The association of proopiomelanocortin polymorphisms with the risk of major depressive disorder and the response to antidepressants via interactions with stressful life events

Hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis is among the most consistent neuroendocrine abnormalities in major depressive disorder (MDD). The peptide adrenocorticotropin hormone (ACTH) mediates HPA axis function during stress and is encoded by the proopiomelanocortin (POMC) gene polycistronically. After screening 39 POMC polymorphisms, we evaluated the association of polymorphisms with susceptibility to MDD in 145 MDD patients and 193 normal subjects; in patients, we also evaluated the response to treatment with antidepressants. Additionally, we investigated the role of gene–environment interaction between POMC haplotypes and stressful life events (SLE) in the treatment response. Although genotypes and haplotypes were not significantly associated with the risk of MDD, non-remitters were more likely to carry haplotype 1 (ht1) and to have no ht2 than were remitters (corrected P = 0.010–0.035). Although observations were limited in patients without SLE, a significant haplotype–SLE interaction was observed (P = 0.020). Additionally, at 1, 2, and 8 weeks of treatment, the 21-item Hamilton Depression Rating scores of MDD subjects with POMC ht2 were significantly (P = 0.003–0.044) lower than those of patients with ht1 in subjects those did not experience SLE. MDD subjects possessing POMC ht2 achieved remission significantly (P = 0.013; survival analysis) faster than patients with ht1. This study suggests that POMC haplotypes, via an interaction with SLE, are associated with antidepressant treatment outcomes in MDD patients. Regarding SLE, haplotypes of the POMC gene could be useful markers for predicting the response to antidepressant treatment in MDD patients.     

Exercise Addiction: Preliminary Evidence on the Role of Psychological Inflexibility

Previous research suggests that psychological inflexibility may play an important role in the development of both substance and behavioral addictions. However, the influence that psychological inflexibility might exert on exercise addiction has still to be investigated. The objective of this study was to look at the influence of psychological inflexibility on exercise addiction. Three hundred and ninety-eight recreational endurance exercisers (381 men and 17 women) aged between 18 and 60 years (M?=?35.62, SD?=?9.43) completed a self-reported questionnaire. A structural equation model was tested. After controlling for the effects of age (β?=???.34, p?<?.001), frequency (β?=?.24, p?<?.01), and the number of hours of practice (β?=?.09, p?=?.17), psychological inflexibility contributed to explaining exercise addiction (β?=?.26, p?<?.001). The model explained 30% of the variance in exercise addiction. Some preliminary evidence is provided suggesting that psychological inflexibility could condition the potential benefits of practising physical exercise; in particular, by favoring the acquisition of an addictive pattern when carrying out such activity.     

Exercise Dependence and Maladaptive Perfectionism: the Mediating Role of Basic Psychological Needs

The main purpose of the present investigation, based on Self-Determination Theory, was to examine the mediating role of basic psychological needs (Autonomy, Competence, and Relatedness) on the relationship between exercise dependence and maladaptive perfectionism. Participants were 169 Italian subjects, of whom 85 were male and 84 were female (age: M?=?22.76; SD?=?4.99), who regularly performed exercise for more than a year. A Structural Equation Modeling (SEM) analysis showed that the full mediation model in which maladaptive perfectionism was only indirectly related to exercise dependence through needs satisfaction and needs thwarting yielded an acceptable fit χ² (99)?=?175.25, p?<?.01; CFI?=?.93; NNFI?=?.91; SRMR?=?.07, RMSEA?=?.07 (90 % CI?=?.05–.08). Maladaptive perfectionism had a direct positive effect on needs thwarting (β?=?.51, p?<?.001; 95 % CI?=?.35 to .66). Exercise dependence was both positively related to needs satisfaction (β?=?.36, p?<?.001; 95 % CI?=?.13 to .57) and to needs thwarting (β?=?.48, p?<?.001; 95 % CI?=?.24 to .69). Furthermore, psychological needs thwarting exclusively mediates the influence of maladaptive perfectionism on exercise dependence (β?=?.21, p?<?.05; 95 % CI?=?.03 to .39). These findings contribute to better understanding the factors that may underpin the relationship between exercise dependence and perfectionism in light of self-determination theory.     

Suicide risk and prevalence of major depressive disorder (MDD) among individuals infected with HIV-1 subtype C versus B in Southern Brazil

Major depressive disorder (MDD) is among the most prevalent neuropsychiatric disorders associated with HIV infection; however, its risks and neurobiologic correlates in diverse cultures are poorly understood. This study aimed to examine the frequency of MDD among HIV+ participants in southern Brazil. We hypothesized that the frequency and severity of MDD would be higher among individuals with HIV+ compared with HIV? and higher in HIV subtype B compared with C. Individuals with HIV (n?=?39) as well as seronegative controls (n?=?22) were enrolled in a cross-sectional, prospective, observational study. Current and lifetime history of MDD was diagnosed by MINI-Plus; symptom severity was assessed by Beck Depression Inventory-II (BDI-II). Current and past episodes of MDD were significantly more frequent in the HIV+ versus HIV? group: current MDD, 15 (38.5 %) vs. 0 (0 %), p?=?0.0004; past MDD, 24 (61.5 %) vs. 3 (13.6 %), p?=?0.0004. The median BDI-II score in the HIV+ group was significantly higher than that in the HIV? (13 (8–27.5) vs. 2.5 (1–5.5); p?<?0.0001). Current suicide risk, defined as during the last month, was found in 18 % of participants in the HIV-positive and none in the HIV-negative group. Neither current MDD frequency (8 (57.1 %) vs. 6 (40 %), p?=?0.47) nor BDI-II score differed across subtypes B and C. HIV+ group may be more likely to experience current MDD than HIV?. This was the first study to compare the frequency and severity of MDD in HIV subtypes B and C; we found no difference between HIV subtypes B and C.     

Positive effects of fampridine on cognition,fatigue and depression in patients with multiple sclerosis over 2 years

Objective

To assess the effects of PR-fampridine on cognitive functioning, fatigue and depression in patients with multiple sclerosis (PwMS).

Methods

Thirty-two PwMS were included in this trial. Cognitive performance was assessed in an open-label and randomized double-blind, placebo-controlled study design using a comprehensive neuropsychological test battery as well as questionnaires examining depression and fatigue.

Results

We found significant improvements in cognitive measures assessing alertness (tonic alertness, p = 0.0244 and phasic alertness, p = 0.0428), psychomotor speed (p = 0.0140) as well as verbal fluency (p = 0.0002) during open-label treatment with PR-fampridine. These effects of performance were paralleled by patients’ perception of reduced fatigue (physical, p = 0.0131; cognitive, p = 0.0225; total, p = 0.0126). Fampridine-induced improvements in phasic alertness (p = 0.0010) and measures of fatigue (physical, p = 0.0014; cognitive, p = 0.0003; total, p = 0.0005) were confirmed during randomized, double-blind, placebo-controlled assessment in the second year. In addition, we found positive effects of PR-fampridine on depressive symptoms (p = 0.0049). We demonstrated persisting beneficial effects of PR-fampridine on fatigue in PwMS over a period of more than 2 years. Drug responsiveness regarding cognitive performance and fatigue was not limited to walking responders.

Conclusions

Our data demonstrate significant positive effects of treatment with PR-fampridine over 2 years on different cognitive domains as well as fatigue and depression in a cohort of PwMS. These findings imply that PR-fampridine should be considered as symptomatic treatment improving aspects of cognition, fatigue and depression in PwMS.

     

Efficacy and safety of nabiximols (Sativex<Superscript>®</Superscript>) on multiple sclerosis spasticity in a real-life Italian monocentric study

Multiple sclerosis (MS) patients frequently suffer from limb spasticity and pain despite antispastic treatments. To investigate nabiximols efficacy and safety in a real-world monocentric Italian cohort, the following data were collected at baseline, week 4, 14 and 48: Ambulation Index (AI), 10-min walking test (10MWT), combined Modified Ashworth scale (cMAS), scores at numerical rating scale for spasticity (sNRS) and pain (pNRS). Responder status was defined as a ≥20 % reduction in sNRS after 4 weeks of treatment. 144 MS patients (123 progressive and 21 relapsing-remitting) complaining of moderate-to-severe spasticity (mean sNRS: 7.5) were included: 138 (95.8 %) completed the first month of therapy and were classified as follows—23.2 % were non-responders, 5.1 % were responders but discontinued treatment due to side effects, 71.7 % were responders with a mean 32 % reduction in sNRS (p < 0.001). In responders sNRS further decreased between 4 and 14 weeks (p = 0.03). Similarly, pNRS improvement was seen during the first month and between 4 and 14 weeks (p < 0.001 and p = 0.004, respectively). Moreover, at 4 weeks responders showed a significant (p < 0.05) improvement in cMAS, AI and 10MWT, which was maintained at 14 weeks. At 1-year follow-up, a benefit was still evident on spasticity and painful symptoms with a low drop-out rate. Confusion/ideomotor slowing, fatigue and dizziness were the most frequent side effects; no major adverse events were reported. Shorter disease duration at treatment start was associated with better response. This real-world study confirms nabiximols efficacy and safety in the treatment of MS-related spasticity and pain, which is maintained up to 48 weeks.     

Treatment with telmisartan,a long-acting angiotensin II receptor blocker,prevents migraine attacks in Japanese non-responders to lomerizine

Lomerizine, calcium channel blocker, is the most used medication for migraine prophylaxis in Japan. The effectiveness of this drug is reported as 50–75%. Telmisartan is angiotensin II receptor blockers which plasma half-life is 24 h. We examined whether telmisartan has preventative benefits in lomerizine non-responsive migraineurs. Lomerizine non-responders received telmisartan (20 mg/day) for 3 months after the investigation period of 3 months. Blood pressure, frequency of headache days/month, headache severity, and doses of triptans and analgesics were analyzed by Wilcoxon signed rank test. Thirty-three migraineurs (25 women and 8 men) participated in this study. Seven patients had migraine with aura and 26 patients had migraine without aura. Mean age (SD) was 46.6 (10.3) years. Mean duration (SD) of migraine was 20.4 (12.5) years. Headache severity exhibited mild degree in 5 patients, moderate degree in 9 patients and severe degree in 19 patients. Mean frequency (SD) of headache days was 10.9 (8.5) days/month. Mean usage (SD) of triptans was 4.8 (5.1) tablets/month and that of analgesics was 15.2 (22.2) tablets/month. Five patients (15%) had hypertension. Telmisartan administration had benefits in 30 patients (90%). This medication significantly decreased frequency of headache days (P < 0.01) and headache severity (P < 0.01). Doses of triptans were reduced at one-third (P < 0.05) and those of analgesia at one-fifth after telmisartan treatment (P < 0.01). After telmisartan, mean (SD) of systolic blood pressure was significantly decreased (P < 0.05). The present study supported that telmisartan treatment had preventive effects in 90% of lomerizine non-responders. Telmisartan non-responders (10%) exhibited chronic migraine and long migraine duration.     

Surgery for intracranial arachnoid cysts in children—a prospective long-term study

Purpose

Intracranial arachnoid cysts are cystic malformations found in both adults and children. While many are asymptomatic, some cause symptoms and warrant surgical treatment. In this prospective population-based study, we aimed to study the short- and long-term outcome after surgical intervention in children with arachnoid cysts referred to our centre.

Methods

Twenty-seven pediatric patients (13 f. 14 m, mean age 9.4 years) with de novo cysts were consecutively included during a 5-year period. The presenting symptoms were headache (n = 12), balance disturbance and dizziness (n = 6), seizures (n = 6), hydrocephalus (n = 5), and macrocephaly (n = 1). Twenty-two patients underwent surgical treatment with either microsurgical (n = 17) or endoscopic fenestration (n = 5) of the cyst wall. Cyst volume was measured with OsiriX® software pre- and postoperatively. Short-term and long-term follow-up of all patients was conducted 3 months and 8.6 years (7–10.5 years) postoperatively.

Results

Three months after surgery, 59 % of the patients were improved regarding at least one major complaint, and average cyst volume was reduced to 33.3 ml (0–145 ml). At the long-term follow-up of 8.6 years, 77 % of the patients were improved regarding at least one symptom but subjective symptoms remained in 59 %. There was no permanent postoperative morbidity. We found no association between radiological reduction of cyst volume and clinical improvement.

Conclusion

Our findings support a restrictive attitude to surgery for intracranial arachnoid cysts, in the absence of objectively verified symptoms and signs or obstruction of CSF pathways.

     

Aortic hemodynamics and white matter hyperintensities in normotensive postmenopausal women

Hypertension is associated with development of white matter hyperintensities (WMH) in the brain, which are risk factors for mild cognitive impairment. Hormonal shifts at menopause alter vascular function putting women at risk for both hypertension and WMH. Elevations in aortic hemodynamics precede the appearance of clinically defined hypertension but the relationship of aortic hemodynamics to development of WMH in women is not known. Therefore, this study aimed to characterize aortic hemodynamics in relationship to WMH in postmenopausal women. Aortic systolic and diastolic blood pressure (BP), aortic augmentation index (Alx) and aortic round trip travel time (Aortic T _R) by tonometry were examined in 53 postmenopausal women (age 60 ± 2 years). WMH was calculated from fluid-attenuated inversion recovery MRI using a semi-automated segmentation algorithm. WMH as a fraction of total white matter volume positively associated with aortic systolic BP (regression coefficient = 0.018; p = 0.04) after adjusting for age. In addition, WMH fraction was positively associated with AIx (0.025; p = 0.04), and inversely associated with Aortic T _R (?0.015; p = 0.04) after adjusting for age. Our results suggest that assessing aortic hemodynamics may identify individuals at risk for accelerated development of WMH and guide early treatment to reduce WMH burden and cognitive impairment in the future.     

<Emphasis Type="Italic">ABCC8</Emphasis> Single Nucleotide Polymorphisms are Associated with Cerebral Edema in Severe TBI

Objective

Cerebral edema (CE) in traumatic brain injury (TBI) is the consequence of multiple underlying mechanisms and is associated with unfavorable outcomes. Genetic variability in these pathways likely explains some of the clinical heterogeneity observed in edema development. A role for sulfonylurea receptor-1 (Sur1) in CE is supported. However, there are no prior studies examining the effect of genetic variability in the Sur1 gene (ABCC8) on the development of CE. We hypothesize that ABCC8 single nucleotide polymorphisms (SNPs) are predictive of CE.

Methods

DNA was extracted from 385 patients. SNPs in ABCC8 were genotyped using the Human Core Exome v1.2 (Illumina). CE measurements included acute CT edema, mean and peak intracranial pressure (ICP), and need for decompressive craniotomy.

Results

Fourteen SNPs with minor allele frequency >0.2 were identified. Four SNPS rs2283261, rs3819521, rs2283258, and rs1799857 were associated with CE measures. In multiple regression models, homozygote-variant genotypes in rs2283261, rs3819521, and rs2283258 had increased odds of CT edema (OR 2.45, p = 0.007; OR 2.95, p = 0.025; OR 3.00, p = 0.013), had higher mean (β = 3.13, p = 0.000; β = 2.95, p = 0.005; β = 3.20, p = 0.008), and peak ICP (β = 8.00, p = 0.001; β = 7.64, p = 0.007; β = 6.89, p = 0.034). The homozygote wild-type genotype of rs1799857 had decreased odds of decompressive craniotomy (OR 0.47, p = 0.004).

Conclusions

This is the first report assessing the impact of ABCC8 genetic variability on CE development in TBI. Minor allele ABCC8 SNP genotypes had increased risk of CE, while major SNP alleles were protective—potentially suggesting an evolutionary advantage. These findings could guide risk stratification, treatment responders, and the development of novel targeted or gene-based therapies against CE in TBI and other neurological disorders.

     

Identification of major depressive disorder among the long-term unemployed

Purpose

Depression is a common mental health disorder among the unemployed, but research on identifying their depression in health care is scarce. The present study aimed to explore the identification of major depressive disorder (MDD) in health care on long-term unemployed and find out if the duration of unemployment correlates with the risk for unidentified MDD.

Methods

The study sample consisted the patient files of long-term unemployed people (duration of unemployment 1–35 years, median 11 years), who in a screening project diagnosed with MDD (n?=?243). The MDD diagnosis was found in the health care records of 101. Binomial logistic regression models were used to explore the effect of the duration of unemployment, as a discrete variable, to the identification of MDD in health care.

Results

MDD was appropriately identified in health care for 42% (n?=?101) of the participants with MDD. The odds ratio for unidentified MDD in health care was 1.060 (95% confidence interval 1.011; 1.111, p?=?0.016) per unemployment year. When unemployment had continued, for example, for five years the odds ratio for having unidentified MDD was 1.336. The association remained significant throughout adjustments for the set of background factors (gender, age, occupational status, marital status, homelessness, criminal record, suicide attempts, number of health care visits).

Conclusions

This study among depressed long-term unemployed people indicates that the longer the unemployment period has lasted, the more commonly these people suffer from unidentified MDD. Health services should be developed with respect to sensitivity to detect signs of depression among the long-term unemployed.

     

Insular multiple sclerosis lesions are associated with erectile dysfunction

Erectile function (EF) is frequently compromised in men with multiple sclerosis (MS). Functional neuroimaging in healthy men identified a network of brain areas, such as the insula, visual and somatosensory association areas, cingulate gyrus, prefrontal cortex, as well as subcortical regions, contributing to EF. This study intended to determine associations between EF deterioration during MS and cerebral MS-associated lesion sites. In 31 men with MS (mean age 38.2 ± 11.2 years), we evaluated MS-related EF deterioration by comparing scores of the 5-item International Index of Erectile Function-5 questionnaire (IIEF5) at the time of study and retrospectively, 3 months prior to MS diagnosis, by calculating score differences as DeltaIIEF5 (DeltaIIEF5 score < 0 indicated EF deterioration). To assess the impact of confounding factors of EF, patient age, disease duration, disease severity, depressiveness, bladder and bowel symptoms, and total cerebral MS lesion volume were correlated with DeltaIIEF5 scores (Spearman rank correlation) and compared between patients with and without EF deterioration (t tests or Mann–Whitney U test). MS lesions were assessed on T2-weighted magnetic resonance imaging (MRI; 1.5 or 3 T). We determined the lesion overlap (prevalence of identical lesion sites among patients), subtracted lesion overlaps in patients without EF deterioration from overlaps in patients with EF deterioration, and compared DeltaIIEF5 scores voxel-wise between patients with and without lesions in a given voxel (t test; significance: p < 0.05). In 14 patients (45.2%), DeltaIIEF5 scores indicated EF deterioration. DeltaIIEF5 scores were not associated with age (ρ = 0.06; p = 0.74), disease duration (ρ = 0.26; p = 0.15), disease severity (ρ = ? 0.19; p = 0.31), depressiveness (ρ = 0.07; p = 0.72), bladder symptoms (ρ = ? 0.11; p = 0.57), bowel symptoms (ρ = 0.17; p = 0.37), and total lesion volume (ρ = ? 0.13; p = 0.47). The voxel-wise analysis showed associations between EF deterioration and MS lesions primarily in the bilateral, and predominantly left juxtacortical insular region. In conclusion, MS lesions particularly in the left insular region, which is activated with sexual arousal, contribute to erectile dysfunction.     

Combined stimulant and antipsychotic treatment in adolescents with attention-deficit/hyperactivity disorder: a cross-sectional observational structural MRI study

Meta-analyses suggest normalizing effects of methylphenidate on structural fronto-striatal abnormalities in patients with attention-deficit/hyperactivity disorder (ADHD). A subgroup of patients receives atypical antipsychotics concurrent with methylphenidate. Long-term safety and efficacy of combined treatment are unknown. The current study provides an initial investigation of structural brain correlates of combined methylphenidate and antipsychotic treatment in patients with ADHD. Structural magnetic resonance imaging was obtained in 31 patients who had received combined methylphenidate and antipsychotic treatment, 31 matched patients who had received methylphenidate but not antipsychotics, and 31 healthy controls (M age 16.7 years). We analyzed between-group effects in total cortical and subcortical volume, and in seven frontal cortical and eight subcortical-limbic volumes of interest, each involved in dopaminergic neurotransmission. Patients in the combined treatment group, but not those in the methylphenidate only group, showed a reduction in total cortical volume compared to healthy controls (Cohen’s d = 0.69, p < 0.004), which was apparent in most frontal volumes of interest. Further, the combined treatment group, but not the methylphenidate group, showed volume reduction in bilateral ventral diencephalon (Left Cohen’s d = 0.48, p < 0.04; Right Cohen’s d = 0.46, p < 0.05) and the left thalamus (Cohen’s d = 0.47, p < 0.04). These findings may indicate antipsychotic treatment counteracting the normalizing effects of methylphenidate on brain structure. However, it cannot be ruled out that pre-existing clinical differences between both patient groups may have resulted in anatomical differences at the time of scanning. The absence of an untreated ADHD group hinders unequivocal interpretation and implications of our findings.     

Exercise Addiction and Psychophysiological Health in Korean Collegiate Students

This study was carried out with collegiate students who took part in an exercise program for 1 year. An exercise addiction (EA) questionnaire was used to classify EA and non-EA (NEA) groups. Exercise dependence (ED), compulsive exercise (CE), and obligatory exercise (OE) questionnaires were used to validate the EA results. A total of 38 male and 37 female college students were selected as the subjects for this study to investigate the effects of EA on psychophysiological health. The psychophysiological health variables were composed of depression, stress, body composition, and muscular joint health. This study showed that EA was significantly associated with ED (r = 0.746; P = 0.001), CE (r = 0.644; P = 0.001), and OE (r = 0.731; P = 0.001), respectively. Although there were no significant differences between EA groups and NEA groups for both males and females on depression (Z = ? 0.813; P = 0.416 and Z = ? 0.148; P = 0.882, respectively), physical stress (Z = ? 0.777; P = 0.437 and Z = ?0.074; P = 0.941, respectively), and emotional stress (Z = ? 1.035; P = 0.300 and Z = ? 0.573; P = 0.567, respectively), the elbow and knee joint functions of EA males were significantly higher compared with those of NEA males. However, the variables of body composition in EA females were not significantly different from those of NEA females. Being addicted to exercise for 1 year resulted in negative effects on the psychological health in both genders, while it had a negative effect on physical health for women only.     

Hemodynamic contribution of transdural collateral flow in adult patients with moyamoya disease

To evaluate the hemodynamic contributions of collateral flow in adult patients with moyamoya disease, neurological deterioration or fluctuation during admission, Suzuki grade, various collateral routes, lesion volume, cerebral blood flow (CBF), and their associations were analyzed. Thirty patients (60 cerebral hemispheres, mean age 45 ± 25 years, and 73.3 % female) who were diagnosed with moyamoya disease or syndrome were enrolled over 3 years. Moyamoya stages from each hemisphere were stratified according to the Suzuki’s criteria through six-vessel angiography into internal carotid arteries (ICAs), external carotid arteries (ECAs), and vertebral arteries (VAs). Collateral routes were categorized into the circle of Willis, leptomeningeal, and transdural. The volume of ipsilateral infarction was analyzed by magnetic resonance imaging. CBF volume was measured using color-coded duplex sonography. Suzuki’s grade was inversely correlated with flow volume of the ICAs (p < 0.001), whereas no association was found with that of the ECAs (p = 0.445) or VAs (p = 0.096). Among hemispheres with ≥ grade 3 (n = 36), patients with transdural ECA collateral flow had less neurological deterioration or fluctuation (0.0 vs. 30.8 %, p = 0.047), smaller lesion volume (2.4 ± 3.6 vs. 27.6 ± 59.3 mL, p = 0.041), lower ICA flow (88.4 ± 45.9 vs. 146.2 ± 121.7 mL/min, p = 0.022), higher ECA flow (205.7 ± 77.7 vs. 135.9 ± 52.7 mL/min, p = 0.046), and a higher ECA/ICA flow volume ratio (31.8 ± 92.8 vs. 1.7 ± 1.9, p = 0.024). Our results suggest that ICA flow volume is inversely correlated with Suzuki grade, and that transdural ECA collaterals appear to be an important detour in adult patients with advanced stage moyamoya disease, suggesting a protector against an impending ischemic attack.     

Lower functional connectivity of default mode network in cognitively normal young adults with mutation of <Emphasis Type="Italic">APP</Emphasis>, <Emphasis Type="Italic">presenilins</Emphasis> and <Emphasis Type="Italic">APOE ε4</Emphasis>

In this study, we used resting-state functional magnetic resonance imaging to explore the genetic effects of amyloid precursor protein (APP) or presenilins mutation and apolipoprotein E (APOE) ε4 on the default-mode network (DMN) in cognitively intact young adults (24.1 ± 2.5 years). Both the APP or presenilin-1/2 group and the APOE ε4 group had significantly lower DMN functional connectivity (FC) in the some brain regions like precuneus/middle cingulate cortices (PCu/MCC) than controls (AlphaSim corrected, P < 0.05). Only a lower FC tendency was demonstrated (control < APOE ε4 < APP or presenilin-1/2 group). Moreover, lower FC in PCu/MCC is correlated with some neuropsychological assessments such as similarity test in APOE ε4 group. These findings indicate that DMN FC alteration in APP or presenilin-1/2 or APOE ε4 subjects is prior to the occurrence of neurological alterations and clinical symptoms, and DMN FC might be a valuable biomarker to detect genetic risk in the preclinical stage.     

Dose-Response Effects of Aerobic Exercise on Quality of Life in Postmenopausal Women: Results from the Breast Cancer and Exercise Trial in Alberta (BETA)

Background

Exercise generally improves quality of life (QoL) and psychosocial functioning in adult populations but few randomized trials have examined dose-response effects.

Purpose

The purpose of the present study was to report the QoL and psychosocial outcomes from the Breast Cancer and Exercise Trial in Alberta (BETA).

Methods

Healthy but inactive postmenopausal women at risk for breast cancer were randomized to a year-long aerobic exercise intervention consisting of either 150 min/week (moderate volume group, n = 200) or 300 min/week (high volume group, n = 200). QoL was assessed at baseline and 1 year using the short form-36 health survey. Sleep quality, depression, anxiety, stress, self-esteem, and happiness were also assessed. Participant preference for group assignment (i.e., exercise volume) was assessed at baseline and tested as a moderator.

Results

There were no statistically significant dose-response effects of aerobic exercise on any QoL, sleep quality, or psychosocial outcome. Participant preference for group assignment did not moderate any QoL, sleep quality, or psychosocial responses. Marital status was a significant moderator (p for interaction = 0.01) and obesity showed a trend towards being a moderator (p for interaction = 0.08) of the dose-response effects of aerobic exercise on global sleep quality such that unmarried and obese women improved sleep quality with the higher volume of aerobic exercise.

Conclusions

A higher volume of aerobic exercise, approximately double the minimum public health guideline, did not provide additional QoL or psychosocial benefits compared to the minimum public health guideline in inactive postmenopausal women, even for women who preferred the higher volume of exercise at baseline.

Trial Registration

Trial Registration clinicaltrials.gov identifier: NCT1435005.