Retinal function and preclinical risk traits in children and adolescents at genetic risk of schizophrenia and bipolar disorder.

BACKGROUND: The millions of children having a parent affected by a major psychiatric disorder may carry, as vulnerability indicators, electroretinographic (ERG) anomalies resembling those seen in adult patients. Our goal was to determine whether ERG anomalies in high-risk youths are related to clinical precursors of a later transition to illness such as the presence of childhood DSM-IV diagnoses, bouts of psychotic like experiences, lower global IQ and social functioning deterioration. METHODS: The 99 youths (53% males) aged 5-27 years had one parent affected by schizophrenia, bipolar disorder or major depressive disorder. They were assessed with a best-estimate DSM-IV diagnoses based on review of medical charts and a structured interview (K-SADS or SCID), global IQ (WISC-V and WAIS-IV), global functioning (GAF scale) and psychotic-like experiences using interviews and a review of medical records. The electroretinogram of rods and cones was recorded. RESULTS: Cone Vmax latency was longer in offspring having psychotic-like experiences, respective adjusted mean [SE] ms of 31.59 [0.27] and of 30.96 [0.14]; P = 0.018). The cone Vmax delayed latency was associated with a lower global IQ (R = -0.18; P = 0.045) and with deteriorated global functioning (GAF; R = -0.25; P = 0.008). In contrast, rods had decreased b-wave amplitude only in offspring with a non-psychotic non-affective DSM diagnoses, respective means [SE] µV of 170.18 [4.90] and of 184.01 [6.12]; P = 0.044). CONCLUSIONS: ERG may mark neurodevelopmental pathways leading to adult illness and have an effect on early pre-clinical traits, giving clues to clinicians for the surveillance of sibling differences in high-risk families.

Assessing the impact of non-dilating the eye on full-field electroretinogram and standard flash response.

We investigated the possibility of performing electroretinography (ERG) in non-pharmacologically dilated eyes using brighter flash (time-integrated) luminance. Photopic (N = 26; background 25.5 cd·m(-2), white LED flashes) and scotopic ERG (N = 23, green LED flashes) luminance response functions were obtained simultaneously in a dilated (DE) and non-dilated eye (NDE). In the NDE, photopic V (max) b-wave amplitude was reduced by 14% (P < 0.0001), implicit time prolonged (P < 0.0001), and retinal sensitivity (log K) decreased by 0.38 log units (P < 0.0001) with no effect on a-wave. Using a xenon strobe light (N = 6) to increase flash luminance, V (max) remained lower by about 12% in the NDE (P = 0.02). V (max) with LED and xenon was achieved at 3.9 ± 1.0 cd·s·m(-2) and 3.3 ± 0.81 cd·s·m(-2) in the DE and 10.6 ± 1.2 cd·s·m(-2) and 12.3 ± 1.90 cd·s·m(-2) in the NDE, that is an increase of 0.43 and 0.57 log unit (P < 0.0001), respectively. Increasing background luminance by 0.50 log units (80 cd·m(-2), N = 4) resulted in implicit time normalization but not V (max) amplitude. Rod V (max) was decreased by 7% in NDE (P < 0.05) and sensitivity reduced by 0.40 log units (P < 0.0001), but our data suggest that the luminance may have not been sufficient to reach V (max) in all participants in the NDE and that the sensitivity change may have been due to an inadequate inter-stimulus interval. For the photopic ERG, increasing flash luminance is not sufficient to compensate for the smaller pupil size, whereas for the scotopic ERG, more data are needed to establish proper inter-stimulus interval to perform recordings in a non-pharmacologically dilated.

Circadian variation in the electroretinogram and the presence of central melatonin.

The light/dark cycle is the most important circadian clock synchronizer for mammals and humans. Circadian rhythms of dopamine and melatonin production in the retina have been reported to follow the light and dark cycle, but their impact on rod and cone functioning is not clear. The purpose of this study was to assess diurnal variations (morning vs. evening) in retinal function as measured with the photopic and scotopic electroretinogram (ERG). We also tried to correlate our results with the presence or absence of melatonin secretion in the saliva. Photopic and scotopic luminance-response functions were obtained in 29 participants at 11:00 (when melatonin should not be present) and 23:00 (when melatonin should be present). From the luminance-response function, Vmax, log K and slope parameters were derived. In scotopic condition, a significant increase of 6% in Vmax amplitude was observed in evening compared to morning (P = 0.03) along with a prolonged b-wave implicit time of 8% (P = 0.01) and an increase in rod sensitivity in evening compared to morning (P = 0.02). As expected, these changes in rod function were accompanied by a higher concentration of melatonin in saliva samples in the evening (P = 0.01). In photopic condition, only a prolonged a-wave implicit time of 5% was observed in evening when compared to morning (P = 0.02). Our findings suggest that the rod system is favored during night time, when circulating melatonin is present. Although statistically significant changes were observed, the day vs. night difference observed in the present study appears to be too small to impact significantly upon clinical assessment of retinal function.