Anthropometry in antipsychotic-naïve first-episode psychosis patients: An exploratory approach to the role of environmental early life events in two independent samples.

BACKGROUND: Patients with schizophrenia exhibit a reduced life expectancy mainly due to medical-related pathologies which might have been initiated due to stressful events during fetal development. Indeed, intra-uterus growth patterns predict anthropometric measures in adulthood, describing risk factors for schizophrenia and metabolic disorders. We aim to evaluate anthropometric values in two cohorts of antipsychotic-naïve first-episode episode psychosis (FEP) and correlated them with surrogate markers of the fetal environment such as birth weight (BW) and season of birth. METHODS: BW, season of birth, and anthropometric values from 2 cohorts of FEP patients (Barcelona and Santander) were evaluated. In cohort B, 91 patients, and 110 controls while in cohort S, 644 and 235 were included respectively. RESULTS: Patients were shorter, slimmer, and with lower BMI compared with controls. In both cohorts, patients, and female patients born in winter displayed the shortest height. Regarding BW, height was significantly associated with the interaction of diagnosis and BW in the whole sample and the male subsample. CONCLUSIONS: Our results confirm reduced anthropometric features in FEP at onset while suggesting the influence of winter birth and BW, highlighting the role of early life events in the later outcome of FEP with sex differences.

The European Portuguese Version of the Brief Negative Symptom Scale.

Negative symptoms reflect a currently much-untreated loss of normal functioning and are frequently found in psychotic disorders. We present the first translation of the Brief Negative Symptom Scale (BNSS) to European Portuguese and evaluate its validity in a sample of Portuguese male patients with a psychotic spectrum disorder. The Portuguese BNSS showed excellent internal consistency, high convergent validity (i.e., strong correlation with the PANSS negative factor), and high discriminant validity (i.e., a lack of association with the PANSS positive factor). In sum, the present European Portuguese BNSS has shown to be reliable, thus extending this instrument's clinical availability worldwide.

Identification of genetic variants and individual genes associated with postpartum hypocalcemia in Holstein cows.

Periparturient hypocalcemia is a complex metabolic disorder that occurs at the onset of lactation because of a sudden irreversible loss of Ca incorporated into colostrum and milk. Some cows are unable to quickly adapt to this demand and succumb to clinical hypocalcemia, commonly known as milk fever, whereas a larger proportion of cows develop subclinical hypocalcemia. The main goal of this study was to identify causative mutations and candidate genes affecting postpartum blood calcium concentration in Holstein cows. Data consisted of blood calcium concentration measured in 2513 Holstein cows on the first three days after parturition. All cows had genotypic information for 79 k SNP markers. Two consecutive rounds of imputation were performed: first, the 2513 Holstein cows were imputed from 79 k to 312 k SNP markers. This imputation was performed using a reference set of 17,131 proven Holstein bulls with 312 k SNP markers. Then, the 2513 Holstein cows were imputed from 312 k markers to whole-genome sequence data. This second round of imputation used 179 Holstein animals from the 1000 Bulls Genome Project as a reference set. Three alternative phenotypes were evaluated: (1) total calcium concentration in the first 24 h postpartum, (2) total calcium concentration in the first 72 h postpartum calculated as the area under the curve; and (3) the recovery of total calcium concentration calculated as the difference in total calcium concentration between 72 and 24 h. The identification of genetic variants associated with these traits was performed using a two-step mixed model-based approach implemented in the R package MixABEL. The most significant variants were located within or near genes involved in calcium homeostasis and vitamin D transport (GC), calcium and potassium channels (JPH3 and KCNK13), energy and lipid metabolism (CA5A, PRORP, and SREBP1), and immune response (IL12RB2 and CXCL8), among other functions. This work provides the foundation for the development of novel breeding and management tools for reducing the incidence of periparturient hypocalcemia in dairy cattle.

Degree of leukochimerism with calf age in Angus-crossbred twin sets.

Twinning in cattle is infrequent and usually undesired. It can result in an increased occurrence of abortion and dystocia, reduced calf survival and a high likelihood of freemartinism in mixed-sex twins. Twin gestations are also commonly associated with the formation of placental vascular anastomoses (PVA) between twins. Through PVA they share blood, hormones (leading to freemartinism in mixed sex twins) and hematopoietic stem cells, which are the progenitors of white blood cells. The sharing of stem cells between twins can result in leukochimeric twin sets. These are twins that have white blood cells derived from both self and the co-twin owing to the fetal migration of hematopoietic stem cells from the extraembryonic mesoderm of the yolk sac to final sites like bone marrow and thymus. This study examined the degree to which this leukochimerism changes with age. DNA was extracted from hair bulbs containing mesenchymal dermal papilla to determine the individual's true genotype and blood samples were obtained at six time points from 1 week to 8 months of age to assess leukochimerism. Samples were genotyped using a medium density SNP chip, and quantitative estimates of allele frequency were determined using SNPs for which members of a twin set had alternative homozygous genotypes. The results indicate statistically significant changes in the proportion of self and co-twin with age and suggest that by 2-4 months of age the genotypic mix in white blood cells represents the hematopoetic stem cell population resident in the individual (i.e. permanently found in thymus and bone marrow).

Negative symptoms in the clinic: we treat what we can describe.

Recent research has led to important changes in the concepts and assessment of negative symptoms in schizophrenia. We review current negative symptom concepts and their clinical implications, as well as new methods of assessing these symptoms. These changes hold promise for improving our understanding and treatment of negative symptoms.

A new era for the negative symptoms of schizophrenia.

Negative symptoms remain one of the major unmet needs for people with schizophrenia, and the past decade has witnessed a surge in interest in negative symptoms. In this themed issue, we present new concepts of negative symptoms and recent findings on their epidemiology and pathophysiology and on therapeutic options for their management.

Preantral follicle numbers and size in heifers carrying Trio, a bovine high fecundity allele.

In brief: The bovine high fecundity allele, Trio, results in the occurrence of multiple ovulations and is characterized by antral follicles that develop slower and acquire ovulatory capacity at smaller sizes. This study provides novel information on the effect of the Trio allele on early folliculogenesis. Abstract: The bovine high fecundity allele, Trio, causes overexpression in granulosa cells (GCs) of SMAD6, an inhibitor of BMP15-activated SMAD signalling. Furthermore, the Trio allele results in antral follicles that develop slower, acquire ovulatory capacity at smaller sizes, and have three-fold greater ovulation rate compared to half-sib non-carriers. The present study was designed to determine preantral follicle numbers and size in Trio carrier and non-carrier cattle testing the hypothesis that inhibition of SMAD signalling would alter preantral follicle activation and/or growth. Ovarian tissues from Trio carrier (n = 12) and non-carrier (n = 12) heifers were obtained by laparotomy after follicle wave synchronization. Follicle numbers and dimensions were determined for each stage of development (primordial, transitional, primary, and secondary) from paraffin-embedded sections. There were no differences in the number of primordial, transitional, or secondary follicles or in antral follicle count, circulating AMH, or ovarian volume between carriers and non-carriers. Trio carriers had ~2.5-fold greater (P < 0.01) number of primary follicles than non-carriers, and transitional and primary follicles were larger (~1.2-fold; P < 0.1) in Trio carriers. Oocyte volume of primordial and transitional follicles was not different between genotypes; however, oocytes were larger (P < 0.05) in primary (~1.3-fold) and secondary (~1.8-fold) follicles for Trio carriers. Granulosa cell numbers were not different (P > 0.3) between carriers and non-carriers, irrespective of the stage of development. These results suggest that, after primordial follicle activation, follicles in Trio carrier cattle have slower progression through the primary stage, hence the larger oocyte and greater number of primary follicles.

Longitudinal effect of clozapine-associated sedation on motivation in schizophrenia: naturalistic longitudinal study.

Negative symptoms of schizophrenia manifest as reduced motivation and pleasure (MAP) and impaired emotional expressivity (EXP). These can occur as primary phenomena, but have also been suggested to occur secondary to other clinical factors, including antipsychotic-induced sedation. However, this relationship has not been established formally. Here, we examined the effect of antipsychotic-induced sedation (assessed via the proxy of total daily sleep duration) on MAP and EXP in a cohort of 187 clozapine-treated patients with schizophrenia followed for over 2 years on average, using multilevel regression and mediation models. MAP, but not EXP, was adversely influenced by sedation, independently of the severity of psychosis or depression. Moreover, clozapine impaired MAP indirectly by worsening sedation, but after accounting for clozapine-induced sedation, clozapine improved MAP. Our results highlight the importance of addressing sedative side-effects of antipsychotics to improve clinical outcomes.

SMAD6 inhibits granulosa cell proliferation and follicle growth rate in carrier and noncarrier heifers of the Trio allele.

In brief: Follicle selection is a key event in monovular species. In this manuscript, we demonstrate the role of SMAD6 in promoting decreased granulosa cell proliferation and follicle growth rate in carriers vs noncarriers of the Trio allele and after vs before follicle deviation. Abstract: Cattle are generally considered a monovular species; however, recently, a bovine high fecundity allele, termed the Trio allele, was discovered. Carriers of Trio have an elevated ovulation rate (3-5), while half-sibling noncarriers are monovular. Carriers of the Trio allele have overexpression in granulosa cells of SMAD6, an inhibitor of oocyte-derived regulators of granulosa cell proliferation and differentiation. In experiment 1, follicle size was tracked for each follicle during a follicular wave. Follicle growth rate was greater before vs after follicle deviation in both carriers and noncarriers. Additionally, follicle growth rate was consistently less in carriers vs noncarriers. In experiment 2, we collected granulosa cells from follicles before and after deviation for evaluation of granulosa cell gene expression. Granulosa cell proliferation was less in carriers vs noncarriers and after vs before follicle deviation (decreased expression of cell cycle genes CCNB1 and CCNA2). The decreased granulosa cell proliferation in noncarriers after deviation was associated with increased SMAD6 expression. Similarly, in experiment 3, decreased expression of SMAD6 in granulosa cells of noncarriers cultured in vitro for 60 h was associated with increased expression of cell cycle genes. This suggests that SMAD6 may not just be inhibiting follicle growth rate in carriers of Trio but may also play a role in the decreased follicle growth after deviation in noncarriers. The hypotheses were supported that (1) follicle growth and granulosa cell proliferation decrease after deviation in both carriers and noncarriers and that (2) granulosa cell proliferation is reduced in carriers compared to noncarriers.

Validation of accelerometry as a digital phenotyping measure of negative symptoms in schizophrenia.

Negative symptoms are commonly assessed via clinical rating scales; however, these measures have several inherent limitations that impact validity and utility for their use in clinical trials. Objective digital phenotyping measures that overcome some of these limitations are now available. The current study evaluated the validity of accelerometry (ACL), a passive digital phenotyping method that involves collecting data on the presence, vigor, and variability of movement. Outpatients with schizophrenia (SZ: n = 50) and demographically matched healthy controls (CN: n = 70) had ACL continuously recorded from a smartphone and smartband for 6 days. Active digital phenotyping assessments, including surveys related to activity context, were also collected via 8 daily surveys throughout the 6 day period. SZ participants had lower scores on phone ACL variables reflecting vigor and variability of movement compared to CN. ACL variables demonstrated convergent validity as indicated by significant correlations with active digital phenotyping self-reports of time spent in goal-directed activities and clinical ratings of negative symptoms. The discriminant validity of ACL was demonstrated by low correlations with clinical rating scale measures of positive, disorganized, and total symptoms. Collectively, findings suggest that ACL is a valid objective measure of negative symptoms that may complement traditional approaches to assessing the construct using clinical rating scales.

Identifying genetic variants and pathways influencing daughter averages for twinning in North American Holstein cattle and evaluating the potential for genomic selection.

Multiple birth in dairy cattle is a detrimental trait both economically for producers and for animal health. Genetics of twinning is complex and has led to several quantitative trait loci regions being associated with increased twinning. To identify variants associated with this trait, calving records from 2 time periods were used to estimate daughter averages for twinning for Holstein bulls. Multiple analyses were conducted and compared including GWAS, genomic prediction, and gene set enrichment analysis for pathway detection. Although pathway analysis did not yield many congruent pathways of interest between data sets, it did indicate two of interest. Both pathways have ties to the strong candidate region on BTA11 from the genome-wide association analysis across data sets. This region does not overlap with previously identified quantitative trait loci regions for twinning or ovulation rate in cattle. The strongest associated SNPs were upstream from 2 candidate genes LHCGR and FSHR, which are involved in folliculogenesis. Genomic prediction showed a moderate correlation accuracy (0.43) when predicting genomic breeding values for bulls with estimates from calving records from 2010 to 2016. Future analysis of the region on BTA11 and the relation of the candidate genes could improve this accuracy.

Early versus late risk factors for deficit and nondeficit schizophrenia.

AIM: We examined whether timing of known risk factors for schizophrenia may influence the development of schizophrenia with primary negative symptoms. METHOD: This cross-sectional single-centre study in England used a clinical cohort of 167 clozapine-treated schizophrenia patients. Deficit and nondeficit schizophrenia models were used as clinical proxies of patients with and without primary negative symptoms respectively. Patients were assessed using the Schedule for the Deficit Syndrome. We examined previously replicated risk factors (family history of psychosis, advanced paternal age, male gender, birth weight <3000g, summer birth, cannabis use, exposure to physical or sexual abuse and/or bullying) as well as other traumatic events for deficit and nondeficit schizophrenia. RESULTS: We found a distinct risk factor pattern for the two groups. Compared to the nondeficit group, patients with deficit schizophrenia reported a significantly lower prevalence of cannabis use (p=0.005) at the time of first-episode psychosis (FEP), physical or sexual abuse (p=0.033) prior to FEP, less exposure to crime-related traumatic events (p=0.012) and significantly associated with summer birth (p=0.017). The groups did not differ in terms of family history of psychosis, advanced paternal age, male gender, or low birth weight. To account for multiple comparisons, a confirmatory analysis was performed using logistic regression which yielded similar results except that summer birth no longer reached statistical significance. CONCLUSION: Our results suggest the timing of the insult may influence the symptom presentation, with insults later in life (cannabis or traumatic events) being associated with psychotic presentation and less with primary negative symptoms.

Defining negative symptoms remission in schizophrenia using the Brief Negative Symptom Scale.

INTRODUCTION: This study aimed to propose criteria for negative symptoms remission (NSR) in schizophrenia using the Brief Negative Symptom Scale (BNSS). MATERIAL AND METHODS: 274 participants were assessed on the Positive and Negative Syndrome Scale (PANSS), BNSS and Social and Occupational Functioning Assessment Scale (SOFAS). Two criteria for NSR on the BNSS were proposed - NSR based on the BNSS domains scores (NSRBNSS_DOMAINS) and NSR based on 5 key items of the BNSS (NSRBNSS_5ITEMS). A SOFAS score of 61 and above was considered as functional remission (FR). Logistic regressions were run to examine the association between FR and NSR. Receiver operating characteristic (ROC) curve analysis was performed for the NSR criteria on FR. Kappa agreement statistic was used to evaluate the agreement between the two NSR criteria. RESULTS: Eighty-nine (32.5%) participants fulfilled NSRBNSS_DOMAINS criterion whereas 70 (25.6%) participants fulfilled NSRBNSS_5ITEMS criterion. The two NSR criteria had substantial agreement (Kappa statistic=0.797) with each other. Sixty-one (25.3%) participants were in FR. FR was significantly associated with NSR, irrespective of the criterion used. To predict FR, the Area Under the Curve for NSRBNSS_DOMAINS and NSRBNSS_5ITEMS were 0.761 (CI: 0.696-0.826, p<0.001) and 0.723 (CI: 0.656-0.790, p<0.001), respectively. Hence, both NSR criteria demonstrated a fair ability to discriminate between functional remitters and non-remitters. CONCLUSIONS: Depending on the setting and needs, clinicians and researchers might employ either the full BNSS or an abbreviated 5-item BNSS scale to identify NSR in schizophrenia. More research is needed to further examine the validity of these criteria in schizophrenia.

Two Factors, Five Factors, or Both? External Validation Studies of Negative Symptom Dimensions in Schizophrenia.

OBJECTIVES: Negative symptom studies frequently use single composite scores as indicators of symptom severity and as primary endpoints in clinical trials. Factor analytic and external validation studies do not support this practice but rather suggest a multidimensional construct. The current study used structural equation modeling (SEM) to compare competing dimensional models of negative symptoms to determine the number of latent dimensions that best capture variance in biological, psychological, and clinical variables known to have associations with negative symptoms. METHODS: Three independent studies (total n = 632) compared unidimensional, two-factor, five-factor, and hierarchical conceptualizations of negative symptoms in relation to cognition, psychopathology, and community functioning (Study 1); trait emotional experience and defeatist performance beliefs (Study 2); and glutamate and gamma-aminobutyric acid levels in the anterior cingulate cortex quantified using proton magnetic resonance spectroscopy (Study 3). RESULTS: SEM favored the five-factor and hierarchical models over the unidimensional and two-factor models regardless of the negative symptom measure or external validator. The five dimensions-anhedonia, asociality, avolition, blunted affect, and alogia-proved vital either as stand-alone domains or as first-order domains influenced by second-order dimensions-motivation and pleasure and emotional expression. The two broader dimensions sometimes masked important associations unique to the five narrower domains. Avolition, anhedonia, and blunted affect showed the most domain-specific associations with external variables across study samples. CONCLUSIONS: Five domains and a hierarchical model reflect the optimal conceptualization of negative symptoms in relation to external variables. Clinical trials should consider using the two dimensions as primary endpoints and the five domains as secondary endpoints.

Defining negative symptoms remission in schizophrenia using the Brief Negative Symptom Scale / Criterios de remisión de síntomas negativos utilizando la Escala Breve de Síntomas Negativos (BNSS)

Introduction: This study aimed to propose criteria for negative symptoms remission (NSR) in schizophrenia using the Brief Negative Symptom Scale (BNSS).Material and methods: 274 participants were assessed on the Positive and Negative Syndrome Scale (PANSS), BNSS and Social and Occupational Functioning Assessment Scale (SOFAS). Two criteria for NSR on the BNSS were proposed – NSR based on the BNSS domains scores (NSRBNSS_DOMAINS) and NSR based on 5 key items of the BNSS (NSRBNSS_5ITEMS). A SOFAS score of 61 and above was considered as functional remission (FR). Logistic regressions were run to examine the association between FR and NSR. Receiver operating characteristic (ROC) curve analysis was performed for the NSR criteria on FR. Kappa agreement statistic was used to evaluate the agreement between the two NSR criteria.Results: Eighty-nine (32.5%) participants fulfilled NSRBNSS_DOMAINS criterion whereas 70 (25.6%) participants fulfilled NSRBNSS_5ITEMS criterion. The two NSR criteria had substantial agreement (Kappa statistic=0.797) with each other. Sixty-one (25.3%) participants were in FR. FR was significantly associated with NSR, irrespective of the criterion used. To predict FR, the Area Under the Curve for NSRBNSS_DOMAINS and NSRBNSS_5ITEMS were 0.761 (CI: 0.696–0.826, p<0.001) and 0.723 (CI: 0.656–0.790, p<0.001), respectively. Hence, both NSR criteria demonstrated a fair ability to discriminate between functional remitters and non-remitters. Conclusions: Depending on the setting and needs, clinicians and researchers might employ either the full BNSS or an abbreviated 5-item BNSS scale to identify NSR in schizophrenia. More research is needed to further examine the validity of these criteria in schizophrenia. (AU)

Introducción: El objetivo de este estudio fue proponer criterios para la remisión de síntomas negativos (NSR) en la esquizofrenia utilizando la Escala Breve de Síntomas Negativos (BNSS). Material y métodos: 274 participantes fueron evaluados con la Escala de Síndrome Positivo y Negativo (PANSS), BNSS y la Escala de Evaluación del Funcionamiento Social y Ocupacional (SOFAS). Se propusieron dos criterios para NSR en el BNSS: NSR basado en las puntuaciones de los dominios BNSS (NSRBNSS_DOMAINS) y NSR basado en 5 elementos clave del BNSS (NSRBNSS_5ITEMS). Una puntuación SOFAS de 61 y superior se consideró como remisión funcional (FR). Se realizaron regresiones logísticas para examinar la asociación entre FR y NSR. El análisis de la curva de características operativas del receptor (ROC) se realizó para los criterios NSR en FR. Se utilizó la estadística de concordancia Kappa para evaluar la concordancia entre los dos criterios de NSR.Resultados: Ochenta y nueve (32,5%) participantes cumplieron el criterio NSRBNSS_DOMAINS mientras que 70 (25,6%) participantes cumplieron el criterio NSRBNSS_5ITEMS. Los dos criterios de NSR tuvieron un acuerdo sustancial (estadística Kappa = 0,797) entre sí. Sesenta y un (25,3%) participantes estaban en FR. La FR se asoció significativamente con la NSR, independientemente del criterio utilizado. Para predecir la FR, el área bajo la curva para NSRBNSS_DOMAINS y NSRBNSS_5ITEMS fueron 0,761 (IC: 0,696-0,826, p <0,001) y 0,723 (IC: 0,656-0,790, p <0,001), respectivamente. Por lo tanto, ambos criterios NSR demostraron una capacidad adecuada para discriminar entre remitentes funcionales y no remitentes. Conclusiones: Dependiendo del entorno y las necesidades, los médicos e investigadores pueden emplear la BNSS completa o una escala BNSS abreviada de 5 ítems para identificar la NSR en la esquizofrenia. Se necesita más investigación para examinar a fondo la validez de estos criterios en la esquizofrenia. (AU)

Early versus late risk factors for deficit and nondeficit schizophrenia / Factores de riesgo tempranos y tardíos para la esquizofrenia deficitaria y no deficitaria

Aim: We examined whether timing of known risk factors for schizophrenia may influence the development of schizophrenia with primary negative symptoms.Method:This cross-sectional single-centre study in England used a clinical cohort of 167 clozapine-treated schizophrenia patients. Deficit and nondeficit schizophrenia models were used as clinical proxies of patients with and without primary negative symptoms respectively. Patients were assessed using the Schedule for the Deficit Syndrome. We examined previously replicated risk factors (family history of psychosis, advanced paternal age, male gender, birth weight <3000g, summer birth, cannabis use, exposure to physical or sexual abuse and/or bullying) as well as other traumatic events for deficit and nondeficit schizophrenia.Results:We found a distinct risk factor pattern for the two groups. Compared to the nondeficit group, patients with deficit schizophrenia reported a significantly lower prevalence of cannabis use (p=0.005) at the time of first-episode psychosis (FEP), physical or sexual abuse (p=0.033) prior to FEP, less exposure to crime-related traumatic events (p=0.012) and significantly associated with summer birth (p=0.017). The groups did not differ in terms of family history of psychosis, advanced paternal age, male gender, or low birth weight. To account for multiple comparisons, a confirmatory analysis was performed using logistic regression which yielded similar results except that summer birth no longer reached statistical significance. (AU)

Objetivo: Examinamos si la cadencia en la aparición de los factores de riesgo conocidos para la esquizofrenia podría influir en el desarrollo de la esquizofrenia con síntomas negativos primarios.Método:Este estudio transversal en un centro en Inglaterra utilizó una cohorte clínica de 167 pacientes con esquizofrenia tratados con clozapina. Los criterios de esquizofrenia deficitaria y no deficitaria se utilizaron como aproximación clínica para categorizar pacientes con y sin síntomas negativos primarios, respectivamente. Los pacientes fueron evaluados utilizando el Inventario para la Esquizofrenia Deficitaria. Examinamos únicamente factores de riesgo previamente replicados (antecedentes familiares de psicosis, edad paterna avanzada, sexo masculino, peso al nacer <3.000g, nacimiento en verano, consumo de cannabis, exposición a abuso físico o sexual y/o acoso escolar), así como otros eventos traumáticos para la esquizofrenia deficitaria y la no deficitaria.Resultados:Encontramos un patrón de factores de riesgo distinto para los dos grupos. En comparación con el grupo sin déficit, los pacientes con esquizofrenia deficitaria presentaron una prevalencia significativamente menor de consumo de cannabis (p=0,005) en el momento del primer episodio de psicosis (PEP), mayor frecuencia de abuso físico o sexual (p=0,033) antes del PEP, menor exposición a eventos traumáticos relacionados con el crimen (p=0,012) y significativamente asociados con el nacimiento en verano (p=0,017). Los grupos no difirieron en términos de antecedentes familiares de psicosis, edad paterna avanzada, sexo masculino o bajo peso al nacer. Para tener en cuenta las comparaciones múltiples se realizó un análisis confirmatorio mediante regresión logística que arrojó resultados similares, excepto que el parto en verano ya no alcanzó significación estadística. (AU)

Machine Learning Identifies Digital Phenotyping Measures Most Relevant to Negative Symptoms in Psychotic Disorders: Implications for Clinical Trials.

BACKGROUND: Digital phenotyping has been proposed as a novel assessment tool for clinical trials targeting negative symptoms in psychotic disorders (PDs). However, it is unclear which digital phenotyping measurements are most appropriate for this purpose. AIMS: Machine learning was used to address this gap in the literature and determine whether: (1) diagnostic status could be classified from digital phenotyping measures relevant to negative symptoms and (2) the 5 negative symptom domains (anhedonia, avolition, asociality, alogia, and blunted affect) were differentially classified by active and passive digital phenotyping variables. METHODS: Participants included 52 outpatients with a PD and 55 healthy controls (CN) who completed 6 days of active (ecological momentary assessment surveys) and passive (geolocation, accelerometry) digital phenotyping data along with clinical ratings of negative symptoms. RESULTS: Machine learning algorithms classifying the presence of a PD diagnosis yielded 80% accuracy for cross-validation in H2O AutoML and 79% test accuracy in the Recursive Feature Elimination with Cross Validation feature selection model. Models classifying the presence vs absence of clinically significant elevations on each of the 5 negative symptom domains ranged in test accuracy from 73% to 91%. A few active and passive features were highly predictive of all 5 negative symptom domains; however, there were also unique predictors for each domain. CONCLUSIONS: These findings suggest that negative symptoms can be modeled from digital phenotyping data recorded in situ. Implications for selecting the most appropriate digital phenotyping variables for use as outcome measures in clinical trials targeting negative symptoms are discussed.