Phenotyping psychosis: Room for neurocomputational and content-dependent cognitive endophenotypes?

Abstract

We propose three novel directions for further psychosis endophenotype research: (1) in addition to such content-independent computational processes, which operate in a similar way regardless of the stimuli, it is important to consider the potential roles of "content-dependent endophenotypes", which operate on different stimuli in consistently different manners. Advances in cognitive studies suggest there may be evolutionarily important aspects of cognition which are content-dependent. We propose that both content-independent and content-dependent processes should be addressed in psychosis research. (2) In line with the emphasis on content, close attention should be paid to the study of "psychopathological endophenotypes" in addition to cognitive endophenotypes. (3) "Neurocomputational endophenotypes" may be defined by parsing cognitive processes into "subsystems" with specific computational processing algorithms and considering key computational parameters suggested from these models. These potential "neurocomputational endophenotypes" (such as neuronal noise, synaptic learning algorithms) are potentially intermediate variables located between the levels of cognition and neurobiology.

The clinical basis of orthorexia nervosa: emerging perspectives

“…Given the theoretical overlap with anorexia and OCD, we might look to the literature concerning the neuropathophysiology of these latter conditions to outline logical starting points for this kind of research. Furthermore, additional mapping of the behavioral and cognitive endophenotypes in orthorexia with experimental neuropsychological methodologies will provide useful clues about proximal biological contributors, in essence providing a “top-down deconstruction” 60 of outwardly complex behavior to simpler component processes. Intermediate endophenotypes may provide better insight into underlying etiology than can symptom-level clinical categories 61 which, given the perplexities surrounding the differential diagnosis of orthorexia, will be advantageous for advancing our understanding of orthorexia more quickly.…”

Potential Endophenotype for Schizophrenia: Neurological Soft Signs

“…It is likely that NSS may emerge as a general endophenotype for a number of disorders rather than a specific endophenotype for schizophrenia. 80 Future studies will shed light on the potential role of NSS as a state or trait variable, while the two are not mutually exclusive.…”

Unique Challenges in Biomarkers for Psychotic Disorders

“…Some important missing bridges in the biomarker hierarchy for psychotic disorders include those that are associated with their core, defining symptoms: hallucinations and delusions. Most of the existing neurocognitive measures studied do not directly address psychotic symptoms, but rather target neurocognitive deficits (i.e., in attempt to fill in the jigsaw pieces located some distance away from the core missing pieces) [22]. This indirect targeting of deficit phenomena (failure of performance) to try to explain spurious functions (hallucination and delusions) is justified by the Jacksonian-or more accurately, Reynoldian-suggestion that brain functions consist of hierarchical layers of function with inhibitory interactions, such that the loss of functioning (deficit) at a "higher layer" may result in disinhibition and spurious expression of anomalous function at a "lower layer" [23].…”

“…Such a paradigm has worked well in neurological scenarios involving the more peripheral sensory and motor brain functions, where one-to-one structure-to-function mapping is more evident. Nevertheless, it may not work as well in a more central associative brain system where connections are typically in many-to-many connected networks [22,24,25]. After all, the deficit-based neuropsychological approach is appealing because of the availability of standardised testing material which depends on neutral stimuli with little individual meaning and which, as a result, is considered to be less vulnerable to "experiential contamination", although it is important to note that the use of neurocognitive functions to identify brain dysfunction in psychosis has met with success mostly via mapping to functioning loss rather than to psychotic symptoms [26].…”