A Single Dominant Gene Can Account for Eye Tracking Dysfunctions and Schizophrenia in Offspring of Discordant Twins

Subtyping schizophrenia: implications for genetic research

“…Subtyping schizophrenia A Jablensky 823 205 Prepulse inhibition of the startle reflex [206][207][208] Deficient gating of the auditory evoked response (P50) [209][210][211] P300 amplitude reduction and latency delay 212 N400 amplitude reduction (semantic context underutilization) 213 Mismatch negativity (MMN) [214][215][216][217] Smooth pursuit eye movement dysfunction (SPEM) [218][219][220][221] Antisaccade error rate (AS) [222][223][224] Composite inhibitory phenotype (P50, AS, SPEM) 225 Multivariate electrophysiological endophenotype (MMN, P50, P300, AS) 226 Neuroimaging markers and endophenotypes Fronto-thalamic-cerebellar gray matter deficit 227 Fronto-striato-thalamic gray matter deficit 228 MRI-derived three-factor phenotype 229 MRI whole-brain nonlinear pattern classification 230 Frontal hypoactivation in response to cognitive tasks (hypofrontality) 231 Atrophic and static (neurodevelopmental) schizophrenia endophenotypes 232 Cognitive markers and endophenotypes Continuous performance tests (CPT, signal/noise ratio) [233][234][235] Attention and vigilance-based subtype 18 Verbal dysmnesic subtype 18 Verbal memory deficit, cortical or subcortical type 236,237 Dysexecutive subtype 18 Prefrontal executive/working memory phenotype 238 Frontal/abstraction deficit profile 239 Spatial working memory 240...…”

Structural neural networks subserving oculomotor function in first-episode schizophrenia

“…Schizophrenia has been associated with abnormalities of smooth pursuit (Levy et al 1994) and more recently increased antisaccadic errors, which are erroneous reflexive saccades made towards a peripheral target when subjects are instructed to direct their gaze to its mirror image location (Crawford et al 1995;Fukushima et al 1990;Katsanis et al 1997;McDowell & Clementz, 1997). Both abnormal smooth pursuit and increased antisaccade errors have been found at illness onset in medication-naïve patients (Sweeney at al, 1992;Lieberman et al 1993;Hutton et al 1998) and in first-degree relatives (Holzman et al 1988;Crawford et al 1998;Ross et al 1998). Thus, oculomotor abnormalities may represent markers of genetic vulnerability to schizophrenia.…”

Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus

“…Various psychophysiological paradigms demonstrate altered brain functions in schizophrenic patients and their relatives that might reflect such inherited traits (9,(11)(12)(13). Many findings indicate basic deficits in the regulation of response to sensory stimuli that may underlie patients' more apparent symptoms, such as hallucinations and delusions (14).…”

“…Although elevated P50 ratios are significantly associated with the apparent genetic risk for schizophrenia, many individuals in the pedigrees who have the deficit are clinically unaffected (45). In that respect, the distribution of the trait resembles several other neurobiological abnormalities in schizophrenics and their relatives, such as deficits in smooth pursuit eye movements and reaction time (11,12). These traits have been proposed to be alternative expressions of a latent trait or endophenotype (12), which, in combination with other pathogenic elements, gives rise to schizophrenia.…”