Psychiatric comorbidity is common in symptom-based diagnoses like autism spectrum disorder (ASD), attention/deficit hyper-activity disorder (ADHD), and obsessive-compulsive disorder (OCD). However, these co-occurring symptoms mediated by shared and/or distinct neural mechanisms are difficult to profile at the individual level. Capitalizing on unsupervised machine learning with a hierarchical Bayesian framework, we derived latent disease factors from resting-state functional connectivity data in a hybrid cohort of ASD and ADHD and delineated individual associations with dimensional symptoms based on canonical correlation analysis. Models based on the same factors generalized to previously unseen individuals in a subclinical cohort and one local OCD database with a subset of patients undergoing neurosurgical intervention. Four factors, identified as variably co-expressed in each patient, were significantly correlated with distinct symptom domains (r = -0.26-0.53, P < 0.05): behavioral regulation (Factor-1), communication (Factor-2), anxiety (Factor-3), adaptive behaviors (Factor-4). Moreover, we demonstrated Factor-1 expressed in patients with OCD and Factor-3 expressed in participants with anxiety, at the degree to which factor expression was significantly predictive of individual symptom scores (r = 0.18-0.5, P < 0.01). Importantly, peri-intervention changes in Factor-1 of OCD were associated with variable treatment outcomes (r = 0.39, P < 0.05). Our results indicate that these data-derived latent disease factors quantify individual factor expression to inform dimensional symptom and treatment outcomes across cohorts, which may promote quantitative psychiatric diagnosis and personalized intervention.
Humans ; Male ; Female ; Attention Deficit Disorder with Hyperactivity ; Obsessive-Compulsive Disorder ; Adult ; Autism Spectrum Disorder ; Bayes Theorem ; Adolescent ; Young Adult ; Magnetic Resonance Imaging ; Middle Aged ; Child ; Brain/metabolism* ; Cohort Studies ; Comorbidity

BACKGROUND/AIMS: Physical and/or emotional stresses are important factors in the exacerbation of symptoms in irritable bowel syndrome (IBS). Several lines of evidence support that a major impact of stress on the gastrointestinal tract occurs via the enteric nervous system. We aimed to evaluate histological changes in the submucosal plexus (SMP) and myenteric plexus (MP) of the distal ileum in concert with the intestinal motor function in a rat model of IBS with diarrhea. METHODS: The rat model was induced by heterotypic chronic and acute stress (CAS). The intestinal transit was measured by administering powdered carbon by gastric gavage. Double immunohistochemical fluorescence staining with whole-mount preparations of SMP and MP of enteric nervous system was used to assess changes in expression of choline acetyltransferase, vasoactive intestinal peptide, or nitric oxide synthase in relation to the pan neuronal marker, anti-Hu. RESULTS: The intestinal transit ratio increased significantly from control values of 50.8% to 60.6% in the CAS group. The numbers of enteric ganglia and neurons in the SMP were increased in the CAS group. The proportions of choline acetyltransferase- and vasoactive intestinal peptide-immunoreactive neurons in the SMP were increased (82.1 ± 4.3% vs. 76.0 ± 5.0%, P = 0.021; 40.5 ± 5.9% vs 28.9 ± 3.7%, P = 0.001), while nitric oxide synthase-immunoreactive neurons in the MP were decreased compared with controls (23.3 ± 4.5% vs 32.4 ± 4.5%, P = 0.002). CONCLUSIONS: These morphological changes in enteric neurons to CAS might contribute to the dysfunction in motility and secretion in IBS with diarrhea.
Animals ; Carbon ; Choline ; Choline O-Acetyltransferase ; Diarrhea* ; Enteric Nervous System ; Fluorescence ; Ganglia ; Gastrointestinal Motility ; Gastrointestinal Tract ; Ileum ; Intestine, Small* ; Irritable Bowel Syndrome* ; Models, Animal* ; Myenteric Plexus ; Neurons* ; Nitric Oxide ; Nitric Oxide Synthase ; Rats* ; Stress, Psychological ; Submucous Plexus ; Vasoactive Intestinal Peptide

Chemical and Drug Induced Liver Injury ; Dimethylformamide ; Humans ; Occupational Exposure

Chemical and Drug Induced Liver Injury ; Humans ; Thrombocytopenia

Objective To investigate the efficacy and safety of Minilase-S on patients with dyspepsia.Methods A randomized,placebo-controlled,double blind and multicenter study was conducted.Two hundred and forty patients with dyspepsia symptoms(anorexia,fullness,abdominal discomfort and distension)were collected according to total symptom scores over 20 with visual analog scales.Each patient was randomly received either Minilase-S(2 capsules t.i.d)or placebo(2 capsules t.i.d)for 2 weeks.The symptoms scores were evaluated at treatment week 1,week 2,and 1 week after discontinued therapy.Results Two hundred and sixteen patients(105 patients in Minilase group and 111 patients in placebo group)finished the study.There was no difference in demographic data,anorexia,fullness,discomfort and distension score and the total symptom score between two groups.However,at treatment week 1,week 2 and 1 week after discontinued therapy,symptoms and total symptom score were significantly decreased in Minilase-S group compared to placebo group(all P value＜0.05).The total effective rates in treatment week 1,week 2 and 1 week after discontinued therapy were 64.76%,77.05%and 66.99%,respectinely,which were higer that those in placebo group(27.93%,37.84% and 29.36%,respectively)(P＜0.05).There was no severe side effects in both Minilase-S and placebo groups.Conclusions Minilase-S can significantly improve symptoms in patients with dyspepsia,which may be as one choice in the management of dyspepsia or in combined therapy.