Distinct Relationships between Visual and Auditory Perceptual Abnormalities and Conversion to Psychosis in a Clinical High-Risk Population

Introduction

Hallucinations are a ubiquitous symptom experienced across psychotic disorders. This symptom, particularly in its auditory form, is widely thought to share a common substrate with other positive symptoms¹. However, only unusual thought content and thought disorganization, but not perceptual abnormalities (e.g., hyperacusis, illusions, momentary hallucinations), predict conversion to psychosis in clinical high-risk (CHR) populations^2,3, despite the high incidence of perceptual abnormalities². Importantly, although the frequencies of auditory and visual perceptual abnormalities in CHR individuals are similar⁴, differences in the prevalence of auditory and visual hallucinations in full psychosis⁵ may suggest distinct neurobiological substrates. Therefore, we hypothesized that auditory and visual perceptual abnormalities would have distinct clinical correlates in CHR individuals.

Methods

Participants were help-seeking CHR outpatients, aged 13–30, in the Center of Prevention and Evaluation (COPE), NYSPI, and part of a longitudinal study approved by the NYSPI IRB. All met criteria for the Attenuated Positive Symptom Syndrome (APSS)⁶ defined in the Structured Interview for Psychosis-Risk Syndromes (SIPS⁶; n=203; 57 converters, 144 non-converters, 2 unknown; Table 1). Symptoms were not better explained by DSM disorders or current substance use. Participants were followed up every 3 months for up to 2 years. Conversion to psychosis was defined based on standard SIPS criteria⁶. Most converters (81%) had follow-up DSM diagnoses of schizophrenia or related disorders.

Table 1.

Demographic and Baseline Clinical Characteristics of Clinical High Risk (CHR) Individuals at Enrollment^a

Characteristic	Non-converters (n=144)	Converters (n=57)	P-valueb
Age, mean (SD) years	20.15 (3.91)	20.09 (3.80)	0.91
Gender, % of females	31.25%	15.79%	0.07
Ethnicity, % Hispanic	28.47%	31.58%	0.68
Medication, % on any	29.86%	26.32%	0.51
Medication, % on antidepressants	13.89%	10.53%	0.52
Medication, % on antipsychotics	5.56%	8.77%	0.40
Medication, % on both drug types	10.42%	7.02%	0.46
SIPS Positive Symptoms Total (PT), mean (SD)	14.15 (3.97)	15.47 (3.94)	0.03
Unusual Thought Content (P1), mean (SD)	3.42 (1.04)	3.93 (1.03)	<0.001
Suspiciousness (P2), mean (SD)	3.33 (1.23)	3.40 (1.31)	0.69
Grandiose Ideas (P3), mean (SD)	2.06 (1.57)	2.19 (1.65)	0.59
Perceptual Abnormalities (P4), mean (SD)	2.82 (1.42)	2.84 (1.52)	0.92
Disorganized Communication (P5), mean (SD)	2.53 (1.29)	3.10 (1.32)	0.005
SIPS Negative Symptoms Total (NT), mean (SD)	16.00 (6.28)	18.91 (7.01)	0.005
SIPS Disorganization Symptoms Total (DT), mean (SD)	9.37 (3.73)	10.88 (3.88)	0.01
SIPS General Symptoms Total (GT), mean (SD)	11.49 (4.33)	11.74 (3.90)	0.71
Global Assessment of Functioning (GAF), mean (SD)	46.32 (7.17)	43.13 (5.89)	0.004

Certified SIPS raters assigned scores to 203 participants meeting criteria for both the SIPS Attenuated Positive Symptoms Syndrome (APSS) and DSM-5 Attenuated Psychosis Syndrome (APS), based on the detailed vignettes and rater comments captured during the baseline interview. Conversion was defined based on the SIPS. Among converters, 81% received a DSM diagnosis of schizophrenia or related disorders (i.e., non-affective psychotic disorders).

^aData presented are mean and standard deviation (SD) for continuous data, and percentage for categorical data.

^bP-values correspond to significant mean differences using two-sample t-tests for continuous data and significant relationships between conversion outcome and other categorical variables using chi-square tests.

Using detailed vignettes and rater comments in the SIPS collected at enrollment (baseline), two independent, SIPS-certified raters (RRG, GB) assigned perceptual-abnormality scores, originally encompassing any abnormalities across sensory domains within the past month (P4)⁶, separately to auditory (denoted P4a, intra-class correlation coefficient r_ICC=0.98) and visual experiences (denoted P4v, r_ICC=0.91; Figure 1). Relationships to conversion were assessed via logistic regression and Cox proportional-hazards regression. Adults provided written informed consent; minors provided assent with written consent by a parent or legal guardian.

Figure 1. Longitudinal relationship between baseline severity of auditory and visual perceptual abnormalities (P4a and P4v, respectively) and clinical outcomes at follow-up.

Panel A shows bar graphs depicting the relationship between P4a (left, red colors) and P4v (right, blue colors) scores at baseline and conversion to psychosis at follow-up. Scores are shown in different shades of color, from brightest (0) to darkest (5). Dotted lines represent fitted regression lines. Pie charts on top represent the baseline frequencies of each score in the complete sample (note that 7% were not assigned any score as raters did not have sufficient information to assign one; these are shown in white; also note that no individuals were assigned the maximum P4v score of 5). Panel B shows the relationship between baseline and follow-up, post-conversion scores in converters with available data for both time points only (n=39). The top bar graph shows mean longitudinal changes (± S.E.M.) in P4a and P4v scores, respectively. The bottom bar graph shows correlations (standardized β ± S.E.M.) between baseline (a: P4a; v: P4v) and follow-up, post-conversion scores within (a-a, v-v) and between domains (a-v, v-a). Asterisks represent statistically significant results at p≤0.05. n.s.: not significant (p>0.05).

Results

Consistent with previous research, the original global P4 scores did not predict conversion status (β=0.01, p=0.92). However, when split into two variables, both P4a and P4v independently predicted conversion status, although in opposite directions (β_a=0.25, p=0.046; β_v=−0.44, p=0.001; Figure 1A). P4a scores were higher than P4v scores (p<0.001; 67% versus 57% scored above 1, p<0.001); P4a and P4v overlapped moderately (R²=0.25; 48% scored above 1 for both). Additionally, P4a, but not P4v, predicted summed scores across P1, P2, P3, and P5 (β_a=0.37, p=0.037; β_v=0.14, p=0.45; β_a>β_v: p=0.014; see Table 1 for item descriptions) cross-sectionally, indicating that auditory abnormalities are more strongly related to other attenuated positive symptoms than are visual abnormalities. Post-conversion P4a and P4v scores remained stable relative to baseline and longitudinally correlated within, but not between, domains (Figure 1B).

Similarly, survival analyses showed that global P4 scores did not predict days to conversion (β=0.01, p=0.95) while P4a and P4v were independent predictors in opposite directions (β_a=0.19, p=0.052; β_v=−0.37, p<0.001). In an extended model controlling for known predictors of conversion (P scores other than P4, NT, DT, GT, GAF, and demographics), P4v was the single strongest (negative) independent predictor of days to conversion (β_v=−0.38, Z=−3.36, p<0.001); P4a, P1, P5, and NT were the only additional (positive) independent predictors that were at least marginally significant (1.64<Z<2.11; p-values 0.073, 0.035, 0.045, 0.099, respectively).

Discussion

Visual perceptual abnormalities strongly predicted lower risk of conversion to psychosis, while auditory abnormalities predicted higher risk, along with P1 and P5 scores. Additionally, our cross-sectional data support that core positive symptoms (including auditory, but not visual, abnormalities) may have a common substrate. Visual abnormalities in the CHR may thus have distinct underlying substrates and forecast distinct clinical outcomes (e.g., less severe or non-psychotic disorders). Further research into the clinical value of concurrently measuring visual and auditory abnormalities and their corresponding neurobiological substrates is warranted.