Blunted pupil light reflex is associated with negative symptoms and working memory in individuals with schizophrenia

Abstract

Two largely separate lines of research have documented altered pupillary dynamics in individuals diagnosed with schizophrenia. An older set of studies has demonstrated reductions in the pupillary light reflex (PLR) in individuals with schizophrenia; however, clinical and cognitive correlates of this blunted PLR have been relatively unexplored. More recently, a large body of work has demonstrated reductions in pupillary dilation in response to cognitive demands in individuals with schizophrenia, and the degree of this blunted pupil dilation has been related to more severe cognitive deficits and motivational negative symptoms. These clinically relevant alterations in the cognitive modulation of pupil size have been interpreted as reflecting insufficient information processing resources or inappropriate effort allocation. To begin to bridge these two lines of work, we investigated the PLR in 34 individuals with schizophrenia and 30 healthy controls and related the amplitude of the PLR to motivational negative symptoms and cognitive performance. Consistent with prior work, we found that the PLR was reduced in individuals with schizophrenia, and furthermore, that these measurements were highly reliable across individuals. Blunted constriction was associated with more severe motivational negative symptoms and poorer working memory among individuals with schizophrenia. These observed correlates provide a bridge between older literature documenting an altered PLR and more recent work reporting associations between negative symptoms, cognition, and blunted pupillary dilation in response to cognitive demands in individuals with schizophrenia. We provide possible mechanistic interpretations of our data and consider a parsimonious explanation for reduced cognitive- and light-related modulation of pupil size.

Keywords: Negative symptoms; Pupil light reflex; Pupillometry; Schizophrenia; Working memory.

Fig. 1.

Averaged pupil waveforms relative to initial pupil diameter across time in healthy controls (HC) and individuals with schizophrenia (PSZ), with standard error represented by shaded error bars. Constriction onset time (blue), light offset time (dotted black), and re-dilation latency within groups (orange and grey) are marked by vertical lines. The graphical inset highlights the time period surrounding the dilation onset time.

Fig. 2.

Raincloud plots representing distribution of pupil dynamics in healthy controls (HC) and individuals with schizophrenia (PSZ). Significant group differences are indicated with an asterisk (*corrected-p < 0.05, **corrected-p < 0.01).

Fig. 3.

A priori Spearman’s correlations between (A) constriction amplitude and social dysfunction and (B) constriction amplitude and working memory. Constriction amplitude was significantly correlated with the Social Dysfunction subscale, such that more severe social dysfunction was associated with smaller constriction amplitude (r_s(31) = − 0.362, p = 0.038). Amplitude was also correlated with working memory, with worse memory being associated with smaller constriction amplitude (r_s(30) = 0.535, p = 0.002).