Thinking clearly about the endophenotype–intermediate phenotype–biomarker distinctions in developmental psychopathology research

  title={Thinking clearly about the endophenotype–intermediate phenotype–biomarker distinctions in developmental psychopathology research},
  author={Mark F. Lenzenweger},
  journal={Development and Psychopathology},
  pages={1347 - 1357}
  • M. Lenzenweger
  • Published 1 November 2013
  • Psychology
  • Development and Psychopathology
Abstract The endophenotype is central to modern developmental psychopathology studies. It is used in studies seeking to connect the genetic substrates of the panoply of major mental disorders with processes, tapped by laboratory and other assessment measures, in the genotype to a behavior/psychopathology pathway. Proposed originally by Gottesman and Shields (1972; Shields & Gottesman, 1973) 41 years ago, the endophenotype concept has gained widespread traction in psychopathology research since… 
Neuropsychological and Structural Neuroimaging Endophenotypes in Schizophrenia
This chapter reviews neuropsychological and structural neuroimaging endophenotypes for schizophrenia and for schizophrenia spectrum disorders, with an emphasis on key conceptual criteria for assessing endophenotype relationships, including their relationships to schizophrenia, to non-psychotic relatives, and to heritability.
Endophenotypes in Schizophrenia for the Perinatal Period: Criteria for Validation.
Changes to the endophenotype validity criteria appropriate to perinatal research are proposed and how application of these modified criteria helped identify a perinatally-usable phenotype of risk for schizophrenia, P50 sensory gating, which was then used to propose a novel per inatal primary prevention intervention.
Neurobiological candidate endophenotypes of social anxiety disorder
Endophenotypes for Alcohol Use Disorder: An Update on the Field
The endophenotype concept was first proposed as a strategy to use (purportedly) genetically simpler phenotypes in gene identification studies for psychiatric disorders, and is distinct from the
PTSD, Endophenotypes, the RDoC, and the DSM-5
The search for endophenotypes that stand between genetics and disease has been applied to the diagnostic entity of Posttraumatic Stress Disorder (PTSD). Advances are being made in understanding the
Arguments for the sake of endophenotypes: Examining common misconceptions about the use of endophenotypes in psychiatric genetics
  • D. Glahn, E. Knowles, L. Almasy
  • Biology, Psychology
    American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
  • 2014
Despite the potential utility of endophenotypes for gene characterization and discovery, there is considerable resistance to endophenotypic approaches in psychiatry.
Developing Psychiatric Biomarkers: a Review Focusing on the Error-Related Negativity as a Biomarker for Anxiety
  • A. Meyer
  • Psychology, Biology
    Current Treatment Options in Psychiatry
  • 2016
It is demonstrated that the ERN relates to diagnoses and dimensional anxiety symptoms concurrently—and can predict new onset disorders prospectively—and the possibility that a psychiatric biomarker can serve as a target of treatment, thereby encouraging the development of novel intervention strategies is raised.
Redefining the endophenotype concept to accommodate transdiagnostic vulnerabilities and etiological complexity
It is suggested that the disorder-specificity requirement of endophenotypes be relaxed, that neural functions are preferable to behaviors as starting points in searches forEndophenotypes, and that future research should focus on interactive effects of multiple endophenotype on complex psychiatric disorders, some of which are ‘phenocopies’ with distinct etiologies.
Thinking clearly about schizotypy: hewing to the schizophrenia liability core, considering interesting tangents, and avoiding conceptual quicksand.
The understanding (and misunderstanding) of the schizophrenia-related schizotypy model, particularly as regards clinical illness, as well as an alternative approach to the construct require vigilance in order to ensure the methodological approach continues to yield the fruit that it can in illuminating the pathogenesis of schizophrenia- related psychopathology.


Endophenotypes in psychopathology research: where do we stand?
With more grounding in animal neuroscience and other aspects of basic biological and psychological science, there is every reason to anticipate that the endophenotype concept will grow more central in the psychopathology literature.
Psychiatric endophenotypes and the development of valid animal models
There exists a need for increased collaboration between clinicians and basic scientists, the result of which should be to improve diagnosis, classification and treatment on one end and to increase the construct relevance of model organisms on the other.
Mark F. Lenzenweger is internationally renowned for his research inschizotypy and has long advocated the view that schizotypic psychopathology is a variant of schizophrenia liability.
The endophenotype concept in psychiatry: etymology and strategic intentions.
The authors discuss the etymology and strategy behind the use of endophenotypes in neuropsychiatric research and, more generally, in research on other diseases with complex genetics.
Schizophrenia: refining the phenotype, resolving endophenotypes.
Endophenotypes: Bridging Genomic Complexity and Disorder Heterogeneity
The handbook of neuropsychiatric biomarkers, endophenotypes and genes
Candidate endophenotypes, important trait markers widely used for genetic studies, are useful for the development of heritable diagnostic and prognostic biomarkers (endophenotype strategy) and are predicted to open new avenues for practically important applications of genetics, neuroscience and “omics” advantages in neuropsychiatry.
Developing constructs for psychopathology research: research domain criteria.
The Research Domain Criteria (RDoC) framework is a heuristic to facilitate the incorporation of behavioral neuroscience in the study of psychopathology, and aims to identify reliable and valid psychological and biological mechanisms and their disruptions, with an eventual goal of understanding how anomalies in these mechanisms drive psychiatric symptoms.
Connectomic Intermediate Phenotypes for Psychiatric Disorders
Research using connectomic techniques to understand how genetic variation influences the connectivity and topology of human brain networks is reviewed, indicating that imaging connectomics provides a powerful framework for understanding how genetic risk for psychiatric disease is expressed through altered structure and function of the human connectome.
Endophenotype: a conceptual analysis
The endophenotype (EP) construct has important potential lessons for etiological research in PDs that can be optimized by considering it as a special case of a broader set of multivariate genetic models, which can be fitted using currently available methodology.