Personalized prediction of transcranial magnetic stimulation clinical response in patients with treatment-refractory depression using neuroimaging biomarkers and machine learning.

BACKGROUND: Functional connectivity between the left dorsolateral prefrontal cortex (DLPFC) and subgenual cingulate (sgACC) may serve as a biomarker for transcranial magnetic stimulation (rTMS) treatment response. The first aim was to establish whether this finding is veridical or artifactually induced by the pre-processing method. Furthermore, alternative biomarkers were identified and the clinical utility for personalized medicine was examined. METHODS: Resting-state fMRI data were collected in medication-refractory depressed patients (n = 70, 16 males) before undergoing neuronavigated left DLPFC rTMS. Seed-based analyses were performed with and without global signal regression pre-processing to identify biomarkers of short-term and long-term treatment response. Receiver Operating Characteristic curve and supervised machine learning analyses were applied to assess the clinical utility of these biomarkers for the classification of categorical rTMS response. RESULTS: Regardless of the pre-processing method, DLPFC-sgACC connectivity was not associated with treatment outcome. Instead, poorer connectivity between the sgACC and three clusters (peak locations: frontal pole, superior parietal lobule, occipital cortex) and DLPFC-central opercular cortex were observed in long-term nonresponders. The identified connections could serve as acceptable to excellent markers. Combining the features using supervised machine learning reached accuracy rates of 95.35% (CI=82.94-100.00) and 88.89% (CI=63.96-100.00) in the cross-validation and test dataset, respectively. LIMITATIONS: The sample size was moderate, and features for machine learning were based on group differences. CONCLUSIONS: Long-term nonresponders showed greater disrupted connectivity in regions involving the central executive network. Our findings may aid the development of personalized medicine for medication-refractory depression.

Associations between Gastro-oesophageal Reflux Disease, Generalised Anxiety Disorder, Major Depressive Episodes, and Healthcare Utilisation: a Community-based Study.

OBJECTIVE: To examine the prevalence and comorbidity of gastro-oesophageal reflux disease (GORD) with generalised anxiety disorder (GAD) and major depressive episodes (MDE) in a general population using DSM-IV, and to evaluate the associations between these conditions and healthcare utilisation. METHODS: A random population-based telephone survey was conducted to record frequency of GORD symptoms, symptoms of GAD and MDE based on DSM-IV, and healthcare utilisation. RESULTS: Of 2011 respondents, 4.2% had weekly GORD and 13.9% had monthly GORD, whereas 3.8% reported GAD and 12.4% reported MDE. Those with monthly GORD had higher risk of GAD (p = 0.01) and MDE (p < 0.001). GORD symptom frequency was independently correlated with MDE and GAD in a dose-response manner. The number of psychiatric diagnoses was independently correlated with GORD. GORD symptom frequency, GAD, and MDE were correlated with consultation frequency. GORD symptom frequency was corelated with high investigation expenditure. CONCLUSION: GORD had a strong dose-response relationship with GAD and MDE in a Hong Kong population. Excessive healthcare utilisation should alert clinicians to the risk of psychiatric comorbidity.

Neurocognitive Characteristics of Individuals with Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is a systems-based brain-gut axis disorder. Cognitive functions reflect central affective and attentional processes that are driven by genetic and epigenetic influences and effect complex brain-gut interactions. These interactions include stress-induced changes in hypothalamic-pituitary-adrenal axis and autonomic nervous system, remodelling of the immune system, and alterations in microbiota composition. This review summarises current neurocognitive findings on patients with IBS. 13 studies of neurocognition in IBS patients were identified from PubMed, Ovid MEDLINE, EMBASE, and PsycINFO. The methodology and relevant findings were systematically analysed. There are alterations in both hot and cold cognitions in IBS patients. Consistently, attentional bias towards negative emotionally valenced and gastrointestinal symptom-related stimuli is found in hot cognition tasks, with other cold cognition differences including frontal executive dysfunction and stress-related hippocampal-mediated cognitive alterations. The effect of psychiatric comorbidity on a disorder level, as well as illness chronicity, on cognitive alterations requires further examination. Attentional bias and executive dysfunction in IBS gave support to its neural network alterations accounting for visceral hypersensitivity. Further prospective neuropsychological studies should examine the effect of chronicity, current symptom severity, and psychiatric comorbidity on the cognition in different IBS subtypes.

Up-regulation of transient receptor potential vanilloid (TRPV) and down-regulation of brain-derived neurotrophic factor (BDNF) expression in patients with functional dyspepsia (FD).

BACKGROUND: The role of immune activation in Functional Dyspepsia (FD) patients without previous infection is unclear. We compare the gastric and circulating brain-derived neurotropic factor (BDNF), receptor potential vanilloid type (TRPV) families and various cytokines in FD patients. METHODS: Consecutive adult FD patients (Rome III) with no recent history of gastroenteritis and asymptomatic healthy controls were recruited for upper endoscopy. Subjects with GERD and IBS as predominant symptoms, diabetes mellitus, current or previous Helicobacter pylori infection, psychiatric illness and recent use of NSAID or PPI were excluded. Corpus biopsies and serum samples were collected. KEY RESULTS: Forty three [M:F=8:35, mean age: 35.0 (9.3)] FD patients were compared with 23 healthy controls [M:F=8:15, mean age: 36.6 (10.2)]. FD patients had postprandial distress syndrome (PDS) as predominant sub-type (PDS: 36, EPS: 2). There was no significant difference in the median inflammation score (FD:0 (0-1) vs Control:0 (0-1), P=.79). However, FD patients had significantly higher mRNA expression of TRPV1 (FD:0.014±0.007, Control:0.003±0.001, 4.6 fold, P=.02) and TRPV2 (FD:0.012±0.006, Control:0.003±0.001, 4 fold, P=.02) compared to controls. The serum (FD:258.0±12.3 ng ml-1 , Control:319.7±18.1 ng ml-1 , P<.01) and gastric BDNF mRNA (FD:0.06±0.008, Control:0.092±0.01, 0.65 fold, P=.02)levels significantly lower in FD patients. Secretion of cytokines (IL-4, IL-5, IL-6, IL-8, IL-10, G-CSF, TGF-ß2, MCP-1)was also highly correlated with dyspeptic symptoms in patients with FD. CONCLUSIONS & INFERENCES: Despite lacking gastric mucosal inflammation, up-regulation of TRPV1 and TRPV2, down-regulation of BDNF were observed in FD patients. These suggest that immune alteration may contribute to the pathogenesis of FD without any previous infection.

Dyspepsia is strongly associated with major depression and generalised anxiety disorder - a community study.

BACKGROUND: The relationship between dyspepsia and psychiatric comorbidity such as anxiety and depression is poorly defined. Previous studies have been limited by lack of standardised diagnostic criteria. AIM: To examine the prevalence and comorbidity of dyspepsia as defined by Rome III (6-month duration) with DSM-IV-TR generalised anxiety disorder (GAD) and major depressive episodes (MDE) in the general population. METHODS: A random population-based telephone survey was done using a questionnaire on symptoms of Rome III Dyspepsia, DSM-IV-TR GAD and MDE and their chronological relationship. RESULTS: Of the 2011 respondents 8.0% currently had Rome III Dyspepsia, 3.8% reported GAD and 12.4% reported MDE respectively. Dyspeptic subjects had a twofold increased risk of GAD (OR = 2.03, 95% CI: 1.06-3.89, P < 0.001) and a threefold increased risk of MDE (OR = 3.56, 95% CI: 2.33-5.43, P < 0.001). MDE and GAD most often coincided with dyspepsia in onset. Dyspepsia (OR = 2.48, 95% CI: 1.65-3.72 P < 0.001), MDE (OR = 2.39, 95% CI: 1.64-3.46, P < 0.001) and female sex (OR = 1.65, 95% CI: 1.21-2.23, P < 0.001) independently predicted frequent medical consultations. GAD independently predicted high investigation expenditure (OR = 4.65, 95% CI: 1.15-18.70, P = 0.03). CONCLUSIONS: With stringently adopted Rome III and DSM-IV-TR criteria, dyspepsia was strongly associated and often coincident in onset with generalised anxiety disorder and major depressive episodes in the community. Excessive healthcare utilisation should alert clinicians to risk of psychiatric comorbidity.