19, p = .03), and putamen (F = 4.82, p = .005). These results clarify previous imaging work identifying cortical atrophy in a mixed SLE and NPSLE group, and suggest that neuroanatomical abnormalities are specific to SLE patients diagnosed with neuropsychiatric symptoms. Future work should help elucidate the underlying mechanisms underlying the emerging neurobiological profile seen in NPSLE, as well as clarify the apparent lack of overlap between cortical thinning and functional activation results and other findings pointing to increased functional activation during cognitive tasks.

Dissecting the imitation faculty: The multiple imitation mechanisms (MIM) hypothesis

Is the imitation faculty one self-contained domain-general mechanism or an amalgamation of multiple content-specific systems? The multiple imitation mechanisms (MIM) hypothesis posits that the imitation faculty consists of distinct content-specific psychological systems that are dissociable both structurally and functionally. This hypothesis is supported by research in the developmental, cognitive, comparative and neural sciences. This body of work suggests that there are dissociable imitation systems that may be distinguished by unique behavioral and neurobiological profiles. The distribution of these different imitation skills in the animal kingdom further suggests a phylogenetic dissociation, whereby some animals specialized in some (but not all possible) imitation types; a reflection of specific selection pressures favoring certain imitation systems. The MIM hypothesis attempts to bring together these different areas of research into one theoretical framework that defines imitation both functionally and structurally.

Obésité et troubles psychopathologiques

Resume L’obesite est une surcharge ponderale par exces de masse grasse qui a des consequences nefastes pour la sante. Trouble chronique, d’origine multifactorielle, elle apparait comme un facteur de risque serieux qui compromet le fonctionnement psychosocial et la qualite de vie des patients. Cependant, elle ne fait pas partie du DSM-IV. L’obesite est une maladie invalidante, dont les particularites neurobiologiques, comportementales et emotionnelles restent a explorer. Neanmoins, un lien semble s’etablir entre les troubles du comportement alimentaire, les perturbations de l’image du corps en lien avec l’estime de soi et la stigmatisation du sujet obese, concepts fondamentaux semblant etre partages avec la maladie addictive.

Neuroprotective effects of estrogen therapy for cognitive and neurobiological profiles of monkey models of menopause

Many postmenopausal women question whether to start or continue hormone therapy because of recent clinical trial negative results. However, evidence from other studies of postmenopausal women, and from studies in menopausal monkeys, indicate that estrogen has neurocognitive protective effects, particularly when therapy is initiated close to the time of menopause before neural systems become increasingly compromised with age. In this review, we present studies of menopausal women and female monkeys that support the concept that estrogen therapies protect both cognitive function and neurobiological processes.

Neural Correlates of Emotional Reactivity in Sensation Seeking

High sensation seeking has been linked to increased risk for drug abuse and other negative behavioral outcomes. This study explored the neurobiological basis of this personality trait using functional magnetic resonance imaging (fMRI). High sensation seekers (HSSs) and low sensation seekers (LSSs) viewed high- and low-arousal pictures. Comparison of the groups revealed that HSSs showed stronger fMRI responses to high-arousal stimuli in brain regions associated with arousal and reinforcement (right insula, posterior medial orbitofrontal cortex), whereas LSSs showed greater activation and earlier onset of fMRI responses to high-arousal stimuli in regions involved in emotional regulation (anterior medial orbitofrontal cortex, anterior cingulate). Furthermore, fMRI response in anterior medial orbitofrontal cortex and anterior cingulate was negatively correlated with urgency. Finally, LSSs showed greater sensitivity to the valence of the stimuli than did HSSs. These distinct neurobiological profiles suggest that HSSs exhibit neural responses consistent with an overactive approach system, whereas LSSs exhibit responses consistent with a stronger inhibitory system.

Neural Correlates of Uncertainty During Adolescence: The Role of Context

Event Abstract Back to Event Neural Correlates of Uncertainty During Adolescence: The Role of Context Adriana Galvan1* 1 University of California, Department of Psychology, United States Suboptimal decision-making during adolescence is often associated with uncertain outcomes. Previous work in adolescents has described a neurobiological profile that is similar to adults in the neural processing of uncertainty. The adult literature has also suggested that frontolimbic circuitry, specifically, the orbitofrontal cortex and amygdala, has a role in representing uncertain decisions made under distinct contexts (DeMartino et al 2008). A neurobiological framework describing neural correlates of uncertainty under different contexts in adolescence remains elusive. In this investigation, social and monetary uncertainty were manipulated in two separate tasks that participants performed while undergoing fMRI. Preliminary analyses reveal distinct neural profiles in adolescents compared to adults during uncertainty. In the social uncertainty task, neutral faces framed in a negative relative to neutral context elicited greater amygdala activity in adolescents relative to adults. When making risky relative to safe choices in the monetary task, adolescents recruited greater striatal activation than adults and adults recruited greater ventromedial orbital frontal cortex activation. Different patterns emerged between adolescents and adults when the risky choice was to gain money (Gain Frame) or to avoid losing money (Loss Frame), with greater frontolimbic circuitry activation in adolescents relative to adults during loss frames and greater amygdala and insula activation in adults compared to adolescents. These results suggest that there are developmental neural changes in processing of uncertainty in both monetary and social decisions. Further, how the uncertain outcome is framed may bias behavioral and neural responeses differentially in adolescents relative to adults. Conference: Conference on Neurocognitive Development, Berkeley, CA, United States, 12 Jul - 14 Jul, 2009. Presentation Type: Oral Presentation Topic: Emotional and social behavior Citation: Galvan A (2009). Neural Correlates of Uncertainty During Adolescence: The Role of Context. Conference Abstract: Conference on Neurocognitive Development. doi: 10.3389/conf.neuro.09.2009.10.030 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 07 Jul 2009; Published Online: 07 Jul 2009. * Correspondence: Adriana Galvan, University of California, Department of Psychology, Los Angeles, United States, agalvan@ucla.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Adriana Galvan Google Adriana Galvan Google Scholar Adriana Galvan PubMed Adriana Galvan Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

The neurobiological profile of girls with ADHD.

Since boys are more commonly diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) than girls, the majority of theories and published research studies of ADHD have been based on samples comprised primarily (or exclusively) of boys. While psychosocial impairment in girls with ADHD is well established, the neuropsychological and neurobiological basis of these deficits is less consistently observed. There is growing evidence that boys' and girls' brains develop and mature at different rates, suggesting that the trajectory of early anomalous brain development in ADHD may also be sex-specific. It remains unclear, however, whether earlier brain maturation observed in girls with ADHD is protective. In this review, we outline the current theory and research findings that seek to establish a unique neurobiological profile of girls with ADHD, highlighting sex differences in typical brain development and among children with ADHD. The review highlights findings from neurological, neurocognitive, and behavioral studies. Future research directions are suggested, including the need for longitudinal neuroimaging and neurobehavioral investigation beginning as early as the preschool years, and continuing through adolescence and adulthood, with consideration of identified sex differences in the development of ADHD.