A resting‐state fMRI study of obese females between pre‐ and postprandial states before and after bariatric surgery

Past studies utilizing resting‐state functional MRI (rsfMRI), have shown that obese humans exhibit altered activity in brain areas related to reward compared to normal‐weight controls. However, to what extent bariatric surgery‐induced weight loss alters resting‐state brain activity in obese humans is less well‐studied. Thus, we measured the fractional amplitude of low‐frequency fluctuations from eyes‐closed, rsfMRI in obese females (n = 11, mean age = 42 years, mean BMI = 41 kg/m²) in both a pre‐ and postprandial state at two time points: four weeks before, and four weeks after bariatric surgery. Several brain areas showed altered resting‐state activity following bariatric surgery, including the putamen, insula, cingulate, thalamus and frontal regions. Activity augmented by surgery was also dependent on prandial state. For example, in the fasted state, activity in the middle frontal and pre‐ and postcentral gyri was found to be decreased after surgery. In the sated state, activity within the insula was increased before, but not after surgery. Collectively, our results suggest that resting‐state neural functions are rapidly affected following bariatric surgery and the associated weight loss and change in diet.     

Integrative brain structural and molecular analyses of interaction between tobacco use disorder and overweight among male adults

Tobacco smoking and overweight lead to adverse health effects, which remain an important public health problem worldwide. Researches indicate overlapping pathophysiology may contribute to tobacco use disorder (TUD) and overweight, but the neurobiological interaction mechanism between the two factors is still unclear. This study used a mixed sample design, including the following four groups: (i) overweight long-term smokers (n = 24, age = 31.80 ± 5.70, cigarettes/day = 20.50 ± 7.89); (ii) normal weight smokers (n = 28, age = 31.29 ± 5.56, cigarettes/day = 16.11 ± 8.35); (iii) overweight nonsmokers (n = 19, age = 33.05 ± 5.60), and (iv) normal weight nonsmokers (n = 28, age = 31.68 ± 6.57), a total of 99 male subjects. All subjects underwent T1-weighted high-resolution MRI. We used voxel-based morphometry to compare gray matter volume (GMV) among the four groups. Then, JuSpace toolbox was used for cross-modal correlations of MRI-based modalities with nuclear imaging derived estimates, to examine specific neurotransmitter system changes underlying the two factors. Our results illustrate a significant antagonistic interaction between TUD and weight status in left dorsolateral prefrontal cortex (DLPFC), and a quadratic effect of BMI on DLPFC GMV. For main effect of TUD, long-term smokers were associated with greater GMV in bilateral OFC compared with nonsmokers irrespective of weight status, and such alteration is negatively associated with pack-year and FTND scores. Furthermore, we also found GMV changes related to TUD and overweight are associated with μ-opioid receptor system and TUD-related GMV alterations are associated with noradrenaline transporter maps. This study sheds light on novel multimodal neuromechanistic about the relationship between TUD and overweight, which possibly provides hints into future treatment for the special population of comorbid TUD and overweight.     

Correlation of serum BDNF levels with hippocampal volumes in first episode, medication-free depressed patients

The hippocampus seems to be affected in MDD, and brain-derived neurotrophic factor (BDNF) has positive effects on neurogenesis within the hippocampus. Although there are inconsistencies among study results, a smaller hippocampal volume in depressed patients is thought to be related to the pathophysiology of the disease. We looked at the correlation between serum BDNF (sBDNF) levels and hippocampal volumes (HCV) of first-episode MDD patients (18 female, 7 male; mean age = 32.1 ± 9.3) and healthy controls (17 female, 5 male; mean age = 29.7 ± 6.4). Region of interest analysis was conducted on the images acquired via MRI. sBDNF levels and HCV correlated only in the MDD group (right: r = 0.46, P = 0.02; left: r = 0.47, P = 0.02); however, HCV did not differ between MDD patients and healthy controls (right: F = 2.45, df = 1.46, P > 0.05; left: F = 0.05, df = 1.46, P > 0.05). BDNF may be a factor underlying HCV differences between MDD and healthy control subjects, which become apparent as severe and multiple episodes are experienced.     

Comparison of volumetric and shape changes of subcortical structures based on 3-dimensional image between obesity and normal-weighted subjects using 3.0 T MRI

The morphological changes of the brain, particularly in the integrity of white and gray matter and the cortical thickness of brain, have been investigated extensively in obese patients. While there has been a growing amount of evidence indicating that subcortical structures are associated with obesity, studies on the volume of subregional level including shape alterations using high-field MRI are very sparse. The aim of this study was to evaluate and compare the volumes of 14 subcortical structures (bilateral thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens) in obese and normal-weighted subjects using 3T MRI for high resolution imaging. Fifty-four volunteers, 27 obesity (age = 23.15 ± 3.22, body mass index (BMI) = 30.12 ± 3.77) and 27 normal weighted controls (age = 26.1 ± 5.78, BMI = 21.76 ± 1.74) participated in the study. Through volumetric analysis, we found that the obese subjects had enlarged bilateral thalamus, putamen, pallidus and hippocampus, reduced bilateral caudate in obese groups in comparison to normal-weighted groups. Furthermore, we found that the medial-dorsal part of bilateral caudate significantly shrank while the lateral-dorsal part of bilateral thalamus significantly increased through vertex-based analysis (p < 0.05). Thus, based on our evidence, we suggest that subcortical structures are associated with feeding behavior and sensory function in obese patients.     

Obesity and coronary risk in patients treated with second-generation antipsychotics

Weight gain leading to obesity is a frequent adverse effect of treatment with atypical antipsychotics. However, the degree of its independent contribution to the risk of coronary heart disease events in patients treated with these drugs has not been elucidated. The aim of this study is to determine whether obesity is an independent risk factor for the 10-year risk of coronary heart disease events in psychiatric patients treated with atypical antipsychotics. We used the Framingham method, which is based on age, gender, blood pressure, smoking, and plasma levels of total and high-density lipoprotein cholesterol, to estimate the 10-year risk of coronary heart disease events in patients treated with second-generation antipsychotics who were obese (N = 44; mean age 38.1 years, 54.5% men) or normal weight (N = 83; mean age 39.9 years, 47.0% men). Excluded were patients with metabolic syndrome and those taking antihypertensive, hypoglycemic, and lipid-lowering drugs. The 10-year risk of coronary artery disease events was very low and virtually identical in the obese and normal weight patients (2.3 ± 3.5 vs. 2.6 ± 4.6, P = 0.68), despite excess of 12 BMI units (P < 0.0001) and 15.7 cm waist circumference (P < 0.0001) in the obese. The risk was similar in obese and normal weight men (3.8 ± 5.9 vs. 2.8 ± 3.4, P = 0.45) and women (1.7 ± 3.7 vs. 1.5 ± 2.5, P = 0.83). The validity of the 10-year prediction for risk of coronary heart disease events in the mentally ill based on the Framingham score system requires prospective confirmation. Obesity does not appear to be an independent predictor for the 10-year risk of coronary heart disease events in patients without metabolic syndrome treated with second-generation antipsychotics.     

Acute vs. Prolonged Screening for Spinal Cord Stimulation in Chronic Pain

Spinal cord stimulation (SCS) was performed to test the hypothesis that pain relief data during acute (15 minute intraoperative) and prolonged (5 day) SCS screening have equivalent predictive value for long‐term successful SCS control of chronic low back pain and/or lower extremity pain. A retrospective series of patients with chronic low back and/or lower extremity pain underwent either percutaneous or open (ie, laminectomy) SCS implantation during which acute intraoperative followed by prolonged screening trials for percentage pain relief (%PR) were performed. Data were analyzed for (a) correlation between positive predictive value (PPV) of acute and prolonged SCS screening for %PR and (b) PPV of acute vs. prolonged screening %PR for long‐term SCS %PR. Fifty‐four patients (male/female = 38/16; mean age ± SEM = 54.2 ± 2.0 years) underwent thoracic (T) (mean level = T9.1 ± 0.4) percutaneous (n = 33) and laminectomy (n = 21) implantation of SCS for acute (15 minute intraoperative) and prolonged (5.0 ± 0.3 days) SCS screening of pain relief. Correlation between successful (> 50%PR) pain relief during acute (n = 53/54, PPV = 98%) and prolonged (n = 47/52, PPV = 90%) screening was significant (Spearman Rank Correlation Coefficient, SRCC = 0.462, p < 0.01). After permanent SCS implantation, at mean follow‐up = 9.4 ± 1.5 months, acute and prolonged SCS screening %PR PPV's were each statistically significant for predicting long‐term SCS relief of chronic pain (n = 31/38, PPV = 82% and n = 31/36, PPV = 86%, SRCC = 0.462 and 0.433, respectively, p < 0.01). We conclude that successful pain relief during acute SCS screening is highly correlated with successful prolonged SCS screening of chronic low back and/or lower extremity pain relief. Acute and prolonged SCS screening appear to have equivalent predictive value for successful long‐term SCS control of chronic low back and/or lower extremity pain. These preliminary results suggest potential justification for eliminating prolonged and retaining acute (intraoperative) SCS screening for selection of permanent SCS implantation candidates.     

Effects of serum Brain Derived Neurotrophic Factor on exercise augmentation treatment of depression

Background

Brain Derived Neurotrophic Factor (BDNF) has potential as a biomarker of depression treatment because serum BDNF in depressed human subjects is decreased and normalizes with treatment. The relationship between serum BDNF and exercise treatment of depression is not known. The Treatment with Exercise Augmentation for Depression (TREAD) study examined dosed exercise augmentation treatment of partial responders to antidepressants. Serum BDNF in TREAD subjects was analyzed to understand its relationship with exercise training.

Methods

Subjects were randomized to high (16 kcal/kg/week or KKW) or low (4 KKW) energy expenditure exercise over 12 weeks. Actual kcal/week expended and IDS-C scores were collected weekly. One hundred four subjects in TREAD provided baseline blood samples; a subset of 70 subjects also provided week 12 samples. Serum BDNF was determined using ELISA. Correlations were examined between change in BDNF and 1) mean kcal/week expended, and 2) change in IDS-C score. Mixed-effects ANOVA examined the effect of baseline BDNF on outcome.

Results

Resting serum BDNF was stable and did not correlate with energy expenditure (p = 0.15) or IDS-C improvement (p = 0.89). Subjects entering the study with higher BDNF improved more rapidly on the IDS-C (p = 0.003).

Limitations

Serum may not be the most sensitive blood fraction in which to measure BDNF change. Pre-treatment with medication may mask exercise effect on BDNF.

Conclusions

These results suggest that change in serum BDNF does not reflect efficacy of exercise augmentation treatment of MDD. Instead BDNF may function as an augmentation moderator. Pre-treatments that raise BDNF may improve the efficacy of exercise treatment of MDD.     

Brain BDNF levels are dependent on cerebrovascular endothelium‐derived nitric oxide

Scientific evidence continues to demonstrate a link between endothelial function and cognition. Besides, several studies have identified a complex interplay between nitric oxide (NO) and brain‐derived neurotrophic factor (BDNF), a neurotrophin largely involved in cognition. Therefore, this study investigated the link between cerebral endothelium‐derived NO and BDNF signaling. For this purpose, levels of BDNF and the phosphorylated form of endothelial NO synthase at serine 1177 (p‐eNOS) were simultaneously measured in the cortex and hippocampus of rats subjected to either bilateral common carotid occlusion (n = 6), physical exercise (n = 6) or a combination of both (n = 6) as experimental approaches to modulate flow‐induced NO production by the cerebrovasculature. Tropomyosin‐related kinase type B (TrkB) receptors and its phosphorylated form at tyrosine 816 (p‐TrkB) were also measured. Moreover, we investigated BDNF synthesis in brain slices exposed to the NO donor glyceryl trinitrate. Our results showed increased p‐eNOS and BDNF levels after exercise and decreased levels after vascular occlusion as compared to corresponding controls, with a positive correlation between changes in p‐eNOS and BDNF (r = 0.679). Exercise after vascular occlusion did not change levels of these proteins. Gyceryl trinitrate increased proBDNF and BDNF levels in brain slices, thus suggesting a possible causal relationship between NO and BDNF. Moreover, vascular occlusion, like exercise, resulted in increased TrkB and p‐TrkB levels, whereas no change was observed with the combination of both. These results suggest that brain BDNF signaling may be dependent on cerebral endothelium‐derived NO production.     

Correlation of BDNF blood levels with interoceptive awareness and maturity fears in anorexia and bulimia nervosa patients

Association studies and rodent models suggest a major role for BDNF (brain-derived neurotrophic factor) in feeding regulation. Altered BDNF blood levels have been associated with eating disorders (ED) and their related psychopathological traits. Since the influence of BDNF on self-reported eating disorder inventory scores (EDI) has not been tested, we investigated the correlation of EDI scales with BDNF plasma levels. BDNF levels were measured by (ELISA), and the EDI questionnaire was administered in a total of 81 ED patients. The relationship between BDNF levels and EDI scores was calculated using a general linear model. After correcting for multiple testing, BDNF plasma levels negatively correlated with the EDI total score (R ² = 0.26; p = 4.09 × 10⁻⁴), interoceptive awareness (R ² = 0.26; p = 1.96 × 10⁻⁴), and maturity fears (R ² = 0.13; p = 6.92 × 10⁻⁴). When subdividing according to the main diagnoses, interoceptive awareness presented significant correlations with BDNF blood levels in both the anorexia nervosa (R ² = 0.33, p = 0.0026) and bulimia nervosa groups (R ² = 0.10; p = 0.008). Our data suggest that BDNF levels may influence the severity of the ED by modulating the associated psychopathology, in particular through the impairment of interoceptive awareness.     

Translating ENIGMA schizophrenia findings using the regional vulnerability index: Association with cognition,symptoms, and disease trajectory

Patients with schizophrenia have patterns of brain deficits including reduced cortical thickness, subcortical gray matter volumes, and cerebral white matter integrity. We proposed the regional vulnerability index (RVI) to translate the results of Enhancing Neuro Imaging Genetics Meta-Analysis studies to the individual level. We calculated RVIs for cortical, subcortical, and white matter measurements and a multimodality RVI. We evaluated RVI as a measure sensitive to schizophrenia-specific neuroanatomical deficits and symptoms and studied the timeline of deficit formations in: early (≤5 years since diagnosis, N = 45, age = 28.8 ± 8.5); intermediate (6–20 years, N = 30, age 43.3 ± 8.6); and chronic (21+ years, N = 44, age = 52.5 ± 5.2) patients and healthy controls (N = 76, age = 38.6 ± 12.4). All RVIs were significantly elevated in patients compared to controls, with the multimodal RVI showing the largest effect size, followed by cortical, white matter and subcortical RVIs (d = 1.57, 1.23, 1.09, and 0.61, all p < 10^?6). Multimodal RVI was significantly correlated with multiple cognitive variables including measures of visual learning, working memory and the total score of the MATRICS consensus cognitive battery, and with negative symptoms. The multimodality and white matter RVIs were significantly elevated in the intermediate and chronic versus early diagnosis group, consistent with ongoing progression. Cortical RVI was stable in the three disease-duration groups, suggesting neurodevelopmental origins of cortical deficits. In summary, neuroanatomical deficits in schizophrenia affect the entire brain; the heterochronicity of their appearance indicates both the neurodevelopmental and progressive nature of this illness. These deficit patterns may be useful for early diagnosis and as quantitative targets for more effective treatment strategies aiming to alter these neuroanatomical deficit patterns.     

Association Study of Brain-Derived Neurotrophic Factor Gene Polymorphisms and Body Weight Change in Schizophrenic Patients Under Long-Term Atypical Antipsychotic Treatment

Schizophrenic patients treated with atypical antipsychotics (AAPs) often develop excessive body weight gain, which may lead to further morbidity and poor treatment compliance. This study examined whether genetic variants in the brain-derived neurotrophic factor (BDNF) gene may be associated with body weight change after AAP treatment. The study included 481 schizophrenic patients treated with clozapine (n = 266), olanzapine (n = 79), or risperidone (n = 136) for an average of 49.2 ± 28.2 months. Three common single-nucleotide polymorphisms (SNPs) of the BDNF gene were chosen as tagging SNPs. In single-marker-based analysis, the BDNF rs11030101-T homozygous genotype was found to be associated with significantly increased body weight gain (P = 0.037). The BDNF Val66Met (rs6265) polymorphism was not found to be associated with body weight gain. Haplotype analysis further showed that the rs11030101-T-allele-related haplotype is also associated with increased body weight gain (P = 0.047). Our findings suggest that there is a nominal association with rs11030101 but did not replicate the previously found relationship between the BDNF Val66Met polymorphism and body weight gain during long-term AAP treatment.     

Hypothalamic Brain‐Derived Neurotrophic Factor Regulates Glucagon Secretion Mediated by Pancreatic Efferent Nerves

Understanding the molecular mechanism of the regulation of glucagon secretion is critical for treating the dysfunction of α cells observed in diabetes. Glucagon‐like peptide (GLP)‐1 analogues reduce plasma glucagon and are assumed to contribute to their action to lower blood glucose. It has previously been demonstrated that the central administration of brain‐derived neurotrophic factor (BDNF) improves glucose metabolism by a mechanism independent of feeding behaviour in obese subjects. Using male rats, we examined whether BDNF influences glucagon secretion from α cells via the the central nervous system. We investigate whether: (i) the central infusion of BDNF stimulates glucagon and/or insulin secretion via the pancreatic efferent nerve from the hypothalamus; (ii) the intraportal infusion of GLP‐1 regulates glucose metabolism via the central and peripheral nervous system; and (iii) BDNF receptor and/or BDNF‐positive fibres are localised near α cells of islets. The portal glucagon level decreased with the central administration of BDNF (n = 6, in each; P < 0.05); in contrast, there was no significant change in portal insulin, peripheral glucagon and insulin levels with the same treatment. This reduction of glucagon secretion was abolished by pancreatic efferent denervation (n = 6, in each; P < 0.05). In an immunohistochemical study, pancreatic α cells were stained specifically with BDNF and tyrosine‐related kinase B, a specific receptor for BDNF, and α cells were also co‐localised with BDNF. Moreover, intraportal administration of GLP‐1 decreased glucagon secretion, as well as blood glucose, whereas it increased the BDNF content in the pancreas; these effects were inhibited with the central infusion of BDNF antibody (n = 6, in each; P < 0.05). BDNF and GLP‐1 affect glucose metabolism and modulate glucagon secretion from pancreatic α cells via the central and peripheral nervous systems.     

Head‐to‐head comparison of 18F‐FP‐CIT and 123I‐FP‐CIT for dopamine transporter imaging in patients with Parkinson's disease: A preliminary study

¹²³I‐FP‐CIT and ¹⁸F‐FP‐CIT are radiotracers which are widely used to diagnose Parkinson's disease (PD). However, to our knowledge, no studies to date have made head‐to‐head comparisons between ¹²³I‐FP‐CIT and ¹⁸F‐FP‐CIT. Therefore, in this study, ¹²³I‐FP‐CIT SPECT/CT was compared with ¹⁸F‐FP‐CIT PET/CT in the same cohort of subjects. Patients with PD and essential tremor (ET) underwent ¹²³I‐FP‐CIT SPECT/CT and ¹⁸F‐FP‐CIT PET/CT. Visual and semiquantitative analyses were conducted. The specific binding ratio (SBR) and putamen to caudate ratio (PCR) were compared between subjects who underwent ¹²³I‐FP‐CIT SPECT/CT and ¹⁸F‐FP‐CIT PET/CT. Visual analysis showed that the striatal uptake of both radiotracers was decreased in the PD group, whereas striatal uptake was intact in the ET group. The SBR between ¹²³I‐FP‐CIT SPECT/CT and ¹⁸F‐FP‐CIT PET/CT showed a positive correlation (r = .78, p < .01). However, the mean SBRs on ¹⁸F‐FP‐CIT PET/CT were higher than those on ¹²³I‐FP‐CIT SPECT/CT (2.19 ± .87 and 1.22 ± .49, respectively; p < .01). The PCRs in these two modalities were correlated with each other (r = .71, p < .01). The mean PCRs on ¹⁸F‐FP‐CIT PET/CT were not significantly higher than those on ¹²³I‐FP‐CIT SPECT/CT (1.31 ± .19 and 0.98 ± .06, respectively; p = .06). These preliminary results indicate that the uptake of both ¹²³I‐FP‐CIT and ¹⁸F‐FP‐CIT was decreased in the PD group when compared with the ET controls. Visual analyses using both methods did not affect the diagnostic accuracy in this study. However, semiquantitative analysis indicated a better contrast of ¹⁸F‐FP‐CIT PET/CT relative to ¹²³I‐FP‐CIT SPECT/CT.     

Low‐volume resistance exercise attenuates the decline in strength and muscle mass associated with immobilization

We determined the effectiveness of low‐volume resistance exercise (EX) for the attenuation of loss of muscle mass and strength during leg immobilization. Men (N = 5) and women (N = 12, age 24 ± 5 years, body mass index 25.4 ± 3.6 kg/m²) were divided into two groups: exercise (EX; n = 12) and control (CON; n = 5). Subjects wore a knee brace on one leg that prevented weight bearing for 14 days. Resistance exercise (EX; 80% of maximal) was performed by the immobilized limb every other day. Immobilization induced a significant reduction (P < 0.05) in muscle fiber and thigh cross‐sectional area (CSA), isometric knee extensor, and plantarflexor strength in the CON (P < 0.01) but not in the EX group. There were significant losses in triceps surae CSA in the CON and EX groups (P < 0.05), but the losses were greater in CON subjects (P < 0.01). A minimal volume (140 contractions in 14 days) of resistive exercise is an effective countermeasure against immobilization‐induced atrophy of the quadriceps femoris but is only partially effective for the triceps surae. Muscle Nerve, 2010     

The effect of acute exercise on blood concentrations of brain‐derived neurotrophic factor in healthy adults: a meta‐analysis

It has been hypothesized that one mechanism through which physical activity provides benefits to cognition and mood is via increasing brain‐derived neurotrophic factor (BDNF) concentrations. Some studies have reported immediate benefits to mood and various cognitive domains after a single session of exercise. This meta‐analysis sought to determine the effect of a single exercise session on concentrations of BDNF in peripheral blood, in order to evaluate the potential role of BDNF in mediating the beneficial effects of exercise on brain health. MEDLINE, Embase, PsycINFO, SPORTDiscus, Rehabilitation & Sports Medicine Source, and CINAHL databases were searched for original, peer‐reviewed reports of peripheral blood BDNF concentrations before and after acute exercise interventions. Risk of bias within studies was assessed using standardized criteria. Standardized mean differences (SMDs) were generated from random effects models. Risk of publication bias was assessed using a funnel plot and Egger's test. Potential sources of heterogeneity were explored in subgroup analyses. In 55 studies that met inclusion criteria, concentrations of peripheral blood BDNF were higher after exercise (SMD = 0.59, 95% CI: 0.46–0.72, P < 0.001). In meta‐regression analysis, greater duration of exercise was associated with greater increases in BDNF. Subgroup analyses revealed an effect in males but not in females, and a greater BDNF increase in plasma than serum. Acute exercise increased BDNF concentrations in the peripheral blood of healthy adults. This effect was influenced by exercise duration and may be different across genders.     

The 5-HTTLPR polymorphism, platelet serotonin transporter activity and platelet serotonin content in underweight and weight-recovered females with anorexia nervosa

Serotonin (5-HT) pathways play an important role in the pathophysiology of anorexia nervosa (AN). In this study, we investigated functional characteristics of the platelet 5-HT transporter and platelet 5-HT content in AN patients at various stages of their illness in comparison to healthy control woman (HCW) controlling for the 5-HTTLPR deletion/insertion polymorphism and other confounding variables. Fasting blood samples of 58 acutely underweight AN patients (acAN, BMI = 15.2 ± 1.4), 26 AN patients of the initial acAN sample after short-term/partial weight restoration (BMI = 17.3 ± 0.9), 36 weight-recovered AN patients (recAN, BMI = 20.7 ± 2.2) and 58 HCW (BMI = 21.6 ± 2.0) were assessed for kinetic characteristics of platelet 5-HT uptake (V _max, K _m) and platelet 5-HT content. Plasma leptin served as an indicator of malnutrition. Mean V _max and K _m values were significantly higher in recAN subjects in comparison to HCW (2.05 ± 0.62 vs. 1.66 ± 0.40 nmol 5-HT/10⁹ platelets min and 432 ± 215 vs. 315 ± 136 nmol, respectively) but there were no differences in platelet 5-HT content (464.8 ± 210.6 vs. 472.0 ± 162.2 ng 5-HT/10⁹ platelets). 5-HT parameters in acAN patients and HCW were similar. 5-HTTLPR variants were not related to 5-HT platelet variables. In the longitudinal part of the study we found significantly increased 5-HT content but unchanged 5-HT uptake in AN patients after short-term/partial weight restoration. Our results highlight the importance of malnutrition for the interpretation of abnormalities in neurotransmitter systems in AN. Changes in platelet 5-HT transporter activity were related to the stage of the illness but not to 5-HTTLPR genotype. Increased V _max and K _m in recovered AN patients might mirror adaptive modulations of the 5-HT system.     

Statins and cognition in late‐life bipolar disorder

Objectives

Recent data suggests that statins have positive effects on cognition in older adults. Studies in patients with mood disorders have found contradicting positive and negative effects of statins on mood and cognition, with limited data in bipolar disorder (BD). The objective of this study was to assess the association between statin use and cognition in older adults with BD.

Methods

In a cross‐sectional sample of 143 euthymic older adults with BD (age ≥ 50), statin users (n = 48) and nonusers (n = 95) were compared for cognitive outcomes: Global and cognitive domain z‐scores were calculated from detailed neuropsychological batteries using normative data from healthy comparators (n = 87).

Results

The sample had a mean age of 64.3 (±8.9) years, 65.0% were female, with an average of 15.1 (±2.79) years of education. Statin users did not differ from nonusers on global (?0.60 [±0.69] vs ?0.49 [±0.68], t[127] = 0.80, P = .42) or individual cognitive domains z‐score.

Conclusions

In older patients with BD, statin use is not independently associated with cognitive impairment. This suggests that in older BD patients, the cognitive dysfunction associated with BD trumps the potential cognitive benefit that is associated with statins in older adults without a psychiatric disorder. Further, statins do not seem to exacerbate this cognitive dysfunction. Future longitudinal studies are needed to confirm these findings.     

Does CPAP treat depressive symptoms in individuals with OSA? An analysis of two 12-week randomized sham CPAP-controlled trials

BackgroundDepression is common in patients with obstructive sleep apnea (OSA). Whether treating OSA with continuous positive airway pressure (CPAP) improves depressive symptoms remains inconclusive. We examined the impact of CPAP on depressive symptoms in OSA patients compared to sham CPAP.MethodsA sub-analysis of two previous randomized sham-controlled trials was conducted. 126 male OSA patients (age = 51 ± 11 years; BMI = 32.0 ± 5.1 kg/m²; apnea hypopnea index = 42.4 ± 22.6 events/hour) were randomised either to therapeutic CPAP (n = 65) or sham CPAP (n = 61). Depressive symptoms were measured using the Depression, Anxiety and Stress Scale (DASS). The main outcome was the change in the DASS depression score (DASSD) after three months between the therapeutic and sham CPAP arms.ResultsThe change in DASSD at three months did not differ between therapeutic and sham CPAP (mean difference: 0.5, 95% CI -3.6 to 4.6, p = 0.80). There was no significant between-group differences within the sub-groups of adherent users (device usage≥4hrs/day), or those with baseline depression (DASSD>9). In a secondary analysis of patients with baseline depression, adherent therapeutic CPAP use was associated with a greater reduction in DASSD scores compared to non-adherers (−10.0, 95% CI -18.3 to −1.8, p = 0.019). Conclusions: Overall, three months of CPAP did not significantly improve depression scores in OSA patients. Adherent use of therapeutic CPAP in patients with baseline depressive symptoms was associated with a reduction in symptom score. Future trials involving OSA patients with higher depressive symptoms will enable us to understand the complex interaction between OSA and depression.     

Chronic high‐caloric diet modifies sleep homeostasis in mice

Obesity prevalence and sleep habit changes are commonplace nowadays, due to modern lifestyle. A bidirectional relationship likely exists between sleep quality and metabolic disruptions, which could impact quality of life. In our study, we investigated the effects of a chronic high‐caloric diet on sleep architecture and sleep regulation in mice. We studied the effect of 3 months high‐caloric diet (HCD, 45% fat) on sleep and the sleep electroencephalogram (EEG) in C57BL/6J mice during 24‐hr baseline (BL) recordings, and after 6‐hr sleep deprivation (SD). We examined the effect of HCD on sleep homeostasis, by performing parameter estimation analysis and simulations of the sleep homeostatic Process S, a measure of sleep pressure, which is reflected in the non‐rapid‐eye‐movement (NREM) sleep slow‐wave‐activity (SWA, EEG power density between 0.5 and 4.0 Hz). Compared to controls (n = 11, 30.7 ± 0.8 g), mice fed with HCD (n = 9, 47.6 ± 0.8 g) showed an increased likelihood of consecutive NREM‐REM sleep cycles, increased REM sleep and decreased NREM sleep EEG SWA. After SD, these effects were more pronounced. The simulation resulted in a close fit between the time course of SWA and Process S in both groups. HCD fed mice had a slower time constant (T_i = 15.98 hr) for the increase in homeostatic sleep pressure compared with controls (5.95 hr) indicating a reduced effect of waking on the increase in sleep pressure. Our results suggest that chronic HCD consumption impacts sleep regulation.     

The link between negative affect,vagal tone,and visceral sensitivity in quiescent Crohn's disease

Autonomic dysfunction and mood disorders are frequently described in Crohn's disease (CD) and are known to influence visceral sensitivity. We addressed the link between vagal tone, negative affect, and visceral sensitivity in CD patients without concomitant features of irritable bowel syndrome (IBS). Rectal distensions to a discomfort threshold of 70% and onset of pain were performed in nine CD patients in remission and eight healthy controls. Autonomic parameters were evaluated with heart rate variability and electrodermal reactivity. We showed that CD patients had (i) higher scores of depressive symptomatology (12 ± 3 in patients vs 4 ± 1 in controls on the Center for Epidemiologic Studies‐Depression Scale; p = 0.038), (ii) reduced vagal tone (HF 257 ± 84 ms² vs 1607 ± 1032 ms², p = 0.043; LF 455 ± 153 ms² vs 1629 ± 585 ms², p = 0.047), (iii) decreased sympathetic reactivity during an aversive stimulus, and (iv) higher tolerance to rectal distension pressures (43 ± 3 mmHg vs 30 ± 2 mmHg, p = 0.002) and low sensitivity index scores. In conclusion, our results provide preliminary evidence that patients with quiescent CD, in the absence of IBS, are hyposensate to experimental rectal distension. These data provide further evidence that anxiety and depressive symptomatology in addition to autonomic dysfunction modulate visceral pain perception in quiescent CD patients in the absence of IBS.