Subtle Visual Dysfunctions Often Precede Early-Stage Psychosis

Batya Swift Yasgur, MA, LSW

August 29, 2022

Subtle subjective visual dysfunctions (VisDys) are common and are associated with poorer outcomes of patients with schizophrenia and recent-onset psychosis or who are at clinical high risk (CHR) for psychosis, new research suggests.

A multinational group of investigators found that VisDys were reported considerably more often by patients with recent-onset psychosis and CHR than by those with recent-onset depression or a group acting as healthy control participants.

In addition, vision problems of higher severity were associated with less functional remission both for patients at CHR and those with recent-onset psychosis. Among patients with CHR, VisDys was also linked to lower quality of life (QOL), higher depressiveness, and more severe impairment of visuospatial constructability.

The researchers used fMRI imaging to compare resting-state functional brain connectivity in participants with recent-onset psychosis, CHR, and recent-onset depression. They found that the occipital (ON) and frontoparietal (FPN) subnetworks were particularly implicated in VisDys.

"Subtle VisDys should be regarded as a frequent phenomenon across the psychosis spectrum, impinging negatively on patients' current ability to function in several settings of their daily and social life, their QOL, and visuospatial abilities," write investigators led by Johanna Schwarzer, Institute for Translational Psychiatry, University of Muenster, Germany.

"These large-sample study findings suggest that VisDys are clinically highly relevant not only in [recent-onset psychosis] but especially in CHR," they state.

The findings were published online August 18 in Neuropsychopharmacology.

Subtle, Underrecognized

Unlike patients with nonpsychotic disorders, approximately 50% to 60% of patients diagnosed with schizophrenia report VisDys involving brightness, motion, form, color perception, or distorted perception of their own face, the researchers report.

These "subtle" VisDys are "often underrecognized during clinical examination, despite their clinical relevance related to suicidal ideation, cognitive impairment, or poorer treatment response," they write.

Most research into these vision problems in patients with schizophrenia has focused on patients in which the illness is in a stable, chronic state ― although VisDys often appear years before the diagnosis of a psychotic disorder.

Moreover, there has been little research into the neurobiological underpinnings of VisDys, specifically in early states of psychosis and/or in comparison to other disorders, such as depression.

The Personalised Prognostic Indicators for Early Psychosis Management (PRONIA) Consortium studied the psychophysiologic phenomenon of VisDys in a large sample of adolescents and young adults. The sample consisted of three diagnostic groups: those with recent-onset psychosis, those with CHR, and those with recent-onset depression.

VisDys in daily life were measured using the Schizophrenia Proneness Instrument-Adult Scale (SPI-A), which assesses basic symptoms that indicate increased risk for psychosis.

Visual Information Processing

Resting-state imaging data on intrinsic brain networks were also assessed in the PRONIA sample and were analyzed across 12,720 functional connectivities between 160 regions of interest across the whole brain.

In particular, the researchers were interested in the primary networks involved in visual information processing, especially the dorsal visual stream, with further focus on the ON and FPN intrinsic subnetworks.

The ON was chosen because it comprises "primary visual processing pathways," while the FPN is "widely suggested to modulate attention related to visual information processing at higher cognitive levels."

The investigators used a machine learning multivariate pattern analysis approach that "enables the consideration of multiple interactions within brain systems."

The current study involved 721 participants from the PRONIA database, including 147 participants with recent-onset psychosis (mean age, 28.45 years; 60.5% men), 143 with CHR (mean age, 26.97 years; about 50% men), 151 with recent-onset depression (mean age, 29.13 years; 47% men), and 280 in the healthy-controls group (mean age, 28.54 years; 39.4% men).

The researchers selected 14 items to assess from the SPI-A that represented different aspects of VisDys. Severity was defined by the maximum frequency within the past 3 months ― from 1 (never) to six (daily).

The 14 items were as follows: oversensitivity to light and/or certain visual perception objects, photopsia, micropsia/macropsia, near and tele-vision, metamorphopsia, changes in color vision, altered perception of a patient's own face, pseudomovements of optic stimuli, diplopia or oblique vision, disturbances of the estimation of distances or sizes, disturbances of the perception of straight lines/contours, maintenance of optic stimuli "visual echoes," partial seeing (including tubular vision), and captivation of attention by details of the visual field.

Participants also completed the Beck Depression Inventory–II scale (BDI-II), the Positive and Negative Syndrome Scale (PANSS), the Functional Remission in General Schizophrenia, and several other scales that measure global and social functioning.

Other assessments included QOL and the Rey-Osterrieth Complex Figure Test, which is a neuropsychological measurement of visuospatial constructability.

Specific to Early-Stage Psychosis?

Results showed that VisDys were reported more frequently in both recent-onset psychosis and CHR groups compared with the recent-onset depression and healthy control groups (50.34% and 55.94% vs 16.56% and 4.28%, respectively).

The investigators note that VisDys sum scores "showed high internal consistency" (Cronbachs α = 0.78 over all participants).

Among those with recent-onset psychosis, a higher VisDys sum score was correlated with lower scores for functional remission (P = .036) and social functioning (P = .014).

In CHR, higher VisDys sum scores were associated with lower scores for health-related functional remission (P = .024), lower physical and psychological QOL (P = .004 and P = .015, respectively), more severe depression on the BDI-II (P = .021), and more impaired visuospatial constructability (P = .027).

Among those with recent-onset depression and their healthy peers, "no relevant correlations were found between VisDys sum scores and any parameters representing functional remission, QOL, depressiveness, or visuospatial constructability," the researchers write.

A total of 135 participants with recent-onset psychosis, 128 with CHR, and 134 with recent-onset depression also underwent resting-state fMRI.

ON functional connectivity predicted presence of VisDys in patients with recent-onset psychosis and those with CHR, with a balanced accuracy of 60.17% (P = .0001) and 67.38% (P = .029), respectively. In the combined recent-onset psychosis plus CHR sample, VisDys were predicted by FPN functional connectivity (balanced accuracy, 61.1%; P = .006).

"Findings from multivariate pattern analysis support a model of functional integrity within ON and FPN driving the VisDys phenomenon and being implicated in core disease mechanisms of early psychosis states," the investigators note.

"The main findings from this large sample study support the idea of VisDys being specific to the psychosis spectrum already at early stages," while being less frequently reported in recent-onset depression, they write. VisDys also "appeared negligible" among those without psychiatric disorders.

Regular Assessment Needed

Commenting for Medscape Medical News, Steven Silverstein, PhD, professor of biopsychosocial medicine and professor of psychiatry, neuroscience, and ophthalmology, Center for Visual Science, University of Rochester Medical Center, New York, called the findings "important" because "they will increase appreciation in the field of mental health for the frequency and disabling nature of visual symptoms and the need for regular assessment in routine clinical practice with people at risk for or with psychotic disorders."

In addition, "the brain imaging findings are providing needed information that could lead to treatments that target the brain networks generating the visual symptoms," such as neurofeedback or brain stimulation, said Silverstein, who was not involved with the research.

The study was funded by a grant for the Personalized Prognostic Indicators for Early Psychosis Management (PRONIA Study). Individual researchers received funding from NARSAD Young Investigator Award of the Brain and Behavior Research Foundation, the Koeln Fortune Program/Faculty of Medicine, the University of Cologne, and the European Unions Horizon 2020 research and innovation program. Open Access funding was enabled and organized by Projekt DEAL. Schwarzer and Silverstein reported no relevant financial relationships. Co-investigators' disclosures are listed in the original article.

Neuropsychopharmacology. Published online August 18, 2022. Full article

Batya Swift Yasgur, MA, LSW, is a freelance writer with a counseling practice in Teaneck, NJ. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).

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