View Full Version : "ADHD Endophenotypes"

01-29-14, 05:49 PM
This thread I would like to learn about Endophenotypes.

What are endophenotypes and how to they help understand ADHD better, etc?

ADHD Endophenotypes

Castellanos and Tannock (2002) have identified three potential neuroscience-based endophenotypes that involve the executive functions of the brain.

1) Hyperactive behavior may be a result of a shortened delay gradient, which decreases the time one is willing to wait for a reward (e.g., recess, food treat, money, etc.). They hypothesize that fidgeting or hyperactivity may reflect a self-regulatory behavior when waiting is enforced.

2) Waiting, even for short times, may be extra difficult for people with ADHD because of differences in temporal processing that skew perceptions of time. Deficits in temporal processing may also be responsible for inattentive behaviors and inconsistent performance often seen in people with ADHD.

3) The final proposed endophenotype reflects a working memory deficit that affects executive functions (including impulse control), ability to maintain attention/focus, and even phonemic awareness deficits (e.g., dyslexia). Deficits in working memory may also promote the shortened reward-delay gradient that characterizes ADHD.

ADHD and Play (


01-29-14, 06:31 PM
..conceptual psychiatric syndromes were never based on an understanding of the brain or its emotional systems.

This is one reason why outdated concepts have caused increasing problems from DSM-I to DSM-IV.

Many fear that current construction of DSM-V will not be immune to those flaws (Hyman, 2007).

Such problems might be alleviated if we could replace (or at least supplement) the old conceptual structures with better visions of the real psychiatric-relevant entities of the mind (e.g., the various endophenotypes of the emotional brain).

Endophenotypes are natural aspects of brain functions that can be studied at the neuroscientific level; for instance, researchers can examine responses as simple as eye-blinks, pupillary dilation or constriction, and startle reflexes (Gottesman & Gould, 2003).

We know that loud noise invariably startle people and animals.

However when exposed to the same noise a second time, the startle response is less pronounced .

This phenomenon, when studied with mild auditory stimuli that allow animals to prepare for much louder sounds, is know as "pre-pulse inhibition", and is often attenuated or absent in schizophrenic individuals.

We can be confident that these preparatory, regulatory responses are controlled by coherent, analyzable circuits within the brain (especially basal ganglia), although we can have no such confidence for psychiatric syndromes, because those are concepts created by human insight and ingenuity.

Through affective neuroscience, endophenotypic thinking (acknowleged almost universally as an important new way of approaching psychiatric science) can include the domain of primary-process emotions.

The natural emotional networks of the brain may provide the most relevant endopehotypes of all, because they go to the affective core of psychiatric matters.

Furthure developments along these lines may help us cut through the Gordian knot that has arisen from the once-revolutionary syndromal thinking of previous eras (Panksepp, 2006a).

-Panksepp/Biven, "The Archaeology of Mind", Brain Emotional Systems and Affective Qualities of Mental Life, P 441.


01-29-14, 06:44 PM
My apologies and thanks, to Tyler Durden (and other members) , who introduced me to the terms endophenotypes and ADHD, and I didn't understand.

Heterogeneity in attention-deficit/hyperactivity disorder (ADHD), with complex interactive operations of genetic and environmental factors, is expressed in a variety of disorder manifestations: severity, co-morbidities of symptoms, and the effects of genes on phenotypes. Neurodevelopmental influences of genomic imprinting have set the stage for the structural-physiological variations that modulate the cognitive, affective, and pathophysiological domains of ADHD. The relative contributions of genetic and environmental factors provide rapidly proliferating insights into the developmental trajectory of the condition, both structurally and functionally. Parent-of-origin effects seem to support the notion that genetic risks for disease process debut often interact with the social environment, i.e., the parental environment in infants and young children. The notion of endophenotypes, markers of an underlying liability to the disorder, may facilitate detection of genetic risks relative to a complex clinical disorder. Simple genetic association has proven insufficient to explain the spectrum of ADHD. At a primary level of analysis, the consideration of epigenetic regulation of brain signalling mechanisms, dopamine, serotonin, and noradrenaline is examined. Neurotrophic factors that participate in the neurogenesis, survival, and functional maintenance of brain systems, are involved in neuroplasticity alterations underlying brain disorders, and are implicated in the genetic predisposition to ADHD, but not obviously, nor in a simple or straightforward fashion. In the context of intervention, genetic linkage studies of ADHD pharmacological intervention have demonstrated that associations have fitted the “drug response phenotype,” rather than the disorder diagnosis. Despite conflicting evidence for the existence, or not, of genetic associations between disorder diagnosis and genes regulating the structure and function of neurotransmitters and brain-derived neurotrophic factor (BDNF), associations between symptoms-profiles endophenotypes and single nucleotide polymorphisms appear reassuring.

Epigenetics in Developmental Disorder: ADHD and Endophenotypes (


01-29-14, 07:19 PM
Neuroscience of Attention Deficit/Hyperactivity Disorder: The search for Endophenotypes.

Research on attention-deficit/hyperactivity disorder (ADHD), a highly prevalent and controversial condition, has, for the most part, been descriptive and atheoretical.

The imperative to discover the genetic and environmental risk factors for ADHD is motivating the search for quantifiable intermediate constructs, termed endophenotypes.

In this selective review, we conclude that such endophenotypes should be solidly grounded in the neurosciences. We propose that three such endophenotypes — a specific abnormality in reward-related circuitry that leads to shortened delay gradients, deficits in temporal processing that result in high intrasubject intertrial variability, and deficits in working memory — are most amenable to integrative collaborative approaches that aim to uncover the causes of ADHD.