Electoretinographic evidence of retinal ganglion cell-dependent function in schizophrenia

Moghimi, Pantea; Jimenez, Nathalia Torres; McLoon, Linda K.; Netoff, Theoden I.; Lee, Michael S.; MacDonald, Angus W.; Miller, Robert F.

doi:10.1016/j.schres.2019.09.005

Cited by 14 publications

(21 citation statements)

References 61 publications

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“…In contrast to the b-wave amplitude, the low-frequency component also can account for inherent variability 69 in the data resulting from studying individuals with schizophrenia. 70 We suggest that an analysis of the low-frequency component be included in fERG analyses of people with schizophrenia to better differentiate their fERGs from those of control subjects.…”

Section: Discussionmentioning

confidence: 99%

Electroretinographic Abnormalities and Sex Differences Detected with Mesopic Adaptation in a Mouse Model of Schizophrenia: A and B Wave Analysis

Jimenez

Lines

Kueppers

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Mesopic flash electroretinography (fERG) as a tool to identify N-methyl-Daspartate receptor (NMDAR) hypofunction in subjects with schizophrenia shows great potential. We report the first fERG study in a genetic mouse model of schizophrenia characterized by NMDAR hypofunction from gene silencing of serine racemase (SR) expression (SR-/-), an established risk gene for schizophrenia. We analyzed fERG parameters under various background light adaptations to determine the most significant variables to allow for early identification of people at risk for schizophrenia, prior to onset of psychosis. SR is a risk gene for schizophrenia, and negative and cognitive symptoms antedate the onset of psychosis that is required for diagnosis. METHODS. The scotopic, photopic, and mesopic fERGs were analyzed in male and female mice in both SR-/and wild-type (WT) mice and also analyzed for sex differences. Amplitude and implicit time of the a-and b-wave components, b-/a-wave ratio, and Fourier transform analysis were analyzed. RESULTS. Mesopic a-and b-wave implicit times were significantly delayed, and b-wave amplitudes, b/a ratios, and Fourier transform were significantly decreased in the male SR-/mice compared to WT, but not in female SR-/mice. No significant differences were observed in photopic or scotopic fERGs between genotype. CONCLUSIONS. The fERG prognostic capability may be improved by examination of background light adaptation, a larger array of light intensities, considering sex as a variable, and performing Fourier transform analyses of all waveforms. This should improve the ability to differentiate between controls and subjects with schizophrenia characterized by NMDAR hypofunction.

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Section: Discussionmentioning

confidence: 99%

Electroretinographic Abnormalities and Sex Differences Detected with Mesopic Adaptation in a Mouse Model of Schizophrenia: A and B Wave Analysis

Jimenez

Lines

Kueppers

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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“…Low acuity could have several causes, ranging from inadequate optical correction (a non-neuronal source) to retinal aberrations (i.e., altered function of lateral inhibition, which sharpens boundaries) to a reduction of the cortical suppressive mechanisms necessary for accurate delineation of object boundaries (cortical acuity limits). We cannot, with the current dataset, address questions of whether acuity or retinal health is predictive of disease state in patients, although there are several known connections [66][67][68][69] . Although other researchers have found group differences in acuity with evidence that the difference is neural in origin 70 , we did not observe overall group differences in acuity in the current study.…”

Section: Discussionmentioning

confidence: 99%

Reduced contrast surround suppression associated with schizophrenia depends on visual acuity and scene context

Pokorny

Schallmo

Sponheim

et al. 2022

Preprint

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Perceptual distortions are core features of psychosis. Weakened surround suppression has been proposed as a neural mechanism of such atypical perceptual experiences. While previous work has measured suppression by asking participants to report the perceived contrast of a low-contrast target surrounded by a high-contrast surround, it is possible to modulate perceived contrast solely by manipulating the orientation of a matched-contrast center and surround. Removing the bottom-up segmentation cue of contrast difference and isolating the orientation-dependent suppression may clarify the neural processes responsible for atypical surround suppression in psychosis. We examined surround suppression across a spectrum of psychotic psychopathology including people with schizophrenia (PSZ; N=31) and bipolar disorder (PBD; N=29), first-degree biological relatives of these patient groups (PBDrel, PSZrel; N=28, N=21, respectively), and healthy controls (N=29). Surround suppression deficits in PSZ, while observable under many stimulus conditions, were absent under the condition that produced the strongest suppression. PBD and PSZrel exhibited intermediate suppression, while PBDrel performed most similarly to controls. Intriguingly, group differences in surround suppression magnitude were moderated by visual acuity. We propose a potential model by which visual acuity and/or focal attention interact with untuned gain control that reproduces the observed pattern of results including the lack of group differences when orientation of center and surround are the same. Our findings further elucidate perceptual mechanisms of impaired center-surround processing in psychosis and provide insights into the effects of visual acuity on orientation-dependent suppression in PSZ.

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“…46,67 In schizophrenia, abnormal ERG findings are well established, and have been reported in several recent studies. 68–70 Using portable hand-held flash ERG (fERG), Demmin and colleagues reported diminished a-wave and b-wave amplitude and latency in both photopic (light-adapted) and scotopic (dark adapted) conditions, suggesting weakened photoreceptor and bipolar cell activity. 68 In contrast, Moghimi and colleagues saw a trend of decreasing b-wave amplitude in schizophrenia patients and healthy controls with regards to a-wave and latency, despite observing a trend towards reduced b-wave amplitude.…”

Section: Schizophreniamentioning

confidence: 99%

“…68 In contrast, Moghimi and colleagues saw a trend of decreasing b-wave amplitude in schizophrenia patients and healthy controls with regards to a-wave and latency, despite observing a trend towards reduced b-wave amplitude. 69 Looking at the findings from a longitudinal standpoint, Hébert reported that cone a-wave and rod b-wave amplitude reductions seen in childhood were present in adults with schizophrenia. 71 Finally, in a large study comparing medicated and stable 150 schizophrenia patients with 151 bipolar patients, both patient groups exhibited diminished cone a-wave amplitude and extended b-wave latency, whereas only schizophrenia patients exhibited diminished cone b-wave amplitude.…”

Section: Schizophreniamentioning

confidence: 99%

Retinal correlates of psychiatric disorders

Almonte

Capellàn

Yap

et al. 2020

Therapeutic Advances in Chronic Disease

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Diagnosis and monitoring of psychiatric disorders rely heavily on subjective selfreports of clinical symptoms, which are complicated by the varying consistency of accounts reported by patients with an impaired mental state. Hence, more objective and quantifiable measures have been sought to provide clinicians with more robust methods to evaluate symptomology and track progression of disease in response to treatments. Owing to the shared origins of the retina and the brain, it has been suggested that changes in the retina may correlate with structural and functional changes in the brain. Vast improvements in retinal imaging, namely optical coherence tomography (OCT) and electrodiagnostic technology, have made it possible to investigate the eye at a microscopic level, allowing for the investigation of potential biomarkers in vivo. This review provides a summary of retinal biomarkers associated with schizophrenia, bipolar disorder and major depression, demonstrating how retinal biomarkers may be used to complement existing methods and provide structural markers of pathophysiological mechanisms that underpin brain dysfunction in psychiatric disorders.

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Electoretinographic evidence of retinal ganglion cell-dependent function in schizophrenia

Cited by 14 publications

References 61 publications

Electroretinographic Abnormalities and Sex Differences Detected with Mesopic Adaptation in a Mouse Model of Schizophrenia: A and B Wave Analysis

Electroretinographic Abnormalities and Sex Differences Detected with Mesopic Adaptation in a Mouse Model of Schizophrenia: A and B Wave Analysis

Reduced contrast surround suppression associated with schizophrenia depends on visual acuity and scene context

Retinal correlates of psychiatric disorders

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