Neurological soft signs in psychometrically identified schizotypy

Patients with schizophrenia often exhibit structural brain abnormalities, as well as neurological soft signs, consistent with its conceptualization as a neurodevelopmental disorder. Neurological soft signs are mild, presumably nonlocalizing, neurological impairments that are inferred from performance deficits in domains such as sensory integration, motor coordination, and motor sequencing. The vulnerability for schizophrenia is presumed to be expressed across a broad continuum of impairment referred to as schizotypy. It is hypothesized that nondisordered people along the schizotypy continuum should exhibit elevated rates of neurological soft signs. The present study examined the relation of psychometrically identified positive and negative schizotypy with neurological soft signs using the Neurological Evaluation Scale (NES) in a nonclinically ascertained sample of young adults (n = 177). As hypothesized, negative, but not positive, schizotypy was related to increased neurological soft signs in tasks that assessed fine and gross motor coordination, motor sequencing, eye movement abnormalities, and memory recall. However, positive schizotypy was associated with increased neurological soft signs in tasks related to sensory integration dysfunction. In general, the positive x negative schizotypy interaction term was unrelated to individual neurological soft sign tasks. The findings support: a) the theory that the vulnerability for schizophrenia is expressed across a broad continuum of subclinical and clinical impairment referred to as schizotypy; b) the multidimensional structure of schizotypy; and c) the notion that schizotypy is an appropriate construct for understanding the etiology and development of schizophrenia-spectrum disorders

The impact of Catechol-O-Methyl transferase on working memory in psychometrically identified schizotypy

Patients with schizophrenia often exhibit impairment in working memory that is influenced by dopamine availability in the prefrontal cortex. Dopamine availability in the prefrontal cortex is regulated in part by the activity of the Catechol-O-Methyl transferase (COMT) gene. The COMT gene contains a functional polymorphism that results in a Valine (Val) to Methionine (Met) amino acid substitution that impacts dopamine availability. COMT impacts working memory performance in patients with schizophrenia such that Val allele load is associated with impaired working memory performance. The present study extended this literature by examining the relationship between COMT and spatial working memory (SWM), and their interactions, in psychometrically identified positive and negative schizotypy in a nonclinically ascertained sample of young adults. As hypothesized, negative schizotypy was associated with the Val allele in an allele dependent fashion. In addition, negative, but not positive, schizotypy was generally associated with deficits in SWM performance. Contrary to hypotheses, poorer SWM was not associated with Val allele load. Additionally, COMT generally did not moderate the relations between SWM and negative schizotypy. The findings support the idea that the neurodevelopmental vulnerability for schizophrenia is expressed across a continuum of impairment referred to as schizotypy, the construct validity of a multidimensional model of schizotypy, and the use of psychometric screening inventories as promising tools to help understand the etiology and development of schizophrenia

Socioeconomic Status and Psychological Function in Children with Chromosome 22q11.2 Deletion Syndrome: Implications for Genetic Counseling

The purpose of this study is to examine the association between parental socio-economic status (SES) and childhood neurocognition and behavior in children with chromosome 22q11.2 deletion syndrome (22q11DS). Although undoubtedly, the deletion of genes in the 22q11.2 interval is primarily responsible for the psychological manifestations, little is known about the role of the environment in either mitigating or contributing to these problems. We examined the association of parental socio-economic status (SES) with cognition and behavior in children with 22q11DS (n?=?65) and matched healthy control subjects (n?=?52), since SES is a component of family resources. We found that in children with 22q11DS, higher SES correlated with better overall functioning (p?<?.01) and social skills (p?<?.01), and less frequent oppositional defiant behavior (p? <?.001). These findings were in contrast to the control subjects in whom SES correlated with cognition and achievement, but not behavior. Our results indicate that environmental factors influence the behavioral phenotype in children with 22q11DS, providing a framework for developing appropriate interventions. As such, genetic counseling for families with 22q11DS may include consideration of family resources and inclusion of other health professionals, such as social workers, to explore with the family available social supports and resources

Pre- and Perinatal Ischemia-Hypoxia, the Ischemia-Hypoxia Response Pathway, and ADHD Risk

This review focuses on how measured pre- and perinatal environmental and (epi)genetic risk factors are interrelated and potentially influence one, of many, common developmental pathway towards ADHD. Consistent with the Developmental Origins of Health and Disease hypothesis, lower birth weight is associated with increased ADHD risk. Prenatal ischemia-hypoxia (insufficient blood and oxygen supply in utero) is a primary pathway to lower birth weight and produces neurodevelopmental risk for ADHD. To promote tissue survival in the context of ischemia-hypoxia, ischemia-hypoxia response (IHR) pathway gene expression is altered in the developing brain and peripheral tissues. Although altered IHR gene expression is adaptive in the context of ischemia-hypoxia, lasting IHR epigenetic modifications may lead to increased ADHD risk. Taken together, IHR genetic vulnerability to ischemia-hypoxia and IHR epigenetic alterations following prenatal ischemia-hypoxia may result in neurodevelopmental vulnerability for ADHD. Limitations of the extant literature and future directions for genetically-informed research are discussed

Neurological soft signs in psychometrically identified schizotypy

Patients with schizophrenia often exhibit structural brain abnormalities, as well as neurological soft signs (NSS), consistent with its conceptualization as a neurodevelopmental disorder. NSS are mild, presumably nonlocalizing, neurological impairments that are inferred from performance deficits in domains such as sensory integration, motor coordination, and motor sequencing. The vulnerability for schizophrenia is presumed to be expressed across a broad continuum of impairment referred to as schizotypy. It is hypothesized that nondisordered people along the schizotypy continuum should exhibit elevated rates of NSS. The present study examined the relation of psychometrically identified positive and negative schizotypy with NSS using the Neurological Evaluation Scale in a nonclinically ascertained sample of young adults (n = 177). As hypothesized, negative, but not positive, schizotypy was related to increased NSS in tasks that assessed fine and gross motor coordination, motor sequencing, eye movement abnormalities, and memory recall. However, positive schizotypy was associated with increased NSS in tasks related to sensory integration dysfunction. In general, the positive × negative schizotypy interaction term was unrelated to individual NSS tasks. The findings support: a) the theory that the vulnerability for schizophrenia is expressed across a broad continuum of subclinical and clinical impairment referred to as schizotypy; b) the multidimensional structure of schizotypy; and c) the notion that schizotypy is an appropriate construct for understanding the etiology and development of schizophrenia-spectrum disorders

Adapting Clinical Services To Accommodate Needs of Refugee Populations

The diversity of the refugee population in the United States requires practicing psychologists to respond by adapting clinical services to meet their mental health needs. However, the available literature on culturally adapted treatments is only a first step in guiding the process for adapting clinical services. This paper describes our experiences with designing and adapting a variety of clinical services for youth and families with refugee status. Guided by Sue\u27s (2006) tenets for culturally competent service delivery, we discuss a therapeutic model of tiered service delivery used to deliver preventative services and treatment to refugee youth and adults. We discuss how we adapted treatments to help overcome access barriers to mental health treatment, and we provide specific examples of how existing treatments were used with refugee populations. In addition, we discuss information and approaches for how practicing psychologists can develop additional skills for working with refugee populations. We conclude by focusing on the need for our field to work toward improving access to mental health treatment for refugee youth and families and developing evidence-based treatments for this population

Neurofibromatosis Type 1 Implicates Ras Pathways in the Genetic Architecture of Neurodevelopmental Disorders

The genetic architecture of neurodevelopmental disorders is largely polygenic, non-specific, and pleiotropic. This complex genetic architecture makes the search for specific etiological mechanisms that contribute to neurodevelopmental risk more challenging. Monogenic disorders provide an opportunity to focus in on how well-articulated signaling pathways contribute to risk for neurodevelopmental outcomes. This paper will focus on neurofbromatosis type 1 (NF1), a rare monogenic disorder that is associated with varied neurodevelopmental outcomes. Specifically, this paper will provide a brief overview of NF1 and its phenotypic associations with autism spectrum disorder, attention-deficit/hyperactivity disorder, and specific learning disorders, describe how variation within the NF1 gene increases risk for neurodevelopmental disorders via altered Ras signaling, and provide future directions for NF1 research to help elucidate the genetic architecture of neurodevelopmental disorders in the general population

Adapting clinical services to accommodate needs of refugee populations.

The diversity of the refugee population in the United States requires practicing psychologists to respond by adapting clinical services to meet their mental health needs. However, the available literature on culturally adapted treatments is only a first step in guiding the process for adapting clinical services. This paper describes our experiences with designing and adapting a variety of clinical services for youth and families with refugee status. Guided by Sue's (2006) tenets for culturally competent service delivery, we discuss a therapeutic model of tiered service delivery used to deliver preventative services and treatment to refugee youth and adults. We discuss how we adapted treatments to help overcome access barriers to mental health treatment, and we provide specific examples of how existing treatments were used with refugee populations. In addition, we discuss information and approaches for how practicing psychologists can develop additional skills for working with refugee populations. We conclude by focusing on the need for our field to work toward improving access to mental health treatment for refugee youth and families and developing evidence-based treatments for this population

Socioeconomic Status and Psychological Function in Children with Chromosome 22q11.2 Deletion Syndrome: Implications for Genetic Counseling

The purpose of this study is to examine the association between parental socio-economic status (SES) and childhood neurocognition and behavior in children with chromosome 22q11.2 deletion syndrome (22q11DS). Although undoubtedly, the deletion of genes in the 22q11.2 interval is primarily responsible for the psychological manifestations, little is known about the role of the environment in either mitigating or contributing to these problems. We examined the association of parental socio-economic status (SES) with cognition and behavior in children with 22q11DS (n=65) and matched healthy control subjects (n=52), since SES is a component of family resources. We found that in children with 22q11DS, higher SES correlated with better overall functioning (p<.01) and social skills (p<.01), and less frequent oppositional defiant behavior (p<.001). These findings were in contrast to the control subjects in whom SES correlated with cognition and achievement, but not behavior. Our results indicate that environmental factors influence the behavioral phenotype in children with 22q11DS, providing a framework for developing appropriate interventions. As such, genetic counseling for families with 22q11DS may include consideration of family resources and inclusion of other health professionals, such as social workers, to explore with the family available social supports and resources

Discovery and Development of Toll-Like Receptor 4 (TLR4) Antagonists: A New Paradigm for Treating Sepsis and Other Diseases

Abstract. Sepsis remains the most common cause of death in intensive care units in the USA, with a current estimate of at least 750,000 cases per year, and 215,000 deaths annually. Despite extensive research still we do not quite understand the cellular and molecular mechanisms that are involved in triggering and propagation of septic injury. Endotoxin (lipopolysaccharide from Gram-negative bacteria, or LPS) has been implicated as a major cause of this syndrome. Inflammatory shock as a consequence of LPS release remains a serious clinical concern. In humans, inflammatory responses to LPS result in the release of cytokines and other cell mediators from monocytes and macrophages, which can cause fever, shock, organ failure and death. A number of different approaches have been investigated to try to treat and/or prevent the septic shock associated with infections caused by Gram-negative bacteria, including blockage of one or more of the cytokines induced by LPS. Recently several novel amphipathic compounds have been developed as direct LPS antagonists at the LPS receptor, TLR4. This review article will outline the current knowledge on the TLR4-LPS synthesis and discuss the signaling, in vitro pre-clinical and in vivo clinical evaluation of TLR4 antagonists and their potential use in sepsis and a variety of diseases such as atherosclerosis as well as hepatic and renal malfunction. KEY WORDS: drug discovery; LPS; sepsis; toll-like receptor antagonists