Deficits in the identification of pleasant odors predict the transition of an at-risk mental state to psychosis

Abstract

Objective

Existing knowledge of the relationship between olfactory identification (OI) ability and clinical risk of psychosis is inconsistent. To address this inconsistency, the aim of the present study was to identify the relationship between OI ability, with regard to the hedonic attributes of odors, and the risk of transition to psychosis in individuals with an ARMS.

Methods

A group of 81 individuals meeting the ARMS criteria according to the Comprehensive Assessment of At Risk Mental State were at baseline administered with the University of Pennsylvania Smell Identification Test. The hedonic attributes of odorants were normatively established. Participants were followed up for transition to psychosis for a mean period of 36.1 months (SD:27.5 months).

Results

The presence of deficits in the identification of pleasant odors was found to be a risk factor for conversion from an ARMS to schizophrenia. The hazard ratio for each point in deficit scores in the Cox regression model was 1.455 (95% CI: 1.211–1.747), p < 0.0001.

Significant deficits in the identification of pleasant odors were associated with a risk for conversion at both early and late time points from baseline.

Conclusions

The findings imply that the impaired identification of pleasant odorants may be a risk factor for the transition of an ARMS into a psychotic disorder, and highlights the need for further research of OI in “at-risk” cohorts, taking into account the hedonic attributes of odors.

Introduction

The olfactory system shares common origins with the central nervous system, and its development is strongly genetically determined (Treloar et al., 2010). Hence, the system has become a subject of interest in studies on the pathogenesis of schizophrenia, which itself is considered a neurodevelopmental disorder with genetic determinants (Murray, 1994). The presence of olfactory impairment in schizophrenia has been widely documented, with an effect size estimated as medium to large (Moberg et al., 1999, Moberg et al., 2014, Turetsky et al., 2009). This impairment manifests itself as a wide variety of abnormalities, including impairments in odor detection threshold (Isseroff et al., 1987, Rupp et al., 2005a, Serby et al., 1990), odor identification (Brewer et al., 2001, Hurwitz et al., 1988, Houlihan et al., 1994, Kamath et al., 2014, Kästner et al., 2013, Kopala et al., 1993) and odor discrimination abilities (Rupp et al., 2005a), as well as odor memory (Campbell and Gregson, 1972, Wu et al., 1993). There is also a growing body of evidence suggesting that the hedonic judgment of smells is also impaired in schizophrenia, with various patterns of misassignment being attributed to the hedonic valence of odors (Crespo-Facorro et al., 2001, Doop and Park, 2006, Hudry et al., 2002, Kamath et al., 2011a, Kamath et al., 2011b, Kamath et al., 2013b, Moberg et al., 2003, Plailly et al., 2006, Rupp et al., 2005b). Neuroanatomical, cellular and even intracellular mechanisms have been recognized to play a role in olfactory deficits in schizophrenia (Borgmann-Winter et al., 2016, Egbujo et al., 2015; for a review see Turetsky et al., 2009).

Some studies report the presence of olfactory identification deficits (OIDs) in non-affected first-degree relatives of patients with schizophrenia, including monozygotic twins discordant for the illness (Kamath et al., 2014, Kopala et al., 1998, Kopala et al., 2001, Roalf et al., 2006, Turetsky et al., 2008). Results from both the clinical and biological domains suggest that OIDs may be a potential vulnerability marker of schizophrenia (Moberg et al., 2014, Turetsky et al., 2008).

In the case of schizophrenia, clinical signs of abnormal functioning are present long before the development of the frank psychosis (Jones et al., 1994). It can therefore be assumed that other manifestations of neurodevelopmental pathology should be present in early phases of the disease, including prodromal ones. Over the years, the concept of the prodrome (Mayer-Gross, 1932) has evolved into that of the ultra-high risk-UHR or at-risk mental state-ARMS (Yung and McGorry, 1996). While the predictive value of ARMS is relatively low when defined based solely on clinical symptoms, with the conversion rate reaching approximately 36% within a three-year follow-up period (Fusar-Poli et al., 2012), the validity of the ARMS concept could be improved with the inclusion of complementary tools addressing, inter alia, neurobiological features (Fusar-Poli et al., 2013, Modinos and McGuire, 2015). One encouraging tool, potentially allowing the evaluation of further risk of transition from ARMS to psychosis, could be the assessment of smell identification ability. Although only few studies regarding olfactory impairment have been performed in clinical high risk for psychosis (CHR) cohorts, some indicate that olfactory deficits are in fact, more common in “at-risk” individuals than healthy controls (Kamath et al., 2014, Woodberry et al., 2010). The results, however, are conflicting, and the findings regarding OID and the future transition of ARMS to psychosis are inconsistent (Brewer et al., 2003, Gill et al., 2014, Lin et al., 2015).

Only one study has attempted to determine the effect of odor hedonic valence on olfactory identification (OI) in CHR individuals; in this case, the hedonic valence of an odor was found to have a significant effect on identification accuracy (Kamath et al., 2013b). No follow-up for transition of CHR state to psychosis was performed in this study. Hence, it is accepted within the field that further studies of olfactory dysfunctions are required in CHR individuals (Moberg et al., 2014, Turetsky et al., 2012). No study has yet investigated the associations between the identification of odors from different hedonic categories and the transition to psychotic disorders.

The objective of the present study was to identify the relationship between general smell identification ability as well as OI performance, according to the hedonic attributes of the odors, and the risk of conversion to psychosis in a cohort of ARMS individuals.