This article provides an introductory overview of the investigative strategy employed to evaluate the genetic basis of 17 endophenotypes examined as part of a 20-year data collection effort from the Minnesota Center for Twin and Family Research. Included are characterization of the study samples, descriptive statistics for key properties of the psychophysiological measures, and rationale behind...

Background Patients with schizophrenia and their unaffected relatives exhibit significant P300 amplitude and latency abnormalities in conjunction with neurocognitive deficits. Both the deficits in the P300 and neurocognition suggest that these indexes may be potential endophenotypes of the disorder. Few studies have examined the relationship between the P300 and neuropsychological measurements ...

Endophenotypes, which involve the same biological pathways as diseases but presumably are closer to the relevant gene actions than diagnostic phenotypes, have emerged as an important concept in the genetic studies of complex diseases. In this report, we develop a formal statistical methodology for validating endophenotypes. The proposed method was motivated by the conditioning strategy used for...

The use of cerebrospinal fluid levels of Aβ42 and pTau181 as endophenotypes for genetic studies of Alzheimer's disease (AD) has led to successful identification of both rare and common AD risk variants. In addition, this approach has provided meaningful hypotheses for the biological mechanisms by which known AD risk variants modulate the disease process. In this article we discuss these success...

Depression is a significant public health problem, but its etiology and pathophysiology remain poorly understood. Such incomplete understanding likely arises from the fact that depression encompasses a heterogeneous set of disorders. To overcome these limitations, renewed interest in intermediate phenotypes (endophenotypes) has resurfaced, and anhedonia has emerged as one of the most promising ...

OBJECTIVE Obsessive-compulsive disorder (OCD) is highly heritable. Attempts to delineate precise genetic contributions have met with limited success. There is an ongoing search for intermediate cognitive brain markers (endophenotypes) that may help clarify genetic contributions. The aim was to assess inhibitory control processes in unaffected first-degree relatives of OCD patients for the first...

Anatomical and functional abnormalities in the cortico-cerebellar-thalamo-cortical circuit have been observed in schizophrenia patients and their unaffected siblings. However, it remains unclear to the relationship between anatomical and functional abnormalities within this circuit in schizophrenia patients and their unaffected siblings, which may serve as potential endophenotypes for schizophr...

This article reviews the concept of an endophenotype, with particular reference to heritability as well as diagnostic specificity. An endophenotype need not be heritable, for example, the possible influence of in utero viral infections for schizophrenia. However, heritability is a useful characteristic for a potential endophenotype, as it can be studied in relation to a plausible candidate gene...