Neuropsychiatry Disorders Research Articles

English

Vesicular monoamine transporters (VMATs) are an important target for biological research in neuropsychiatric disorders. Recent studies indicated that VMAT1 is expressed in the brain, thus making transporter plausible candidate genes for neuropsychiatric disorders. Furthermore, several recent genetic case-control studies have documented an association between common missense variations in the VMAT1 gene and susceptibility to bipolar disorder and schizophrenia. Until now, there are no reports of VMAT 1 allele frequencies in Emirati population. Hence, the aim of the present work was to study VMAT1 genetic polymorphism in Healthy Emirati population. Saliva samples were collected from 248 healthy Emiratis and genotyping was done for rs2270641 by PCR-RFLP, and rs2270637 and rs1390938 by Taqman assay. The minor allele frequencies of rs2270641, rs2270637 and rs1390938 were 0.48, 0.20 and 0.18, respectively, which were compared with that of available HapMap population data. In conclusion, the present study is first of its kind in Emirati population that established the allele and genotype frequency for various VMAT1 alleles which can be exploited to design future studies on the genetic association of neuropsychiatry disorders. Key words: Neuropsychiatry disorders, bipolar, monoamine, vesicular monoamine transporters, vesicular monoamine transporter (VMATs).

Vitamin B12 deficiency induced psychosis – a case report

Vitamin B12 is one of the most essential vitamins affecting various systems of the body. Cases of neuropsychiatry disorders due to its deficiency are more common in elderly patients with prevalence of 10–20%. The most common psychiatry symptoms reported in the literature associated with vitamin B12 deficiency was depression, mania, psychotic symptoms, cognitive impairment and delirium. Here, we report a case of vitamin B12 deficiency in a 52-year-old male who presented with psychotic features: persecutory delusions, tactile and auditory hallucinations. Patient had neither recorded psychiatry history nor any drug abuse. Medical history includes hypertension, diabetes mellitus and glaucoma. The patient was not a vegetarian. All relevant laboratory evaluations and head CT were normal except vitamin B12. The patient was treated with antipsychotics (risperidone 3 mg/day) and intramuscular vitamin B12. One week after, there was total remission of psychotic symptoms. In the follow-up during the next four months, psychiatry symptoms did not recur at any time. This case reports a rare case of vitamin B12 deficiency induced psychosis. Although there was concurrent administration of an antipsychotic along with vitamin B12, it underlines the importation of evaluation of vitamin B12 and other potential reversible causes of psychosis.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Cathodal/Anodal technique use of repetitive transcrainal Magnetic stimulation in treatment of neuropsychiatry disorders

Objective: To investigate the possible effect of rTMS in Neuropsychiatry Disorders using multiple alternative brain area stimulation with both stimulatory and inhibitory protocols in the same session.

Test-retest reliability of functional connectivity networks during naturalistic fMRI paradigms.

Functional connectivity analysis has become a powerful tool for probing the human brain function and its breakdown in neuropsychiatry disorders. So far, most studies adopted resting-state paradigm to examine functional connectivity networks in the brain, thanks to its low demand and high tolerance that are essential for clinical studies. However, the test-retest reliability of resting-state connectivity measures is moderate, potentially due to its low behavioral constraint. On the other hand, naturalistic neuroimaging paradigms, an emerging approach for cognitive neuroscience with high ecological validity, could potentially improve the reliability of functional connectivity measures. To test this hypothesis, we characterized the test-retest reliability of functional connectivity measures during a natural viewing condition, and benchmarked it against resting-state connectivity measures acquired within the same functional magnetic resonance imaging (fMRI) session. We found that the reliability of connectivity and graph theoretical measures of brain networks is significantly improved during natural viewing conditions over resting-state conditions, with an average increase of almost 50% across various connectivity measures. Not only sensory networks for audio-visual processing become more reliable, higher order brain networks, such as default mode and attention networks, but also appear to show higher reliability during natural viewing. Our results support the use of natural viewing paradigms in estimating functional connectivity of brain networks, and have important implications for clinical application of fMRI. Hum Brain Mapp 38:2226-2241, 2017. © 2017 Wiley Periodicals, Inc.

Microbiome: The Missing Link in Neuropsychiatric Disorders

The relationship between intestinal microbiota and the brain has been the focus of attention of the scientific world in recent years; >90% of the articles discussing the microbiome have been published only recently.1 There is a strong and bidirectional relationship between the brain and the gut. Gut bacteria communicate with the intestinal epithelium and the immune system cells, with this communication causing many autoimmune, metabolic, and neuropsychiatric diseases. New horizons have been opened in the understanding and treatment of neuropsychiatry disorders. Microbiota dysbiosis can be restored with faecal microbiota transplantation, dietary arrangements, and probiotics. The efficacy of faecal microbiota transplantation in neuropsychiatric disorders is being investigated currently, and through the manipulation of the composition of intestinal bacteria in a conscious way, the treatment of neuropsychiatric disorders may be performed in a cheaper, easier, and natural way in the near future. Searching through the relevant literature on PubMed, EMBASE, and Google Scholar electronic databases, this is one of the first articles to discuss faecal microbiota transplantation in neuropsychiatric disorders in detail.

Prospects for Medications to Reverse Causative Epigenetic Processes in Neuropsychiatry Disorders.

Prospects for Medications to Reverse Causative Epigenetic Processes in Neuropsychiatry Disorders

Development of semi-chronic microdrive system for large-scale circuit mapping in macaque mesolimbic and basal ganglia systems.

The development of novel neurotechnologies for treating refractory neuropsychiatry disorders depends on understanding and manipulating the dynamics of neural circuits across large-scale brain networks. The mesolimbic pathway plays an essential role in reward processing and mood regulation and disorders of this pathway underlie many neuropsychiatric disorders. Here, we present the design of a customized semi-chronic microdrive array that precisely targets the anatomical structures of non-human primate (NHP) mesolimbic and basal ganglia systems. We present an integrated experimental paradigm that uses this device to map and manipulate large-scale neural circuits. The system combines electrophysiology, spatiotemporal multisite patterned intracortical microstimulation (ICMS), and diffusion tractography. We propose that this system provides a flexible platform for exploring and identifying neural signatures which can serve as novel targets for closed-loop stimulation in the clinical treatment of neuropsychiatric disorders.

Potential Treatment for Neuropsychiatry Disorders with TRPC5 Modulators

Patent Application Title: Quinazoline-2,4(1H,3H)-dione Derivatives as TRPC5 Modulators for the Treatment of Neuropsychiatry Disorders Patent Application Number: WO 2016/023826 Al Publication date: 18 February 2016 Priority Application: US 62/035,578 Priority date: 11 August 2014 Inventors: Chenard, B. L.; Gallaschun, R. J. Applicants: Hydra Biosciences, Inc.; 45 Moulton Street, Cambridge, MA, 02138, USA Boehringer Ingelheim International Gmbh; Binger Strasse 173, 55216 Ingelheim am Rhein (DE) Disease Area: Neuropsychiatry Disorders Biological Target: Short transient receptor potential channel 5 (TRPC5) Summary: The invention in this patent application relates to novel quinazoline-2,4(1H,3H)-dione derivatives. These compounds are TRPC5 modulators and may be used as medication for the treatment of conditions such as neuropsychiatric disorder, neurodegenerative disorder, nephropathy, and seizure disorder. Ion channel proteins mediate the ion flux across cellular membranes. Their proper expressions and functions are important for the maintenance of cell function as well as intracellular communications. Ion channels are important in modulating membrane potential and ion flux in cells. The misregulation of membrane potential and aberrant calcium handling are implicated in the pathogenesis of numerous diseases. Therefore, compounds that can either promote or inhibit particular ion channels are of great interest and may potentially provide therapy for different diseases. The short transient receptor potential channel 5 (TRPC5) is one of seven mammalian transient receptor potential channel proteins. TRPC5 is a multipass cation channel membrane protein that modulates the flux of calcium and sodium ions across cellular membranes. The influx of sodium and calcium leads to a depolarization of the cell, which in turn increases the probability that voltage-gated ion channels will reach the threshold required for activation. Thus, activation of nonselective cation channels can increase electrical excitability and the frequency of several voltage-dependent events including, but not limited to, neuronal action potentials, cardiac action potentials, smooth muscle contraction, cardiac muscle contraction, and skeletal muscle contraction. In addition, the activation of nonselective cation channels such as TRPC5 causes calcium influx and alters the intracellular free calcium concentrations. This has profound effects on signal transduction, gene expression, and cellular phenotype. Gene expression events include, but are not limited to, production of mRNAs encoding cell surface receptors, ion channels, and kinases. These changes in gene expression can lead to hyperexcitability in that cell. TRPC5 protein may form homomultimeric species such as a homo-TRPC5 tetramer, or it may form heteromultimeric structures with other transient receptor proteins such as TRPC1, TRPC3, and TRPC4. The term TRPC5 is used generically to include either polymeric form. Compounds that can modulate the function of TRPC5, such as the compounds described in this patent application, can maintain calcium homeostasis, modulate intracellular calcium levels, modulate membrane polarization, and potentially treat or prevent several diseases and disorders associated with calcium and/or sodium homeostasis or dys-homeostasis.

Dietary behaviors of female marriage immigrants residing in Gwangju, Korea

Purpose: This cross-sectional study aimed to document the dietary behaviors, dietary changes, and health status of female marriage immigrants residing in Gwangju, Korea. Methods: The survey included 92 female immigrants attending Korean language class at a multi-cultural family support center. General characteristics, health status, anthropometric data, dietary behaviors, and dietary changes were collected. Results: Mean age of subjects was 31.3 years, and home countries of subjects were Vietnam (50.0%), China (26.0%), Philippines (12.0%), and others (12.0%). Frequently reported chronic diseases were digestive diseases (13.2%), anemia (12.1%), and neuropsychiatry disorder (8.9%). Seventeen percent of the subjects was obese (BMI ≥ 25 kg/㎡). Dietary score by Mini Dietary Assessment was 3.45 out of 5 points. Dietary scores for dairy foods, meat/fish/egg/bean intake, meal regularity, and food variety were low, and those for fried foods and high fat meat intake were also low. Thirty-three percent of subjects answered that they have changed their diet and increased their consumption of fruits and vegetables after immigration. Length of residence in Korea was positively associated with BMI and waist circumference. Length of residence tends to be positively associated with dietary changes and obesity as well as inversely associated with disease prevalence. Conclusion: The study shows that length of residence is inversely related to disease prevalence. However, this association is thought to be due to the relatively short period of residence in Korea and thus the transitional phase to adapting to dietary practices. As the length of residence increases, disease patterns related to obesity are subject to change. Healthy dietary behaviors and adaptation to dietary practices in Korea in female marriage immigrants will not only benefit individuals but also their families and social structure. Therefore, varied, long-term, and target-specific studies on female marriage immigrants are highly needed.

Pediatric autoimmune neuropsychiatric disorder associated with group a streptococcal infection: the role of surgical treatment.

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) is a well-defined syndrome in which tics (motor and/or vocal) and/or obsessive compulsive disorders (OCD) consistently exacerbate in temporal correlation to a Group A beta-haemolytic streptococcal infection. In children with PANDAS, there is speculation about whether tonsillectomy or adenotonsillectomy might improve the neuropsychiatric course. Our objective was to examine whether such surgery impacted remission or, in patients without remission, modified clinical course of the disease, streptococcal antibody titers, neuronal antibodies or clinical severity of Obsessive-Compulsive Disorder (OCD) and/or tics. Study participants (n = 120) with positive PANDAS criteria were recruited, examined, and divided into surgical or non-surgery groups. The surgical group consisted of children with tonsillectomy or adenotonsillectomy (n=56). The remaining children were categorized as non-surgery (n=64). Clinical follow-up was made every 2 months for more than 2 years. Surgery did not affect symptomatology progression, streptococcal and neuronal antibodies, or the clinical severity of neuropsychiatric symptoms in these children. In conclusion, in our series clinical progression, antibody production, and neuropsychiatric symptom severity did not differ on the basis of surgical status. We cannot uphold surgical management as likely to impact positive remission rates, course of OCD/tics, or antibody concentrations in children with PANDAS.

Prevalence of anxiety disturbs in patients with Tourette syndrome and tic disturb

Tourette syndrome (TS) is characterized by a wide phenotypic polymorphism and this heterogeneity is due partly to the association with several neuropsychiatry disorders. These comorbidities are showed in the 90% of TS cases. The aim of this transversal study is to analyze the presence and prevalence of different psychopathological conditions that could be expressed with tic disorder (TD) and specifically in TS. We examined a sample of 102 patients, between 7 and 17.6 years old, with a diagnosis DSM-IV-TR of TD, using the self-report SAFA. Different correlations between these comorbidities and clinical variables are also analyzed. Our data underlined most of all a prevalence of anxiety disorders in the 31.4% of our patients with TD, of depression in the 27.44%, and of somatization symptoms in the 22.54%. Anxiety disorders seem to be linked with the variables of patients'age, duration of disease, gender, pharmacological treatment and presence of comorbidity for obsessive-compulsion disorder (OCD). This study suggests the important prevalence of non-OCD anxiety disorders in TD patients and shows they have a central role in their psychopathological profile. However, the basilar question if these disturbs are primary or secondary to the TD is still to be clarify.

Overexpression of 12/15-lipoxygenase increases anxiety behavior in female mice

The 12/15-lipoxygenase (12/15-LO) is an enzyme widely distributed in the central nervous system, and it has been involved in the neurobiology of Alzheimer's disease. However, whether this pathway is also involved in neuropsychiatry disorders including anxiety remain to be investigated. In this study we investigated whether genetic over-expression of 12/15-LO (H12/15-LO) modulates some elevated plus maze and Y-maze behaviors. While we observed that H12/15LO mice at the age of 12 months did not differ from wild type in the elevated plus maze paradigm, when they reached the age of 15 months, they manifested an increased anxiety-like behavior compared with controls. By contrast, no differences between the 2 groups at both ages when they were tested for working memory in the Y-maze paradigm. Additionally, we found that the change in anxiety was associated with a reduction in phosphorylation of the transcription factor CREB (cAMP response element-binding protein), and a significant increase in the synaptic protein synaptophysin. Taken together our findings suggest a novel role for 12/15-LO in the pathogenesis of anxiety-like behavior.

Correlation between platelet and brain PLA2 activity

The phospholipase A2 (PLA2) enzymes have been implicated in several neuropsychiatry disorders and activity alterations have been described in brain and platelet. Since brain tissue is not readily available for the measurement of PLA2 activity, it would be of interest to test directly whether PLA2 activities in both tissues are correlated. We performed this task assessing PLA2 activity in platelets and hippocampus collected simultaneously from 19 patients undergoing temporal lobectomy for treatment of refractory epilepsy. Our findings suggest that total PLA2 activity in platelets may reflect the total activity of the enzyme in the brain (rs=0.59, p=0.008). However in our sample no correlations were found between the subgroups of the enzyme in brain and in platelets. This lack of correlations may be due to different effects of drug treatment on the PLA2 subtypes. In face of the difficulty to obtain brain tissues from living patients, further studies with larger drug-free samples are warranted to clarify whether the use of platelets is a reliable strategy to reflect the subtypes of PLA2 activity in the brain.

PSYCHOPHARMACOLOGICAL ACTIVITY;

Objective: The purpose of this study was to screen some herbal medicine as psychotropic drugs those has strong modulatingeffect on brain and behavior. Material & methods: Herbal drug Reserpine, Nux- Vomica, Anacardium and Chlorpromazine with a wide range ofpharmacological actions. In our present study, we evaluate the effectiveness of these drugs as Psychotropic agents and accessed bybiochemical-parameters. Rats (weighing 180-250g) and Mice (22-32g) either sex were used in this study. One group was kept as control fordrugs. Mice were kept under room temperature. Tap-water was allowed ad-Libitum. Animals were observed during and after 21 days. A tabletcrushed in 10ml of water, 1cc was given. Screening method used was swimming induced-despair. Results: Among these, Strychnos Nux-Vomica has strong action on cholinergic system, CNS activity and observed as an antispasmodic. Rauwolfia serpentine is an active alkaloidparticularly present in reserpine are used to treat essential hypertension and in certain neuropsychiatry disorders. It has sedative andtranquilizing effects, as it depletes catecholamine from the central nervous system. Keeping in view, the medicinal importance of these herbs,our present study was designed to screen these herbs as for CNS activity on Albino mice and rats.

Clinical Utility of Lisdexamfetamine for the Management of Attention-Deficit Hyperactivity Disorder

ADHD is the most common neuropsychiatry disorder affecting children and adolescents, and may cause impairment in many domains of social and occupational functioning. Despite proven efficacy of existing treatments, recent focus has been on the development of newer, once-daily medications. Lisdexamfetamine (LDX) was first released in 2007 and is approved for the treatment of ADHD in ages 6 and above. LDX is a uniquely formulated stimulant, a prodrug which requires an enzymatic hydrolytic reaction to be converted to active dextroamphetamine. LDX has a longer duration of action compared to other stimulants and has less potential to be misused or abused. LDX has repeatedly demonstrated improvement in ADHD symptoms compared to placebo, and seems to be at least as effective as other stimulants. LDX still carries the risks and disadvantages of other stimulants and may be more expensive than other stimulants. LDX can be expected to be increasingly used as a first-line agent for the treatment of ADHD.

Neuropsychiatrie disorders in Parkinson's disease and their correction with the MAO-B inhibitor rasagiline (Azilect®)

Parkinson's disease (PD) is a multisystemic neurodegenerative disease with a broad spectrum of not only movement, but also neuropsychiatry disorders (NPD). The efficiency of dopamine therapy in correcting NPD needs to be clarified. Objective: to evaluate the impact of therapy with the MAO-B inhibitor rasagiline (Azilect®) on NPD in patients with extended stages of PD. Subjects and methods. Twenty PD (disease duration 10.2+5.08 years; stage 2.4+0.5) patients with the wearing-of phenomenon were given rasagiline ' mg/day in addition to antiparkinsonian drugs. Following 6 and 24 weeks of therapy, its efficiency was evaluated using the unified PD rating scale, the motor fluctuation rating scale, the Beck depression inventory, the PD fatigue scale, the PD sleep scale, the Epworth sleeping scale, and the PD quality of life scale (PDQ-39). Results. There were reductions in the severity of nocturnal and morning hypokinesia, daytime off periods, depression, insomnia, overfatigue and improved quality of life. The positive effect of therapy was stable within further 6 follow-up months.

The social recognition test of memory in the rat: A reliable primary in-vivo cognition assay for guiding drug discovery/development decision-making relevant to neuropsychiatric diseases

The social recognition test of memory in the rat: A reliable primary in-vivo cognition assay for guiding drug discovery/development decision-making relevant to neuropsychiatric diseases

P02-553 - Database of MNI stereotactic coordinates for deep brain stimulation targets in neuropsychiatric disorders

IntroductionDeep brain stimulation (DBS) is a promising therapy option for otherwise treatment-resistant neuropsychiatrie disorders, especially in obsessive-compulsive disorder (OCD), major depression (TRD) and Tourette's Syndrome (TS).ObjectiveThe brain coordinates of the DBS targets are mainly reported using measurements in original, unnormalized brains. In the neuroimaging community stereotactic data are mainly indicated in the standardized Montreal Neurological Institute (MNI) space, i.e. a three-dimensional proportional grid system.AimsImproved comparability between targets in DBS studies and molecular and functional neuroimaging data from PET, SPECT, MRI, fMRI, mostly published with stereotactic data.MethodsA comprehensive and systematic literature search for published DBS case reports or studies in TRD, OCD and TS was performed. We extracted the tip positions of electrode leads as provided in the publications or by the authors, and transferred individual coordinates to the standard brain in the MNI space.Results46 publications fulfilled the inclusion criteria. The main targets for the specific disorders and one or two examples of their calculated MNI coordinates are indicated in the table:[MNI coordinates of the main DBS targets]ConclusionsWe provide DBS data of neuropsychiatrie disorders in the MNI space, improving the comparability to molecular, functional and structural neuroimaging data.

Infectious psychosis: Cryptococcal meningitis presenting as a neuropsychiatry disorder

Infectious psychosis: Cryptococcal meningitis presenting as a neuropsychiatry disorder

Autism Susceptibility Genes Identification by Linkage Analysis: A Review

Autism is a complex neuropsychiatry disorder that is heterogeneous both in its phenotypic expression and etiology. It is characterized by deficits in verbal communications, impairments in social in...