Hana Kuzelova

Comparing Bioinformatic Gene Expression Profiling Methods: Microarray and RNA-Seq

Understanding the control of gene expression is critical for our understanding of the relationship between genotype and phenotype. The need for reliable assessment of transcript abundance in biological samples has driven scientists to develop novel technologies such as DNA microarray and RNA-Seq to meet this demand. This review focuses on comparing the two most useful methods for whole transcriptome gene expression profiling. Microarrays are reliable and more cost effective than RNA-Seq for gene expression profiling in model organisms. RNA-Seq will eventually be used more routinely than microarray, but right now the techniques can be complementary to each other. Microarrays will not become obsolete but might be relegated to only a few uses. RNA-Seq clearly has a bright future in bioinformatic data collection.

Dopamine D4 receptor gene DRD4 and its association with psychiatric disorders

Summary Dopamine receptors control neural signals that modulates behavior. Dopamine plays an important role in normal attention; that is the reason for studying the genes of the dopaminergic system, mainly in connection with disorders of attention. DRD4 influences the postsynaptic action of dopamine and is implicated in many neurological processes, exhibits polymorphism and is one of the most studied genes in connection with psychiatric disorders. Associations were found with ADHD (attention deficit hyperactivity disorder), substance dependences, several specific personality traits, and reaction to stress. These findings have implications for pharmacogenetics. This article reviews the principle published associations of DRD4 variants with psychiatric disorders.

Disruptive patterns of eating behaviors and associated lifestyles in males with ADHD

Background Attention deficit hyperactivity disorder (ADHD) is a neurological/behavioral disorder characterized by inattention or hyperactivity and impulsivity, or combined symptomatology. Children with ADHD are predisposed to irregular and/or impulsive eating patterns often leading to compromised physical condition. The goal of the present study was to statistically evaluate parental scoring of patterned eating behaviors and associated lifestyles within a cohort of 100 boys diagnosed with ADHD in comparison to age-matched male controls. Material/Methods The study population consisted of 100 boys aged 6–10 years diagnosed with mixed type ADHD by DSM-IV criteria and 100 aged-matched healthy male control subjects. Patterns of eating behaviors and associated lifestyles were scored by structured parental interviews using a nominal rating scale. Results Interview scores indicated statistically significant differences in patterned eating behaviors in subjects with ADHD in comparison to healthy controls. Notably, subjects diagnosed with ADHD exhibited markedly diminished adherence to a traditional breakfast, lunch, and dinner schedule, which was linked to a significantly higher frequency (>5/day) of irregular eating times. In the ADHD cohort, disruptive patterns of eating behaviors were associated with diminished nutritional value of ingested food (expressed as lowered content of fruits and vegetables) and increased consumption of sweetened beverages. Conclusions Disruptive patterns of eating behaviors, metabolically unfavorable nutritional status, and diminished physical activities of male children diagnosed with ADHD are linked to compromised growth and development and appearance of metabolic diseases in adulthood.

Parkinson’s disease, L-DOPA, and endogenous morphine: A revisit

Summary Clinical observations stemming from widespread employment of restorative L-3,4-dihydroxyphenylalanine (L-DOPA) therapy for management of dyskinesia in Parkinson’s Disease (PD) patients implicate a regulatory role for endogenous morphine in central nervous system dopamine neurotransmission. Reciprocally, it appears that restorative L-DOPA administration has provided us with a compelling in vivo pharmacological model for targeting peripheral sites involved in endogenous morphine expression in human subjects. The biological activities underlying endogenous morphine expression and its interaction with its major precursor dopamine strongly suggest that endogenous morphine systems are reciprocally dysregulated in PD. These critical issues are examined from historical and current perspectives within our short review.

Low dose morphine adjuvant therapy for enhanced efficacy of antipsychotic drug action: Potential involvement of endogenous morphine in the pathophysiology of schizophrenia

Summary Major thematic threads linking extensive preclinical and clinical efforts have established a working mechanistic scheme whereby atypical antipsychotic drugs ameliorate negative DSM IV diagnostic criteria by effecting relatively potent blockade of serotonin (5-HT)(2A) receptors coupled with weaker antagonism of dopamine D(2) receptors in frontal cortical areas. These contentions are more or less supported by in vitro binding experiments employing cloned receptors on cultured cells, although significant functional involvement of 5-HT(2C) receptors has also been proposed. It is interesting that a key statistical analysis indicates a major shift in usage back to typical antipsychotic agents for management of schizophrenia from 1995–2008, whereas off-label usage of atypical antipsychotic agents was markedly increased or expanded for bipolar affective disorder. Importantly, meta-analyses generally did not support efficacy differences between the other atypical antipsychotics compared with the older typical agents. A critical examination of putative functional linkages of morphine and its type-selective mu opioid receptor to higher order cortical regulation of cognitive processes may provide novel insights into human behavioral processes that are severely impaired in schizophrenia spectrum disorders.

Effect of stimulants on growth of ADHD children: A critical review

Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed childhood psychiatric disorders manifested in almost every part of children’s behavior. The most common treatment of ADHD is medication with stimulants, by specific amphetamine and methylphenidate. It is known that the treatment by stimulants may be accompanied by side effects from among decrease of appetite or changes in development as growth suppression and loss of weight which may present very serious phenomenon. Although many studies have monitored changes in growth and weight during medication, they did not provide definite results that the growth and weight suppression are caused by medication or not. According to many studies the height deficit is approximately amounted to 1 cm/year during the first 3 years of the treatment and can be clinically serious. Contrary to these findings some authors reported that the growth or weight changes can be a natural symptom of ADHD and not just a consequence of medication. The present article reviews key studies monitoring changes in parameters of growth in medicated children with ADHD, compares their results and suggest methodology improvements for further studies.

2762 – Life style in ADHD children - comparative study

Introduction Attention Deficit Hyperactivity Disorder (ADHD) is the ADHD is the most commonly diagnosed behavioral disorder of childhood. It affects about 3 - 5% of school aged children. ADHD is diagnosed more often in boys than in girls. ADHD has a wide range of symptoms. It may affect cognitive and executive functions; it may also lead to behavioral problems and further psychiatric symptoms and disorders. Currently it has been hypothesized that ADHD may also lead to specific lifestyle that is influenced by core symptoms of ADHD. This specific lifestyle may negatively influence or even induce further mental and somatic problems. Objectives and aims The aim of the study was to compare lifestyle of ADHD and non ADHD boys in age of 6 - 10 years. Methods We have assessed a group of ADHD boys (n=50) and non ADHD boys (n=50) with structured interview oriented to life style in nutrition and health and free time and social life. Results In our pilot study we identified that lifestyle of ADHD boys substantially differs from non ADHD boys - in most of all monitored areas, especially in nutrition and way of spending free time. ADHD life style is characterized by lower level of organization. Conclusions Upon the presented study we may suggest that ADHD may lead to specific lifestyle that is characterized by lack of organization and stability. This may lead to further mental or even somatic problems. Clinicians and researchers should pay more attention to these questions.

Targeted D4 dopamine receptors: implications for drug discovery and therapeutic development.

A wealth of preclinical and clinical literature has established functional associations of CNS dopamine (DA) and its multiple G protein-coupled receptor (GPCR) types in the integration of key neurological processes linked to complex behavioral activities. Conversely, an equivalent vast literature supports the role of aberrant CNS DA expression and DA receptor signaling in the etiology and persistence of major psychiatric illnesses and has established selective targeting of DA-ergic systems as a cornerstone of pharmacotherapeutic intervention and current neuroleptic drug development. The present short review focuses on potential functional/behavioral alterations linked to polymorphisms in the primary DNA sequence of the DA receptor type 4 (DRD4) gene in reference to major psychiatric illnesses. The potential clinical relevance of major polymorphisms of the DRD4 gene are discussed within the context of practical aspects of typical and atypical neuroleptic drug usage within afflicted populations of psychiatric patients. It is anticipated that additional complementary molecular, biochemical, and behavioral studies of DRD4 gene polymorphisms will provide essential information for selective targeting of heterogeneous populations of CNS D4 receptors and advance drug discovery and therapeutic development efforts for highly efficacious treatment of psychiatric illnesses.

EPA-0888 – Validity of retrospective statements in test and interview of adults with institutional care in childhood

Many research results show problematic nature of retrospective answers (Hardt, Rutter, 2004). Statements based on memories suffer from lower accurate correspondence with real events; however such statements express a subjective meaning which individuals give to their experiences. This ambivalence must be considered within the research design and during interpretation of data. In the research, we examine the impact of institutional care during childhood on social and psychological development in adulthood. The sample consisted of 127 adults who spent their childhood or its part out of the original family. All individuals filled the set of standardized psychodiagnostic tools, including CTQ and Rohners method of family diagnostics and extended anamnestic questionnaire. After four weeks, selected 20 individuals were asked for interviews covering similar topics as previous tests. Data gathered via oral and written inquiries were compared. The analysis shows the differences in described experiences on three levels: 1. the factual nature of experiences (process of events, time and space localization), 2. the emotional load of experiences (expressed feelings), 3. the hierarchy of experiences (different subjective meanings and mutual relations). It was find out that correspondence between oral and written answers decreases if questions with certain parameters are used. Moreover, crucial finding is that the validity of retrospective answers increases if methods for data collection are cumulated. Supported by J&T Foundation

EPA-0855 – Educational trajectory of adults with experience of institutional and family care in childhood

As many studies show, the life of a child in institutional care has a significant influence on his development in different areas of further life. One of the aims of our research is to find typical educational trajectory, including process of schooling and education as a value. We verify the hypothesis whether the course of educational trajectory and access to education as such differ between two groups - people who went through a foster or institutional care during childhood (n=127) in comparison with those who grew up in original families (n=104). All subjects answer nn anamnestic questionnaire which was focused among others on attitudes toward education or the course of educational trajectory. Twenty selected respondents with the experience in substitute form of family care subsequently provided the individual interview which cover the schoul experience and support for schooling given by significant others. The data obtained from the anamnestic questionnaires and interviews were processed by both statistical and qualitative procedures. The results show that various forms of substitute family care have impact on the educational trajectory and access to education in the lives of individuals. Regarding to the experience of the substitute family care, satisfaction with the achieved level of education differs.