The kids are not alright: A preliminary report of Post-COVID syndrome in university students.

OBJECTIVE: To investigate the prevalence and features of protracted COVID-19 symptoms in non-hospitalized university students who experienced mild-to-moderate acute illness. PARTICIPANTS: COVID-19 positive participants with symptoms ≥ 28 days (N = 22), herein referred to as post-COVID syndrome, were compared to those who fully recovered (N = 21) and those never diagnosed with the disease (N = 58). METHODS: Students completed online study to earn research credit for class. RESULTS: 51% of COVID-19 positive participants were classified with post-COVID syndrome. During acute illness, those with post-COVID syndrome experienced more chest pain, fatigue, fever, olfactory impairment, headaches, and diarrhea compared to fully recovered participants. They also reported more current exercise intolerance, dyspnea, chest pain, olfactory impairment, lymphadenopathy, gustatory impairment, and appetite loss than students who never contracted COVID-19. CONCLUSIONS: Our results contradict the perception that this yet to be defined post-COVID syndrome predominantly affects middle-aged adults. Student health centers should closely monitor those who contract COVID-19 for lingering effects.

Impairments in odour detection and hedonic ratings of unpleasant smells in asymptomatic university students as SARS-Cov-2 emerged locally.

Sudden olfactory loss in the absence of concurrent nasal congestion is now a well-recognized symptom of COVID-19. We examined olfaction using standardized objective tests of odour detection, identification and hedonics collected from asymptomatic university students before and as SARS-CoV-2 emerged locally. Olfactory performance of students who were tested when the virus is known to be endemic (n = 22) was compared to students tested in the month prior to viral circulation (n = 25), a normative sample assessed during the previous 4 years (n = 272) and those tested in prior years during the same time period. Analyses showed significantly reduced odour detection for the virus exposed cohort compared to students tested before (t = 2.60; P = .01; d = 0.77; CI 0.17, 1.36) and to the normative sample (D = 0.38; P = .005). Odour identification scores were similar, but the exposed cohort rated odours as less unpleasant (P < .001, CLES = 0.77). Hyposmia increased 4.4-fold for students tested 2 weeks before school closure (N = 22) and increased 13.6-fold for students tested in the final week (N = 11). While the unavailability of COVID-19 testing is a limitation, this naturalistic study demonstrates week-by-week increase in hyposmia in asymptomatic students as a virus was circulating on campus, consistent with increasing airborne viral loads. The specific hedonic deficit in unpleasantness appraisal suggests a deficit in the TAAR olfactory receptor class, which conveys the social salience of odours. Assessment of odour detection and hedonic ratings may aid in early detection of SARS-CoV-2 exposure in asymptomatic and pre-symptomatic persons.

The effects of a positional feedback device on rollator walker use: a validation study.

BACKGROUND: According to clinical guidelines, rolling walker users should walk with their feet between the posterior wheels of the walker; however approximately 50% of users do not. OBJECTIVE: To describe the development and effects of a custom device designed to attach to a walker and provide visual feedback to encourage improved user position. METHODS: Fourteen older adults participated in this study to validate the effects of this device when a 10% decrease in the users' habitual distance away from the walker was encouraged via feedback. Users' relative distances were recorded using a non-contact distance sensor within the device, while kinematics were measured using commercial wearable wireless inertial sensors. RESULTS: Individuals were able to ambulate on average 20% closer or more to their walker when prescribed the visual feedback. This was primarily achieved through a reduction in shoulder flexion. Trunk and cervical postures were less generalizable as only small and variable changes were observed. CONCLUSIONS: These findings suggest that the device has promise, as individuals attended to the device and walked in a position closer to that recommended by clinical guidelines. The device did not appear to improve posture. Future work is needed to determine long-term effects.

The Kids Are Not Alright: A Preliminary Report of Post-COVID Syndrome in University Students.

Background: Post-COVID syndrome is increasingly recognized by the medical community but has not been studied exclusively in young adults. This preliminary report investigates the prevalence and features of protracted symptoms in non-hospitalized university students who experienced mild-to-moderate acute illness. Methods: 148 students completed an online study to earn research credit for class. Data from COVID-19 positive participants with symptoms ≥28 days (N=22) were compared to those who fully recovered (N=21) and those not diagnosed with COVID-19 (N=58). Results: 51% of participants who contracted COVID-19 (N=43) experienced symptoms ≥28 days and were classified as having post-COVID syndrome; all but one (96%) were female. During acute illness the post-COVID group, compared to those who fully recovered, experienced significantly more chest pain (64% vs 14%; P=.002), fatigue (86% vs 48%; P=.009), fever (82% vs 48%; P=.02), olfactory impairment (82% vs 52%; P=.04), headaches (32% vs 5%; P<.05), and diarrhea (32% vs 5%; P<.05). Compared to those not diagnosed with COVID-19, the post-COVID syndrome group more frequently experienced exercise intolerance (43% vs. 0%; P<.001), dyspnea (43% vs. 0%; P<.001), chest pain (31% vs 7%; P=.002), olfactory impairment (19% vs 0%; P=.004), lymphadenopathy (19% vs 0%; P=.004), gustatory impairment (14% vs 0%; P=.02), and appetite loss (36% vs 14%; P=.02). Interpretation: Our results contradict the perception that this "yet to be defined" post-COVID syndrome predominantly affects middle-aged adults and suggest that exercise intolerance, dyspnea, chest pain, chemosensory impairment, lymphadenopathy, rhinitis, and appetite loss may differentiate post-COVID syndrome from general symptoms of pandemic, age, and academic related stress. These findings are also consistent with previous reports that females are more vulnerable to this post viral syndrome. Large-scale population-based studies are essential to discerning the magnitude and characterization of post-COVID syndrome in young adults as well as more diverse populations.

Ineffective risk-reward learning in schizophrenia.

The underpinnings of poor decision-making in schizophrenia could reflect excessively risky or inhibited behaviors. This study employed the Balloon Analogue Risk Task (BART) to compare decision-making in schizophrenia cases to that of healthy controls. Individuals with schizophrenia performed significantly differently across three trials, failing to improve their performance as shown by the control group. In the control group, cognitive ability, measured with the Wechsler Adult Intelligence Scale (WAIS-III) showed that Perceptual Organization scores predicted Average Inflations per Trial, Total Balloon Pops, and Total Earnings. Although the schizophrenia cases failed to learn, group performance on the BART was not associated with cognitive ability, but regression analyses showed 41.4% of average inflations per trial were explained by Excitement, Delusions, Emotional Withdrawal, and Poor Rapport; total balloon pops were only explained by emotional withdrawal and Total Earnings were reduced by Delusions, Excitement and Poor Rapport. Only healthy participants demonstrated a relation between cognitive ability performance improvement across trials. Schizophrenia cases showed less risk-taking, and earned significantly less money overall. Identifying the determinants of poor decision-making could inform interventions and possible treatments to improve their function and perhaps be of relevance to public safety if decisions are overly risky.

Reduced odor detection and hedonic changes in asymptomatic university students as SARS-CoV-2 emerged locally.

Aerosol droplets have emerged as the primary mode of SARS-Cov-2 transmission and can be spread by infectious asymptomatic/pre-symptomatic persons rendering indicators of latent viral infection essential. Olfactory impairment is now a recognized symptom of COVID-19 and is rapidly becoming one of the most reliable indicators of the disease. We compared olfaction data from asymptomatic students, who were assessed as SARS-CoV-2 was unknowingly spreading locally, to students tested prior to the arrival of the virus. This study was naturalistic by design as testing occurred in the context of four research studies, all of which used the same inclusion/exclusion criteria and the same protocol to objectively assess odor detection, identification, and hedonics with physiological tests. Data from students (Cohort II; N=22) with probable SARS-CoV-2 exposure were compared to students tested just prior to local virus transmission (Cohort I; N=25), and a normative sample of students assessed over the previous four years (N=272). Students in Cohort II demonstrated significantly reduced odor detection sensitivity compared to students in Cohort I (t=2.60; P=.01; d=0.77; CI, 0.17, 1.36), with a distribution skewed towards reduced detection sensitivity (D=0.38; P=.005). Categorically, the exposed group was significantly more likely to have hyposmia (OR=7.74; CI, 3.1, 19.40), particularly the subgroup assessed in the final week before campus closure (OR=13.61; CI, 3.40, 35.66;). The exposed cohort also rated odors as less unpleasant (P<.001, CLES=0.77). A limitation of our study is that participants were not tested for COVID-19 as testing was unavailable in the area. Objective measures of olfaction may detect olfactory impairment in asymptomatic persons who are otherwise unaware of smell loss. The development of cost-effective, objective olfaction tests that could be self-administered regularly could aid in early detection of SARS-CoV-2 exposure, which is vital to combatting this pandemic.

Features of schizophrenia following premorbid eating disorders.

OBJECTIVE: Eating disorders (ED) and schizophrenia are frequently comorbid and schizophrenia shares genetic susceptibility with anorexia. Many factors associated with schizophrenia can disrupt eating, but ED can present years before schizophrenia. If premorbid ED distinguishes a particular subtype of schizophrenia, then phenotypic features may differ between schizophrenia cases with and without premorbid ED. METHOD: This secondary analysis used data from an inpatient schizophrenia research study that comprehensively assessed life course psychiatric disorders (DIGS interview), intelligence (WAIS), global assessments of function (GAF) and assessed symptoms during medication-free and fixed dose neuroleptic phases (PANSS). RESULTS: Premorbid ED was identified in 27 of the 288 schizophrenia cases (9.4%). This group had more females than the group without premorbid ED (74.1% vs. 30%); premorbid ED was 5-fold more common in female than male cases (χ2 (17.9, P < .0001). Only the premorbid ED group had gustatory hallucinations. They also demonstrated significantly more severe psychotic and disorganization symptoms during medication-free and fixed dose treatment phases, despite similar negative symptoms and GAF scores, as other cases. The premorbid ED group had significantly better cognition overall, but relatively lower nonverbal than verbal intelligence. DISCUSSION: Premorbid ED may define a specific subtype of schizophrenia that is common in females. Their more severe psychotic symptoms and better IQ, despite similarly impaired function and negative symptoms as other cases, suggests a distinct pathophysiology. Premorbid ED should be considered in evaluating risk states for schizophrenia, and as a relevant phenotype for treatment resistant schizophrenia.

Relative importance of symptoms, cognition, and other multilevel variables for psychiatric disease classifications by machine learning.

This study used machine-learning algorithms to make unbiased estimates of the relative importance of various multilevel data for classifying cases with schizophrenia (n = 60), schizoaffective disorder (n = 19), bipolar disorder (n = 20), unipolar depression (n = 14), and healthy controls (n = 51) into psychiatric diagnostic categories. The Random Forest machine learning algorithm, which showed best efficacy (92.9% SD: 0.06), was used to generate variable importance ranking of positive, negative, and general psychopathology symptoms, cognitive indexes, global assessment of function (GAF), and parental ages at birth for sorting participants into diagnostic categories. Symptoms were ranked most influential for separating cases from healthy controls, followed by cognition and maternal age. To separate schizophrenia/schizoaffective disorder from bipolar/unipolar depression, GAF was most influential, followed by cognition and paternal age. For classifying schizophrenia from all other psychiatric disorders, low GAF and paternal age were similarly important, followed by cognition, psychopathology and maternal age. Controls misclassified as schizophrenia cases showed lower nonverbal abilities, mild negative and general psychopathology symptoms, and younger maternal or older paternal age. The importance of symptoms for classification of cases and lower GAF for diagnosing schizophrenia, notably more important and distinct from cognition and symptoms, concurs with current practices. The high importance of parental ages is noteworthy and merits further study.

Traumatic experiences and cognitive profiles of schizophrenia cases influenced by the BDNF Val66met polymorphism.

The association of early trauma exposure with current cognition was examined in a research series of 56 schizophrenia cases with respect to the BDNF Val66Met polymorphism (rs6265, Val66Val, Val66Met, Met66Met), as met allele carriers have reduced neurotrophic activity. The Perceptual Organization Index had a significant negative correlation with trauma exposures only in met carriers, including early physical abuse, general trauma after age 18 years, and physical abuse. Within the Val66Val subgroup, there were no significant correlations between WAIS indices and traumatic experiences.

Normal sexual dimorphism in theory of mind circuitry is reversed in Schizophrenia.

The ability to mentalize, or theory of mind (ToM), is sexually dimorphic in humans and impaired in schizophrenia. This sex-stratified study probed cognitive (indexed by intelligence) and affective (indexed by olfactory tasks) contributions to ToM performance in 37 individuals with schizophrenia and 31 healthy controls. The schizophrenia group showed impairments in mental state identification and inferring intentions compared to controls. Higher intelligence was correlated with mental state identification and inferring intentions in healthy females, whereas better smell identification was associated with mental state identification in healthy males. Conversely, higher intelligence was associated with mental state identification and inferring intentions in schizophrenia males, while better smell identification was correlated with mental state identification in schizophrenia females. These findings suggest that for ToM circuitry, the cognitive influences in healthy females and affective influences in healthy males are reversed in schizophrenia and may be displaced to lower circuitries by disease pathology. Symptom associations with emotion and cognition are also dimorphic, plausibly due to similar pathology superimposed on normal sex-specific circuitries. Males appear to rely on limbic processing for ToM, and disruption to this circuitry may contribute to development of negative symptoms. These findings highlight the importance of utilizing sex-stratified designs in schizophrenia research.

Sex differences in hedonic judgement of odors in schizophrenia cases and healthy controls.

The neurocircuitries subserving affective and olfactory processes overlap, are sexually dimorphic, and show disruptions in schizophrenia, suggesting their intersection may be a window on the core process producing psychosis. This study investigated diagnostic and sex differences in hedonic judgments of odors and smell identification in 26 schizophrenia cases and 27 healthy controls. Associations between olfaction measures and psychiatric symptoms were also examined. Cases and controls had similar identification accuracy of unpleasant odors, but cases were significantly less accurate in naming pleasant odors. In cases, greater negative symptom severity was related to abnormal hedonic judgments; specifically, higher pleasantness ratings for unpleasant odors and higher unpleasantness ratings for pleasant odors. Greater positive symptom severity was associated with lower pleasantness ratings for neutral odors. Regarding sex differences, male cases and female controls rated pleasant odors as significantly more unpleasant than male controls. Correlations between depression severity and pleasantness ratings of neutral odors were in opposite directions in male and female cases. These results suggest that a normal sexual dimorphism in the circuitry for hedonic odor judgments may interact with schizophrenia pathology, supporting the utility of olfactory hedonics as a sex-specific biomarker of this pathology.

Telomere length and early trauma in schizophrenia.

BACKGROUND: Childhood trauma is emerging as a risk factor for schizophrenia, but its mechanism with respect to etiology is unknown. One possible pathway is through leucocyte telomere length (LTL) shortening, a measure of cellular aging associated with trauma. This study examined early trauma and LTL shortening in schizophrenia and considered sex effects. METHODS: The early trauma inventory (ETI) was administered to 48 adults with DSM-5 schizophrenia and 18 comparison participants. LTL was measured using qPCR. OUTCOMES: Cases had significantly more global trauma (F=4.10, p<0.01) and traumatic events (F=11.23, p<0.001), but case and control groups had similar LTL (1.91±0.74 and 1.83±0.62: p=0.68). The association of early trauma and LTL differed by sex in cases and controls (Fisher's R: Z<0.05). Significant negative associations were shown in male cases and, conversely, in female controls. For example, physical punishment was associated LTL shortening in males' cases (r=-0.429, p<01). Only female controls showed significant telomere shortening in association with early trauma. INTERPRETATION: This data confirms the substantial excess of early trauma among schizophrenia cases. There were significant sex-differences in the relationship of the trauma to LTL, with only male cases showing the expected shortening. There were converse sex effects in the control group. Mean LTL was notably similar in cases and controls, despite the trauma-related shortening in male cases, cigarette smoking, older age and chronic illness of the cases. Factors may lengthen LTL in some schizophrenia cases. The converse sex differences in the cases are consistent with findings defective sexual differentiation in schizophrenia, consistent with other findings in the field.

Rare missense coding variants in oxytocin receptor (OXTR) in schizophrenia cases are associated with early trauma exposure, cognition and emotional processing.

BACKGROUND: Oxytocin is a peptide hormone that influences the integration of social cognition with behavior and affect regulation. Oxytocin also prominently directs the transition of neuronal GABA neurotransmission from excitatory to inhibitory after birth. The oxytocin receptor (OXTR) is linked to schizophrenia, a heterogeneous syndrome. Relationships of OXTR polymorphisms with specific clinical features could aid in evaluating any role of oxytocin in the pathogenesis of schizophrenia. METHOD: Schizophrenia cases with rare missense coding OXTR single nucleotide variants (SNVs) were identified from a well-characterized sample of cases and controls who were assessed for symptoms, cognition and early life trauma. RESULTS: Five of 48 cases showed rare OXTR variants. Compared to the other cases they had less severe negative symptoms (deficits in emotional expression and motivation) and less severe general psychopathology scores (depression and anxiety). They demonstrated lower nonverbal (performance) than verbal intelligence due to deficient perceptual organization and slow processing speed. They also reported greater early trauma exposure (physical and sexual abuse and emotional trauma). CONCLUSION: Cases carrying rare OXTR SNVs had less negative and affective symptoms than other cases, but similar psychotic symptoms, along with specific cognitive deficits. The clinical characterization of these cases occurred in association with environmental exposure to early trauma, especially sexual abuse, which may have influenced the expression of schizophrenia in subjects harboring specific SNVs in the OXTR.

Factor Structure of the Positive and Negative Syndrome Scale (PANSS) Differs by Sex.

Although the Positive and Negative Syndrome Scale (PANSS) is widely used in clinical research, factor analytic studies of the scale have been inconsistent and questions remain about the underlying factor structure of schizophrenia symptoms. The purpose of this study was to examine whether the factor structure of the PANSS differs in men and women with schizophrenia. Principal components analysis (PCA) with equamax rotation was used to examine the factor structure of the PANSS separately in 124 males and 74 females with schizophrenia-related psychoses. In males, a four-factor structure was identified: 1) Negative, 2) Cognitive, 3) Positive, and 4) Hostility. In females, a four-factor structure also emerged: 1) Negative, 2) Cognitive, 3) Positive, and 4) Depression. The most notable difference between the male and female PCAs was the presence of a depression factor in the females and a hostility factor in males. These results support sex differences in the factor structure of schizophrenia symptoms, which has important implications for clinical research.

Phenotypically distinct subtypes of psychosis accompany novel or rare variants in four different signaling genes.

BACKGROUND: Rare gene variants are important sources of schizophrenia vulnerability that likely interact with polygenic susceptibility loci. This study examined if novel or rare missense coding variants in any of four different signaling genes in sporadic schizophrenia cases were associated with clinical phenotypes in an exceptionally well-characterized sample. METHOD: Structured interviews, cognition, symptoms and life course features were assessed in 48 ethnically-diverse cases with psychosis who underwent targeted exome sequencing of PTPRG (Protein Tyrosine Phosphatase, Receptor Type G), SLC39A13 (Solute Carrier Family 39 (Zinc Transporter) Member 13), TGM5 (transglutaminase 5) and ARMS/KIDINS220 (Ankyrin repeat-rich membrane spanning protein or Kinase D-Interacting Substrate of 220kDa). Cases harboring rare missense coding polymorphisms or novel mutations in one or more of these genes were compared to other cases not carrying any rare missense coding polymorphisms or novel mutations in these genes and healthy controls. FINDINGS: Fifteen of 48 cases (31.25%) carried rare or novel missense coding variants in one or more of these genes. The subgroups significantly differed in important features, including specific working memory deficits for PTPRG (n=5); severe negative symptoms, global cognitive deficits and poor educational attainment, suggesting a developmental disorder, for SLC39A13 (n=4); slow processing speed, childhood attention deficit disorder and milder symptoms for TGM5 (n=4); and global cognitive deficits with good educational attainment suggesting neurodegeneration for ARMS/KIDINS220 (n=5). Case vignettes are included in the appendix. INTERPRETATION: Genes prone to missense coding polymorphisms and/or mutations in sporadic cases may highlight influential genes for psychosis and illuminate heterogeneous pathways to schizophrenia. Ethnicity appears less important at the level of genetic variability. The sequence variations that potentially alter the function of specific genes or their signaling partners may contribute to particular subtypes of psychosis. This approach may be applicable to other complex disorders.

Paternal age effect: Replication in schizophrenia with intriguing dissociation between bipolar with and without psychosis.

Advanced paternal age (APA) is a risk factor for schizophrenia (Sz) and bipolar disorder (BP). Putative mechanisms include heritable genetic factors, de novo mutations, and epigenetic mechanisms. Few studies have explored phenotypic features associated with APA. The Genomic Psychiatry Cohort established a clinically characterized repository of genomic samples from subjects with a Sz-BP diagnosis or unaffected controls, 12,975 with parental age information. We estimated relative risk ratios for Sz, schizoaffective depressed and bipolar types (SA-D, SA-B), and BP with and without history of psychotic features (PF) relative to the control group, comparing each paternal age group to the reference group 20-24 years. All tests were two-sided with adjustment for multiple comparisons. Subjects with fathers age 45+ had significantly higher risk for all diagnoses except for BP w/o PF. APA also bore no significant relation to family psychiatric history. In conclusion, we replicated APA as a risk factor for Sz. To our knowledge, this is the first published report of APA in a BP sample stratified by psychosis history, extending this association only in BP w/PF. This suggests that phenotypic expression of the APA effect in Sz-BP spectrum is psychosis, per se, rather than other aspects of these complex disorders. The lack of a significant relationship between paternal age and familial disease patterns suggests that underlying mechanisms of the paternal age effect may involve a complex interaction of heritable and non-heritable factors. The authors discuss implications and testable hypotheses, starting with a focus on genetic mechanisms and endophenotypic expressions of dopaminergic function. © 2015 Wiley Periodicals, Inc.

Parental age effects on odor sensitivity in healthy subjects and schizophrenia patients.

A schizophrenia phenotype for paternal and maternal age effects on illness risk could benefit etiological research. As odor sensitivity is associated with variability in symptoms and cognition in schizophrenia, we examined if it was related to parental ages in patients and healthy controls. We tested Leukocyte Telomere Length (LTL) as an explanatory factor, as LTL is associated with paternal age and schizophrenia risk. Seventy-five DSM-IV patients and 46 controls were assessed for detection of PEA, WAIS-III for cognition, and LTL, assessed by qPCR. In healthy controls, but not schizophrenia patients, decreasing sensitivity was monotonically related to advancing parental ages, particularly in sons. The relationships between parental aging and odor sensitivity differed significantly for patients and controls (Fisher's R to Z: χ(2) = 6.95, P = 0.009). The groups also differed in the association of odor sensitivity with cognition; lesser sensitivity robustly predicted cognitive impairments in patients (<0.001), but these were unassociated in controls. LTL was unrelated to odor sensitivity and did not explain the association of lesser sensitivity with cognitive deficits.Parental aging predicted less sensitive detection in healthy subjects but not in schizophrenia patients. In patients, decreased odor sensitivity strongly predicted cognitive deficits, whereas more sensitive acuity was associated with older parents. These data support separate risk pathways for schizophrenia. A parental age-related pathway may produce psychosis without impairing cognition and odor sensitivity. Diminished odor sensitivity may furthermore be useful as a biomarker for research and treatment studies in schizophrenia. © 2015 Wiley Periodicals, Inc.

Neuropsychological functioning and profile validity on the Personality Assessment Inventory (PAI): An investigation in multiple psychiatric settings.

Psychologists in medical settings are frequently tasked with providing comprehensive evaluations of patients with complex medical and psychiatric conditions. In order to achieve these aims, standardized measures of neurocognitive and psychological functioning are often employed to empirically assess a patient's level of functioning across an array of relevant clinical domains. However, less is known about the degree to which cognitive impairment affects a patient's ability to complete these more comprehensive assessments, raising questions about test validity. The current study sought to contribute to this growing body of literature by examining whether neurocognitive functioning is associated with profile validity on the Personality Assessment Inventory (PAI) in both outpatient (N = 321) and inpatient (N = 131) psychiatric settings. In Study 1, results indicate that while multiple cognitive domains are associated with overall profile validity in psychiatric outpatients, attentional impairment specifically was found to be a significant predictor of profile invalidity after accounting for the effects of overall intellectual functioning (accounting for 13% of the variance overall). The magnitude of attentional impairment specifically, and number of impaired cognitive domains more generally, were also found to be meaningfully associated with overall profile validity. Likewise, in Study 2, PAI profile validity was found to be meaningfully associated with gross cognitive impairment on the WMS-IV Brief Cognitive Status Examination (BCSE) in an inpatient psychiatric setting, with almost half of the patients in the most impaired group yielding invalid PAI profiles. The clinical implications of these findings are discussed.

Rare variants in the neurotrophin signaling pathway implicated in schizophrenia risk.

Multiple lines of evidence corroborate impaired signaling pathways as relevant to the underpinnings of schizophrenia. There has been an interest in neurotrophins, since they are crucial mediators of neurodevelopment and in synaptic connectivity in the adult brain. Neurotrophins and their receptors demonstrate aberrant expression patterns in cortical areas for schizophrenia cases in comparison to control subjects. There is little known about the contribution of neurotrophin genes in psychiatric disorders. To begin to address this issue, we conducted high-coverage targeted exome capture in a subset of neurotrophin genes in 48 comprehensively characterized cases with schizophrenia-related psychosis. We herein report rare missense polymorphisms and novel missense mutations in neurotrophin receptor signaling pathway genes. Furthermore, we observed that several genes have a higher propensity to harbor missense coding variants than others. Based on this initial analysis we suggest that rare variants and missense mutations in neurotrophin genes might represent genetic contributions involved across psychiatric disorders.