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Defects in experiencing disgust may contribute to obesity by allowing for the overconsumption of food. However, the relationship of disgust proneness and its associated neural locus has yet to be explored in the context of obesity. Thirty-three participants (17 obese, 16 lean) completed the Disgust Propensity and Sensitivity Scale-Revised and a functional magnetic resonance imaging paradigm where images from 4 categories (food, contaminates, contaminated food or fixation) were randomly presented. Independent two-sample t-tests revealed significantly lower levels of Disgust Sensitivity for the obese group (mean score = 14.7) compared with the lean group (mean score = 17.6, P = 0.026). The obese group had less activation in the right insula than the lean group when viewing contaminated food images. Multiple regression with interaction analysis revealed one left insula region where the association of Disgust Sensitivity scores with activation differed by group when viewing contaminated food images. These interaction effects were driven by the negative correlation of Disgust Sensitivity scores with beta values extracted from the left insula in the obese group (r = -0.59) compared with a positive correlation in the lean group (r = 0.65). Given these body mass index-dependent differences in Disgust Sensitivity and neural responsiveness to disgusting food images, it is likely that altered Disgust Sensitivity may contribute to obesity., (© The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.)

The serotonergic neurotoxin, 3,4-methylenedioxymethamphetamine (MDMA/Ecstasy), is a highly popular recreational drug. Human recreational MDMA users have neurocognitive and neuropsychiatric impairments, and human neuroimaging data are consistent with animal reports of serotonin neurotoxicity. However, functional neuroimaging studies have not found consistent effects of MDMA on brain neurophysiology in human users. Several lines of evidence suggest that studying MDMA effects in visual system might reveal the general cortical and subcortical neurophysiological consequences of MDMA use. We used 3 T functional magnetic resonance imaging during visual stimulation to compare visual system lateral geniculate nucleus (LGN) and Brodmann Area (BA) 17 and BA 18 activation in 20 long abstinent (479.95±580.65 days) MDMA users and 20 non-MDMA user controls. Lifetime quantity of MDMA use was strongly positively correlated with blood oxygenation level-dependent (BOLD) signal intensity in bilateral LGN (r(s)=0.59; p=0.007), BA 17 (r(s)=0.50; p=0.027), and BA 18 (r(s)=0.48; p=0.031), and with the spatial extent of activation in BA 17 (r(s)=0.059; p=0.007) and BA 18 (r(s)=0.55; p=0.013). There were no between-group differences in brain activation in any region, but the heaviest MDMA users showed a significantly greater spatial extent of activation than controls in BA 17 (p=0.031) and BA 18 (p=0.049). These results suggest that human recreational MDMA use may be associated with a long-lasting increase in cortical excitability, possibly through loss of serotonin input to cortical and subcortical regions. When considered in the context of previous results, cortical hyper-excitability may be a biomarker for MDMA-induced serotonin neurotoxicity.

Background: Cerebrospinal fluid (CSF) sodium levels have been reported to rise during episodic migraine. Since migraine frequently starts in early morning or late afternoon, we hypothesized that natural sodium chronobiology may predispose susceptible persons when extracellular CSF sodium increases. Since no mammalian brain sodium rhythms are known, we designed a study of healthy humans to test if cation rhythms exist in CSF., Methods: Lumbar CSF was collected every ten minutes at 0.1 mL/min for 24 h from six healthy participants. CSF sodium and potassium concentrations were measured by ion chromatography, total protein by fluorescent spectrometry, and osmolarity by freezing point depression. We analyzed cation and protein distributions over the 24 h period and spectral and permutation tests to identify significant rhythms. We applied the False Discovery Rate method to adjust significance levels for multiple tests and Spearman correlations to compare sodium fluctuations with potassium, protein, and osmolarity., Results: The distribution of sodium varied much more than potassium, and there were statistically significant rhythms at 12 and 1.65 h periods. Curve fitting to the average time course of the mean sodium of all six subjects revealed the lowest sodium levels at 03.20 h and highest at 08.00 h, a second nadir at 09.50 h and a second peak at 18.10 h. Sodium levels were not correlated with potassium or protein concentration, or with osmolarity., Conclusion: These CSF rhythms are the first reports of sodium chronobiology in the human nervous system. The results are consistent with our hypothesis that rising levels of extracellular sodium may contribute to the timing of migraine onset. The physiological importance of sodium in the nervous system suggests that these rhythms may have additional repercussions on ultradian functions.

Objectives: Improvements in electronic health record (EHR) system development will require an understanding of psychiatric clinicians' views on EHR system acceptability, including effects on psychotherapy communications, data-recording behaviors, data accessibility versus security and privacy, data quality and clarity, communications with medical colleagues, and stigma., Design: Multidisciplinary development of a survey instrument targeting psychiatric clinicians who recently switched to EHR system use, focus group testing, data analysis, and data reliability testing., Measurements: Survey of 120 university-based, outpatient mental health clinicians, with 56 (47%) responding, conducted 18 months after transition from a paper to an EHR system., Results: Factor analysis gave nine item groupings that overlapped strongly with five a priori domains. Respondents both praised and criticized the EHR system. A strong majority (81%) felt that open therapeutic communications were preserved. Regarding data quality, content, and privacy, clinicians (63%) were less willing to record highly confidential information and disagreed (83%) with including their own psychiatric records among routinely accessed EHR systems., Limitations: single time point; single academic medical center clinic setting; modest sample size; lack of prior instrument validation; survey conducted in 2005., Conclusions: In an academic medical center clinic, the presence of electronic records was not seen as a dramatic impediment to therapeutic communications. Concerns regarding privacy and data security were significant, and may contribute to reluctances to adopt electronic records in other settings. Further study of clinicians' views and use patterns may be helpful in guiding development and deployment of electronic records systems.

Unlabelled: Depression is characterized by blunted behavior and neuroendocrine function that generally improve with antidepressant treatment. This study examined intrinsic variability in brain neurotransmitter function, since it may be a source of blunted behavior and neuroendocrine function in depression and a marker for the illness, and has not previously been analyzed using wavelet decomposition. To measure variability in monoamine metabolites, lumbar cerebrospinal fluid (CSF) was collected in serial samples in depressed patients before and after treatment. We hypothesized that changes in variability would be observed after treatment. Mechanisms that control such variability may be critical to the pathophysiology of depression., Method: Time series data was obtained from serial ten-min sampling over a 24-hr period (N=144) from thirteen depressed patients, with a repeat collection after 5 weeks of antidepressant (sertraline or bupropion) treatment. Concentrations of tryptophan (TRP), the monoamine metabolites 5-HIAA (metabolite of serotonin) and HVA (metabolite of dopamine), and the HVA:5HIAA ratio were transformed to examine power in slowly (160 min/cycle) to rapidly (20 min/cycle) occurring events. Power, the sum of the squares of the coefficients in each d (detail) wavelet, reflects variability within a limited frequency bandwidth for that wavelet. Pre-treatment to post-treatment comparisons were conducted with repeated measures ANOVA., Results: Antidepressant treatment was associated with increased power in the d2 wavelet from the HVA (p=0.03) and the HVA:5-HIAA ratio (p=0.03) series. The d1 and d3 wavelets showed increased power following antidepressant treatment for the ratio series (d1, p=0.01; d3, p=0.05). Significant changes in power were not observed for the 5-HIAA data series. Power differences among analytes suggest that the findings are specific to each system., Conclusion: The wavelet transform analysis shows changes in neurochemical signal variability following antidepressant treatment. Patterns or degrees of variability may be as important as, or possibly more important than, the mean levels of monoamine transmitters. Studies of variability observed in healthy individuals and a larger depressed sample will be needed to verify a relationship with mood and treatment response. Neurochemical measures of time-variability may be a pivotal marker in depression.

Unipolar and bipolar depressions show abnormal behavioral manifestations of ultradian (less than 24 h) rhythms, but abnormal rhythms of the central neurotransmitters thought to be important for depression pathophysiology (eg dopamine (DA) and serotonin (5-HT)) have not been shown in this time frame. Since antidepressant treatments normalize disrupted rhythms in depression (eg rapid-eye-movement sleep and hormonal rhythms), we hypothesized that depression-related changes in ultradian oscillations of DA and 5-HT might be revealed during antidepressant treatment. Cerebrospinal fluid (CSF) samples collected q10 min for 24 h in 13 patients experiencing major depressive episodes (MDE) before and after treatment for 5 weeks with sertraline or bupropion were assayed for levels of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), and their ratio was calculated. Data were analyzed in the frequency domain using Fourier transforms and multivariate permutation testing. Antidepressant treatments were associated with decreased variance for 5-HIAA, increased variance for HVA, and markedly increased variance for the HVA : 5-HIAA ratio (p<0.05, p<0.02, and p<0.003, respectively). With treatment, the correlations between 5-HIAA and HVA weakened (p=0.06). Power spectral density (PSD-the Fourier magnitude squared) of the 5-HIAA signals at periods of 1.75 and 3.7 h (both p<0.05) decreased, while circadian cycling of HVA levels (p<0.05) and of the ratio (p<0.005) increased after treatment. The PSD of the full-length HVA : 5-HIAA ratio series after treatment increased in rapid variability (20-103 min periods, p<0.05). Spectrographic windowing demonstrated a focal span of enhanced HVA : 5-HIAA ratio variability following antidepressant treatment, in an approximately 84-min period through the evening (p<0.05). Periodic neurotransmitter relationships in depressed patients were altered by treatment in this analysis of a small data set. This may represent a baseline abnormality in the regulation of periodic functions involved in the depression pathophysiology, but it could also be due to an unrelated antidepressant effect. Further studies including comparisons with healthy subject data are in progress.

This work studies association between relapse during acute tryptophan depletion (ATD) and CSF level of tryptophan (TRP) in remitted depressives treated with sertraline or bupropion. Eight medication-responding depressives ingested an ATD amino acid mixture during 48-h continuous CSF sampling before and after treatment. Mood rating scores were compared with nadir levels of TRP in CSF. CSF TRP nadirs averaged 8.7% of am baselines in remitted patients. Mood relapsed whenever the CSF nadir was below 40 nmol/l TRP in remitted patients, and never when above (Fisher's exact test, P=0.029). Relapsing medication responders also showed very low preantidepressant ATD-induced nadirs. ATD-induced relapses were associated with low CSF TRP levels. Individual susceptibility to depletion may be independent of antidepressant treatment, mood state, or treatment status. Resistance to relapse may invoke an undefined, protective CNS mechanism against extremely low CSF levels of TRP during ATD.

A variety of biologic studies have demonstrated abnormal regulation of the norepinephrine (NE) system in patients with major depression, suggesting a role for NE in the etiology of depression. Brain NE and dopamine levels can be rapidly reduced by blocking synthesis with the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMPT). In the current investigation, AMPT was administered to drug-free depressed patients to evaluate the effect on mood of diminished catecholamine levels. Seventeen drug-free patients meeting DSM-III-R criteria for major depressive episode were tested with AMPT and an active placebo control, diphenhydramine. Testing was accomplished in a double-blind, crossover fashion, with random assignment to test conditions. Each test included baseline evaluation, 2 days with administration of either AMPT or diphenhydramine, and a follow-up day. Diphenhydramine was used as an active control because of the significant sedation associated with AMPT. Behavioral ratings, including visual analogue scales for a variety of feeling states, the Hamilton Depression Rating Scale (HDRS), and plasma for 3-methoxy-4-hydroxyphenelethyleneglycol (MPHG) and homovanillic acid (HVA) levels, were obtained. AMPT significantly reduced plasma HVA by 70% and MHPG by 50%, but it had no significant effects on the HDRS. AMPT also significantly increased visual analogue ratings of "tired" and decreased ratings of "energetic." Diphenhydramine significantly decreased HDRS scores, but the change was small and was not clinically apparent. The lack of AMPT effects on depressed mood, in conjunction with a prior report that large reductions in plasma tryptophan do not systematically alter depressed mood, indicate that monoamine deficiency by itself is insufficient explanation of the cause of depression. The role of the noradrenergic system needs to be considered in relationship to the many other neurobiologic factors that could be involved in the pathophysiology of depression.

Small angle x-ray scattering has been used to investigate the structure of synaptoneurosomal (SNM) membranes from rat cerebral cortex. Electron micrographs of the preparation showed SNM with classical synaptic appositions intact, other vesicles, occasional mitochondria, and some myelin. An immunoassay for myelin basic protein placed the myelin content of normal rat SNM at less than 2% by weight of the total membrane present. X-Ray diffraction patterns showed five diffraction orders with a unit cell repeat for the membrane of 71 to 78 A at higher hydration states. At lower hydration, 11 orders appeared; the unit cell repeat was 130 A, indicating that the unit cell contained two membranes. Electron density profiles for the 130-A unit cell were determined; they clearly showed the two opposed asymmetrical membranes of the SNM vesicles. SNM membrane/buffer partition coefficients (Kp) of imidazobenzodiazepine and 1,4-dihydropyridine (DHP) calcium channel drugs were measured; Kp's for DHP drugs were approximately five times higher in rabbit light sarcoplasmic reticulum than in SNM. Ro 15-1788 and the DHP BAY K 8644 bind primarily to the outer monolayer of vesicles of intact SNM membranes. Nonspecific equilibrium binding of Ro 15-1788 occurs mainly in the upper acyl chain of the bilayer in lipid extracts of SNM membrane.