A systematic review of comparative efficacy of treatments and controls for depression

Background

Although previous meta-analyses have examined effects of antidepressants, psychotherapy, and alternative therapies for depression, the efficacy of these treatments alone and in combination has not been systematically compared. We hypothesized that the differences between approved depression treatments and controls would be small.

Methods and Findings

The authors first reviewed data from Food and Drug Administration Summary Basis of Approval reports of 62 pivotal antidepressant trials consisting of data from 13,802 depressed patients. This was followed by a systematic review of data from 115 published trials evaluating efficacy of psychotherapies and alternative therapies for depression. The published depression trials consisted of 10,310 depressed patients. We assessed the percentage symptom reduction experienced by the patients based on treatment assignment. Overall, antidepressants led to greater symptom reduction compared to placebo among both unpublished FDA data and published trials (F = 38.5, df = 239, p<0.001). In the published trials we noted that the magnitude of symptom reduction with active depression treatments compared to controls was significantly larger when raters evaluating treatment effects were un-blinded compared to the trials with blinded raters (F = 2.17, df = 313, p<0.05). In the blinded trials, the combination of antidepressants and psychotherapy provided a slight advantage over antidepressants (p = 0.027) and psychotherapy (p = 0.022) alone. The magnitude of symptom reduction was greater with psychotherapies compared to placebo (p = 0.019), treatment-as-usual (p = 0.012) and waiting-list (p<0.001). Differences were not seen with psychotherapy compared to antidepressants, alternative therapies or active intervention controls.

Conclusions

In conclusion, the combination of psychotherapy and antidepressants for depression may provide a slight advantage whereas antidepressants alone and psychotherapy alone are not significantly different from alternative therapies or active intervention controls. These data suggest that type of treatment offered is less important than getting depressed patients involved in an active therapeutic program. Future research should consider whether certain patient profiles might justify a specific treatment modality.     

The neural substrate of positive bias in spontaneous emotional processing

Even in the presence of negative information, healthy human beings display an optimistic tendency when thinking of past success and future chances, giving a positive bias to everyday''s cognition. The tendency to actively select positive thoughts suggests the existence of a mechanism to exclude negative content, raising the issue of its dependence on mechanisms like those of effortful control. Using perfusion imaging, we examined how brain activations differed according to whether participants were left to prefer positive thoughts spontaneously, or followed an explicit instruction to the same effect, finding a widespread dissociation of brain perfusion patterns. Under spontaneous processing of emotional material, recruitment of areas associated with effortful attention, such as the dorsolateral prefrontal cortex, was reduced relative to instructed avoidance of negative material (F _1,58 = 26.24, p = 0.047, corrected). Under spontaneous avoidance perfusion increments were observed in several areas that were deactivated by the task, including the perigenual medial prefrontal cortex. Furthermore, individual differences in executive capacity were not associated with positive bias. These findings suggest that spontaneous positive cognitive emotion regulation in health may result from processes that, while actively suppressing emotionally salient information, differ from those associated with effortful and directed control.     

Dorsal striatum and its limbic connectivity mediate abnormal anticipatory reward processing in obesity

Obesity is characterized by an imbalance in the brain circuits promoting reward seeking and those governing cognitive control. Here we show that the dorsal caudate nucleus and its connections with amygdala, insula and prefrontal cortex contribute to abnormal reward processing in obesity. We measured regional brain glucose uptake in morbidly obese (n = 19) and normal weighted (n = 16) subjects with 2-[18F]fluoro-2-deoxyglucose ([¹⁸F]FDG) positron emission tomography (PET) during euglycemic hyperinsulinemia and with functional magnetic resonance imaging (fMRI) while anticipatory food reward was induced by repeated presentations of appetizing and bland food pictures. First, we found that glucose uptake rate in the dorsal caudate nucleus was higher in obese than in normal-weight subjects. Second, obese subjects showed increased hemodynamic responses in the caudate nucleus while viewing appetizing versus bland foods in fMRI. The caudate also showed elevated task-related functional connectivity with amygdala and insula in the obese versus normal-weight subjects. Finally, obese subjects had smaller responses to appetizing versus bland foods in the dorsolateral and orbitofrontal cortices than did normal-weight subjects, and failure to activate the dorsolateral prefrontal cortex was correlated with high glucose metabolism in the dorsal caudate nucleus. These findings suggest that enhanced sensitivity to external food cues in obesity may involve abnormal stimulus-response learning and incentive motivation subserved by the dorsal caudate nucleus, which in turn may be due to abnormally high input from the amygdala and insula and dysfunctional inhibitory control by the frontal cortical regions. These functional changes in the responsiveness and interconnectivity of the reward circuit could be a critical mechanism to explain overeating in obesity.     

Differences in Prefrontal,Limbic, and White Matter Lesion Volumes According to Cognitive Status in Elderly Patients with First-Onset Subsyndromal Depression

The purpose of this preliminary study was to test the hypothesis that subsyndromal depression is associated with the volume of medial prefrontal regional gray matter and that of white matter lesions (WMLs) in the brains of cognitively normal older people. We also explored the relationships between subsyndromal depression and medial prefrontal regional gray matter volume, limbic regional gray matter volume, and lobar WMLs in the brains of patients with mild cognitive impairment (MCI) and Alzheimer''s disease (AD). We performed a cross-sectional study comparing patients with subsyndromal depression and nondepressed controls with normal cognition (n = 59), MCI (n = 27), and AD (n = 27), adjusting for sex, age, years of education, and results of the Mini-Mental State Examination. Frontal WML volume was greater, and right medial orbitofrontal cortical volume was smaller in cognitively normal participants with subsyndromal depression than in those without subsyndromal depression. No volume differences were observed in medial prefrontal, limbic, or WML volumes according to the presence of subsyndromal depression in cognitively impaired patients. The absence of these changes in patients with MCI and AD suggests that brain changes associated with AD pathology may override the changes associated with subsyndromal depression.     

Childhood Emotional Maltreatment Severity Is Associated with Dorsal Medial Prefrontal Cortex Responsivity to Social Exclusion in Young Adults

Children who have experienced chronic parental rejection and exclusion during childhood, as is the case in childhood emotional maltreatment, may become especially sensitive to social exclusion. This study investigated the neural and emotional responses to social exclusion (with the Cyberball task) in young adults reporting childhood emotional maltreatment. Using functional magnetic resonance imaging, we investigated brain responses and self-reported distress to social exclusion in 46 young adult patients and healthy controls (mean age = 19.2±2.16) reporting low to extreme childhood emotional maltreatment. Consistent with prior studies, social exclusion was associated with activity in the ventral medial prefrontal cortex and posterior cingulate cortex. In addition, severity of childhood emotional maltreatment was positively associated with increased dorsal medial prefrontal cortex responsivity to social exclusion. The dorsal medial prefrontal cortex plays a crucial role in self-and other-referential processing, suggesting that the more individuals have been rejected and maltreated in childhood, the more self- and other- processing is elicited by social exclusion in adulthood. Negative self-referential thinking, in itself, enhances cognitive vulnerability for the development of psychiatric disorders. Therefore, our findings may underlie the emotional and behavioural difficulties that have been reported in adults reporting childhood emotional maltreatment.     

Regional Brain Structural Abnormality in Meal-Related Functional Dyspepsia Patients: A Voxel-Based Morphometry Study

Background and Aims

Brain dysfunction in functional dyspepsia (FD) has been identified by multiple neuroimaging studies. This study aims to investigate the regional gray matter density (GMD) changes in meal-related FD patients and their correlations with clinical variables, and to explore the possible influence of the emotional state on FD patients’s brain structures.

Methods

Fifty meal-related FD patients and forty healthy subjects (HS) were included and underwent a structural magnetic resonance imaging scan. Voxel-based morphometry analysis was employed to identify the cerebral structure alterations in meal-related FD patients. Regional GMD changes'' correlations with the symptoms and their durations, respectively, have been analyzed.

Results

Compared to the HS, the meal-related FD patients showed a decreased GMD in the bilateral precentral gyrus, medial prefrontal cortex (MPFC), anterior cingulate cortex (ACC) and midcingulate cortex (MCC), left orbitofrontal cortex (OFC) and right insula (p<0.05, FWE Corrected, Cluster size>50). After controlling for anxiety and depression, the meal-related FD patients showed a decreased GMD in the bilateral middle frontal gyrus, left MCC, right precentral gyrus and insula (p<0.05, FWE Corrected, Cluster size>50). Before controlling psychological factors, the GMD decreases in the ACC were negatively associated with the symptom scores of the Nepean Dyspepsia Index (NDI) (r = −0.354, p = 0.048, Bonferroni correction) and the duration of FD (r = −0.398, p = 0.02, Bonferroni correction) respectively.

Conclusions

The regional GMD of meal-related FD patients, especially in the regions of the homeostatic afferent processing network significantly differed from that of the HS, and the psychological factors might be one of the essential factors significantly affecting the regional brain structure of meal-related FD patients.     

Subjective Somatosensory Experiences Disclosed by Focused Attention: Cortical-Hippocampal-Insular and Amygdala Contributions

In order to explore the neurobiological foundations of qualitative subjective experiences, the present study was designed to correlate objective third-person brain fMRI measures with subjective first-person identification and scaling of local, subtle, and specific somatosensory sensations, obtained directly after the imaging procedure. Thus, thirty-four volunteers were instructed to focus and sustain their attention to either provoked or spontaneous sensations of each thumb during the fMRI procedure. By means of a Likert scale applied immediately afterwards, the participants recalled and evaluated the intensity of their attention and identified specific somatosensory sensations (e.g. pulsation, vibration, heat). Using the subject''s subjective scores as covariates to model both attention intensity and general somatosensory experiences regressors, the whole-brain random effect analyses revealed activations in the frontopolar prefrontal cortex (BA10), primary somatosensory cortex (BA1), premotor cortex (BA 6), precuneus (BA 7), temporopolar cortex (BA 38), inferior parietal lobe (BA 39), hippocampus, insula and amygdala. Furthermore, BA10 showed differential activity, with ventral BA10 correlating exclusively with attention (r(32) = 0.54, p = 0.0013) and dorsal BA10 correlating exclusively with somatosensory sensation (r(32) = 0.46, p = 0.007). All other reported brain areas showed significant positive correlations solely with subjective somatosensory experiences reports. These results provide evidence that the frontopolar prefrontal cortex has dissociable functions depending on specific cognitive demands; i.e. the dorsal portion of the frontopolar prefrontal cortex in conjunction with primary somatosensory cortex, temporopolar cortex, inferior parietal lobe, hippocampus, insula and amygdala are involved in the processing of spontaneous general subjective somatosensory experiences disclosed by focused and sustained attention.     

Denitrification and anammox in tropical aquaculture settlement ponds: an isotope tracer approach for evaluating n(2) production

Settlement ponds are used to treat aquaculture discharge water by removing nutrients through physical (settling) and biological (microbial transformation) processes. Nutrient removal through settling has been quantified, however, the occurrence of, and potential for microbial nitrogen (N) removal is largely unknown in these systems. Therefore, isotope tracer techniques were used to measure potential rates of denitrification and anaerobic ammonium oxidation (anammox) in the sediment of settlement ponds in tropical aquaculture systems. Dinitrogen gas (N₂) was produced in all ponds, although potential rates were low (0–7.07 nmol N cm⁻³ h⁻¹) relative to other aquatic systems. Denitrification was the main driver of N₂ production, with anammox only detected in two of the four ponds. No correlations were detected between the measured sediment variables (total organic carbon, total nitrogen, iron, manganese, sulphur and phosphorous) and denitrification or anammox. Furthermore, denitrification was not carbon limited as the addition of particulate organic matter (paired t-Test; P = 0.350, n = 3) or methanol (paired t-Test; P = 0.744, n = 3) did not stimulate production of N₂. A simple mass balance model showed that only 2.5% of added fixed N was removed in the studied settlement ponds through the denitrification and anammox processes. It is recommended that settlement ponds be used in conjunction with additional technologies (i.e. constructed wetlands or biological reactors) to enhance N₂ production and N removal from aquaculture wastewater.     

Genetic variations in plasma circulating DNA of HBV-related hepatocellular carcinoma patients predict recurrence after liver transplantation

Background

Recurrence prediction of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT) present a great challenge because of a lack of biomarkers. Genetic variations play an important role in tumor development and metastasis.

Methods

Oligonucleotide microarrays were used to evaluate the genetic characteristics of tumor DNA in 30 HBV-related HCC patients who were underwent LT. Recurrence-related single-nucleotide polymorphism were selected, and their prognostic value was assessed and validated in two independent cohorts of HCC patients (N = 102 and N = 77), using pretransplant plasma circulating DNA. Prognostic significance was assessed by Kaplan-Meier survival estimates and log-rank tests. Multivariate analyses were performed to evaluate prognosis-related factors.

Results

rs894151 and rs12438080 were significantly associated with recurrence (P = .003 and P = .004, respectively). Multivariate analyses demonstrated that the co-index of the 2 SNPs was an independent prognostic factor for recurrence (P = .040). Similar results were obtained in the third cohort (N = 77). Furthermore, for HCC patients (all the 3 cohorts) exceeding Milan criteria, the co-index was a prognostic factor for recurrence and survival (P<.001 and P = .002, respectively).

Conclusions

Our study demonstrated first that genetic variations of rs894151 and rs12438080 in pretransplant plasma circulating DNA are promising prognostic markers for tumor recurrence in HCC patients undergoing LT and identify a subgroup of patients who, despite having HCC exceeding Milan criteria, have a low risk of post-transplant recurrence.     

The effectiveness of online cognitive behavioral treatment in routine clinical practice

Context

Randomized controlled trails have identified online cognitive behavioral therapy as an efficacious intervention in the management of common mental health disorders.

Objective

To assess the effectiveness of online CBT for different mental disorders in routine clinical practice.

Design

An uncontrolled before-after study, with measurements at baseline, posttest, 6-week follow-up, and 1-year follow-up.

Participants & Setting

1500 adult patients (female: 67%; mean age: 40 years) with a GP referral for psychotherapy were treated at a Dutch online mental health clinic for symptoms of depression (n = 413), panic disorder (n = 139), posttraumatic stress (n = 478), or burnout (n = 470).

Interventions

Manualized, web-based, therapist-assisted CBT, of which the efficacy was previously demonstrated in a series of controlled trials. Standardized duration of treatment varied from 5 weeks (online CBT for Posttraumatic stress) to 16 weeks (online CBT for Depression).

Main Outcome Measures

Validated self-report questionnaires of specific and general psychopathology, including the Beck Depression Inventory, the Impact of Event Scale, the Panic Disorder Severity Scale-Self Report, the Oldenburg Burnout Inventory, and the Depression Anxiety Stress Scales.

Results

Treatment adherence was 71% (n = 1071). Study attrition was 21% at posttest, 33% at 6-week FU and 65% at 1-year FU. Mixed-model repeated measures regression identified large short-term reductions in all measures of primary symptoms (d = 1.9±0.2 to d = 1.2±0.2; P<.001), which sustained up to one year after treatment. At posttest, rates of reliable improvement and recovery were 71% and 52% in the completer sample (full sample: 55%/40%). Patient satisfaction was high.

Conclusions

Results suggest that online therapist-assisted CBT may be as effective in routine practice as it is in clinical trials. Although pre-treatment withdrawal and long-term outcomes require further study, results warrant continued implementation of online CBT.     

Default-Mode Network Changes in Huntington’s Disease: An Integrated MRI Study of Functional Connectivity and Morphometry

Previous MRI studies of functional connectivity in pre-symptomatic mutation carriers of Huntington’s disease (HD) have shown dysfunction of the Default-Mode Network (DMN). No data however are currently available on the DMN alterations in the symptomatic stages of the disease, which are characterized by cortical atrophy involving several DMN nodes. We assessed DMN integrity and its possible correlations with motor and cognitive symptoms in 26 symptomatic HD patients as compared to 22 normal volunteers, by analyzing resting state functional MRI data, using the Precuneal Cortex/Posterior Cingulate Cortices (PC/PCC) as seed, controlling at voxel level for the effect of atrophy by co-varying for gray matter volume. Direct correlation with PC/PCC was decreased, without correlation with atrophy, in the ventral medial prefrontal cortex (including anterior cingulate and subgenual cortex), right dorso-medial prefrontal cortex, and in the right inferior parietal cortex (mainly involving the angular gyrus). Negative correlations with PC/PCC were decreased bilaterally in the inferior parietal cortices, while a cluster in the right middle occipital gyrus presented increased correlation with PC/PCC. DMN changes in the ventral medial prefrontal cortex significantly correlated with the performance at the Stroop test (p = .0002). Widespread DMN changes, not correlating with the atrophy of the involved nodes, are present in symptomatic HD patients, and correlate with cognitive disturbances.     

Extrapunitive and Intropunitive Individuals Activate Different Parts of the Prefrontal Cortex under an Ego-Blocking Frustration

Different people make different responses when they face a frustrating situation: some punish others (extrapunitive), while others punish themselves (intropunitive). Few studies have investigated the neural structures that differentiate extrapunitive and intropunitive individuals. The present fMRI study explored these neural structures using two different frustrating situations: an ego-blocking situation which blocks a desire or goal, and a superego-blocking situation which blocks self-esteem. In the ego-blocking condition, the extrapunitive group (n = 9) showed greater activation in the bilateral ventrolateral prefrontal cortex, indicating that these individuals prefer emotional processing. On the other hand, the intropunitive group (n = 9) showed greater activation in the left dorsolateral prefrontal cortex, possibly reflecting an effortful control for anger reduction. Such patterns were not observed in the superego-blocking condition. These results indicate that the prefrontal cortex is the source of individual differences in aggression direction in the ego-blocking situation.     

Increased sleep fragmentation leads to impaired off-line consolidation of motor memories in humans

A growing literature supports a role for sleep after training in long-term memory consolidation and enhancement. Consequently, interrupted sleep should result in cognitive deficits. Recent evidence from an animal study indeed showed that optimal memory consolidation during sleep requires a certain amount of uninterrupted sleep.Sleep continuity is disrupted in various medical disorders. We compared performance on a motor sequence learning task (MST) in relatively young subjects with obstructive sleep apnea (n = 16; apnea-hypopnea index 17.1±2.6/h [SEM]) to a carefully matched control group (n = 15, apnea-hypopnea index 3.7±0.4/h, p<0.001. Apart from AHI, oxygen nadir and arousal index, there were no significant differences between groups in total sleep time, sleep efficiency and sleep architecture as well as subjective measures of sleepiness based on standard questionnaires. In addition performance on the psychomotor vigilance task (reaction time and lapses), which is highly sensitive to sleep deprivation showed no differences as well as initial learning performance during the training phase. However there was a significant difference in the primary outcome of immediate overnight improvement on the MST between the two groups (controls = 14.7±4%, patients = 1.1±3.6%; P = 0.023) as well as plateau performance (controls = 24.0±5.3%, patients = 10.1±2.0%; P = 0.017) and this difference was predicted by the arousal index (p = 0.02) rather than oxygen saturation (nadir and time below 90% saturation. Taken together, this outcome provides evidence that there is a clear minimum requirement of sleep continuity in humans to ensure optimal sleep dependent memory processes. It also provides important new information about the cognitive impact of obstructive sleep apnea and challenges its current definitions.     

A new estimation of global soil greenhouse gas fluxes using a simple data-oriented model

Soil greenhouse gas fluxes (particularly CO₂, CH₄, and N₂O) play important roles in climate change. However, despite the importance of these soil greenhouse gases, the number of reports on global soil greenhouse gas fluxes is limited. Here, new estimates are presented for global soil CO₂ emission (total soil respiration), CH₄ uptake, and N₂O emission fluxes, using a simple data-oriented model. The estimated global fluxes for CO₂ emission, CH₄ uptake, and N₂O emission were 78 Pg C yr⁻¹ (Monte Carlo 95% confidence interval, 64–95 Pg C yr⁻¹), 18 Tg C yr⁻¹ (11–23 Tg C yr⁻¹), and 4.4 Tg N yr⁻¹ (1.4–11.1 Tg N yr⁻¹), respectively. Tropical regions were the largest contributor of all of the gases, particularly the CO₂ and N₂O fluxes. The soil CO₂ and N₂O fluxes had more pronounced seasonal patterns than the soil CH₄ flux. The collected estimates, including both the previous and the present estimates, demonstrate that the means of the best estimates from each study were 79 Pg C yr⁻¹ (291 Pg CO₂ yr⁻¹; coefficient of variation, CV = 13%, N = 6) for CO₂, 21 Tg C yr⁻¹ (29 Tg CH₄ yr⁻¹; CV = 24%, N = 24) for CH₄, and 7.8 Tg N yr⁻¹ (12.2 Tg N₂O yr⁻¹; CV = 38%, N = 11) for N₂O. For N₂O, the mean of the estimates that was calculated by excluding the earliest two estimates was 6.6 Tg N yr⁻¹ (10.4 Tg N₂O yr⁻¹; CV = 22%, N = 9). The reported estimates vary and have large degrees of uncertainty but their overall magnitudes are in general agreement. To further minimize the uncertainty of soil greenhouse gas flux estimates, it is necessary to build global databases and identify key processes in describing global soil greenhouse gas fluxes.     

Isolation by elevation: genetic structure at neutral and putatively non-neutral loci in a dominant tree of subtropical forests, Castanopsis eyrei

Background

The distribution of genetic diversity among plant populations growing along elevational gradients can be affected by neutral as well as selective processes. Molecular markers used to study these patterns usually target neutral processes only, but may also be affected by selection. In this study, the effects of elevation and successional stage on genetic diversity of a dominant tree species were investigated controlling for neutrality of the microsatellite loci used.

Methodology/Principal Findings

Diversity and differentiation among 24 populations of Castanopsis eyrei from different elevations (251–920 m) and successional stages were analysed by eight microsatellite loci. We found that one of the loci (Ccu97H18) strongly deviated from a neutral model of differentiation among populations due to either divergent selection or hitchhiking with an unknown selected locus. The analysis showed that C. eyrei populations had a high level of genetic diversity within populations (A_R = 7.6, H_E = 0.82). Genetic variation increased with elevation for both the putatively selected locus Ccu97H18 and the neutral loci. At locus Ccu97H18 one allele was dominant at low elevations, which was replaced at higher elevations by an increasing number of other alleles. The level of genetic differentiation at neutral loci was similar to that of other Fagaceae species (F_ST = 0.032,  = 0.15). Population differentiation followed a model of isolation by distance but additionally, strongly significant isolation by elevation was found, both for neutral loci and the putatively selected locus.

Conclusions/Significance

The results indicate higher gene flow among similar elevational levels than across different elevational levels and suggest a selective influence of elevation on the distribution of genetic diversity in C. eyrei. The study underlines the importance to check the selective neutrality of marker loci in analyses of population structure.     

Evidence That Personal Genome Testing Enhances Student Learning in a Course on Genomics and Personalized Medicine

An emerging debate in academic medical centers is not about the need for providing trainees with fundamental education on genomics, but rather the most effective educational models that should be deployed. At Stanford School of Medicine, a novel hands-on genomics course was developed in 2010 that provided students the option to undergo personal genome testing as part of the course curriculum. We hypothesized that use of personal genome testing in the classroom would enhance the learning experience of students. No data currently exist on how such methods impact student learning; thus, we surveyed students before and after the course to determine its impact. We analyzed responses using paired statistics from the 31 medical and graduate students who completed both pre-course and post-course surveys. Participants were stratified by those who did (N = 23) or did not (N = 8) undergo personal genome testing. In reflecting on the experience, 83% of students who underwent testing stated that they were pleased with their decision compared to 12.5% of students who decided against testing (P = 0.00058). Seventy percent of those who underwent personal genome testing self-reported a better understanding of human genetics on the basis of having undergone testing. Further, students who underwent personal genome testing demonstrated an average 31% increase in pre- to post-course scores on knowledge questions (P = 3.5×10⁻⁶); this was significantly higher (P = 0.003) than students who did not undergo testing, who showed a non-significant improvement. Undergoing personal genome testing and using personal genotype data in the classroom enhanced students'' self-reported and assessed knowledge of genomics, and did not appear to cause significant anxiety. At least for self-selected students, the incorporation of personal genome testing can be an effective educational tool to teach important concepts of clinical genomic testing.     

Heritable variation in garter snake color patterns in postglacial populations

Global climate change is expected to trigger northward shifts in the ranges of natural populations of plants and animals, with subsequent effects on intraspecific genetic diversity. Investigating how genetic diversity is patterned among populations that arose following the last Ice Age is a promising method for understanding the potential future effects of climate change. Theoretical and empirical work has suggested that overall genetic diversity can decrease in colonial populations following rapid expansion into postglacial landscapes, with potential negative effects on the ability of populations to adapt to new environmental regimes. The crucial measure of this genetic variation and a population''s overall adaptability is the heritable variation in phenotypic traits, as it is this variation that mediates the rate and direction of a population''s multigenerational response to selection. Using two large full-sib quantitative genetic studies (N_Manitoba = 144; N_{South Dakota} = 653) and a smaller phenotypic analysis from Kansas (N_Kansas = 44), we compared mean levels of pigmentation, genetic variation and heritability in three pigmentation traits among populations of the common garter snake, Thamnophis sirtalis, along a north-south gradient, including a postglacial northern population and a putative southern refuge population. Counter to our expectations, we found that genetic variance and heritability for the three pigmentation traits were the same or higher in the postglacial population than in the southern population.     

De novo lipogenesis in adipose tissue is associated with course of morbid obesity after bariatric surgery

Objective

De novo lipogenesis is involved in fatty acid biosynthesis and could be involved in the regulation of the triglyceride storage capacity of adipose tissue. However, the association between lipogenic and lipolytic genes and the evolution of morbidly obese subjects after bariatric surgery remains unknown. In this prospective study we analyze the association between the improvement in the morbidly obese patients as a result of bariatric surgery and the basal expression of lipogenic and lipolytic genes.

Methods

We study 23 non diabetic morbidly obese patients who were studied before and 7 months after bariatric surgery. Also, we analyze the relative basal mRNA expression levels of lipogenic and lipolytic genes in epiploic visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT).

Results

When the basal acetyl-CoA carboxylase 1 (ACC1), acetyl-CoA synthetase 2 (ACSS2) and ATP citrate lyase (ACL) expression in SAT was below percentile-50, there was a greater decrease in weight (P = 0.006, P = 0.034, P = 0.026), body mass index (P = 0.008, P = 0.033, P = 0.034) and hip circumference (P = 0.033, P = 0.021, P = 0.083) after bariatric surgery. In VAT, when the basal ACSS2 expression was below percentile-50, there was a greater decrease in hip circumference (P = 0.006). After adjusting for confounding variables in logistic regression models, only the morbidly obese patients with SAT or VAT ACSS2 expression≥P50 before bariatric surgery had a lower percentage hip circumference loss (P = 0.039; VAT: P = 0.033).

Conclusions

A lower basal ACSS2, ACC1 and ACL expression, genes involved in de novo lipogenesis, is associated with a better evolution of anthropometric variables after bariatric surgery. Thus, the previous state of the pathways involved in fatty acid metabolism may have repercussions on the improvement of these patients.     

Analysis for Distinctive Activation Patterns of Pain and Itchy in the Human Brain Cortex Measured Using Near Infrared Spectroscopy (NIRS)

Pain and itch are closely related sensations, yet qualitatively quite distinct. Despite recent advances in brain imaging techniques, identifying the differences between pain and itch signals in the brain cortex is difficult due to continuous temporal and spatial changes in the signals. The high spatial resolution of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) has substantially advanced research of pain and itch, but these are uncomfortable because of expensiveness, importability and the limited operation in the shielded room. Here, we used near infrared spectroscopy (NIRS), which has more conventional usability. NIRS can be used to visualize dynamic changes in oxygenated hemoglobin and deoxyhemoglobin concentrations in the capillary networks near activated neural circuits in real-time as well as fMRI. We observed distinct activation patterns in the frontal cortex for acute pain and histamine-induced itch. The prefrontal cortex exhibited a pain-related and itch-related activation pattern of blood flow in each subject. Although it looked as though that activation pattern for pain and itching was different in each subject, further cross correlation analysis of NIRS signals between each channels showed an overall agreement with regard to prefrontal area involvement. As a result, pain-related and itch-related blood flow responses (delayed responses in prefrontal area) were found to be clearly different between pain (τ = +18.7 sec) and itch (τ = +0.63 sec) stimulation. This is the first pilot study to demonstrate the temporal and spatial separation of a pain-induced blood flow and an itch-induced blood flow in human cortex during information processing.