Development Of Neuropsychiatric Disorders Research Articles

Whole-exome sequencing in obsessive-compulsive disorder identifies rare mutations in immunological and neurodevelopmental pathways.

Studies of rare genetic variation have identified molecular pathways conferring risk for developmental neuropsychiatric disorders. To date, no published whole-exome sequencing studies have been reported in obsessive-compulsive disorder (OCD). We sequenced all the genome coding regions in 20 sporadic OCD cases and their unaffected parents to identify rare de novo (DN) single-nucleotide variants (SNVs). The primary aim of this pilot study was to determine whether DN variation contributes to OCD risk. To this aim, we evaluated whether there is an elevated rate of DN mutations in OCD, which would justify this approach toward gene discovery in larger studies of the disorder. Furthermore, to explore functional molecular correlations among genes with nonsynonymous DN SNVs in OCD probands, a protein–protein interaction (PPI) network was generated based on databases of direct molecular interactions. We applied Degree-Aware Disease Gene Prioritization (DADA) to rank the PPI network genes based on their relatedness to a set of OCD candidate genes from two OCD genome-wide association studies (Stewart et al., 2013; Mattheisen et al., 2014). In addition, we performed a pathway analysis with genes from the PPI network. The rate of DN SNVs in OCD was 2.51 × 10−8 per base per generation, significantly higher than a previous estimated rate in unaffected subjects using the same sequencing platform and analytic pipeline. Several genes harboring DN SNVs in OCD were highly interconnected in the PPI network and ranked high in the DADA analysis. Nearly all the DN SNVs in this study are in genes expressed in the human brain, and a pathway analysis revealed enrichment in immunological and central nervous system functioning and development. The results of this pilot study indicate that further investigation of DN variation in larger OCD cohorts is warranted to identify specific risk genes and to confirm our preliminary finding with regard to PPI network enrichment for particular biological pathways and functions.

Multivariate pattern classification of pediatric Tourette syndrome using functional connectivity MRI.

Tourette syndrome (TS) is a developmental neuropsychiatric disorder characterized by motor and vocal tics. Individuals with TS would benefit greatly from advances in prediction of symptom timecourse and treatment effectiveness. As a first step, we applied a multivariate method – support vector machine (SVM) classification – to test whether patterns in brain network activity, measured with resting state functional connectivity (RSFC) MRI, could predict diagnostic group membership for individuals. RSFC data from 42 children with TS (8–15 yrs) and 42 unaffected controls (age, IQ, in‐scanner movement matched) were included. While univariate tests identified no significant group differences, SVM classified group membership with ~70% accuracy (p < .001). We also report a novel adaptation of SVM binary classification that, in addition to an overall accuracy rate for the SVM, provides a confidence measure for the accurate classification of each individual. Our results support the contention that multivariate methods can better capture the complexity of some brain disorders, and hold promise for predicting prognosis and treatment outcome for individuals with TS.

Inborn Errors of Long-Chain Fatty Acid β-Oxidation Link Neural Stem Cell Self-Renewal to Autism.

Inborn errors of metabolism (IEMs) occur with high incidence in human populations. Especially prevalent among these are inborn deficiencies in fatty acid β-oxidation (FAO), which are clinically associated with developmental neuropsychiatric disorders, including autism. We now report that neural stem cell (NSC)-autonomous insufficiencies in the activity of TMLHE (an autism risk factor that supports long-chain FAO by catalyzing carnitine biosynthesis), of CPT1A (an enzyme required for long-chain FAO transport into mitochondria), or of fatty acid mobilization from lipid droplets reduced NSC pools in the mouse embryonic neocortex. Lineage tracing experiments demonstrated that reduced flux through the FAO pathway potentiated NSC symmetric differentiating divisions at the expense of self-renewing stem cell division modes. The collective data reveal a key role for FAO in controlling NSC-to-IPC transition in the mammalian embryonic brain and suggest NSC self renewal as a cellular mechanism underlying the association between IEMs and autism.

Evolving insights into the qualitative nature of RNA and its functional diversity in the brain

Event Abstract Back to Event Evolving insights into the qualitative nature of RNA and its functional diversity in the brain Timothy Bredy1* 1 University of Queensland, Queensland Brain Institute, Australia This lecture will discuss emerging concepts surrounding the qualitative nature of RNA and its role in the regulation of adaptive behaviour associated with the development of neuropsychiatric disorders. It will also share this group’s recent discoveries surrounding novel base modifications in the adult brain and suggest how this new insight will create new opportunities for understanding the fundamental nature of gene-environment interactions and their impact on health and disease. Keywords: RNA, gene-environment interactions, brain function, neuropsychiatric disorders, base modification Conference: 14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016. Presentation Type: Symposium 4: The Living Chemistry of RNA Topic: 14th Meeting of the Asian-Pacific Society for Neurochemistry Citation: Bredy T (2016). Evolving insights into the qualitative nature of RNA and its functional diversity in the brain. Conference Abstract: 14th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00020 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: 26 Jul 2016; Published Online: 11 Aug 2016. * Correspondence: Prof. Timothy Bredy, University of Queensland, Queensland Brain Institute, Brisbane, Queensland, Australia, tbredy@uci.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 Timothy Bredy Google Timothy Bredy Google Scholar Timothy Bredy PubMed Timothy Bredy 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 study of EEG Characteristics in ADHD children

Event Abstract Back to Event The study of EEG Characteristics in ADHD children Irma Khachidze1* 1 I. Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia, Cognition, Georgia Purpose: The study aimed to detect EEG biomarkers of ADHD patients. Methods: The EEG of 30 children aged 9 to 13 years with ADHD (10 boys and 10 girls) and EEG of 10 healthy ones of the same age and gender served as a control group was studied. QEEG signals were digitally recorded using a set of 21 scalp electrodes according to International 10−20 system. EEG Recording in all patients was carried out in the morning during of quiet wakefulness. EEG fragments for each patient were performed and Fourier transformed to provide absolute (AP) value of frequency bands(delta, theta, alpha and beta-1, beta-2) Results; Preliminary analysis of the results showed: ADHD Boys; AP in Delta increased in frontal-central-temporal areas(p<0.05). ADHD Girls; AP in Delta increased in frontal areas(p<0.05). ADHD Boys; Retardation of basic rhythms manifested mainly in frontal-central regions of brain in all low frequency ranges in ADHD boys, whereas in girls only enhancement Beta activity was recorded predominantly in frontal-parietal lobes. Conclusions: Comparison of indices obtained in ADHD groups of boys and girls revealed of changes. The different regions of the brain develop in a different sequence, in girls compared with boys. Different EEG rhythms reflect function of a variety of intracerebral mechanisms. QEEG analysis represent important technique providing objective and physiologically based data and some features can be added to the psycho-biological basis of ADHD. The study of age-related sex and brain’s regional differences in ADHD children may aid in understanding the mechanism of several developmental neuropsychiatric disorders.

Stem Cell Models to Investigate the Role of DNA Methylation Machinery in Development of Neuropsychiatric Disorders.

Epigenetic mechanisms underlie differentiation of pluripotent stem cells into different lineages that contain identical genomes but express different sets of cell type-specific genes. Because of high discordance rates in monozygotic twins, epigenetic mechanisms are also implicated in development of neuropsychiatric disorders such as schizophrenia and autism. In support of this notion, increased levels of DNA methyltransferases (DNMTs), DNMT polymorphisms, and dysregulation of DNA methylation network were reported among schizophrenia patients. These results point to the importance of development of DNA methylation machinery-based models for studying the mechanism of abnormal neurogenesis due to certain DNMT alleles or dysregulated DNMTs. Achieving this goal is strongly confronted by embryonic lethality associated with altered levels of epigenetic machinery such as DNMT1 and expensive approaches in developing in vivo models. In light of literature evidence that embryonic stem cells (ESCs) are tolerant of DNMT mutations and advancement in the technology of gene targeting, it is now possible to introduce desired mutations in DNMT loci to generate suitable ESC lines that can help understand the underlying mechanisms by which abnormal levels of DNMTs or their specific mutations/alleles result in abnormal neurogenesis. In the future, these models can facilitate development of suitable drugs for treatment of neuropsychiatric disorders.

Altered Brain Structure-Function Relationships Underlie Executive Dysfunction in 22q11.2 Deletion Syndrome

22q11.2 deletion syndrome (22q11DS) is a neurogenetic disorder associated with elevated rates of developmental neuropsychiatric disorders and impaired executive function (EF). Disrupted brain structure-function relationships may underlie EF deficits in 22q11DS. We administered the Behavior Rating Inventory of Executive Function (BRIEF) to assess real-world EF in patients with 22q11DS and matched controls (n = 86; age 6-17 years), along with cognitive measures that tap behavioral regulation and metacognition aspects of EF. Using FreeSurfer's whole-brain vertex cortical thickness pipeline, we investigated brain structure-EF relationships in patients with 22q11DS and controls. Behaviorally, patients with 22q11DS were impaired on multiple EF measures. Right orbitofrontal cortical thickness showed a differential relationship between real-world EF in patients with 22q11DS and controls. We also observed a group difference in the relationship between behavioral regulation and metacognition measures with thickness of ventral and dorsolateral prefrontal regions, respectively. Our findings suggest that executive dysfunction characteristic of 22q11DS is underscored by altered prefrontal cortical structure.

Increased prevalence of attention deficit hyperactivity disorder in children with Familial Mediterranean Fever

Attention deficit hyperactivity disorder (ADHD) is a developmental neuropsychiatric disorder characterized by inappropriate levels of inattention, impulsivity and hyperactivity. The cause of ADHD is unknown, but may involve both genetic and environmental factors. It has been suggested that exposure to inflammation in infancy may increase the risk for ADHD in later life. Familial Mediterranean Fever (FMF) is the most common inherited autoinflammatory disorder. In many FMF patients the inflammation persists in attack-free periods. The prevalence of ADHD among FMF patients has not been studied previously.

Neuroimaging in Tourette Syndrome: Research Highlights From 2014-2015.

Tourette Syndrome (ts) is a developmental neuropsychiatric disorder of the central nervous system defined by the presence of chronic tics. While investigations of the underlying brain mechanisms have provided valuable information, a complete understanding of the pathophysiology of ts remains elusive. Neuroimaging methods provide remarkable tools for examining the human brain, and have been used to study brain structure and function in ts. In this article, we review ts neuroimaging studies published in 2014-2015. We highlight a number of noteworthy studies due to their innovative methods and interesting findings. Yet, we note that many of the recent studies share common concerns, specifically susceptibility to motion artifacts and modest sample sizes. Thus, we encourage future work to carefully address potential methodological confounds and to study larger samples to increase the potential for replicable results.

Morning glory sendromu ve otizm: Bir olgu sunumu

Autism is a developmental neuropsychiatric disorder that starts in early years of life, lasts lifelong, and characterized by the triad of impaired social skills, delayed speech, and repetitive or unusual behaviours. Morning glory syndrome (MGS) is a congenital anomaly of the optic disc, first described in 1970 and named by Kindler due to a resemblance to the flower of the same name. Congenital anomalies are more common in autistics compared to normal population. Among all types of congenital anomalies, the frequency of autism is higher with brain and/or eye anomalies. In this paper, we reported a 2-year-old female, who was diagnosed to have morning glory syndrome when she was 14-months old and admitted to our clinic because of delayed speech and lack of communication. Although congenital eye anomalies and autism comorbidity is high, there is only one case diagnosed to have MGS with autism reported in the literature. We aimed to report this case because of the difference in visual impairment than previous case and to impress on the relationship between MGS and autism, which stems from the early development phase of embryological life, when there is increased sensitivity for genetic and environmental factors.

Prenatal immune activation alters hippocampal place cell firing characteristics in adult animals.

Prenatal maternal immune activation (MIA) is a risk factor for several developmental neuropsychiatric disorders, including autism, bipolar disorder and schizophrenia. Adults with these disorders display alterations in memory function that may result from changes in the structure and function of the hippocampus. In the present study we use an animal model to investigate the effect that a transient prenatal maternal immune activation episode has on the spatially-modulated firing activity of hippocampal neurons in adult animals. MIA was induced in pregnant rat dams with a single injection of the synthetic cytokine inducer polyinosinic:polycytidylic acid (poly I:C) on gestational day 15. Control dams were given a saline equivalent. Firing activity and local field potentials (LFPs) were recorded from the CA1 region of the adult male offspring of these dams as they moved freely in an open arena. Most neurons displayed characteristic spatially-modulated 'place cell' firing activity and while there was no between-group difference in mean firing rate between groups, place cells had smaller place fields in MIA-exposed animals when compared to control-group cells. Cells recorded in MIA-group animals also displayed an altered firing-phase synchrony relationship to simultaneously recorded LFPs. When the floor of the arena was rotated, the place fields of MIA-group cells were more likely to shift in the same direction as the floor rotation, suggesting that local cues may have been more salient for these animals. In contrast, place fields in control group cells were more likely to shift firing position to novel spatial locations suggesting an altered response to contextual cues. These findings show that a single MIA intervention is sufficient to change several important characteristics of hippocampal place cell activity in adult offspring. These changes could contribute to the memory dysfunction that is associated with MIA, by altering the encoding of spatial context and by disrupting plasticity mechanisms that are dependent on spike timing synchrony.

Allergic fetal priming leads to developmental, behavioral and neurobiological changes in mice

The state of the mother's immune system during pregnancy has an important role in fetal development and disruptions in the balance of this system are associated with a range of neurologic, neuropsychiatric and neurodevelopmental disorders. Epidemiological and clinical reports reveal various clues that suggest a possible association between developmental neuropsychiatric disorders and family history of immune system dysfunction. Over the past three decades, analogous increases have been reported in both the incidence of neurodevelopmental disorders and immune-related disorders, particularly allergy and asthma, raising the question of whether allergic asthma and characteristics of various neurodevelopmental disorders share common causal links. We used a mouse model of maternal allergic asthma to test this novel hypothesis that early fetal priming with an allergenic exposure during gestation produces behavioral deficits in offspring. Mothers were primed with an exposure to ovalbumin (OVA) before pregnancy, then exposed to either aerosolized OVA or vehicle during gestation. Both male and female mice born to mothers exposed to aerosolized OVA during gestation exhibited altered developmental trajectories in weight and length, decreased sociability and increased marble-burying behavior. Moreover, offspring of OVA-exposed mothers were observed to have increased serotonin transporter protein levels in the cortex. These data demonstrate that behavioral and neurobiological effects can be elicited following early fetal priming with maternal allergic asthma and provide support that maternal allergic asthma may, in some cases, be a contributing factor to neurodevelopmental disorders.

Enhancement of Frequency Rate of Basolateral Amygdala Neurons Activity by Mglur1 Receptors Agonist in Developmental Schizophrenic Models

Schizophrenia is a developmental neuropsychiatric disorder which affects nearly 1% of the world population. Disturbances in dopaminergic and glutamatergic transmission have been implicated in the pathological mechanism of this disease. Psychosocial stress in the form of maternal deprivation and social isolation (SI) during early postnatal life results in long-term effect on neuroendocrine, immune adaptation, disrupt brain development and profoundly affect wide-range of behaviours in adult animals. Recent studies indicated that in awake rats, blocker of Ionotropic of Glutamate receptors increased corticolimbic firing activity. In this present study demonstrated alternation of single-unit record of basolateral amygdala nucleus (BLA) represented in activity of mGluR1 in post-weaning SI. Firing rates increased during injection of mGluR1agonist and SI states. Short-latency auditory responses (12–25 msec) were found in the BLA(p

Serotonin deficiency alters susceptibility to the long-term consequences of adverse early life experience

Brain 5-HT deficiency has long been implicated in psychiatric disease, but the effects of 5-HT deficiency on stress susceptibility remain largely unknown. Early life stress (ELS) has been suggested to contribute to adult psychopathology, but efforts to study the long-term consequences of ELS have been limited by a lack of appropriate preclinical models. Here, we evaluated the effects of 5-HT deficiency on several long-term cellular, molecular, and behavioral responses of mice to a new model of ELS that combines early-life maternal separation (MS) of pups and postpartum learned helplessness (LH) training in dams. Our data demonstrate that this paradigm (LH/MS) induces depressive-like behavior and impairs pup retrieval in dams. In addition, we show that brain 5-HT deficiency exacerbates anxiety-like behavior induced by LH/MS and blunts the effects of LH/MS on acoustic startle responses in adult offspring. Although the mechanisms underlying these effects remain unclear, following LH/MS, 5-HT-deficient animals had significantly less mRNA expression of the mineralocorticoid receptor in the amygdala than wild-type animals. In addition, 5-HT-deficient mice exhibited reduced mRNA levels of the 5-HT2a receptor and p11 in the hippocampus regardless of stress. LH/MS decreased the number of doublecortin+ immature neurons in the hippocampus in both wild-type (WT) and 5-HT-deficient animals. Our data emphasize the importance of complex interactions between genetic factors and early life experience in mediating long-term changes in emotional behavior. These findings may have important implications for our understanding of the combinatorial roles of 5-HT deficiency, ELS, and postpartum depression in the development of neuropsychiatric disorders.

Sleep in Tourette Syndrome

Tourette syndrome (TS) is a heritable developmental neuropsychiatric disorder and is defined as part of a spectrum of motor and vocal tic disorders (TD). Sleep problems are a common feature associated with TS/TD. They may affect daytime tic expression and neurobehavioral functioning. However, sleep studies on TS/TD are still scarce, and firm conclusions about the relationship of tics and sleep are difficult to draw. In this review, we summarize the existing knowledge about sleep problems in TS/TD and advocate for better understanding of their nature. Neglected links between the neurobiology of sleep and the psychophysiology of TS/TD and their psychiatric comorbidity, as well as medication for TS/TD, are highlighted, and future trends in sleep research on TS/TD are proposed.

Response inhibition and interference control in obsessive-compulsive spectrum disorders.

Over the past 20 years, motor response inhibition and interference control have received considerable scientific effort and attention, due to their important role in behavior and the development of neuropsychiatric disorders. Results of neuroimaging studies indicate that motor response inhibition and interference control are dependent on cortical–striatal–thalamic–cortical (CSTC) circuits. Structural and functional abnormalities within the CSTC circuits have been reported for many neuropsychiatric disorders, including obsessive–compulsive disorder (OCD) and related disorders, such as attention-deficit hyperactivity disorder, Tourette’s syndrome, and trichotillomania. These disorders also share impairments in motor response inhibition and interference control, which may underlie some of their behavioral and cognitive symptoms. Results of task-related neuroimaging studies on inhibitory functions in these disorders show that impaired task performance is related to altered recruitment of the CSTC circuits. Previous research has shown that inhibitory performance is dependent upon dopamine, noradrenaline, and serotonin signaling, neurotransmitters that have been implicated in the pathophysiology of these disorders. In this narrative review, we discuss the common and disorder-specific pathophysiological mechanisms of inhibition-related dysfunction in OCD and related disorders.

Single and combined effects of prenatal immune activation and peripubertal stress on parvalbumin and reelin expression in the hippocampal formation.

Exposure to prenatal infection and traumatizing experiences in peripubertal life are two environmental risk factors for developmental neuropsychiatric disorders. Modeling the cumulative neuronal impact of these factors in a translational animal model has led to the recent identification of pathological interactions between these environmental adversities in the development of adult brain dysfunctions. The present study explored the consequences of combined prenatal immune challenge and peripubertal stress on discrete cellular abnormalities in the γ-aminobutyric acid (GABA) system of the hippocampus. Pregnant mice were treated with the viral mimetic poly(I:C) (=polyriboinosinic-polyribocytidilic acid) or control solution, and offspring born to poly(I:C)-exposed or control mothers were then left undisturbed or subjected to unpredictable sub-chronic stress during peripubertal development. Stereological estimations of parvalbumin-expressing cells revealed a significant reduction of these GABAergic interneurons in the ventral dentate gyrus of adult offspring exposed to combined immune activation and stress. Single exposure to either environmental factor was insufficient to cause similar neuropathology. We further found that peripubertal stress exerted opposite effects on reelin-immunoreactive cells in the dorsal cornu ammonis (CA) region of the hippocampus, with stress increasing and decreasing reelin expression in control offspring and prenatally immune challenged animals, respectively. The present data suggest that the combination of two environmental risk factors, which have each been implicated in the etiology of major neuropsychiatric disease, induces significant but restricted neuropathological effects on hippocampal GABAergic cell populations known to be affected in brain disorders with neurodevelopmental components.

Early gut microbiota composition ő a possible target to reduce the risk of developing neuropsychiatric disorders? (637.11)

Background: Although genetic factors can determine a propensity for neuropsychiatric disorders, environmental exposures, particularly early microbial contact, may shape the risk during a critical period of maturation.Objective: To address whether early gut microbiota composition and its modification by probiotics could be related to the increasing emergence of attention deficit hyperactivity disorder (ADHD) and Asperger syndrome (AS).Methods: 75 infants who were randomized to receive Lactobacillus rhamnosus GG (ATCC 53103) or placebo prenatally and during the first six months of life were followed‐up for 13 years. Gut microbiota was assessed at the age of 3 weeks, 3 and 6 months and 13 years using several molecular methods. ADHD and AS were diagnosed by a child neurologist or psychiatrist on the basis of ICD‐10 diagnostic criteria.Results: At the age of 13 years ADHD and/or AS was diagnosed in 6/35 (17.1%) children in the placebo and none in the probiotic group (p=0.008). The affected children manifested lower numbers of Bifidobacterium species bacteria in feces, in particular less Bifidobacterium longum, than healthy children during the first six months of life (p=0.03, p=0.045, respectively).Interpretation: The composition of the gut microbiota and probiotic supplementation early in life may have an impact on the development of neuropsychiatric disorders later in childhood; our preliminary study suggests both an intriguing link between gut microbiota and behavior and a potential treatment target.Grant Funding Source: Supported by the Academy of Finland

The Involvement of Secondary Neuronal Damage in the Development of Neuropsychiatric Disorders Following Brain Insults

Neuropsychiatric disorders are one of the leading causes of disability worldwide and affect the health of billions of people. Previous publications have demonstrated that neuropsychiatric disorders can cause histomorphological damage in particular regions of the brain. By using a clinical symptom-comparing approach, 55 neuropsychiatric signs or symptoms related usually to 14 types of acute and chronic brain insults were identified and categorized in the present study. Forty percent of the 55 neuropsychiatric signs and symptoms have been found to be commonly shared by the 14 brain insults. A meta-analysis supports existence of the same neuropsychiatric signs or symptoms in all brain insults. The results suggest that neuronal damage might be occurring in the same or similar regions or structures of the brain. Neuronal cell death, neural loss, and axonal degeneration in some parts of the brain (the limbic system, basal ganglia system, brainstem, cerebellum, and cerebral cortex) might be the histomorphological basis that is responsible for the neuropsychiatric symptom clusters. These morphological alterations may be the result of secondary neuronal damage (a cascade of progressive neural injury and neuronal cell death that is triggered by the initial insult). Secondary neuronal damage causes neuronal cell death and neural injury in not only the initial injured site but also remote brain regions. It may be a major contributor to subsequent neuropsychiatric disorders following brain insults.

Modulation of 3,4-Methylenedioxymethamphetamine Effects by Endocannabinoid System

The amphetamine derivative 3, 4 Methylenedioxymethanphetamine (MDMA) is a powerful central nervous system stimulant that displays numerous pharmacological effects, including neurotoxicity. MDMA, or ecstasy, acts by inducing the release of different neurotransmitters depending on the animal species and, in particular, it produces the release of serotonin and dopamine. MDMA induces rewarding and reinforcing effects in rodents, primates and humans, and is currently consumed as an illicit psychostimulant among young people. One of the most reported side effects is the hyperthermic effect and the neurotoxicity on central serotonergic and dopaminergic neurons, depending on the species of animal. It seems that MDMA may also produce neurotoxic effects in humans. To date, the most consistent findings associated to MDMA consumption in humans relate to cognitive deficits in heavy users. MDMA when consumed as an illicit psychostimulant is commonly co-used with other abusers, being frequently associated with cannabinoids. The interaction between MDMA and cannabis effects is complex. Cannabis derivatives act on endocannabinoid system. Thus, at cellular levels, cannabinoids acting through CB1 cannabinoid receptors display opposite effects to those induced by MDMA, and they have been reported to develop neuroprotective actions, including the blockage of MDMA induced neurotoxicity, in laboratory animals. However, cannabis use is a recognized risk factor in the presentation and development of neuropsychiatric disorders, and also contributes to the development of psychological problems and cognitive failures observed in MDMA users. This paper represents a brief overview of the pharmacological interaction between MDMA and cannabis derivatives acting in the endocannabinoid system. We have evaluated recent findings in the literature of the most representative pharmacological effects displayed by both types of drugs. We analyze both, the synergic and opposite effects produced by these two compounds and we have found a gap regarding the negative consequences of long-term human consumption of MDMA alone or in combination with cannabis.