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Olfactory dysfunction is manifested in a wide range of neurological and psychiatric diseases, and often emerges prior to the onset of more classical symptoms and signs. From a behavioral perspective, olfactory deficits typically arise in conjunction with impairments of cognition, motivation, memory, and emotion. However, a conceptual framework for explaining the impact of olfactory processing on higher brain functions in health and disease remains lacking. Here we aim to provide circuit-level insights into this question by synthesizing recent advances in olfactory network connectivity with other cortical brain regions such as the prefrontal cortex. We will focus on social cognition as a representative model for exploring and critically evaluating the relationship between olfactory cortices and higher-order cortical regions in rodent models. Although rodents do not recapitulate all dimensions of human social cognition, they have experimentally accessible neural circuits and well-established behavioral tests for social motivation, memory/recognition, and hierarchy, which can be extrapolated to other species including humans. In particular, the medial prefrontal cortex (mPFC) has been recognized as a key brain region in mediating social cognition in both rodents and humans. This review will highlight the underappreciated connectivity, both anatomical and functional, between the olfactory system and mPFC circuitry, which together provide a neural substrate for olfactory modulation of social cognition and social behaviors. We will provide future perspectives on the functional investigation of the olfactory-mPFC circuit in rodent models and discuss how to translate such animal research to human studies.

Nitric oxide (NO) signalling has been implicated in the pathogenesis of several mental illnesses; however, its specific contribution remains unclear. We investigated whether peripheral NO concentration is associated with specific diagnoses, and whether there is a correlation with genetic variation in NO synthase (NOS) genes. We included 185 participants in the study; 52 healthy controls, 43 major depressive disorder (MDD) patients, 41 bipolar disorder (BPD) patients, and 49 schizophrenia (SCZ) patients. Clinical, genetic, and biochemical data were collected at admission to a psychiatric hospital and at discharge. Serum was used to quantify concentration of the stable NO metabolites nitrite and nitrate. Individuals were genotyped for the NOS1 exon 1f variable number of tandem repeats 1 (VNTR1) polymorphism, and single nucleotide polymorphisms (SNPs) in the NOS1, NOS1AP and NOS3 genes. At admission, SCZ patients were found to have significantly higher peripheral NO metabolite (NOx-) concentrations compared to healthy controls, MDD and BPD patients. NOS1 exon 1f VNTR1 short allele carriers were found to have significantly increased NOx- concentration. Moreover, this result was still significant in patients even at discharge. The data also revealed that patients who did not remit in their depressive symptoms had significantly increased NOx- concentration compared to remitters at discharge, supported by the finding of a significant positive correlation between depression symptom severity and NOx- concentration. Taken together, it is possible that elevated peripheral NOx- concentration is associated with increased severity of psychopathology, potentially due to NOS1 exon1f VNTR1 genotype. Our results further implicate NO signalling in mental illness pathogenesis, supporting its possible use as a peripheral biomarker, and imply that NOS genotype may play a significant role in regulating peripheral NOx- concentration.

Olfactory functional deficits have been reported in psychotic disorders. Olfactory dysfunction has a predictive value for prognosis and disease course. Thus, it is important to know which specific symptoms and cognitive changes are associated with olfactory dysfunction in early-stage psychosis. Deficits in social cognition are a difficult problem in psychosis. Here we conduct a detailed assessment of odor function and face processing and show that odor discrimination capacity is specifically associated with face processing function in patients with first episode psychosis. This finding indicates that the high-throughput olfactory assessment may aid a prediction of the difficult clinical dimension from early-stage psychosis.

PurposeTo develop a 3D downfield magnetic resonance spectroscopic imaging (DF-MRSI) protocol with whole brain coverage and post-processing pipeline for creation of metabolite maps.MethodsA 3D, circularly phase-encoded version of the previously developed 2D DF-MRSI sequence withspectral-spatial excitation and frequency selective refocusing was implemented and tested in 5 healthy volunteers at 3T. Downfield metabolite maps with a nominal spatial resolution of 0.7 cm3were recorded in 8 slices at 3T in a scan time of 22m 40s. An MRSI post-processing pipeline was developed to create DF metabolite maps. Metabolite concentrations and uncertainty estimates were compared between region differences for nine downfield peaks.ResultsLCModel analysis showed CRLB average values of 3-4% for protein amide resonances in the three selected regions (anterior cingulate (ACC), dorsolateral prefrontal cortex (DLPFC), and centrum semiovale (CSO)); CRLBs were somewhat higher for individual peaks but for the most part were less than 20%. While DF concentration maps were visually quite homogeneous throughout the brain, general linear regression analysis corrected for multiple comparisons found significant differences between CSO and DLPFC for peaks at 7.09 ppm (p= 0.014), 7.90 ppm (p=0.009), 8.18 ppm (p=0.009), combined amides (p=0.009), and between ACC and DLPFC for the 7.30 ppm peak (p=0.020). CRLB values were not significantly different between brain regions for any of the DF peaks.Conclusion3D DF-MRSI of the human brain at 3T with wide spatial coverage for the mapping of exchangeable amide and other resonances is feasible at a nominal spatial resolution of 0.7 cm3.

Olfactory dysfunction has been reproducibly reported in patients with psychosis. Consistently, some studies have reported structural abnormalities in the olfactory bulb (OB) in psychotic disorders with modest sample size. Air pollution and viral infections in the upper respiratory tract, including those of SARS-CoV-2, are reportedly risk factors for brain dysfunction and mental disorders. These risk factors can disturb the olfactory epithelium (OE) that is connected with the OB via direct neuronal projections. Nevertheless, it is unknown whether and how a disturbance of the OE could possibly affect the structure of OB in the pathophysiological context of psychotic disorders. To address this knowledge gap, we first utilized an inducible OE inflammation mouse model (IOI model) and found that OE inflammation could induce a significant reduction in the OB volume, shrinkage of the glomerular layer and the external plexiform layer of OB, and decrease in the immunoreactivity of OMP (olfactory sensory neuron marker), Vglut2 (glutamatergic presynaptic marker), CCK8 (tufted cell marker), and PGP9.5 (mitral cell marker) in the glomerular layer of OB in IOI mice compared to control mice. We then analyzed 3 Tesla magnetic resonance imaging and molecular expression profiles of olfactory neuronal cells (ONCs) biopsied from living human subjects. Interestingly, we also observed a significant reduction in the OB volume, as well as alterations in the expression profiles in ONCs in first episode psychosis (FEP) patients compared to healthy controls. Higher expression levels of IOI immune genes (genes coding immune-related transcription factors up-regulated in IOI mice) in ONCs was significantly associated with smaller volumes of the OB in FEP patients. The subgroup of FEP patients with an up-regulation of IOI immune genes had significantly smaller OB volumes than other FEP patients. Together, our study implied the existence and connections between OE and OB pathologies in psychotic disorders.

Background Previous studies have linked disturbances in the kynurenine pathway, responsible for the main catabolism of tryptophan and a key regulator of the immune system, to mental disorders such as major depressive disorder (MDD), bipolar disorder (BD) or schizophrenia (SCZ). However, the relationship between tryptophan catabolism and the presentation of psychiatric disorders seems to be rather complex, as up to now results have mostly been inconsistent or even contradictory. In this study, we measured plasma levels of tryptophan catabolites (TRYCATs: tryptophan, kynurenine, kynurenic acid and quinolinic acid) in a sample of in total 175 participants consisting of individuals suffering from an acute disease episode seeking inpatient treatment as well as healthy controls (HC) to investigate whether individual metabolites could serve as a biomarker for differential diagnosis. Results Significantly decreased levels of tryptophan, kynurenine, kynurenic acid and quinolinic acid were found in the patient group as a whole. This was mainly driven by the difference between BD patients and HC. Specifically, the manic symptom domain in manic and mixed phase BD patients displayed significantly lower kynurenine and kynurenic acid levels. We could not find significant differences between the psychiatric disorders disqualifying TRYCATs as biomarkers for differential diagnosis. None of the assessed potential demographic or pharmaceutical confounding factors revealed a significant correlation to TRYCAT concentrations. Upon reaching (partial) remission, the changes in TRYCAT levels partially normalized in the patient group. Conclusions Our data suggests an involvement of the kynurenine pathway in mental disorders, especially BD. Although we cannot prove a causal relationship, underlying mechanisms might include pro-inflammatory states in the central nervous system and/or increased neurotoxicity contributing to the immune assault. Also considering the manifold, but inconsistent previous analyses regarding TRYCAT concentrations in psychiatric disease, larger, cross-sectional and longitudinal studies will be needed for detangling the mystery about the role the tryptophan catabolism plays in the pathophysiology of mental disorders and for answering the burning question if it might constitute a possible therapeutic target in the future.

Olfactory dysfunction is reproducibly reported in psychotic disorders, particularly in association with negative symptoms. The superior frontal gyrus (SFG) has been frequently studied in patients with psychotic disorders, in particular with their associations with negative symptoms. The relationship between olfactory functions and brain structure has been studied in healthy controls (HCs). Nevertheless, the studies with patients with psychotic disorders are limited. Here we report the olfactory-brain relationship in a first episode psychosis (FEP) cohort through both hypothesis-driven (centred on the SFG) and data-driven approaches. Using data from 88 HCs and 76 FEP patients, we evaluated the correlation between olfactory functions and structural/resting-state functional magnetic resonance imaging (MRI) data. We found a significant correlation between the left SFG volume and odour discrimination in FEP patients, but not in HCs. We also observed a significant correlation between rs-fMRI connectivity involving the left SFG and odour discrimination in FEP patients, but not in HCs. The data-driven approach didn’t observe any significant correlations, possibly due to insufficient statistical power. The left SFG may be a promising brain region in the context of olfactory dysfunction and negative symptoms in FEP.

Background: Olfactory dysfunction has been reproducibly reported in patients with psychosis, including first episode psychosis (FEP) patients. Consistently, structural abnormalities in the olfactory bulb (OB), a key region of the peripheral olfactory system, have also been reported in psychotic disorders. Meanwhile, air pollution and viral infections in the upper respiratory tract, including those of SARS-CoV-2, are reportedly risk factors for brain dysfunction and mental disorders. These risk factors can disturb the olfactory epithelium (OE) that is located adjacent to the OB and connected via direct neuronal projections. Nevertheless, it is unknown how a disturbance of the OE possibly affects the OB in the pathophysiological context of psychotic disorders. Methods: We examined the volume of the OB in FEP patients and healthy controls from 3 Tesla magnetic resonance imaging and molecular expression profiles of olfactory neuronal cells (ONCs) enriched from freshly biopsied OE. Results: We observed a reduction of the OB volume in FEP patients compared with healthy controls. We also observed a significant alteration in gene expression profiles in the ONCs from FEP patients, supporting the pathological changes in the OE. Among such molecular changes, immune-related molecules and pathways were underscored in association with the OB volume changes in FEP patients. Conclusions: Our data support the OB and OE pathologies in FEP patients. Immune-related molecular changes in the OE can biologically link adverse factors in the nasal cavity, such as air pollution and viral infection, with the OB structural change, both of which have been reported for psychotic disorders.

Previous research has identified that patterns of cooccurring conditions (CoCs) associated with autism spectrum disorder (ASD) differ based on the presence of intellectual disability (ID). This study explored the association of documented CoCs among 8-year-old children with ASD and ID (ASD+ID, n = 2416) and ASD without ID (ASD-ID, n = 5372) identified by the Autism and Developmental Disabilities Monitoring Network, surveillance years (SYs) 2012 and 2014. After adjusting for demographic variables, record source, surveillance site, and SY, children with ASD+ID, as compared with children with ASD-ID, were more likely to have histories of nonspecific developmental delays and neurological disorders documented in their records but were less likely to have behavioral and psychiatric disorders. ID plays a key role on how children with ASD would experience other CoCs. Our results emphasize how understanding the pattern of CoCs in ASD+ID and ASD-ID can inform comprehensive and multidisciplinary approaches in assessment and management of children in order to develop targeted interventions to reduce possible CoCs or CoCs-related impairments.

Aims Autism Spectrum Disorder (ASD) is a disabling psychiatric disorder. About half of the ASD patients present with comorbid psychiatric disorders and may require inpatient psychiatric hospitalization during illness exacerbation ( Munesue et al., 2008 ). The present study examines the prevalence of co-existing psychiatric disorders among adult ASD patients admitted to a psychiatric safety-net hospital. Methods Patients admitted to UT Health Harris County Psychiatric Center between January 2012-December 2013 were enrolled (HSC-MS-14-0274) to the study. Patients diagnosed with ASD based on ICD-9 criteria were identified, and sociodemographic and clinical characteristics, including admission diagnoses, were documented. Patients diagnosed with ASD were then divided into three groups based on major admitting diagnosis (mood, psychosis, and other diagnoses) based upon ICD-9 criteria. Results Of 14,253 inpatients, 72 were diagnosed as ASD. 61.1 % of ASD patients had an admitting diagnosis of any mood disorders, 18.1 % with a co-morbid psychotic spectrum disorder, and 20.8 % with other co-morbid admitting disorders. Major diagnostic groups differed significantly for ASD and non-ASD patients (X2 = 540.247, p Conclusions 96.6 % of patients with ASD had a primary psychiatric disorder at admission, and the most common disorder was a mood disorder (61.1 %). Increased readmission rates among adult ASD patients may indicate a higher severity of their condition than those not diagnosed with ASD.

The National Curriculum in Reproductive Psychiatry (NCRP) provides standardized education for psychiatry residency training programs. The authors hypothesized that residents' preparedness to treat reproductive psychiatric concerns and their medical knowledge would improve following teaching with the NCRP.Pre- and post-assessments were administered to residents enrolled in two waves of pilot NCRP training (Early-Modules and All-Modules). Data were collected by individual survey, and pre- and post-responses matched via anonymous ID. Statistical analyses were conducted using R version 3.5.3 and included paired Student's t-tests and a chi-square test.Thirty-eight residents completed the Early-Modules survey and 16 the All-Modules survey. In both groups, there was significant improvement in preparedness to treat pregnant and postpartum women with mental illness (p0.05). Scores on the 29-point knowledge test rose by 2.5 points in the Early-Modules group and 4.3 points in the All-Modules group (p0.001 for both). In both cohorts, a majority of residents felt reproductive psychiatry was among the top three specialties needed to become competent independent adult psychiatrists.Classroom training with local faculty using a standardized curriculum is feasible and results in substantial and significant improvements in both feelings of preparedness and medical knowledge. Psychiatry trainees view training in reproductive psychiatry as an important and missing aspect of their education. Dissemination of a standardized curriculum may help to forge a path toward subspecialty certification for reproductive psychiatry, and can be used as a model for other specialties.

Physical inactivity is discussed as one of the most detrimental influences for lifestyle-related medical complications such as obesity, heart disease, hypertension, diabetes and premature mortality in in- and outpatients with major depressive disorder (MDD). In contrast, intervention studies indicate that moderate-to-vigorous-intensity physical activity (MVPA) might reduce complications and depression symptoms itself. Self-reported data on depression [Beck-Depression-Inventory-II (BDI-II)], general habitual well-being (FAHW), self-esteem and physical self-perception (FAHW, MSWS) were administrated in a cross-sectional study with 76 in- and outpatients with MDD. MVPA was documented using ActiGraph wGT3X + ® accelerometers and fitness was measured using cardiopulmonary exercise testing (CPET). Subgroups were built according to activity level (low PA defined as MVPA 45 min/day). Statistical analysis was performed using a Mann–Whitney U and Kruskal–Wallis test, Spearman correlation and mediation analysis. BDI-II scores and MVPA values of in- and outpatients were comparable, but fitness differed between the two groups. Analysis of the outpatient group showed a negative correlation between BDI-II and MVPA. No association of inpatient MVPA and psychopathology was found. General habitual well-being and self-esteem mediated the relationship between outpatient MVPA and BDI-II. The level of depression determined by the BDI-II score was significantly higher in the outpatient low- and moderate PA subgroups compared to outpatients with high PA. Fitness showed no association to depression symptoms or well-being. To ameliorate depressive symptoms of MDD outpatients, intervention strategies should promote habitual MVPA and exercise exceeding the duration recommended for general health (≥ 30 min/day). Further studies need to investigate sufficient MVPA strategies to impact MDD symptoms in inpatient settings. Exercise effects seem to be driven by changes of well-being rather than increased physical fitness.

BackgroundOlfactory dysfunction has been reproducibly reported in patients with psychosis, including first episode psychosis (FEP) patients. Consistently, structural abnormalities in the olfactory bulb (OB), a key region of the peripheral olfactory system, have also been reported in psychotic disorders. Meanwhile, air pollution and viral infections in the upper respiratory tract, including those of SARS-CoV-2, are reportedly risk factors for brain dysfunction and mental disorders. These risk factors can disturb the olfactory epithelium (OE) that is located adjacent to the OB and connected via direct neuronal projections. Nevertheless, it is unknown how a disturbance of the OE possibly affects the OB in the pathophysiological context of psychotic disorders.MethodsWe examined the volume of the OB in FEP patients and healthy controls from 3 Tesla magnetic resonance imaging and molecular expression profiles of olfactory neuronal cells (ONCs) enriched from freshly biopsied OE.ResultsWe observed a reduction of the OB volume in FEP patients compared with healthy controls. We also observed a significant alteration in gene expression profiles in the ONCs from FEP patients, supporting the pathological changes in the OE. Among such molecular changes, immune-related molecules and pathways were underscored in association with the OB volume changes in FEP patients.ConclusionsOur data support the OB and OE pathologies in FEP patients. Immune-related molecular changes in the OE can biologically link adverse factors in the nasal cavity, such as air pollution and viral infection, with the OB structural change, both of which have been reported for psychotic disorders.

The clinical importance of social cognition is well acknowledged in patients with psychosis, in particular those with first episode psychosis (FEP). Nevertheless, its brain substrates and circuitries remain elusive, lacking precise analysis between multimodal brain characteristics and behavioral sub-dimensions within social cognition. In the present study, we examined face processing of social cognition in 79 FEP patients and 80 healthy controls (HCs). We looked for a possible correlation between face processing and multimodal MRI characteristics such as resting-state functional connectivity (rsFC) and brain volume. We observed worse recognition accuracy, longer recognition response time, and longer memory response time in FEP patients when compared with HCs. Of these, memory response time was selectively correlated with specific rsFCs, which included the right subcallosal sub-region of BA24 in the ACC (scACC), only in FEP patients. The volume of this region was also correlated with memory response time in FEP patients. The scACC is functionally and structurally important in FEP-associated abnormalities of face processing measures in social cognition.

Interest in genetic testing and prophylactic surgery has increased in recent years. Going through a genetic test, making decisions following recommended guidelines, and prophylactic surgery are challenging for individuals. Psychiatric care and counseling for prophylactic surgery play a crucial role in the management of patients because of the high prevalence of mental disorders in the general population, and particularly, in individuals undergoing prophylactic surgery. Considering the high psychiatric comorbidity and its effect on decision-making, treatment, and outcome of prophylactic surgery patients, a comprehensive psychiatric assessment should be performed throughout the genetic counseling, pre, and postoperative setting. Screening patients for acute psychiatric disorders, observation of mental health status during genetic testing, decision-making, and in the pre and postoperative stages would support providing appropriate psychological and psychiatric services of persons at high-risk for psychological distress, identification of individuals with a co-occurring psychiatric disorder, and prevention of reoccurrence of a psychiatric disorder. We elaborate on these steps that would prevent complications and improve outcomes of patients undergoing prophylactic surgery.

Background An association between first-episode presentation of bipolar mania and concurrent cannabis use disorder has been well established in the current literature (Bally et al., 2014, Baethge et al., 2008). Previous studies have shown that 30–70% of patients admitted for a first manic episode had concurrent cannabis use (Bally et al., 2014). The exact mechanism of this association has yet to be confirmed. Aims We aim to evaluate the prevalence of cannabis use in patients with bipolar disorder (BD) admitted to UTHealth Harris County Psychiatric Center (HCPC) for a first manic episode. Methods In this retrospective cohort study, 15,969 inpatient records of patients admitted to HCPC between 2012–2013 were examined to identify patients admitted with a first manic episode according to ICD-9 criteria (single episode mania). The prevalence of multiple sociodemographic and clinical variables including cannabis positivity in urine drug screening (UDS) were examined. Results Twenty patients were admitted for a first manic episode. Half of the patients were females; mean age was 28.65 ± 10.56 years and mean length of stay (LOS) was 7.15 ± 3.72 days. Fifteen patients received a UDS. Of these fifteen, seven were positive for cannabinoids (47%). One patient was positive for phencyclidine (in addition to cannabis) and one patient was positive for amphetamine (but not cannabis). Conclusions The prevalence of cannabis use was higher in first-episode mania patients compared to the general population. The influence of cannabis on the first episode of mania requires additional study.