Vidyulata Kamath

The influences of age on olfaction: a review

Decreased olfactory function is very common in the older population, being present in over half of those between the ages of 65 and 80 years and in over three quarters of those over the age of 80 years. Such dysfunction significantly influences physical well-being and quality of life, nutrition, the enjoyment of food, as well as everyday safety. Indeed a disproportionate number of the elderly die in accident gas poisonings each year. As described in this review, multiple factors contribute to such age-related loss, including altered nasal engorgement, increased propensity for nasal disease, cumulative damage to the olfactory epithelium from viral and other environmental insults, decrements in mucosal metabolizing enzymes, ossification of cribriform plate foramina, loss of selectivity of receptor cells to odorants, changes in neurotransmitter and neuromodulator systems, and neuronal expression of aberrant proteins associated with neurodegenerative disease. It is now well established that decreased smell loss can be an early sign of such neurodegenerative diseases as Alzheimers disease and sporadic Parkinsons disease. In this review we provide an overview of the anatomy and physiology of the aging olfactory system, how this system is clinically evaluated, and the multiple pathophysiological factors that are associated with its dysfunction.

A meta-analysis of emotion perception and functional outcomes in schizophrenia

INTRODUCTION Emotion perception (EP) is impaired in schizophrenia, is stable across clinical state, resistant to antipsychotic treatment and linked to symptom severity. Given its pervasive nature, there is a need to quantitatively examine whether this dysfunction impacts functional outcomes. We used a meta-analytic strategy to combine results from several studies and examine synthesized effect sizes. METHODS A Meta-analysis of Observational Studies in Epidemiology standard was used to extract data following a PubMed and PsychInfo search. Studies reporting correlations between measures of EP and functional outcomes in schizophrenia spectrum disorders were selected. The impact of potential methodological (task type), demographic (sex, age, race, education, marital status) and clinical (age of onset, duration of illness, setting, symptoms, anti-psychotic medication) moderators on effect sizes were examined. RESULTS Twenty-five studies met inclusion criteria and included 1306 patients who were 37 years old, with 12 years of education, 64% male and 63% Caucasian. There was a significant relationship between EP and functional outcomes in individuals with schizophrenia or schizoaffective disorder, with effect sizes in the medium range. Medium to large range positive correlations were observed between emotion identification and functional outcome domains involving social problem solving, social skills and community functioning. Significant moderators included task type (emotion identification tasks), sex (% male in sample), race (% Caucasian in sample) and clinical symptoms (negative and positive). CONCLUSIONS Emotion identification deficits are associated with functional impairments in schizophrenia and moderated by sex, race and symptoms. This has implications for treatment efforts to improve outcomes.

Meta-Analysis of Olfactory Function in Schizophrenia, First-Degree Family Members, and Youths At-Risk for Psychosis

BACKGROUND Previous research has provided compelling support for olfactory dysfunction in schizophrenia patients, their first-degree relatives, and youth at-risk for psychosis. A previous meta-analysis revealed large effect sizes across olfactory tasks but was limited to 2 olfactory tasks and did not examine moderator variables. Thus, the current meta-analysis was undertaken to incorporate additional studies, risk cohorts, olfactory test domains, and moderator variable analyses. METHOD A meta-analysis was conducted on 67 publications examining olfactory function in schizophrenia patients and 15 publications examining olfactory functioning in youth at-risk for psychosis, first-degree relatives of schizophrenia patients, and individuals with schizotypy. RESULTS Results revealed medium-to-large olfactory deficits in schizophrenia patients though significant heterogeneity was evident. Several variables moderated overall study effects. At-risk youths similarly demonstrated medium-to-large effect sizes, whereas first-degree relatives and individuals with schizotypy showed small effects. CONCLUSIONS Findings suggest robust olfactory deficits in schizophrenia and at-risk youths. In schizophrenia, several variables had significant impact on these deficits and warrant consideration in prospective studies. Our findings also indicate that olfactory measures may be a useful marker of schizophrenia risk status.

Olfactory processing in schizophrenia, non-ill first-degree family members, and young people at-risk for psychosis

Abstract Objectives. While deficits in odor identification and discrimination have been reported in schizophrenia, few studies have examined the relative specificity of these deficits in patients and at-risk youth. Method. Sniffin’ Sticks odor identification and discrimination were assessed in schizophrenia outpatients and non-ill first-degree relatives (Study One), as well as youth at clinical (CR) or genetic (GR) risk for schizophrenia (Study Two). Scores were z-transformed, using the performance of a demographically-matched adult or adolescent comparison group. Results. Patients and relatives were impaired on odor identification, but odor discrimination impairment was limited to the patient group. A similar pattern of impairment emerged in at-risk youth. GR youth were impaired on odor identification but not discrimination, while CR youth were impaired on both tasks. In patients, olfactory impairment was correlated with negative symptomatology. Conclusions. To our knowledge, this is the first study to show that CR youth are impaired on both olfactory tasks, as observed in adult schizophrenia patients. GR youth were impaired only on odor identification like their adult counterparts. These data suggest that odor identification impairment, in isolation, may represent a genetic marker of vulnerability for schizophrenia, while odor discrimination deficits may be a biomarker associated with the development of psychosis.

Olfaction and apathy in Alzheimer's disease, mild cognitive impairment, and healthy older adults

Objectives: Apathy is a prevalent neuropsychiatric manifestation in individuals with Alzheimers disease (AD) that is associated with decreased social functioning and increased caregiver burden. Olfactory deficits are also commonly observed in AD, and prior work has indicated a link between increased apathy and olfactory dysfunction in individuals with Parkinsons disease. Here, we examined odor identification performance in patients with probable AD (n = 172), individuals with mild cognitive impairment (MCI; n = 112), and neurologically and psychiatrically healthy older adults (n = 132) and its relation to apathy, depression, and overall psychopathology. Method: Participants were administered the Sniffin’ Sticks odor identification test and measures assessing severity of apathy, depression, and overall neuropsychiatric symptomatology. Results: Consistent with previous research, AD and MCI patients were significantly worse at identifying odors than healthy older adults. Additionally, a sex by diagnosis interaction was observed. AD patients had significantly higher levels of apathy relative to MCI and control participants. Of note, across the entire sample odor identification deficits were correlated with level of apathy at the level of p < 0.01, but not with depression or neuropsychiatric symptom severity, when controlling for Mini-Mental State Examination (MMSE) score. Conclusion: Collectively, these data suggest that olfactory disturbance and apathy in AD may result from the progression of disease pathology in shared neural substrates.

Identification of pleasant, neutral, and unpleasant odors in schizophrenia

Recent work on odor hedonics in schizophrenia has indicated that patients display abnormalities in hedonic judgments of odors in comparison to healthy comparison participants. In the current study, identification accuracy for pleasant, neutral, and unpleasant odors in individuals with schizophrenia and healthy controls was examined. Thirty-three schizophrenia patients (63% male) and thirty-one healthy volunteers (65% male) were recruited. The groups were well matched on age, sex, and smoking status. Participants were administered the University of Pennsylvania Smell Identification Test, which was subsequently divided into 16 pleasant, 15 neutral, and 9 unpleasant items. Analysis of identification z-scores for pleasant, neutral, and unpleasant odors revealed a significant diagnosis by valence interaction. Post-hoc analysis revealed that schizophrenia participants made more identification errors on pleasant and neutral odors compared to healthy controls, with no differences observed for unpleasant odors. No effect was seen for sex. The findings from the current investigation suggest that odor identification accuracy in patients is influenced by odor valence. This pattern of results parallels a growing body of literature indicating that patients display aberrant pleasantness ratings for pleasant odors and highlights the need for additional research on the influence of odor valence on olfactory identification performance in individuals with schizophrenia.

Olfaction and schizophrenia clinical risk status: Just the facts

Dear Editors, The recent meta-analysis by Cohen et al. (2012) offered a review of the evidence regarding olfactory dysfunction in both schizophrenia patients and individuals at risk for the illness. Their analysis supported the presence of a robust olfactory identification deficit in patients. However, concerning the study of at-risk individuals, they concluded as follows: “Overall, the present findings failed to find evidence that olfaction identification deficits are a meaningful vulnerability marker of schizophrenia pathology..(We) believe that conducting further studies…is not a particularly promising endeavor.” It is our opinion that this assertion could have an unwarranted and unfortunate chilling effect on future research, as it does not accurately reflect the current status of the field. In reviewing 16 studies purported to examine schizophrenia risk status, the authors conflate three very different categories of risk. Five were studies of otherwise-healthy individuals who scored high on a psychometric scale of schizotypal features (e.g. Schizotypal Personality Questionnaire). Nine were studies of unaffected family members of schizophrenia patients. Only two were studies of “ultra-high risk” individuals in the sub-psychotic or prodromal state, as assessed by the Structured Interview for Prodromal Syndromes (SIPS). The incidence of future conversion to overt psychosis is very different in these sub-categories. Grouping them together presents a distorted picture that can lead to erroneous conclusions. Conversion rates among prodromal individuals with symptoms severe enough to prompt clinical referral have been reported as approximately 35% within 2.5 years (Cannon et al., 2008). Unaffected first-degree relatives of schizophrenia patients, in contrast, have a lifetime psychosis incidence of approximately 10% (Karlsson, 1982). Since most of the published family studies were of older adults (i.e., parents and siblings of schizophrenia probands), many of whom were already past the peak ages of illness onset, the actual incidence in this group was likely substantially lower. In the two existing large-scale longitudinal studies of individuals with psychometrically defined schizotypy, one reported zero cases of psychosis among 91 “at-risk” subjects after 5 years (Gooding et al., 2005). The other reported 10 cases of psychosis among 182 subjects (5.5%) after 10 years (Chapman et al., 1994). Clearly, the risk for psychosis among ultra-high risk subjects greatly exceeds the risk among individuals in the other two categories. A sensitive and specific marker of disease vulnerability should, ideally, reflect this heightened risk profile. Indeed, any vulnerability marker that cannot distinguish among these three groups has very little predictive utility. The results for odor identification, as reported by Cohen, are entirely consistent with these expectations regarding an ideal vulnerability marker. He determined the effect size for the ultra-high risk group to be −0.67 (a moderate to large effect), whereas the effect sizes for unaffected family members and psychometrically defined schizotypals were −0.21 and −0.14, respectively (small to insignificant effects). The facts regarding olfaction and clinical high-risk status are the following. There have been a total of three published studies of olfactory deficits in clinical high-risk subjects relative to demographically comparably healthy individuals (Brewer et al., 2003; Kamath et al., 2012; Woodberry et al., 2010). The overall effect size in the Brewer study was −0.48 (Woods, S.J. Personal communication). The effect size, as listed in the Woodbury manuscript, was −0.89 (not −0.84 as reported by Cohen). The effect sizes in the Kamath study — which was not included in Cohen’s review due to its recent publication — were −1.26 for odor identification and −1.11 for odor discrimination. A meta-analysis of all available data from these three studies yields a composite effect size of −0.77, rather than −0.67. Importantly, the Brewer and Woodberry studies also included longitudinal follow-ups of their clinical high-risk participants, which allowed them to examine separately the baseline data from those subjects who subsequently became psychotic. The effect sizes for these future-psychosis subsamples were substantially higher than for the high-risk groups as a whole, −0.68 and −1.32, respectively. Brewer’s future-psychosis sample was large enough to be further parsed into those who developed schizophrenia and those who developed other psychotic illnesses. The effect size for odor identification deficits in those who subsequently developed schizophrenia was −1.12; for those who developed other psychoses, it was −0.24. So the facts, as opposed to the fiction, regarding olfaction and clinical high-risk status are these. There have been three independent studies to date, with three sets of positive findings, a large composite effect, and initial evidence to suggest that this impairment is indicative of a future schizophrenia-spectrum psychotic disorder. The magnitude, consistency and predictive potential of this deficit collectively establish olfactory impairment as one of the most viable biomarkers of the psychosis clinical high-risk state yet identified. Our confidence in making this assertion would, of course, be greater if it were based on a greater number of studies, and it may ultimately be proven false. But to conclude, based on current evidence, that further study is unwarranted would be a truly egregious error.

Doubt and the decision-making process in obsessive-compulsive disorder

The diagnosis of obsessive-compulsive disorder (OCD) is based on the presence of specific symptoms and their consequence in the lives of those that exhibit them. It is likely that these symptoms emerge from a neurocognitive vulnerability in the mental life of the individual which has a basis in neurophysiology. The prominence of doubt/uncertainty/lack of confidence (These terms are used interchangeably in this paper.), in the clinical presentation of many patients suffering from OCD leads to our consideration of the cognitive basis for this phenomenon. In this paper, we propose that OCD emerges from a perturbation in the decision-making process. Specifically, we hypothesize that there is diminished confidence, conviction, or certainty with regard to assimilating the information necessary to reach a decision. Recent advances in the neuroscience of decision-making provide an opportunity to further our understanding of the vulnerability underlying OCD.

Association of schizophrenia with the phenylthiocarbamide taste receptor haplotype on chromosome 7q.

Phenylthiocarbamide (PTC) taste sensitivity is an inherited trait determined primarily by allelic variation of the taste-receptor gene TAS2R38 on chromosome 7q. Results of prior studies examining the ability to taste PTC in patients with schizophrenia have been mixed because of the difficulties in measuring PTC taste sensitivity behaviorally. In the current study, we examined the TAS2R38 genotypes of schizophrenia patients to determine whether the increased prevalence of nontasters in this patient population was indicative of a specific genetic association. Our a-priori hypothesis was that schizophrenia patients would show an increased prevalence of the nontaster phenotype compared with controls. The genotypes of two nonsynonymous coding single-nucleotide polymorphisms in TAS2R38 were assayed for 176 schizophrenia patients and 229 healthy control individuals, and the two-allele haplotypes were estimated. There was an over-representation of the major PTC nontaster haplotype among patients of European descent, relative to control individuals of similar ancestry. Patients and controls of African ancestry did not differ. The PTC nontaster haplotype is a genetic marker that may be used to identify subsets of schizophrenia patients who potentially harbor vulnerability genes in this region of chromosome 7q.

Olfactory Functioning in First-Episode Psychosis

Background Though olfactory deficits are well-documented in schizophrenia, fewer studies have examined olfactory performance profiles across the psychosis spectrum. The current study examined odor identification, discrimination, and detection threshold performance in first-episode psychosis (FEP) patients diagnosed with schizophrenia, schizoaffective disorder, bipolar disorder with psychotic features, major depression with psychotic features, and other psychotic conditions. Method FEP patients (n = 97) and healthy adults (n = 98) completed birhinal assessments of odor identification, discrimination, and detection threshold sensitivity for lyral and citralva. Participants also completed measures of anticipatory pleasure, anhedonia, and empathy. Differences in olfactory performances were assessed between FEP patients and controls and within FEP subgroups. Sex-stratified post hoc analyses were employed for a complete analysis of sex differences. Relationships between self-report measures and olfactory scores were also examined. Results Individuals with psychosis had poorer scores across all olfactory measures when compared to the control group. Within the psychosis cohort, patients with schizophrenia-associated psychosis had poorer odor identification, discrimination, and citralva detection threshold scores relative to controls. In schizophrenia patients, greater olfactory disturbance was associated with increased negative symptomatology, greater self-reported anhedonia, and lower self-reported anticipatory pleasure. Patients with mood-associated psychosis performed comparable to controls though men and women in this cohort showed differential olfactory profiles. Conclusions These findings indicate that olfactory deficits extend beyond measures of odor identification in FEP with greater deficits observed in schizophrenia-related subgroups of psychosis. Studies examining whether greater olfactory dysfunction confers greater risk for developing schizophrenia relative to other forms of psychosis are warranted.