Faculty Bibliography
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person:malasd01
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347
Gut and oral microbiome modulate molecular and clinical markers of schizophrenia-related symptoms: A transdiagnostic, multilevel pilot study
Although increasing evidence links microbial dysbiosis with the risk for psychiatric symptoms through the microbiome-gut-brain axis (MGBA), the specific mechanisms remain poorly characterized. In a diagnostically heterogeneous group of treated psychiatric cases and nonpsychiatric controls, we characterized the gut and oral microbiome, plasma cytokines, and hippocampal inflammatory processes via proton magnetic resonance spectroscopic imaging (1H-MRSI). Using a transdiagnostic approach, these data were examined in association with schizophrenia-related symptoms measured by the Positive and Negative Syndrome Scale (PANSS). Psychiatric cases had significantly greater heterogeneity of gut alpha diversity and an enrichment of pathogenic taxa, like Veillonella and Prevotella, in the oral microbiome, which was an accurate classifier of phenotype. Cases exhibited significantly greater positive, negative, and general PANSS scores that uniquely correlated with bacterial taxa. Strong, positive correlations of bacterial taxa were also found with cytokines and hippocampal gliosis, dysmyelination, and excitatory neurotransmission. This pilot study supports the hypothesis that the MGBA influences psychiatric symptomatology in a transdiagnostic manner. The relative importance of the oral microbiome in peripheral and hippocampal inflammatory pathways was highlighted, suggesting opportunities for probiotics and oral health to diagnose and treat psychiatric conditions.
PMID: 37331068
ISSN: 1872-7123
CID: 5542462
Baroreflex sensitivity is associated with markers of hippocampal gliosis and dysmyelination in patients with psychosis
PURPOSE:Hippocampal dysfunction plays a key role in the pathology of psychosis. Given hippocampal sensitivity to changes in cerebral perfusion, decreased baroreflex function could contribute to psychosis pathogenesis. This study had two aims: (1) To compare baroreflex sensitivity in participants with psychosis to two control groups: participants with a nonpsychotic affective disorder and participants with no history of psychiatric disease; (2) to examine the relationship between hippocampal neurometabolites and baroreflex sensitivities in these three groups. We hypothesized that baroreflex sensitivity would be reduced and correlated with hippocampal neurometabolite levels in participants with psychosis, but not in the control groups. METHODS:-MR spectroscopic (MRS) imaging and were compared with baroreflex sensitivities in the three groups. RESULTS:Vagal baroreflex sensitivity (BRS-V) was reduced in a significantly larger proportion of participants with psychosis compared with patients with nonpsychotic affective disorders, whereas participants with psychosis had increased adrenergic baroreflex sensitivity (BRS-A) compared with participants with no history of psychiatric disease. Only in psychotic cases were baroreflex sensitivities associated with hippocampal metabolite concentrations. Specifically, BRS-V was inversely correlated with myo-inositol, a marker of gliosis, and BRS-A was positively correlated with energy dependent dysmyelination (choline, creatine) and excitatory activity (GLX). CONCLUSIONS:Abnormal baroreflex sensitivity is common in participants with psychosis and is associated with MRS markers of hippocampal pathology. Future longitudinal studies are needed to examine causality.
PMID: 36877302
ISSN: 1619-1560
CID: 5542032
Early trauma and schizophrenia onset: preliminary results of an outpatient cohort in Brazil
OBJECTIVE:To assess the prevalence of early trauma in individuals with onset of schizophrenia at early (≤ 18 years) and adult (> 18 years) ages (EOP and AOP, respectively). and explore relationship between the onset of disease and clinical variables, including traumatic events, psychotic and mood symptoms. METHODS:Subjects with SZ (n=71) and EOP and AOP were compared for the history of psychological trauma, sexual abuse, and physical punishment through the Early Trauma Inventory Self Report - Short Form (ETISR-SF); a history of comorbidities and affective disorders through the Diagnostic Interview for Psychosis and Affective Disorders, Positive and Negative Syndrome Scale, Liebowitz Social Anxiety Scale and the Calgary Depression Scale for Schizophrenia was correlated with the disease duration. RESULTS:Early trauma was significantly associated with an early onset psychotic episode (r = -0.315, p < 0.01). General trauma and depressive symptoms in adulthood were also associated (r = 0.442, p < 0.01), as well as social anxiety symptoms and early trauma (r = 0.319, p < 0.01). ETISR-SF global scores and the psychical abuse item were significantly higher in the EOP than in the AOP. In the hierarchical regression, PANSS scores were better predicted by the duration of disease and age of first psychotic episode (R=0.303). CONCLUSIONS:Our results support the hypothesis that early trauma, including physical abuse, may play a relevant role in schizophrenia symptoms, such as an earlier psychotic occurrence, as well as features of other psychiatric disorders, such as greater severity of social anxiety and depression.
PMID: 33872478
ISSN: 2238-0019
CID: 4846822
An integrative study of the microbiome gut-brain-axis and hippocampal inflammation in psychosis: Persistent effects from mode of birth
The mechanism producing psychosis appears to include hippocampal inflammation, which could be associated with the microbiome-gut-brain-axis (MGBS). To test this hypothesis we are conducting a multidisciplinary study, herein described. The procedures are illustrated with testing of a single subject and group level information on the impact of C-section birth are presented.
PMID: 34625336
ISSN: 1573-2509
CID: 5067852
Patient-reported exposures and outcomes link the gut-brain axis and inflammatory pathways to specific symptoms of severe mental illness
We developed a "gut-brain-axis questionnaire" (GBAQ) to obtain standardized person-specific "review of systems" data for microbiome-gut-brain-axis studies. Individual items were compared to PANSS symptom measures using dimensional, transdiagnostic and traditional categorical approaches.
PMID: 35462090
ISSN: 1872-7123
CID: 5217222
Neural correlates of negative and disease-specific emotional stimuli in panic disorder: a functional magnetic resonance imaging study
OBJECTIVE:Decades of research have highlighted the involvement of the prefrontal cortex, anterior cingulated cortex, and limbic areas (amygdala) in panic disorder (PD). However, little attention has been given specifically to the inferior frontal gyrus. The current study aimed to investigate the neural substrates, including the inferior frontal gyrus, of both panic-related and negative conditions among individuals with PD and healthy controls. METHODS:We examined 13 medication-free PD patients and 14 healthy controls with functional magnetic resonance imaging (fMRI) during exposure to negative and neutral pictures and a set of specific panic-related pictures. RESULTS:Subtraction between the conditions indicated activation of the left amygdala region and the right inferior frontal gyrus in PD patients during the specific panic-related condition, whereas the left amygdalar region and left inferior frontal gyrus were activated during the negative condition in controls. CONCLUSION/CONCLUSIONS:These results suggest that in patients with PD, a prominent bottom-up process is involved in specific panic-related conditions, which might be associated with weak modulation of the left frontal area. These data add to our current understanding of the neural correlates of PD and can contribute to future clinical interventions targeting the functional reestablishment of these regions.
PMID: 33787758
ISSN: 1809-452x
CID: 4830832
The kids are not alright: A preliminary report of Post-COVID syndrome in university students
OBJECTIVE/UNASSIGNED:To investigate the prevalence and features of protracted COVID-19 symptoms in non-hospitalized university students who experienced mild-to-moderate acute illness. PARTICIPANTS/UNASSIGNED: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/UNASSIGNED:Students completed online study to earn research credit for class. RESULTS/UNASSIGNED: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/UNASSIGNED: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.
PMID: 34242539
ISSN: 1940-3208
CID: 4933652
Letter to the Editor
PMID: 34128057
ISSN: 1745-1701
CID: 4911542
Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.
PMID: 34002096
ISSN: 1546-1718
CID: 4876872
World psychiatry : official journal of the World Psychiatric Association (WPA). 2021:20(1):4-33.DOI: 10.1002/wps.20809
The clinical characterization of the patient with primary psychosis aimed at personalization of management
The current management of patients with primary psychosis worldwide is often remarkably stereotyped. In almost all cases an antipsychotic medica-tion is prescribed, with second-generation antipsychotics usually preferred to first-generation ones. Cognitive behavioral therapy is rarely used in the vast majority of countries, although there is evidence to support its efficacy. Psychosocial interventions are often provided, especially in chronic cases, but those applied are frequently not validated by research. Evidence-based family interventions and supported employment programs are seldom implemented in ordinary practice. Although the notion that patients with primary psychosis are at increased risk for cardiovascular diseases and diabetes mellitus is widely shared, it is not frequent that appropriate measures be implemented to address this problem. The view that the management of the patient with primary psychosis should be personalized is endorsed by the vast majority of clinicians, but this personalization is lacking or inadequate in most clinical contexts. Although many mental health services would declare themselves "recovery-oriented", it is not common that a focus on empowerment, identity, meaning and resilience is ensured in ordinary practice. The present paper aims to address this situation. It describes systematically the salient domains that should be considered in the characterization of the individual patient with primary psychosis aimed at personalization of management. These include positive and negative symptom dimensions, other psychopathological components, onset and course, neurocognition and social cognition, neurodevelopmental indicators; social functioning, quality of life and unmet needs; clinical staging, antecedent and concomitant psychiatric conditions, physical comorbidities, family history, history of obstetric complications, early and recent environmental exposures, protective factors and resilience, and internalized stigma. For each domain, simple assessment instruments are identified that could be considered for use in clinical practice and included in standardized decision tools. A management of primary psychosis is encouraged which takes into account all the available treatment modalities whose efficacy is supported by research evidence, selects and modulates them in the individual patient on the basis of the clinical characterization, addresses the patient's needs in terms of employment, housing, self-care, social relationships and education, and offers a focus on identity, meaning and resilience.
PMID: 33432763
ISSN: 1723-8617
CID: 4746662
