Neuropsychiatric Research Articles

Evaluating the Clinical Validity and Reliability of Artificial Intelligence-Enabled Diagnostic Tools in Neuropsychiatric Disorders

Evaluating the Clinical Validity and Reliability of Artificial Intelligence-Enabled Diagnostic Tools in Neuropsychiatric Disorders

From microbes to mind: germ-free models in neuropsychiatric research.

The gut-microbiota-brain axis refers to the bidirectional communication system between the gut, its microbial community, and the brain. This interaction involves a complex interplay of neural pathways, chemical transmitters, and immunological mechanisms. Germ-free animal models have been extensively employed to investigate gut-microbiota-brain interactions, significantly contributing to our current understanding of the role of intestinal microbes in brain function. However, despite the many benefits, this absence of microbiota is not futile. Germ-free animals present physiological and neurodevelopmental alterations that can persist even after reconstitution with normal microbiota. Therefore, the main goal of this minireview is to discuss how some of the inherent limitations of this model can interfere with the conclusion obtained when using these animals to study the complex nature of neuropsychiatric disorders. Furthermore, we examine the inclusion and use of antibiotic-based treatments as an alternative in the research of gut-brain interactions.

Causal relationship between IgA nephropathy and common neuropsychiatric disorders: A two-sample Mendelian randomization analysis

ObjectiveUtilizing two-sample Mendelian randomization (TSMR), this study seeks to determine the causal relationship between IgA nephropathy and five prevalent neuropsychiatric disorders. By exploring the genetic associations between IgA nephropathy and neuropsychiatric disorders, this research aims to contribute to the prevention of neuropsychiatric disorders in patients with IgA nephropathy. MethodsPublic genome-wide association study databases were searched, with IgA nephropathy as the exposure factor, including 15,587 patients with IgA nephropathy and 462,197 healthy controls. The outcome factors were five common neuropsychiatric disorders (bipolar disorder, depressive disorder, schizophrenia, anorexia nervosa, and Alzheimer's disease), with outcome data drawn from five datasets in the PGC and GWAScatalog databases. Inverse-variance weighting served as the primary method for causal effect estimation, supplemented by MR-Egger, weighted median, weighted mode, and simple mode methods. Heterogeneity was tested using Cochran's Q test, and sensitivity analysis was conducted using MR-Egger and MR-presso. ResultsMR analysis indicated a positive causal relationship between IgA nephropathy and depressive disorder (OR = 1.010, 95%CI: 1.003–1.017, P = 3.27 × 10−3), and a potential positive causal relationship between IgA nephropathy and anorexia nervosa (OR = 1.165, 95%CI: 1.030–1.319, P = 0.015). ConclusionThere is a positive causal relationship between IgA nephropathy and depressive disorder, and a potential positive causal relationship with anorexia nervosa. No causal relationship was found with schizophrenia, bipolar disorder, or Alzheimer's disease.

Evaluation of MMP-9 enzyme in drug-induced suicide cases admitted to the emergency room

ObjectiveThis study investigates MMP-9 enzyme levels in patients who attempted suicide by taking high doses of drugs, considering their sociodemographic characteristics. MethodsThe study included 45 patients who attempted suicide by high-dose drug intake admitted to the emergency room and 45 healthy volunteers with no neuropsychiatric disorders. Blood samples were collected to measure MMP-9 levels, and informed consent was obtained. The samples were centrifuged and analyzed using the ELISA method, with results statistically compared. ResultsFindings indicate that being single and a student significantly increased suicide tendencies (p = 0.002 and p = 0.001, respectively). Psychiatric disorders were the most common cause at 40.0%, followed by antidepressants (55.6%), analgesics (20.0%), and antidiabetics (8.9%) as the most used drugs for suicide. MMP-9 levels were significantly higher in patients who attempted suicide compared to controls (83.74 (±7.14) ng/mL vs. 54.97 (±12.27) ng/mL, p = 0.001). Additionally, MMP-9 levels were higher in single patients compared to married or divorced individuals (p = 0.008). MMP-9 levels were lower in patients with psychiatric disorders, recent psychiatric services, family history of psychiatric disorders, and previous suicide attempts (p = 0.014, p = 0.046, p = 0.035, p = 0.034). ConclusionsThis study shows MMP-9 enzyme can be a potential biomarker for drug-induced suicide attempts, emphasizing the importance of evaluating MMP-9 levels to assess suicide risk and develop prevention strategies.

Integrative genomics approach identifies glial transcriptomic dysregulation and risk in the cortex of individuals with Alcohol Use Disorder.

Alcohol use disorder (AUD) is a prevalent neuropsychiatric disorder that is a major global health concern, affecting millions of people worldwide. Past molecular studies of AUD used underpowered single cell analysis or bulk homogenates of postmortem brain tissue, which obscures gene expression changes in specific cell types. Here we performed single nuclei RNA-sequencing analysis of 73 post-mortem samples from individuals with AUD (N=36, Nnuclei= 248,873) and neurotypical controls (N=37, Nnuclei= 210,573) in both sexes across two institutional sites. We identified 32 clusters and found widespread cell type-specific transcriptomic changes across the cortex in AUD, particularly affecting glia. We found the greatest dysregulation in novel microglial and astrocytic subtypes that accounted for the majority of differential gene expression and co-expression modules linked to AUD. Analysis for cell type-specific enrichment of aggregate genetic risk for AUD identified subtypes of glial and neuronal cell types as potential key players not only affected by but causally linked to the progression of AUD. Most of the enrichments for genetic risk for AUD were in glial cell types. These results highlight the importance of cell-type specific molecular changes in AUD and offer opportunities to identify novel targets for treatment.

Assembloid model to study loop circuits of the human nervous system.

Neural circuits connecting the cerebral cortex, the basal ganglia and the thalamus are fundamental networks for sensorimotor processing and their dysfunction has been consistently implicated in neuropsychiatric disorders 1-9 . These recursive, loop circuits have been investigated in animal models and by clinical neuroimaging, however, direct functional access to developing human neurons forming these networks has been limited. Here, we use human pluripotent stem cells to reconstruct an in vitro cortico-striatal-thalamic-cortical circuit by creating a four-part loop assembloid. More specifically, we generate regionalized neural organoids that resemble the key elements of the cortico-striatal-thalamic-cortical circuit, and functionally integrate them into loop assembloids using custom 3D-printed biocompatible wells. Volumetric and mesoscale calcium imaging, as well as extracellular recordings from individual parts of these assembloids reveal the emergence of synchronized patterns of neuronal activity. In addition, a multi-step rabies retrograde tracing approach demonstrate the formation of neuronal connectivity across the network in loop assembloids. Lastly, we apply this system to study heterozygous loss of ASH1L gene associated with autism spectrum disorder and Tourette syndrome and discover aberrant synchronized activity in disease model assembloids. Taken together, this human multi-cellular platform will facilitate functional investigations of the cortico-striatal-thalamic-cortical circuit in the context of early human development and in disease conditions.

Cognitive Behavioral Therapy in Cardiovascular Disease.

The influence of cognitive behavioral therapy (CBT) and its modalities on various neuropsychiatric conditions is herein explored together with their impact on specific cardiovascular (CV) diseases (CVD). A comprehensive review of the literature was undertaken via the PubMed, Scopus and Google Scholar on the above relevant topics. The focus was on large randomized controlled trials and meta-analyses. Among the various neuropsychiatric disorders, depression and anxiety commonly occur in CVD patients, frequently eluding clinician's attention. This reciprocal liaison may incur higher rates of morbidity/mortality, through physiological and behavioral mechanisms. Multimodal psychiatric interventions, using medications and psychotherapies, such as CBT, seem promising. Such mindfulness-based interventions have the potential to be an efficacious complementary strategy to address psychological stress in CVD patients. As the cost of CBT is relatively low, such a supportive approach for stress management provides high patient acceptability, with a positive impact on improving quality of life, by promoting CV health and mitigating CV complications. There is ample evidence of a reciprocal liaison between heart and mind. Several CV risk factors are strongly affected by diseases of the mind, and the clinical course of various CVDs is influenced by affective or other psychiatric disorders. CBT and relevant mindfulness-based interventions have a significant supportive role in patients with various CVDs by targeting CV risk factor(s) or the underlying specific CVD and by identifying and addressing psychosocial issues. In this direction, various CBT interventions can provide the means to favorably influence both CV risk factors and CVDs.

Sex Differences in Hierarchical and Modular Organization of Functional Brain Networks: Insights from Hierarchical Entropy and Modularity Analysis.

Existing studies have demonstrated significant sex differences in the neural mechanisms of daily life and neuropsychiatric disorders. The hierarchical organization of the functional brain network is a critical feature for assessing these neural mechanisms. But the sex differences in hierarchical organization have not been fully investigated. Here, we explore whether the hierarchical structure of the brain network differs between females and males using resting-state fMRI data. We measure the hierarchical entropy and the maximum modularity of each individual, and identify a significant negative correlation between the complexity of hierarchy and modularity in brain networks. At the mean level, females show higher modularity, whereas males exhibit a more complex hierarchy. At the consensus level, we use a co-classification matrix to perform a detailed investigation of the differences in the hierarchical organization between sexes and observe that the female group and the male group exhibit different interaction patterns of brain regions in the dorsal attention network (DAN) and visual network (VIN). Our findings suggest that the brains of females and males employ different network topologies to carry out brain functions. In addition, the negative correlation between hierarchy and modularity implies a need to balance the complexity in the hierarchical organization of the brain network, which sheds light on future studies of brain functions.

Functional associations of the gut microbiome with dopamine, serotonin, and BDNF in schizophrenia: a pilot study

BackgroundSchizophrenia is a complex neuropsychiatric disorder with various etiologic factors. Aberrant levels of neurotransmitters or growth factors such as dopamine, serotonin, and BDNF have been shown to cause cognitive impairment in schizophrenia. Recently, the gut microbiome has also been suggested as a factor in the development of the disorder. To explore this potential link, we conducted a pilot study to examine the relationship between the gut microbiome and plasma levels of neurotransmitters and growth factors in schizophrenia. Shotgun metagenome sequencing of total RNA from fecal samples were used to profile the gut microbiome of schizophrenia patients (SCZ) and healthy controls (HC). The MetaPhlAn2 and HUMaN2 pipelines were used for bioinformatic analyses. ELISA was used to measure the plasma levels of dopamine, serotonin, and BDNF. Spearman’s rank correlation coefficient was used for correlation analysis.ResultsWe found that butyrate-producing bacteria were enriched in HC, whereas succinate-producing bacteria, namely Phascolarctobacterium succinatutens and Paraprevotella clara, were enriched in SCZ. The gut microbiota of SCZ was enriched in lipid biosynthesis pathways related to bile-resistant bacteria, whereas phospholipid pathways linked with butyrate-producing bacteria were enriched in HC. Alistipes indistinctus, Dorea longicatena, and Roseburia inulinivorans were negatively correlated with dopamine levels. Roseburia intestinalis and Parabacteroides goldsteini were negatively correlated with serotonin and BDNF levels, respectively. We found a significant correlation between dopamine and serotonin levels, and the super-pathway of purine deoxyribonucleoside degradation.ConclusionsThis study provides further support that gut microbiota could modulate neurotransmitter levels. The results suggest that gut microbiome-targeted therapies may help to rebalance neurotransmitter levels, offering new hope for the treatment of schizophrenia.

Ai-powered Drug Discovery and Mental Health Therapy: Uniting Technologies for Holistic Healthcare

AI is making its way into health, especially in manners of approach toward this complex challenge. This paper looks at how AI-powered drug discovery and personalized mental health therapy merge into one holistic approach. AI analyzes large datasets for the identification of novel drug candidates, thereby accelerating drug discovery with the aim of reducing the cost and time-to-market for new treatments. Meanwhile, the development of AI-driven mental health interventions, such as natural language processing and machine learning algorithms, speaks to personalized therapeutic solutions fit for individual needs. This unitedly brings into view a synergistic model wherein AI works not only in optimizing drug discovery but also in the enhancement of care in mental health by way of individualized treatment. This paper, therefore, emphasizes key methodologies including deep learning, reinforcement learning for drug discovery, and RNNs for mental health interventions; with major emphasis on the use of AI to develop targeted treatments for ailments such as depression, anxiety, and neuropsychiatric disorders. An approach of that nature will not only provide much more depth in terms of health solutions but will also help bridge the mind-body gap, furthering both the concept and reality of personalized medicine and improving patient outcomes.

Exploring the Neuropsychiatric Dimensions of Psoriasis: Pathophysiology, Clinical Implications, and Integrated Care Approaches

<p><span lang="RO">Psoriasis is a long-term inflammatory skin disorder that significantly affects a patient's quality of life in addition to having notable physical symptoms. Recent research has increasingly focused on the neuropsychiatric dimensions of psoriasis, recognizing the complex interplay between psychological health and dermatological disease. There is growing recognition of the correlation between psoriasis and neuropsychiatric conditions such as anxiety, depression, and cognitive decline, indicating the reciprocal interaction of the skin and brain. This study explores the prevalence and implications of neuropsychiatric disorders among 3,850 psoriasis patients, of whom 458 were diagnosed with neuropsychiatric conditions. The results emphasize the value of treating psoriasis with a multidisciplinary approach. Integrating care that addresses dermatological and neuropsychiatric health is crucial for improving patient outcomes and quality of life.</span></p><p><em><span lang="RO"><br /></span></em></p>

Longitudinal multi-omics reveals pathogenic TSC2 variants disrupt developmental trajectories of human cortical organoids derived from Tuberous Sclerosis Complex.

Tuberous Sclerosis Complex (TSC), an autosomal dominant condition, is caused by heterozygous mutations in either the TSC1 or TSC2 genes, manifesting in systemic growth of benign tumors. In addition to brain lesions, neurologic sequelae represent the greatest morbidity in TSC patients. Investigations utilizing TSC1/2 -knockout animal or human stem cell models suggest that TSC deficiency-causing hyper-activation of mTOR signaling might precipitate anomalous neurodevelopmental processes. However, how the pathogenic variants of TSC1/2 genes affect the longitudinal trajectory of human brain development remains largely unexplored. Here, we employed 3-dimensional cortical organoids derived from induced pluripotent stem cells (iPSCs) from TSC patients harboring TSC2 variants, alongside organoids from age- and sex-matched healthy individuals as controls. Through comprehensively longitudinal molecular and cellular analyses of TSC organoids, we found that TSC2 pathogenic variants dysregulate neurogenesis, synaptogenesis, and gliogenesis, particularly for reactive astrogliosis. The altered developmental trajectory of TSC organoids significantly resembles the molecular signatures of neuropsychiatric disorders, including autism spectrum disorders, epilepsy, and intellectual disability. Intriguingly, single cell transcriptomic analyses on TSC organoids revealed that TSC2 pathogenic variants disrupt the neuron/reactive astrocyte crosstalk within the NLGN-NRXN signaling network. Furthermore, cellular and electrophysiological assessments of TSC cortical organoids, along with proteomic analyses of synaptosomes, demonstrated that the TSC2 variants precipitate perturbations in synaptic transmission, neuronal network activity, mitochondrial translational integrity, and neurofilament formation. Notably, similar perturbations were observed in surgically resected cortical specimens from TSC patients. Collectively, our study illustrates that disease-associated TSC2 variants disrupt the neurodevelopmental trajectories through perturbations of gene regulatory networks during early cortical development, leading to mitochondrial dysfunction, aberrant neurofilament formation, impaired synaptic formation and neuronal network activity.

One path, two solutions: Network-based analysis identifies targetable pathways for the treatment of comorbid type II diabetes and neuropsychiatric disorders

Comorbid diseases complicate patient outcomes and escalate healthcare costs, necessitating the need for a deeper mechanistic understanding. Neuropsychiatric disorders (NPDs) such as Neurotic Disorder, Major Depression, Bipolar Disorder, Anxiety Disorder, and Schizophrenia significantly exacerbate Type 2 Diabetes Mellitus (DM2), often leading to suboptimal treatment outcomes. The neurobiological mechanisms underlying this comorbidity remain poorly understood. To address this gap, we developed a novel pathway-based network computational framework to identify critical shared disease mechanisms between DM2 and these five prevalent comorbid NPDs. Our approach involves reconstructing an integrated DM2 ∩ NPDs KEGG pathway-pathway network and employs two complementary analytical methods, including the "minimum path to comorbidity" method to identify the shortest path fostering comorbid development. This analysis uncovered shared pathways like the PI3K-Akt signaling pathway and highlighted key nodes such as calcium signaling, MAPK, estrogen signaling, and apoptosis pathways. Dysregulation of these pathways likely contributes to the development of DM2-NPDs comorbidity. These findings have significant clinical implications, as they identify promising therapeutic targets that could lead to more effective treatments addressing both DM2 and NPDs simultaneously. Our model not only elucidates the intricate molecular interactions driving this comorbidity but also identifies promising therapeutic targets, paving the way for innovative treatment strategies. Additionally, the framework developed in this study can be adapted to study other complex comorbid conditions, advancing personalized medicine for comorbidities and improving patient care.

Systematic review and meta-analysis of standalone digital interventions for cognitive symptoms in people without dementia

Cognitive symptoms are prevalent across neuropsychiatric disorders, increase distress and impair quality of life. Self-guided digital interventions offer accessibility, scalability, and may overcome the research-to-practice treatment gap. Seventy-six trials with 5214 participants were identified. A random-effects meta-analysis investigated the effects of all digital self-guided interventions, compared to controls, at post-treatment. We found a small-to-moderate positive pooled effect on cognition (k = 71; g = −0.51, 95%CI −0.64 to −0.37; p < 0.00001) and mental health (k = 30; g = −0.41, 95%CI −0.60 to −0.22; p < 0.0001). Positive treatment effects on fatigue (k = 8; g = −0.27, 95%CI −0.53 to −0.02; p = 0.03) and quality of life (k = 22; g = −0.17, 95%CI −0.34 to −0.00; p = 0.04) were only marginally significant. No significant benefit was found for performance on activities of daily living. Results were independent of control groups, treatment duration, risk of bias and delivery format. Self-guided digital transdiagnostic interventions may benefit at least a subset of patients in the short run, yet their impact on non-cognitive outcomes remains uncertain.

Effect of environmental air pollutants on placental function and pregnancy outcomes: a molecular insight.

Air pollution has become a major health concern, particularly for vulnerable populations such as the elderly, children, and pregnant women. Studies have reported a strong association between prenatal exposure to air pollutants and adverse pregnancy outcomes, including lower birth weight, reduced fetal growth, and an increased frequency of preterm births. This review summarizes the harmful effects of air pollutants, such as particulate matter, on pregnancy and outlines the mechanistic details associated with these adverse outcomes. Particulate pollutant matter may be able to cross the placenta barrier, and alterations in placental functions are central to the detrimental effects of these pollutants. In addition to associations with preeclampsia and gestational hypertension, air pollutants also induce oxidative stress, inflammation, and epigenetic alteration in the placenta. These pollutants can also affect placental homeostasis and endocrine function, contributing to pregnancy complications and possible transgenerational effects. Prenatal air pollution exposure has been linked to reduced cognitive and motor function in infants and newborns, increasing the predisposition to autism spectrum disorders and other neuropsychiatric disorders. This review also summarizes the use of various animal models to study the harmful effects of air pollution on pregnancy and postnatal outcomes. These findings provide valuable insight into the molecular events associated with the process and can aid in risk mitigation and adopting safety measures. Implementing effective environmental protocols and taking appropriate steps may reduce the global disease burden, particularly for developing nations with poor regulatory compliance and large populations of pregnant women.

Efficacy of transcranial magnetic stimulation treatment in reducing neuropsychiatric symptomatology after traumatic brain injury.

Neuropsychiatric disorders are highly disabling in traumatic brain injury (TBI) patients, and psychopharmacological treatments often fail to adequately mitigate their detrimental effects. Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment in neurology and psychiatry, showing potential in treating psychiatric disorders. This study investigates the efficacy of a novel, dual-site sequential rTMS protocol designed to treat neuropsychiatric symptoms in a TBI patient who was refractory to conventional treatments. A 34-year-old woman with severe head trauma and complex psychopathology underwent 20 daily sessions of focal-coil rTMS, combining inhibitory stimulation (1 Hz) on the right dorsolateral prefrontal cortex (DLPFC) and excitatory (10 Hz) on the left DLPFC, guided by a neuronavigation system. Psychiatric and neurocognitive assessments were conducted at baseline and at 2, 4, and 8 weeks following the beginning of rTMS treatment. After 2 weeks of treatment, the patient showed decreased impulsivity and obsessive-compulsive symptoms, along with improvements in attention and processing speed. After 4 weeks, impulsivity further declined, though no other significant changes were noted. At 8 weeks, a persistent positive effect was observed, including enhanced positive emotions. These findings suggest that guided, alternating neurostimulation of the DLPFC may modulate activity within cortico-striato-thalamo-cortical circuits, providing a promising alternative for managing neuropsychiatric symptoms in TBI patients who are resistant to traditional treatments.

RNA m6A methyltransferase activator affects anxiety-related behaviours, monoamines and striatal gene expression in the rat.

Modification of mRNA by methylation is involved in post-transcriptional regulation of gene expression by affecting the splicing, transport, stability and translation of mRNA. Methylation of adenosine at N6 (m6A) is one of the most common and important cellular modification occurring in the mRNA of eukaryotes. Evidence that m6A mRNA methylation is involved in regulation of stress response and that its dysregulation may contribute to the pathogenesis of neuropsychiatric disorders is accumulating. We have examined the acute and subchronic (up to 18 days once per day intraperitoneally) effect of the first METTL3/METTL14 activator compound CHMA1004 (methyl-piperazine-2-carboxylate) at two doses (1 and 5 mg/kg) in male and female rats. CHMA1004 had a locomotor activating and anxiolytic-like profile in open field and elevated zero-maze tests. In female rats sucrose consumption and swimming in Porsolt's test were increased. Nevertheless, CHMA1004 did not exhibit strong psychostimulant-like properties: CHMA1004 had no effect on 50-kHz ultrasonic vocalizations except that it reduced the baseline difference between male and female animals, and acute drug treatment had no effect on extracellular dopamine levels in striatum. Subchronic CHMA1004 altered ex vivo catecholamine levels in several brain regions. RNA sequencing of female rat striata after subchronic CHMA1004 treatment revealed changes in the expression of a number of genes linked to dopamine neuron viability, neurodegeneration, depression, anxiety and stress response. Conclusively, the first-in-class METTL3/METTL14 activator compound CHMA1004 increased locomotor activity and elicited anxiolytic-like effects after systemic administration, demonstrating that pharmacological activation of RNA m6A methylation has potential for neuropsychiatric drug development.

Selecting a Brief Cognitive Screening Test Based on Patient Profile: It Is Never Too Early to Start

Introduction: Cognitive impairment, marked by a decline in memory and attention, is frequently underdiagnosed, complicating effective management. Cardiovascular risk factors (CVR) and anticholinergic burden (ACB) are significant contributors to dementia risk, with ACB often stemming from medications prescribed for neuropsychiatric disorders. This study evaluates cognitive profiles through three brief cognitive tests, analyzing the impact of CVR and ACB presence. Methods: This cross-sectional study was performed between 2019 and 2023 in community pharmacies and an outpatient clinic in Valencia, Spain. Eligible participants were patients with subjective memory complaints 50 years or older with clinical records of cardiovascular factors. Patients with conflicting information regarding diabetes diagnosis or not taking concomitant medications were excluded. Three brief cognitive tests (Memory Impairment Screening (MIS), Semantic Verbal Fluency Test, and SPMSQ) were assessed. CVR was calculated using the European SCORE2 table, and ACB was assessed using the CALS scale. Results: Among 172 patients with memory complaints and CVR factors, 60% failed at least one cognitive test. These patients were on significantly more medications and had higher blood pressure and HbA1c levels. An increase in CVR and ACB was associated with more failed tests. Additionally, elevated SCORE2 scores were associated with a greater failure rate on the MIS test, while patients with elevated ACB more frequently failed the SPMSQ test. Conclusions: Selecting an adequate brief cognitive test according to patients’ characteristics offers an opportunity to screen patients who are probably cognitively impaired. Whereas the MIS test may be helpful for patients with cardiovascular risk, SPMSQ stands out among patients with significant ACB.

A meta-analysis of the prevalence of neuropsychiatric disorders and their association with disease onset in myotonic dystrophy.

There is a high prevalence of neuropsychiatric disorders in myotonic dystrophy types 1 and 2 (DM1 and DM2), including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) in DM1, and depression and anxiety in both DMs. The aim of this systematic review and meta-analysis was to estimate the prevalence of ASD, ADHD, depression and anxiety in the population with DM, and their association with disease onset. A systematic search of Medline, Scopus, Web of Science, and the Cochrane Library was conducted from inception to November 2023. Observational studies estimating the prevalence of these disorders in DM1 or DM2 were included. A meta-analysis of the prevalence of these disorders and an association study with disease onset by prevalence ratio meta-analysis were performed. Thirty-eight studies were included. In DM1, the prevalence of ASD was 14%, with congenital onset being 79% more common than juvenile onset, while the prevalence of ADHD was 21%, with no difference between congenital and juvenile onset, and the prevalence of depression and anxiety were 14% and 16%. Depression was more common in the adult onset. Finally, the prevalence of depression in DM2 was 16%. A higher prevalence of neuropsychiatric disorders is observed in individuals with DM1 and DM2 than in the general population. Therefore, actively screening for congenital and juvenile neurodevelopmental disorders in DM1 and emotional disorders in DM1 and DM2 may improve the quality of life of those affected.

Postsynaptic Density Proteins and Their Role in the Trafficking of Group I Metabotropic Glutamate Receptors.

Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system that regulates multiple different forms of synaptic plasticity, including learning and memory. Glutamate transduces its signal by activating ionotropic glutamate receptors and metabotropic glutamate receptors (mGluRs). Group I mGluRs belong to the G protein-coupled receptor (GPCR) family. Regulation of cell surface expression and trafficking of the glutamate receptors represents an important mechanism that assures proper transmission of information at the synapses. There is growing evidence implicating dysregulated glutamate receptor trafficking in the pathophysiology of several neuropsychiatric disorders. The postsynaptic density (PSD) region consists of many specialized proteins which are assembled beneath the postsynaptic membrane of dendritic spines. Many of these proteins interact with group I mGluRs and have essential roles in group I mGluR-mediated synaptic function and plasticity. This review provides up-to-date information on the molecular determinants regulating cell surface expression and trafficking of group I mGluRs and discusses the role of few of these PSD proteins in these processes. As substantial evidences link mGluR dysfunction and maladaptive functioning of many PSD proteins to the pathophysiology of various neuropsychiatric disorders, understanding the role of the PSD proteins in group I mGluR trafficking may provide opportunities for the development of novel therapeutics in multiple neuropsychiatric disorders.