Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Endophenotype strategies for the study of neuropsychiatric disorders

The identification of genes that contribute to a susceptibility to complex neuropsychiatric disorders such as schizophrenia, major depression and bipolar disorders has been not very successful using conventional genetic approach.

There are several problems associating with this conventional approach including carriers of genes cannot be identified in the absence of manifest symptoms and the heterogeneity of neuropsychiatric disorders.

A new direction that appears encouraging is the identification of neurobiological or neurobehavioural characteristics associated with these complex neuropsychiatric disorders, or endophenotypes, that may be more closely linked to gene expression. Endophenotype is a biomarker associating with genetic components as well as the clinical symptoms of neuropsychiatric disorders. It plays an important role to bridge the gap between microscopic level and macroscopic level of neuropsychiatric disorders.

The identification of endophenotype, along with the advanced genetic analysis such genomewise association studies, is very crucial to the identification of genes that predispose someone to neuropsychiatric disorders. Therefore, the study of endophenotype is of particular useful for us to understand the underlying mechanism of the illness process of neuropsychiatric disorders, aiding the clinicians to make accurate diagnosis and for early detection purposes.

With the supported from the National Basic Research Programme of China (973 Progamme) (2007CB512302), The Key Laboratory of Mental Health of the Institute of Psychology, Chinese Academy of Sciences has organized a strategic symposium for endophenotypes, titled ""Endophenotype strategy for psychotic disorders and summit meeting of Key Laboratory of Mental Health, Institute of Psychology, CAS". International renowned scholars of this field presented their updated findings on endophenotypes. Professor Irving Gottesman, the founder of the endophenotype for neuropsychiatric disorders, was also giving a video lecture to all the participants. Their work was published in the special issue of Chinese Science Bulletin, 2011, Vol. 56(32).

Cognitive deficits have been widely recognized as core features of schizophrenia, and as major contributors to the clinical outcome of the disorder. They are also studied widely as 'endophenotypes', reflecting a growing consensus that schizophrenia is a broader, more multidimensional illness than the diagnostic criteria required for its formal diagnosis. Stone and Hsi adopted this evolving view of cognition underlying its utilization in recent initiatives for intervention and assessment in schizophrenia, and illustrated it with the use of the MATRICS Cognitive Consensus Battery, a standardized battery of neuropsychological tests developed to assess the effectiveness of cognitive enhancing treatments in schizophrenia. They then further provided evidence to show the utilization of neuropsychological deficits in the identification, validation and remediation of a liability syndrome for schizophrenia ('schizotaxia'). Taken together, the inclusion of cognition in broader consortium and other collaborative efforts to assess interrelationships across multiple dimensions of function will provide important catalysts for progress in each individual dimension. Utilization of cognition underscores its functional importance in the clinical outcome of schizophrenia. Moreover, it helps to illuminate indicators of liability for schizophrenia that might be amenable to remediation.

On the other hand, Prof. Pak Sham and colleagues have addressed the statistical issues and approaches in endophenotype research. In this paper, they argued that in reality, a putative endophenotype is unlikely to be a perfect representation of the genetic component of disease liability. The magnitude of the correlation between a putative endophenotype and the genetic component of disease liability can be estimated by fitting multivariate genetic models to twin data. A number of statistical methods have been developed for incorporating endophenotypes in genetic linkage and association analyses with the aim of improving statistical power. The most recent of such methods can handle multiple endophenotypes simultaneously for the greatest increase in power. In addition to increasing statistical power, endophenotype research plays an important role in helping to understand the mechanisms which connect the associated genetic variants with disease occurrence. The causal pathways are likely to be very complicated and involve endophenotypes at multiple levels: from RNA expression profiles and patterns of protein expression, through neuronal and synaptic properties, to neurophysiological and neurocognitive function. Novel statistical approaches may be required for the analysis of the complex relationships between endophenotypes at different levels and how they converge to cause the occurrence of disease.

In the paper of Consortium for the Human Information and Neurocognitive Endophenotype (CHINE) in mainland China: An example from neurological soft signs for neuropsychiatric disorders, Chan made a strategic paper on endophenotypes and argued the need for establishing a central consortium for neuropsychiatric disorders in mainland China, namely the CHINE. The CHINE is intentionally established to pave the roadmap for neuropsychiatric disorders research. It not only identifies the biosignatures for neuropsychiatric disorders but also serves as the central databank for examining the etiologies of major complex neuropsychiatric disorders as well as serving as the main basis for corresponding treatment development. The CHINE emphasizes on two main features, i.e., the supposedly universal basic cognitive functioning such as attention, and the supposedly culturally specific social cognitive functioning such as emotion perception and expression. In this consortium, data collected highlights the genetic level (susceptibility genes associating with major neuropsychiatric disorders, neuroanatomical level (structural and functional imaging data), and behavioural level (neurocognitive function performances, social cognitive functioning, neurological and clinical manifestations). Target groups include both the clinically diagnosed patients suffering from neuropsychiatric disorders (mainly schizophrenia and bipolar disorders at the current moment, but will be extended to other clinical groups later), non-psychotic first-degree relatives of the patients, and healthy controls. Chan specifically illustrated an example of a promising endophenotype for schizophrenia, namely neurological soft signs, in detailing the steps for building the consortium. It is also noteworthy that the potential translational usage of neurological soft signs as a quick, quantifiable, sensitive and user-friendly bedside early detection and screening tool for clinical practice.

See the articles:

STONE William S & HSI Xiaolu. Recent developments in neuropsychological endophenotypes for schizophrenia: Development of the MATRICS battery, liability syndromes and the near future. Chinese Science Bulletin, 2011, 56(32), 3385-3393.

SHAM Pak Chung, CHERNY Stacey S & HALL Mei-Hua. Statistical issues and approaches in endophenotype research. Chinese Science Bulletin, 2011, 56(32), 34033408.

CHAN Raymond C K. Consortium for the Human Information and Neurocognitive Endophenotype (CHINE) in mainland China: An example from neurological soft signs for neuropsychiatric disorders. Chinese Science Bulletin, 2011, 56(32), 3409-3415.

CHAN chor-kiu Raymond | EurekAlert!
Further information:

More articles from Health and Medicine:

nachricht Resolving the mystery of preeclampsia
21.10.2016 | Universitätsklinikum Magdeburg

nachricht New potential cancer treatment using microwaves to target deep tumors
12.10.2016 | University of Texas at Arlington

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>