Computer-vision analysis of craniofacial dysmorphology in 22q11.2 deletion syndrome and psychosis spectrum disorders.

BACKGROUND: Minor physical anomalies (MPAs) are congenital morphological abnormalities linked to disruptions of fetal development. MPAs are common in 22q11.2 deletion syndrome (22q11DS) and psychosis spectrum disorders (PS) and likely represent a disruption of early embryologic development that may help identify overlapping mechanisms linked to psychosis in these disorders. METHODS: Here, 2D digital photographs were collected from 22q11DS (n = 150), PS (n = 55), and typically developing (TD; n = 93) individuals. Photographs were analyzed using two computer-vision techniques: (1) DeepGestalt algorithm (Face2Gene (F2G)) technology to identify the presence of genetically mediated facial disorders, and (2) Emotrics-a semi-automated machine learning technique that localizes and measures facial features. RESULTS: F2G reliably identified patients with 22q11DS; faces of PS patients were matched to several genetic conditions including FragileX and 22q11DS. PCA-derived factor loadings of all F2G scores indicated unique and overlapping facial patterns that were related to both 22q11DS and PS. Regional facial measurements of the eyes and nose were smaller in 22q11DS as compared to TD, while PS showed intermediate measurements. CONCLUSIONS: The extent to which craniofacial dysmorphology 22q11DS and PS overlapping and evident before the impairment or distress of sub-psychotic symptoms may allow us to identify at-risk youths more reliably and at an earlier stage of development.

Gender and ethnic/racial diversity in clinical neuropsychology: Updates from the AACN, NAN, SCN 2020 practice and "salary survey".

OBJECTIVE: Examination of gender and diversity issues within clinical neuropsychology, using data from the 2020 professional practice and "salary survey." METHODS: Clinical neuropsychologists in the U.S. and Canada were invited to participate in an online survey. The final sample consisted of 1677 doctoral-level practitioners. RESULTS: Approximately, 60% of responding neuropsychologists are women and 53.8% of those women identify as early career psychologists (ECPs). Conversely, a majority of men in the sample are advanced career psychologists (ACPs). Both genders work predominantly in institutions, but more men than women work in private practice. ACP men produce a greater number of peer-reviewed publications and conference presentations. Across all work settings, women earn significantly less than men, and are less satisfied with their incomes. Establishing and maintaining family life is the biggest obstacle to attaining greater income and job satisfaction for both genders. Ethnic/racial minority status was identified in 12.9% of respondents, with 59.2% being ECPs. Job satisfaction and hostility in the workplace vary across ethnic/racial minority groups. Hispanic/Latino(a) and White neuropsychologists report higher incomes, but there were no statistically significant differences between any of the groups. CONCLUSIONS: Income and select practice differences persist between female and male neuropsychologists. There is a slow rate of increased ethnic/racial diversity over time, which is much more apparent among early career practitioners. Trajectories and demographics suggest that the gender income gap is unlikely to be improved by the next survey iteration in 2025, whereas it is very likely that ethnic/racial diversity will continue to increase gradually.

A systematic review and meta-analysis of intellectual, neuropsychological, and psychoeducational functioning in neurofibromatosis type 1.

Neurofibromatosis Type 1 (NF1) is a common genetic disorder frequently associated with cognitive deficits. Despite cognitive deficits being a key feature of NF1, the profile of such impairments in NF1 has been shown to be heterogeneous. Thus, we sought to quantitatively synthesize the extant literature on cognitive functioning in NF1. A random-effects meta-analysis of cross-sectional studies was carried out comparing cognitive functioning of patients with NF1 to typically developing or unaffected sibling comparison subjects of all ages. Analyses included 50 articles (Total NNF1 = 1,522; MAge = 15.70 years, range = 0.52-69.60), yielding 460 effect sizes. Overall moderate deficits were observed [g = -0.64, 95% CI = (-0.69, -0.60)] wherein impairments differed at the level of cognitive domain. Deficits ranged from large [general intelligence: g = -0.95, 95% CI = (-1.12, -0.79)] to small [emotion: g = -0.37, 95% CI = (-0.63, -0.11)]. Moderation analyses revealed nonsignificant contributions of age, sex, educational attainment, and parental level of education to outcomes. These results illustrate that cognitive impairments are diffuse and salient across the lifespan in NF1. Taken together, these results further demonstrate efforts should be made to evaluate and address cognitive morbidity in patients with NF1 in conjunction with existing best practices.

International consensus statement on allergy and rhinology: Olfaction.

BACKGROUND: The literature regarding clinical olfaction, olfactory loss, and olfactory dysfunction has expanded rapidly over the past two decades, with an exponential rise in the past year. There is substantial variability in the quality of this literature and a need to consolidate and critically review the evidence. It is with that aim that we have gathered experts from around the world to produce this International Consensus on Allergy and Rhinology: Olfaction (ICAR:O). METHODS: Using previously described methodology, specific topics were developed relating to olfaction. Each topic was assigned a literature review, evidence-based review, or evidence-based review with recommendations format as dictated by available evidence and scope within the ICAR:O document. Following iterative reviews of each topic, the ICAR:O document was integrated and reviewed by all authors for final consensus. RESULTS: The ICAR:O document reviews nearly 100 separate topics within the realm of olfaction, including diagnosis, epidemiology, disease burden, diagnosis, testing, etiology, treatment, and associated pathologies. CONCLUSION: This critical review of the existing clinical olfaction literature provides much needed insight and clarity into the evaluation, diagnosis, and treatment of patients with olfactory dysfunction, while also clearly delineating gaps in our knowledge and evidence base that we should investigate further.

Clinical neuropsychology in Canada: Results from the 2020 AACN, NAN, SCN professional practice and "salary survey".

Objective: The current study summarizes the results of a 2020 survey that solicited information regarding backgrounds, beliefs, practices, and incomes of clinical neuropsychologists who practice in Canada. Methods: Clinical neuropsychologists who practice in Canada were invited to participate in an online survey that was available from 1/17/20 to 4/02/20. Available survey findings were obtained from 111 respondents, which reflects a response rate of 51.3% of the 216 doctoral-level Canadian neuropsychologists identified in at least one major North American or international professional organization membership list (AACN, INS, NAN, or SCN). Results: Most of the current respondents were White/Caucasian women who identified as adult providers and worked full-time in urban institutional settings. Four Canadian provinces (Alberta, British Columbia, Ontario, Quebec) accounted for more than 91% of the current respondent sample. Incomes and career satisfactions were largely encouraging, though some important variations were noted by province, work setting, and professional identity. Incomes were significantly associated with forensic practices and years of clinical experience. Most respondents made use of technician support in their practices, largely to increase productivity and patient volume. Only a small minority of respondents were board-certified and there was generally limited interest in future board certification. Conclusions: While important similarities were observed in the current Canadian sample relative to recent survey findings obtained in a U.S. sample, results also reveal a number of important differences that serve as important areas of future consideration.

Professional practices, beliefs, and incomes of U.S. neuropsychologists: The AACN, NAN, SCN 2020 practice and "salary survey".

OBJECTIVE: This portion of the 2020 survey updates practice information, beliefs, and income data of clinical neuropsychologists who practice within the United States. Methods: Doctoral-level neuropsychology practitioners were invited via numerous methods, with multiple reminders, to participate in a web-based survey from January 17 through April 2, 2020. The useable U.S. sample of 1677 doctoral-level practitioners was 6.2% larger than the comparable group in the prior 2015 practice survey. Results: Whereas women practitioners predominate, which continues a steeply increasing trend across time, increases in overall ethnic/racial diversity continue at a slow pace. Median age has remained very similar over the last 30 years, reflecting a continuous influx of young practitioners. A relatively small minority of neuropsychologists work part time. The proportion of board-certified neuropsychologists continues to show meaningful increase; interest in subspecialization certification is relatively high. Reliance on technicians remains popular, especially for neuropsychologists who work in institutions or are board certified. Although implementation of new CPT codes in 2019 and related payor policies appear to have had more negative than positive effects, psychology-related annual incomes of neuropsychologists have again increased compared to prior surveys. Variables such as specific work setting, state, region, years in practice, forensic practice hours, board certification, and basis for determining income (e.g. hours billed, revenue collected, relative value units) have an impact on income. More than half of practitioners engage in forensic neuropsychology, with the number of related practice hours per week again increasing. There is very high agreement regarding the use of response validity measures in clinical practice and forensic practice. Neurologists remain the number one referral source whether working in an institution, private practice, or a combination of both, and regardless of maintaining a pediatric, adult, or lifespan practice. Career satisfaction ratings for income, job, and work-life balance remain high, with the majority of ratings regarding the future of the specialty in the positive range. Additional data summaries related to a wide range of professional and practice topics are provided. Conclusions: Updating and comparing survey information at five-year intervals continues to provide insights and perspectives regarding relative stabilities and changes in practice activities, beliefs, and incomes of U.S. clinical neuropsychologists. Such information also provides guidance regarding the future of the specialty.

Professional Practices, Beliefs, and Incomes of Postdoctoral Trainees: The AACN, NAN, SCN 2020 Practice and 'Salary Survey'.

OBJECTIVE: Within a portion of the 2020 professional practice and "salary survey," to update key information regarding neuropsychology postdoctoral trainees. METHODS: Postdoctoral trainees were contacted via a variety of membership listings, including the listserv used by the program directors of the Association of Postdoctoral Programs in Clinical Neuropsychology (APPCN). Invitations sent in multiple waves to members of numerous neuropsychological organizations via e-messages and physical postcards included the request that postdoctoral trainees participate. The survey website was opened on January 17, 2020 and closed on April 2, 2020, during which time a total of 178 postdoctoral trainees in the USA and 3 in Canada participated. RESULTS: Response rate was estimated to be 56.4%, which adequately represents the target sample. The modal postdoctoral trainee is a woman whose internship was American Psychological Association (APA)-accredited and whose postdoctoral training is in an APPCN program that adheres to Houston Conference training guidelines. Extensive clinical experiences in neuropsychology in the form of externship practica and during internship were reported by the majority of trainees prior to postdoctoral training. There are few differences between APPCN and non-APPCN trainees and reported training experiences. Job satisfaction is high. Salaries appear to have increased substantially in recent years. There is universal interest in pursuing board certification. Support for the empirical foundations justifying assessment of response validity is high. CONCLUSIONS: Surveys of postdoctoral trainees continue to provide valuable perspectives regarding training background, clinical experiences, practice beliefs, and incomes of individuals who will soon launch their careers in clinical neuropsychology.

Efficacy of Noninvasive Brain Stimulation (tDCS or TMS) Paired with Language Therapy in the Treatment of Primary Progressive Aphasia: An Exploratory Meta-Analysis.

Noninvasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS), paired with behavioral language therapy, have demonstrated the capacity to enhance language abilities in primary progressive aphasia (PPA), a debilitating degenerative neurological syndrome that leads to declines in communication abilities. The aim of this meta-analysis is to systematically evaluate the efficacy of tDCS and TMS in improving language outcomes in PPA, explore the magnitude of effects between stimulation modalities, and examine potential moderators that may influence treatment effects. Standard mean differences for change in performance from baseline to post-stimulation on language-related tasks were evaluated. Six tDCS studies and two repetitive TMS studies met inclusion criteria and provided 22 effects in the analysis. Random effect models revealed a significant, heterogeneous, and moderate effect size for tDCS and TMS in the enhancement of language outcomes. Findings demonstrate that naming ability significantly improves due to brain stimulation, an effect found to be largely driven by tDCS. Future randomized controlled trials are needed to determine long-term effectiveness of noninvasive brain stimulation techniques on language abilities, further delineate the efficacy of tDCS and TMS, and identify optimal parameters to enable the greatest gains for persons with PPA.

A quantitative meta-analysis of brain glutamate metabolites in aging.

Glutamate (Glu) is a key molecule in cellular metabolism, the most abundant excitatory neurotransmitter in the brain, and the principal neurotransmitter of cortical efferents. Glutamate dysfunction, on the other hand, is common in neurodegenerative disorders, and likely contributes to age-related declines in behavioral and cognitive functioning. Nonetheless, the extant literature measuring age-related changes in brain glutamate in vivo has yet to be comprehensively and quantitatively summarized. This meta-analysis examines proton spectroscopy (1HMRS) measures of Glu-related brain metabolites across 589 healthy young and older adults. Glu (Cohen's d = -0.82) and Glu+glutamine (Cohen's d = -0.51) concentrations were significantly lower in older compared with younger adults, whereas the concentration of glutamine (d = 0.43) was significantly higher in older individuals. Notably, 1HMRS methodological choices impacted effect sizes for age-related Glu differences. Glu metabolite change appears to be a robust marker of aging-related neurological change; however, additional studies are needed to elucidate age-related trajectories of glutamatergic alterations and their relationship to cognitive phenotypes.

Meta-analysis of olfactory dysfunction in 22q11.2 deletion syndrome.

A quantitative review of literature concerning olfactory function in 22q11.2 deletion syndrome (22q11DS) patients was performed detailing the scope/magnitude of deficits and probing possible moderators. We searched MEDLINE, EMBASE and PubMed to identify studies for inclusion. Effect sizes were based on differences in psychophysical olfactory tests between 22q11DS patients (n = 194) and typically developing comparison subjects (n = 466). 22q11DS patients exhibited marked olfactory dysfunction (d=-1.11, 95% CI=-1.29<δ<-0.92) that was homogeneous (p = 0.86). Diffuse olfactory deficits were seen which were not moderated by age or sex. 22q11DS patients exhibit large/diffuse deficits in olfactory function that are of a similar magnitude to observed neuropsychological impairments.

Longitudinal Development of Brain Iron Is Linked to Cognition in Youth.

Brain iron is vital to multiple aspects of brain function, including oxidative metabolism, myelination, and neurotransmitter synthesis. Atypical iron concentration in the basal ganglia is associated with neurodegenerative disorders in aging and cognitive deficits. However, the normative development of brain iron concentration in adolescence and its relationship to cognition are less well understood. Here, we address this gap in a longitudinal sample of 922 humans aged 8-26 years at the first visit (M = 15.1, SD = 3.72; 336 males, 486 females) with up to four multiecho T2* scans each. Using this sample of 1236 imaging sessions, we assessed the longitudinal developmental trajectories of tissue iron in the basal ganglia. We quantified tissue iron concentration using R2* relaxometry within four basal ganglia regions, including the caudate, putamen, nucleus accumbens, and globus pallidus. The longitudinal development of R2* was modeled using generalized additive mixed models (GAMMs) with splines to capture linear and nonlinear developmental processes. We observed significant increases in R2* across all regions, with the greatest and most prolonged increases occurring in the globus pallidus and putamen. Further, we found that the developmental trajectory of R2* in the putamen is significantly related to individual differences in cognitive ability, such that greater cognitive ability is increasingly associated with greater iron concentration through late adolescence and young-adulthood. Together, our results suggest a prolonged period of basal ganglia iron enrichment that extends into the mid-twenties, with diminished iron concentration associated with poorer cognitive ability during late adolescence.SIGNIFICANCE STATEMENT Brain tissue iron is essential to healthy brain function. Atypical basal ganglia tissue iron levels have been linked to impaired cognition in iron deficient children and adults with neurodegenerative disorders. However, the normative developmental trajectory of basal ganglia iron concentration during adolescence and its association with cognition are less well understood. In the largest study of tissue iron development yet reported, we characterize the developmental trajectory of tissue iron concentration across the basal ganglia during adolescence and provide evidence that diminished iron content is associated with poorer cognitive performance even in healthy youth. These results highlight the transition from adolescence to adulthood as a period of dynamic maturation of tissue iron concentration in the basal ganglia.

Olfactory Dysfunction in Neurodevelopmental Disorders: A Meta-analytic Review of Autism Spectrum Disorders, Attention Deficit/Hyperactivity Disorder and Obsessive-Compulsive Disorder.

Olfactory dysfunction is recognized in neurodevelopmental disorders and may serve as an early indicator of global dysfunction. The present meta-analysis measures olfaction effect sizes in attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASDs), and obsessive-compulsive disorder (OCD). Meta-analysis included 320 ADHD, 346 ASD, and 208 OCD individuals as compared to 910 controls. Olfactory performance deficits were small-to-moderate and heterogeneous (d = - 0.42, 95% CI = - 0.59 < δ < - 0.25). Meta-analytic results indicate that olfactory dysfunction is evident in individuals with ASD and OCD, with small-to-negligible effects in ADHD. These findings imply olfactory dysfunction is related to clinical phenotype in ASD and OCD, but not ADHD, and warrant inclusion in clinical assessment and evaluation of certain neurodevelopmental disorders.

Determining a Short Form Montreal Cognitive Assessment (s-MoCA) Czech Version: Validity in Mild Cognitive Impairment Parkinson's Disease and Cross-Cultural Comparison.

The Montreal Cognitive Assessment (MoCA) is one of the most common screening instruments for mild cognitive impairment. However, the standard MoCA is approximately two times longer to administer than the Mini-Mental State Examination. A total of 699 Czech and 175 American participants received the standard MoCA Czech and English versions and in the clinical part, a sample of 102 nondemented patients with Parkinson's disease (PD). We created a validated Czech short version (s-MoCA-CZ) from the original using item response theory. As expected, s-MoCA-CZ scores were highly correlated with the standard version (Pearson r = .94, p < .001). s-MoCA-CZ also had 80% classification accuracy in the differentiation of PD mild cognitive impairment from PD without impairment. The s-MoCA-CZ, a brief screening tool, is shorter to administer than the standard MoCA. It provides high-classification accuracy for PD mild cognitive impairment and is equivalent to that of the standard MoCA-CZ.

A Quantitative Meta-analysis of Olfactory Dysfunction in Epilepsy.

Olfactory dysfunction in epilepsy is well-documented in several olfactory domains. However, the clinical specificity of these deficits remains unknown. The aim of this systematic meta-analysis was to determine which domains of olfactory ability were most impaired in individuals with epilepsy, and to assess moderating factors affecting olfactory ability. Extant peer-reviewed literature on olfaction in epilepsy were identified via a computerized literature search using PubMed, MEDLINE, PsycInfo, and Google Scholar databases. Twenty-one articles met inclusion criteria. These studies included a total of 912 patients with epilepsy and 794 healthy comparison subjects. Included studies measured olfaction using tests of odor identification, discrimination, memory, and detection threshold in patients with different types of epilepsy, including temporal lobe epilepsy (TLE), mixed frontal epilepsy (M-F), and mixed epilepsy (MIX). Olfactory deficits were robust in patients with epilepsy when compared to healthy individuals, with effect sizes in the moderate to large range for several olfactory domains, including odor identification (d = -1.59), memory (d = -1.10), discrimination (d = -1.04), and detection threshold (d = -0.58). Olfactory deficits were most prominent in patients with TLE and M-F epilepsy. Amongst patients with epilepsy, sex, age, smoking status, education, handedness, and age of illness onset were significantly related to olfactory performance. Overall, these meta-analytic findings indicate that the olfactory system is compromised in epilepsy and suggest that detailed neurobiological investigations of the olfactory system may provide further insight into this disorder.

Older Adult Normative Data for the Sniffin' Sticks Odor Identification Test.

OBJECTIVE: The current study establishes normative Sniffin' Sticks Odor Identification Test (SS-OIT) scores for cognitively intact older adults. METHOD: Two hundred and twenty-six cognitively normal older adults were identified as eligible for the current study (Mean Age = 70.49 years; 71.7% female). Important demographic covariates were identified using step-wise regression, and a normative regression equation was developed. RESULTS: Analyses of the effects of demographic variables (including age, education, and sex) on SS-OIT performance revealed that age was the only significant predictor, b = -0.07, SEb = .01, p < .01. A final regression equation was determined and normative data are reported in 5-year increments for a number of percentile ranks. CONCLUSIONS: Normative performance on the SS-OIT for adults over the age of 50 was established in a large and demographically diverse sample. These data are needed in order for clinicians to be able to include olfactory testing, a sensitive marker of neurodegeneration, in their assessment armamentarium.

Olfactory deficits and psychosis-spectrum symptoms in 22q11.2 deletion syndrome.

Olfactory functioning is a promising biomarker for psychosis in 22q11.2 deletion syndrome (22q11DS) but has not been well studied to date. This is a pilot effort to evaluate the potential for tests of olfactory functioning to contribute to risk and resilience prediction in 22q11DS, and is the first study to evaluate relationships among olfactory deficits, cognition and psychosis-spectrum symptoms. Odor identification and discrimination were evaluated in 32 individuals with 22q11DS and 110 healthy comparison subjects (HC). Individuals with 22q11DS also underwent cognitive testing with the Penn Computerized Neurocognitive Battery, which evaluates executive functioning, episodic memory, complex cognition, and social cognition. Positive, negative, disorganized and general psychosis-spectrum symptoms were rated according to the Scale of Prodromal Symptoms. Age-normalized scores were calculated for odor identification and discrimination based on normative data. Both odor identification (p < 0.001, Cohen's d = -2.15, 95% CI [-2.62, -1.68]) and discrimination (p < 0.001, Cohen's d = -1.81, 95% CI [-2.26, -1.35]) were significantly impaired in 22q11DS relative to HC. There were no sex differences in either group. Neither odor identification nor discrimination was correlated with overall cognition or any specific cognitive domain in 22q11DS. Impairment in odor discrimination was correlated with higher negative and overall psychosis-spectrum symptoms. There was no significant effect of catechol-O-methyltransferase Val(158)Met genotype or presence of velopharyngeal insufficiency on olfactory functioning. Olfactory deficits, particularly olfactory discrimination, are robust in 22q11DS and appear to be independent of cognitive deficits. They are also clinically relevant and related to psychosis-spectrum symptoms. Olfactory functioning appears to be a promising biomarker for psychosis in 22q11DS.

Neurocognitive Functioning in Patients with 22q11.2 Deletion Syndrome: A Meta-Analytic Review.

The 22q11.2 deletion syndrome (22q11.2DS) is a known risk factor for development of schizophrenia and is characterized by a complex neuropsychological profile. To date, a quantitative meta-analysis examining cognitive functioning in 22q11.2DS has not been conducted. A systematic review of cross-sectional studies comparing neuropsychological performance of individuals with 22q11.2DS with age-matched healthy typically developing and sibling comparison subjects was carried out. Potential moderators were analyzed. Analyses included 43 articles (282 effects) that met inclusion criteria. Very large and heterogeneous effects were seen for global cognition (d = - 1.21) and in specific neuropsychological domains (intellectual functioning, achievement, and executive function; d range = - 0.51 to - 2.43). Moderator analysis revealed a significant role for type of healthy comparison group used (typically developing or siblings), demographics (age, sex) and clinical factors (externalizing behavior). Results revealed significant differences between pediatric and adult samples, with isolated analysis within the pediatric sample yielding large effects in several neuropsychological domains (intellectual functioning, achievement, visual memory; d range = - 0.56 to - 2.50). Large cognitive deficits in intellectual functioning and specific neuropsychological variables in individuals with 22q11.2DS represent a robust finding, but these deficits are influenced by several factors, including type of comparison group utilized, age, sex, and clinical status. These findings highlight the clinical relevance of characterizing cognitive functioning in 22q11.2DS and the importance of considering demographic and clinical moderators in future analyses.

Quantitative assessment of finger tapping characteristics in mild cognitive impairment, Alzheimer's disease, and Parkinson's disease.

BACKGROUND: Fine motor impairments are common in neurodegenerative disorders, yet standardized, quantitative measurements of motor abilities are uncommonly used in neurological practice. Thus, understanding and comparing fine motor abilities across disorders have been limited. OBJECTIVES: The current study compared differences in finger tapping, inter-tap interval, and variability in Alzheimer's disease (AD), Parkinson's disease (PD), mild cognitive impairment (MCI), and healthy older adults (HOA). METHODS: Finger tapping was measured using a highly sensitive light-diode finger tapper. Total number of finger taps, inter-tap interval, and intra-individual variability (IIV) of finger tapping was measured and compared in AD (n = 131), PD (n = 63), MCI (n = 46), and HOA (n = 62), controlling for age and sex. RESULTS: All patient groups had fine motor impairments relative to HOA. AD and MCI groups produced fewer taps with longer inter-tap interval and higher IIV compared to HOA. The PD group, however, produced more taps with shorter inter-tap interval and higher IIV compared to HOA. CONCLUSIONS: Disease-specific changes in fine motor function occur in the most common neurodegenerative diseases. The findings suggest that alterations in finger tapping patterns are common in AD, MCI, and PD. In addition, the present results underscore the importance of motor dysfunction even in neurodegenerative disorders without primary motor symptoms.

Olfactory processing in bipolar disorder, major depression, and anxiety.

OBJECTIVES: Although olfactory abnormalities are well established in schizophrenia, considerably less work has examined olfactory performance in other neuropsychiatric conditions. In the current study, we examined odor identification, odor discrimination, detection threshold, and odor hedonic processing performance in individuals with bipolar I disorder (n = 43; n = 13 with psychotic features), bipolar II disorder (n = 48), major depressive disorder (MDD) (n = 134), anxiety (n = 48), and no mental disorder (n = 72) who participated in a community-based family study. METHODS: Best estimate DSM-IV diagnoses were based on in-depth personal interviews as well as interviews with family members. Olfactory tests were administered during an in-person clinical visit and were compared using robust linear regression adjusting for age, sex, and psychiatric medication use, as well as nicotine use when necessary. RESULTS: Compared to controls, odor identification performance was lower among individuals with MDD (b = -1.37, 95% confidence interval [CI]: -2.50, -0.24) and bipolar I disorder (b = -1.79, 95% CI: -3.51, -0.67). Among the latter group, performance was only reduced among those with psychotic features (b = -3.49, 95% CI: -6.33, -0.65), particularly for pleasant odors (b = -1.46, 95% CI: -2.51, -0.42). Those with MDD showed lower identification accuracy for neutral odors (b = -0.63, 95% CI: -1.20, -0.06). Performances on measures of odor discrimination and detection threshold did not differ by diagnostic group. CONCLUSIONS: Collectively, these findings indicate that odor identification difficulties may exist in mood disorders, especially when psychotic features are present. In contrast, the global olfactory dysfunction observed in schizophrenia may not be a feature of other neuropsychiatric conditions.

Structural anomalies of the peripheral olfactory system in psychosis high-risk subjects.

BACKGROUND: Olfactory impairments are prominent in both schizophrenia and the preceding at-risk state. Their presence prior to illness predicts poor functional outcome. In schizophrenia, these impairments reflect peripheral olfactory structural abnormalities, which are hypothesized to arise during early embryonic development. If this is correct, then similar structural anomalies should be apparent among clinical high-risk subjects. METHODS: Thirty-nine clinical high-risk (CR) subjects (24M/15F) were compared to 36 low-risk (LR) subjects (19M/17F). Olfactory measures derived from 3T MRI scans included olfactory bulb volume, primary olfactory cortical gray matter volume, and the depth of the olfactory sulcus overlying the bulb. Additionally, nasal cavity volumes were assessed with acoustic rhinometry. RESULTS: Male CR subjects exhibited bilateral reductions in olfactory bulb volume and abnormal asymmetries of the posterior nasal cavities and olfactory sulci (left reduced relative to right). Post-hoc contrasts also indicated reduced left, but not right, olfactory cortical gray matter volume. Female CRs had no significant abnormalities, although they exhibited similar trend effects. Left olfactory bulb volume correlated, across all CR subjects, with negative, but not positive, symptoms. In a classification analysis, with 80% target specificity, olfactory measurements distinguished male CR from male LR subjects with 93% sensitivity. Among females, the comparable sensitivity was 69%. CONCLUSION: Psychosis-risk youths exhibit an array of sexually dimorphic and laterally asymmetric anomalies of the peripheral olfactory system. These are consistent with a developmental disruption primarily affecting male fetuses. These structural biomarkers may enhance the identification of at-risk subjects with poor prognosis, before their clinical trajectory is apparent.