MR spectroscopy frequency and phase correction using convolutional neural networks.

PURPOSE: To introduce a novel convolutional neural network (CNN)-based approach for frequency-and-phase correction (FPC) of MR spectroscopy (MRS) spectra to achieve fast and accurate FPC of single-voxel MEGA-PRESS MRS data. METHODS: Two neural networks (one for frequency and one for phase) were trained and validated using published simulated and in vivo MEGA-PRESS MRS dataset with wide-range artificial frequency and phase offsets applied. The CNN-based approach was subsequently tested and compared to the current deep learning solution: multilayer perceptrons (MLP). Furthermore, random noise was added to the original simulated dataset to further investigate the model performance at varied signal-to-noise ratio (SNR) levels (i.e., 10, 5, and 2.5). Additional frequency and phase offsets (i.e., small, moderate, large) were also applied to the in vivo dataset, and the CNN model was compared to the conventional approach SR and model-based SR implementation (mSR). RESULTS: The CNN model is more robust to noise compared to the MLP-based approach due to having smaller mean absolute errors in both frequency (0.01 ± 0.01 Hz at SNR = 10 and 0.01 ± 0.02 Hz at SNR = 2.5) and phase (0.12 ± 0.09° at SNR = 10 and -0.07 ± 0.44° at SNR = 2.5) offset prediction. Furthermore, better performance was demonstrated for FPC when compared to the MLP-based approach, and SR when applied to the in vivo dataset for both with and without additional offsets. CONCLUSION: A CNN-based approach provides a solution to the automated preprocessing of MRS data, and the experimental results demonstrate the quantitatively improved spectra quality compared to the state-of-the-art approach.

Genetic interactions in the adrenergic system genes: analysis of antipsychotic-induced weight gain.

UNLABELLED: Atypical antipsychotics (AP) have high affinity for many neurotransmitter receptors. Among these receptors, APs are antagonist at α-adrenergic and ß-adrenergic receptors, and this pharmacological property has been postulated to be involved in the mechanism of action of these drugs with respect to both clinical response and adverse effects. OBJECTIVE: We tested the hypotheses that AP-induced weight gain is associated with genetic variation in adrenergic receptors and pathway enzymes. We analyzed nine genetic polymorphisms across seven adrenergic genes (ADRA1A, ADRA2A, ADRA2C, ADRB3, DBH, MAOA and COMT). METHODS: One hundred thirty-nine patients with schizophrenia were prospectively assessed for AP-induced weight gain. The HelixTree software (Golden Helix, Bozeman, MT, USA) was employed to detect differences in genotypic distribution between weight gainer and non-weight gainer groups. Furthermore, for the dopamine ß-hydroxylase haplotype, we were able to obtain both the molecular and the statistical phases, analyzing the phenotype considering both phases. RESULTS: Weight gain was not associated with any adrenergic gene. CONCLUSIONS: Our results suggest that genetic polymorphisms in the adrenergic system may not play a major role in AP-induced weight gain; however, adrenergic 2A receptor gene that produced previously the most consistent associations with this phenotype showed a significant interaction with the monoamine oxidase A in weight gainers.

Effects of haloperidol, clozapine, and quetiapine on sensorimotor gating in a genetic model of reduced NMDA receptor function.

RATIONALE: Reduced N-methyl D-aspartate (NMDA) receptor function is hypothesized to contribute to the pathophysiology of schizophrenia. In order to model chronic and developmental NMDA receptor hypofunction, a mouse line was developed that expresses low levels of the NMDA R1 (NR1) subunit of the NMDA receptor. These mice show increased acoustic startle reactivity and deficits in prepulse inhibition (PPI) of acoustic startle. OBJECTIVES: The present study tested the hypothesis that these altered acoustic startle responses in the NR1 hypomorphic (NR1-/-) mice would be affected by antipsychotic drug treatment. METHODS: Mice were injected with drugs 30 min before assessment of acoustic startle responses with and without prepulse stimuli. RESULTS: Haloperidol (0.5 or 1.0 mg/kg) did not reduce the increased startle reactivity in the NR1-/- mice, but did increase PPI in both the mutant and wild type mice. Clozapine (3 mg/kg) and quetiapine (20 mg/kg) reduced startle magnitude and increased PPI in both the wild type and mutant mice. The antidepressant drug imipramine (10 and 20 mg/kg) had minimal effects on startle amplitude in NR1-/- or wild type mice. However, for the 20-mg/kg dose of imipramine, a significant increase in PPI was observed in the wild type animals, but not in the mutant mice. CONCLUSIONS: The results demonstrate that PPI can be increased in a mouse model of chronic NMDA receptor hypofunction by typical and atypical antipsychotic drugs. The similar effects of typical and atypical antipsychotic drugs to increase PPI in the wild type and mutant mice indicates that the assessment of behavior of the NR1 hypomorphic mice in the PPI paradigm offers no advantage over the wild type controls for identifying new clozapine-like drugs.

A longitudinal study of neurocognitive function in individuals at-risk for psychosis.

INTRODUCTION: Clinically defined prodromal diagnostic criteria identify at-risk individuals with a 35-40% likelihood of developing a psychotic disorder within a year. The time course and predictive value of cognitive deficits in the development of psychosis has not been established. METHODS: A comprehensive neurocognitive battery and clinical assessments were administered to 37 subjects meeting Criteria of Prodromal States (COPS) criteria for being at risk for psychosis, and two comparison groups: 59 first episode and 47 healthy subjects. Subjects were also evaluated at 6-month and 1-year follow-up periods. Primary analyses used a neurocognitive composite score derived from individual neurocognitive measures, including measures of vigilance, verbal memory, working memory, and processing speed. RESULTS: At-risk subjects performed more poorly than healthy subjects (t=2.93, P=0.01), but better than first episode subjects (t=4.72, p<0.0001). At-risk subjects were particularly impaired on measures of vigilance and processing speed. Cognitive composite scores were significantly lower in at-risk subjects who progressed to psychosis (N=11; z=-1.2), while those at-risk subjects who did not progress to psychosis (N=17) performed better (z=-0.5), and not significantly different from controls. Poor CPT performance combined with better WAIS-R digit symbol performance predicted progression to psychosis. Severity of neurocognitive deficits was not related to duration of prodrome or to time to development of psychosis and neurocognitive function improved in all subjects except those who progressed to psychosis. CONCLUSION: Neurocognitive impairment emerges early in the course of psychotic illness. Performance on tests of neurocognition may prove to be an early risk predictor for subsequent development of psychotic disorders.

Comparing the effects of antidepressants: consensus guidelines for evaluating quantitative reviews of antidepressant efficacy.

With increasing numbers of treatment options available for patients with major depression over the last decade and the growing body of evidence describing their efficacy and safety, clinicians often find it difficult to determine the best and most appropriate evidence-based treatment for each patient. Systematic reviews utilizing statistical methods that synthesize and evaluate data from a number of studies have become increasingly more available over the past decade. We review major findings and lessons learned from salient examples of quantitative analyses of antidepressant research and provide recommendations for meta-analysts, journal and grant reviewers, and research 'consumers' (ie, clinicians) for conducting, reporting, and evaluating such analyses.

Presynaptic dopaminergic function is largely unaltered in mesolimbic and mesostriatal terminals of adult rats that were prenatally exposed to cocaine.

Fast-scan cyclic voltammetry in brain slices and postmortem tissue content assessment were used to evaluate presynaptic dopaminergic function in the caudate putamen and nucleus accumbens of adult male rats (180+ days old) that were prenatally treated with either cocaine or saline. Experiments were carried out to test whether there were differences in dopamine release, reuptake, autoreceptor function or the tissue levels of dopamine and its metabolites between cocaine- and saline-exposed rats. We report that presynaptic dopaminergic function remains largely intact in adult rats that were prenatally exposed to cocaine. The ability of terminals in the caudate putamen and nucleus accumbens to release and regulate dopamine is unaltered by prenatal cocaine exposure. However the tissue content of dopamine in the caudate putamen was decreased, representing a diminution in the dopamine storage pool. We conclude, therefore, that behavioral changes that have previously been observed in rats that were prenatally exposed to cocaine are not mediated through alteration of presynaptic dopaminergic mechanisms in these brain regions.

Cost-benefit analysis of second-generation antipsychotics and placebo in a randomized trial of the treatment of psychosis and aggression in Alzheimer disease.

CONTEXT: Second-generation antipsychotics (SGAs) are prescribed for psychosis, aggression, and agitation in Alzheimer disease (AD). OBJECTIVE: To conduct a cost-benefit analysis of SGAs and placebo (taken to represent a "watchful waiting" treatment strategy) for psychosis and aggression in outpatients with AD. DESIGN: Randomized placebo-controlled trial of alternative SGA initiation strategies. SETTING: Forty-two outpatient clinics. PARTICIPANTS: Outpatients with AD and psychosis, aggression, or agitation (N = 421). Intervention Participants were randomly assigned to treatment with olanzapine, quetiapine fumarate, risperidone, or placebo with the option of double-blind rerandomization to another antipsychotic or citalopram hydrobromide or open treatment over 9 months. MAIN OUTCOME MEASURES: Monthly interviews documented health service use and costs. The economic perspective addressed total health care and medication costs. Costs of study drugs were estimated from wholesale prices with adjustment for discounts and rebates. Quality-adjusted life-years (QALYs) were assessed with the Health Utilities Index Mark 3 and were supplemented with measures of functioning, activities of daily living, and quality of life. Primary analyses were conducted using all available data. Secondary analyses excluded observations after the first medication change (ie, phase 1 only). Cost-benefit analysis was conducted using the net health benefits approach in a sensitivity analysis in which QALYs were valued at $50,000 per year and $100,000 per year. RESULTS: Average total health costs, including medications, were significantly lower for placebo than for SGAs, by $50 to $100 per month. There were no differences between treatments in QALYs or other measures of function. Phase 1-only analyses were broadly similar. Net-benefit analysis showed greater net health benefits for placebo as compared with other treatments, with probabilities ranging from 50% to 90%. CONCLUSIONS: There were no differences in measures of effectiveness between initiation of active treatments or placebo (which represented watchful waiting) but the placebo group had significantly lower health care costs. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00015548.