Neurobiological support to the diagnosis of ADHD in stimulant-naïve adults: pattern recognition analyses of MRI data.

OBJECTIVE: In adulthood, the diagnosis of attention-deficit/hyperactivity disorder (ADHD) has been subject of recent controversy. We searched for a neuroanatomical signature associated with ADHD spectrum symptoms in adults by applying, for the first time, machine learning-based pattern classification methods to structural MRI and diffusion tensor imaging (DTI) data obtained from stimulant-naïve adults with childhood-onset ADHD and healthy controls (HC). METHOD: Sixty-seven ADHD patients and 66 HC underwent high-resolution T1-weighted and DTI acquisitions. A support vector machine (SVM) classifier with a non-linear kernel was applied on multimodal image features extracted on regions of interest placed across the whole brain. RESULTS: The discrimination between a mixed-gender ADHD subgroup and individually matched HC (n = 58 each) yielded area-under-the-curve (AUC) and diagnostic accuracy (DA) values of up to 0.71% and 66% (P = 0.003) respectively. AUC and DA values increased to 0.74% and 74% (P = 0.0001) when analyses were restricted to males (52 ADHD vs. 44 HC). CONCLUSION: Although not at the level of clinically definitive DA, the neuroanatomical signature identified herein may provide additional, objective information that could influence treatment decisions in adults with ADHD spectrum symptoms.

State-dependent microstructural white matter changes in drug-naïve patients with first-episode psychosis.

BACKGROUND: Diffusion tensor imaging (DTI) studies have consistently shown white matter (WM) microstructural abnormalities in schizophrenia. Whether or not such alterations could vary depending on clinical status (i.e. acute psychosis v. remission) remains to be investigated. METHODS: Twenty-five treatment-naïve first-episode psychosis (FEP) patients and 51 healthy-controls (HC) underwent MRI scanning at baseline. Twenty-one patients were re-scanned as soon as they achieved sustained remission of symptoms; 36 HC were also scanned twice. Rate-of-change maps of longitudinal DTI changes were calculated for in order to examine WM alterations associated with changes in clinical status. We conducted voxelwise analyses of fractional anisotropy (FA) and trace (TR) maps. RESULTS: At baseline, FEP presented reductions of FA in comparison with HC [p < 0.05, false-discovery rate (FDR)-corrected] affecting fronto-limbic WM and associative, projective and commissural fasciculi. After symptom remission, patients showed FA increase over time (p < 0.001, uncorrected) in some of the above WM tracts, namely the right anterior thalamic radiation, right uncinate fasciculus/inferior fronto-occipital fasciculus, and left inferior fronto-occipital fasciculus/inferior longitudinal fasciculus. We also found significant correlations between reductions in PANSS scores and FA increases over time (p < 0.05, FDR-corrected). CONCLUSIONS: WM changes affecting brain tracts critical to the integration of perceptual information, cognition and emotions are detectable soon after the onset of FEP and may partially reverse in direct relation to the remission of acute psychotic symptoms. Our findings reinforce the view that WM abnormalities in brain tracts are a key neurobiological feature of acute psychotic disorders, and recovery from such WM pathology can lead to amelioration of symptoms.

A Selective Association between Central and Peripheral Lithium Levels in Remitters in Bipolar Depression: A 3T-(7) Li Magnetic Resonance Spectroscopy Study.

OBJECTIVE: The objective of this study was to evaluate brain lithium levels using (7) Li magnetic resonance spectroscopy after 6 weeks of lithium therapy in bipolar depression to test the hypothesis that brain and plasma lithium are correlated. It was also tested whether responders and remitters have different pharmacokinetics, blood and brain lithium levels (ratio) compared with those presenting suboptimal antidepressant improvement. METHOD: Twenty-three patients with bipolar disorder (I and II) during depressive episodes were included and followed up for 6 weeks at the University of Sao Paulo using flexible dose of lithium (450-900 mg/day). Sixteen patients were drug-naïve. At endpoint, patients underwent a (7) Li-MRS scan and brain lithium concentrations were calculated. RESULTS: A significant association between central and peripheral lithium levels was found only in remitters (r = 0.7, P = 0.004) but not in non-remitters (r = -0.12, P = 0.76). Also, brain lithium (but not plasma) was inversely correlated with age (r = -0.46, P = 0.025). Plasma lithium did not correlate with any clinical outcome, lithium dosage or adverse effects. CONCLUSION: These findings suggest that non-remitters may not transport lithium properly to the brain, which may underlie treatment resistance to lithium in BD. Future studies with (7) Li-MRS integrated with the evaluation of blood-brain barrier transport mechanisms and longitudinal clinical outcomes in BD and aging are warranted.

Cytochrome P450 genotypes are not associated with refractoriness to antipsychotic treatment.

Evidence validating the influence of the cytochrome P450 (CYP) 2D6 and 2C19 enzymes genetic polymorphisms in the response to antipsychotics is scarce. We examined the hypothesis that a higher prevalence of CYP2D6 and/or CYP2C19 ultra rapid metabolizers might be found among refractory schizophrenia patients. Three groups were studied: refractory and non-refractory schizophrenia patients, and healthy controls. Participants were genotyped for CYP2D6 and CYP2C19 polymorphisms and classified in metabolic phenotypes. No between-group differences in the distribution of the phenotypes were found. Therefore, our findings do not support the CYPs 2D6 and 2C19 genotyping in the prediction of therapeutic response in schizophrenia.

What determines continuing grey matter changes in first-episode schizophrenia and affective psychosis?

BACKGROUND: Magnetic resonance imaging (MRI) studies have shown that brain abnormalities in psychosis might be progressive during the first years of illness. We sought to determine whether first-episode psychosis (FEP) subjects show progressive regional grey matter (GM) changes compared with controls, and whether those changes are associated with diagnosis, illness course or antipsychotic (AP) use. METHOD: Thirty-two subjects with first-episode schizophrenia-spectrum disorders (FESZ), 24 patients with first-episode affective psychoses (FEAP) and 34 controls recruited using a population-based design underwent structural MRI scanning at baseline and at a 5-year follow-up. Regional GM volumes were assessed with voxel-based morphometry (VBM). Patients were treated at community settings, and about half of them remained mainly untreated. RESULTS: No significant progressive changes in GM regional volumes were observed in either the FESZ or FEAP group overall. However, FESZ subjects with a non-remitting course showed GM decrements in the left superior temporal gyrus (STG) and insula relative to remitted FESZ subjects. Non-remitted FEAP subjects exhibited a GM decrease in the dorsolateral prefrontal cortex (DLPFC) bilaterally in comparison to remitted FEAP subjects. Among FESZ subjects, AP use was associated with regional GM decrements in the right insula and increments in the cerebellum. CONCLUSIONS: Our results suggest that the progression of brain abnormalities in FEP subjects is restricted to those with a poor outcome and differs between diagnosis subgroups. AP intake is associated with a different pattern of GM reductions over time.

Accuracy of a new monoclonal stool antigen test in post-eradication assessment of Helicobacter pylori infection: comparison with the polyclonal stool antigen test and urea breath test.

BACKGROUND AND AIM: The enzyme immunoassay based on polyclonal antibodies (HpSA) represents a valid method for the detection of Helicobacter pylori antigens in stool specimens, but some controversial results were reported in post-eradication setting. A new monoclonal enzyme immunoassay (FemtoLab H. pylori, Connex) has been developed. The present study compares the diagnostic accuracy of the two tests after eradication therapy. PATIENTS AND METHODS: Stool samples were collected and urea breath test and endoscopy performed in 325 patients (161 F, 164 M, age 17-78 years), 4-8 weeks after standard triple eradication therapy. The FemtoLab and HpSA tests were performed in accordance with the manufacturer's protocol. H. pylori infection was confirmed if culture alone or both urease test and histology were positive and was considered absent if all three tests were negative. RESULTS: H. pylori was eradicated in 231 patients (71.1%). Urea breath test showed the best performances with sensitivity 98.9% and specificity 99.5%. The sensitivity of FemtoLab was 88.3%, specificity 94.8%, positive and negative predictive values 87.4% and 95.2%. Corresponding HpSA values were 73.4%, 97.8%, 93.2% and 90%. Sensitivity and negative predictive value of FemtoLab were significantly better than HpSA. Adjusting the cut-offs according to a ROC curve improved not significantly the sensitivity of the two tests. CONCLUSIONS: Urea breath test shows the best accuracy in the assessment of H. pylori infection. Between the stool tests, the FemtoLab due to its higher sensitivity is to prefer in the post-eradication assessment of H. pylori infection.

Relationship between intestinal metaplasia of the gastro-oesophageal junction, Helicobacter pylori infection and gastro-oesophageal reflux disease: a prospective study.

BACKGROUND: The role of Helicobacter pylori infection and/or gastro-oesophageal reflux disease in pathogenesis of intestinal metaplasia in gastric cardia is still unclear. AIMS: To prospectively evaluate prevalence of inflammation and intestinal metaplasia of cardia in relationship to Helicobacter pylori infection in patients with gastro-oesophageal reflux disease and in healthy controls. PATIENTS: A total of 122 consecutive patients with gastro-oesophageal reflux disease and 49 control subjects were included. METHODS: During endoscopy, a total of six biopsies were taken from antrum, corpus and cardia. Helicobacter pylori infection was assessed by histology and rapid urease test. Degree of chronic gastritis, inflammatory activity and Helicobacter pylori colonization were scored from 0 to 3. RESULTS: No difference in prevalence was observed between gastro-oesophageal reflux disease patients and controls as far as concerns Helicobacter pylori (41% vs 38%), inflammation of cardia (59.5% vs 70%) and intestinal metaplasia of cardia (18% vs 19%). Inflammation of cardia was significantly (p<0.001) associated with Helicobacter pylori irrespective of gastro-oesophageal reflux disease symptoms. Cardial intestinal metaplasia was more frequently (p=0.03) found in infected subjects ((27%) than in uncolonized subjects (13%). No relationship was observed between gastro-oesophageal reflux disease and carditis and cardial intestinal metaplasia. Cardial intestinal metaplasia was more frequently detected in association with carditis (26% vs 6%, p=0.001). CONCLUSIONS: Inflammation and intestinal metaplasia of the gastric cardia are not markers of gastro-oesophageal reflux disease but are related to Helicobacter pylori.

Omeprazole-based dual and triple therapy for the treatment of Helicobacter pylori infection in peptic ulcer disease: a randomized trial.

OBJECTIVES: It was our goal to evaluate the efficacy and safety and patient compliance with omeprazole-based dual and triple therapy for eradication of Helicobacter pylori in peptic ulcer disease. MATERIALS AND METHODS: One hundred seventy-five consecutive patients with H. pylori infection and associated active peptic ulcer were included. H. pylori infection was assessed by rapid urease test and histological analysis. Patients were randomized among three treatments: group 1 (56 patients): omeprazole, 20 mg bid, and amoxicillin, 1 gm bid, for 2 weeks; group 2 (61 patients): omeprazole, 20 mg bid, plus amoxicillin, 1 gm bid, and metronidazole, 500 mg bid, for 1 week; and group 3 (58 patients): omeprazole, 20 mg bid, plus amoxicillin, 1 gm bid, and clarithromycin, 500 mg bid, for 1 week. Ulcer healing and cure of infection were evaluated at 4 to 6 weeks after cessation of therapy. Eradication rate was calculated per-protocol and by an intention-to-treat analysis. RESULTS: At posttreatment endoscopy, duodenal ulcer was healed in 98.3% of patients. Eleven patients (6%) were lost to follow-up. H. pylori infection was treated successfully in 55% (95% confidence interval [CI] = 41%-69%) of patients of group 1; 86% (95% CI = 77%-95%) of group 2 (p < .001 vs. group 1); and 93% (95% CI = 85%-100%) of group 3 (p < .001 vs. group 1). On intention-to-treat analysis, eradication was 52%, 80%, and 86% in groups 1, 2, and 3, respectively. A good compliance was observed in more than 90% of patients of all groups. Side effects were reported by 7% of patients in group 1, 9% in group 2, and 11% in group 3. None of the patients stopped therapy because of side effects. CONCLUSIONS: Dual-therapy omeprazole-amoxicillin for 2 weeks is associated with significantly lower eradication rate than is 1-week omeprazole-based triple therapies. Triple therapy is well-tolerated and produces side effects similar to those of dual therapy. The highest cure rate of H. pylori infection was achieved with triple therapy of omeprazole, amoxicillin, and clarithromycin for 1 week.