INT.J.PSYCHOL.RES. 2016; 9 (1): 6-8

Neurocognitive

Endophenotypes: an update on the field Endofenotipos Neurocognitivos: una actualización en el área

E d i t o r i a l a b Jorge Mauricio Cuartas * and Douglas Londoño

a Facultad de Psicología, Universidad de San Buenaventura, Medellín, Colombia.

b Department of and Human Genetics Institute, Rutgers University, Piscataway, New Jersey.USA.

The endophenotype construct, initially flexible behavior and self-regulation before the reward formulated by Lewis and Gottesman in the 1960s, according to their and attentional referred to an indicator of vulnerability, not necessarily performance, allows us to successfully evolve in expressed as a clinical marker of status. However, this response to the stressor. subclinical marker was established in the phenotype as Showing all these efficient conducts as a a component that co-segregated with the genetic species, determine the great evolution that we have disease background. The endophenotype not only had in the frontal lobes. These lobes are organized determined both potential and differentiated types hierarchically and comprise 20% of the neocortex. The within the same phenotype of interest, but also related is the main structure that accounts for to changes in the prognosis and evolution of the human behavior and that has enabled our species to syndrome or disorder. It increased or decreased the colonize the current evolutionary time called by Steven risk and outlined the pathogenesis of the syndrome Pinker as the "cognitive niche" (Pinker 1999). This term itself at the molecular level while exhibiting a refers to the use of abstraction and social cohesion as continuous variation in the general population. an evolutionary and intelligent way that favors human’s Every endophenotypes must fulfill various problem solving and self-regulated behavior. criteria to be validated as an intermediate phenotype Taken into account the phylogenetic heritage of involved in a syndrome. It must be closely related to cognitive function, to delineate the temporary disease, independent of its state and heritable and architecture of behavior it is helpful to evaluate the stable over the time. Therefore, endophenotypes may different executive domains. This allows contribute to the discrimination of complex diseases circumscription of the neuropsychological network such as mental illness or psychopathology as well as of operating in three regions of the prefrontal cortex: molecular pathways underlying genetic effects dorsolateral prefrontal cortex, medial or paralimbic (Cuartas, 2011). prefrontal cortex and orbital prefrontal cortex. This Different approaches to searching for cortical topology is formed of a large network of cortico- endophenotypes have used neuroimaging, subcorticales interconnections that supports the neurophysiology, allelic variants and neurochemistry. operating mode. Neurocognitive findings and their potential as candidate Today, different studies have identified endophenotypes are a novel approach to the clinical candidate executive domains that, together with genetic treatment of mental or psychopathological syndromes. factors, explain greater than 40% of the phenotype Recently, changes in executive function have been variance (González-Giraldo, et al. 2015). Even though studied as candidate endophenotypes. Executive for mental disorders there is a high heritability, is not functioning is an integral component for human clear yet what genes are directly responsible. This is development of adaptive cognitive and behavioral mainly due to both the large pre-existing genetic patterns to favor the success as a species. In fact, heterogeneity and lack of consistent replication of aspects such as problems solving, decisions making, specific allelic variants in association studies.

*Corresponding author: Jorge Mauricio Cuartas Arias, Facultad de Psicología, Universidad de San Buenaventura, Medellín, Colombia. Email address: [email protected].

* ISSN printed 2011-2084 ISSN electronic 2011-2079 C or re 6 sp on di ng E D I T O R I A L

INTERNATIONAL JOURNAL OF PSYCHOLOGICAL RESEARCH Neurocognitive Endophenotypes

In this context, the underlying genetic causes of measuring reaction time of the cognitive responses, mental disorders affect multiple cortical and subcortical time should be recorded in milliseconds. It is likely that neural systems. That is, networks such as some findings related to executive performance and dopaminergic, serotonergic, and glutamatergic among their potential as candidate endophenotypes for others. They regulate the expression of neurocognitive subdomains, have been influenced by the lack of processes thereby reshaping the phenotypic sensitivity regarding the processing speed. expression in language, attention, memory, learning, Accordingly, one of the main variables when evaluating self-appreciation and emotional activation. Also, they neurocognitive assessment of a syndrome should be regulate inhibitory control and social cognition such as reaction times. (Nikolas & Nigg 2015). neuropsychological domains and As an example, evaluating motor which are differentially seen in the clinical features of impulsiveness with either a self-reported scale or a the disorder. neuropsychological test that does not discriminate In this context, Halford and collaborators reaction times, would not allow determination of (Halford et al. 2010) focused on the relational changes in the inhibitory control. Instead, we could knowledge as a cognitive process of higher order that choose to assess (PPI or startle underlies the goal-directed behaviors and that reflex): the presence of sub-threshold stimuli prior to the correspond to the skills of reasoning, categorization, startle stimulus which manage to decrease the planning and language expression. From this magnitude of the response. PPI activates inhibitory perspective, Hansell and his group proposed an mechanisms and processes of filtering sensory approach to what can be called a ‘cognitive complexity information. Assessing PPI could allow us to infer the metric’ that can be conceptualized as relational phenotype of the as response behavior that processing. This approach is consistent with that of emerges from deficits in inhibitory control with higher Halford et al. and potentially sensitive to changes in sensitivity. brain activation in the prefrontal cortex. Such changes The neural basis of PPI is the hippocampal have been frequently associated with response which currently constitutes one of the best psychopathological, neurological and psychiatric evaluated endophenotypes in , autism problems (Christoff, et al. 2001). Not only the prefrontal and some neurodevelopmental disorders. Its high cortex is associated with the ability of complex heritability observed through robust experimental processes at the relational level, it is also the designs (Greenwood, et al. 2015; Osumi, et al. 2015; connectivity system from which the frontoparietal and Russos, et al. 2015), have allowed the exploration of girdle-opercular networks are established. Here its genetics structure and the discrimination of different underlies all the genetic architecture corresponding to etiopathogenic within the same syndrome. This, in turn, the variable expression of performance and activation will impact the clinical and pharmacological intervention of the cortical areas. The work of Hansell found the of the disease in the future. relational processing to be a strong potential For now, the challenge is to develop more neurocognitive endophenotypes. The relational sensitive neuropsychological measures to refine the processing is essential for both reasoning and working cognitive metrics using tools that determine reaction memory (Hansell, et al. 2015). These findings are times and processing speed (from seconds to consistent with those reported by Ragland JD and co- milliseconds), in tasks related to the executive function. authors (Ragland, et al. 2012), who reported a high This will allow the exploration of the scope of variation heritability (67%). That is, 67% for the trait of relational to brain and cognitive level. With this type of population variation of processing can be explained by methodologies and also with the incorporation of genetic factors. The limitations in handling and neuroimaging and psychophysiological measures, interpreting complex relationships suggest a central improve the sample sizes, controlling population axis in the general cognitive processing. This axis, in stratification, using designs based on families or turn, operates through genetic factors shaping couples of brothers, and homogenize the clinical neurobiological ways of molecular expressions, criteria; It is the progress in identifying or validate particularly in the prefrontal cortex. neurocognitive endophenotypes which outlining the A measure that raises the cognitive construct is pathogenesis of mental disorders and the therapeutic the processing speed. However, many of the targets in the future. neuropsychological tests incorporate the variable time in seconds. Still, in order to increase the sensitivity of

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