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Bone pathology is frequent in stressed individuals. A comprehensive examination of mechanisms linking life stress, depression and disturbed bone homeostasis is missing. In this translational study, mice exposed to early life stress (MSUS) were examined for bone microarchitecture (μCT), metabolism (qPCR/ELISA), and neuronal stress mediator expression (qPCR) and compared with a sample of depressive patients with or without early life stress by analyzing bone mineral density (BMD) (DXA) and metabolic changes in serum (osteocalcin, PINP, CTX-I). MSUS mice showed a significant decrease in NGF, NPYR1, VIPR1 and TACR1 expression, higher innervation density in bone, and increased serum levels of CTX-I, suggesting a milieu in favor of catabolic bone turnover. MSUS mice had a significantly lower body weight compared to control mice, and this caused minor effects on bone microarchitecture. Depressive patients with experiences of childhood neglect also showed a catabolic pattern. A significant reduction in BMD was observed in depressive patients with childhood abuse and stressful life events during childhood. Therefore, future studies on prevention and treatment strategies for both mental and bone disease should consider early life stress as a risk factor for bone pathologies.
Background Aversive stimuli in the environment influence human actions. This includes valence-dependent influences on action selection, e.g., increased avoidance but decreased approach behavior. However, it is yet unclear how aversive stimuli interact with complex learning and decision-making in the reward and avoidance domain. Moreover, the underlying computational mechanisms of these decision-making biases are unknown. Methods To elucidate these mechanisms, 54 healthy young male subjects performed a two-step sequential decision-making task, which allows to computationally model different aspects of learning, e.g., model-free, habitual, and model-based, goal-directed learning. We used a within-subject design, crossing task valence (reward vs. punishment learning) with emotional context (aversive vs. neutral background stimuli). We analyzed choice data, applied a computational model, and performed simulations. Results Whereas model-based learning was not affected, aversive stimuli interacted with model-free learning in a way that depended on task valence. Thus, aversive stimuli increased model-free avoidance learning but decreased model-free reward learning. The computational model confirmed this effect: the parameter lambda that indicates the influence of reward prediction errors on decision values was increased in the punishment condition but decreased in the reward condition when aversive stimuli were present. Further, by using the inferred computational parameters to simulate choice data, our effects were captured. Exploratory analyses revealed that the observed biases were associated with subclinical depressive symptoms. Conclusion Our data show that aversive environmental stimuli affect complex learning and decision-making, which depends on task valence. Further, we provide a model of the underlying computations of this affective modulation. Finally, our finding of increased decision-making biases in subjects reporting subclinical depressive symptoms matches recent reports of amplified Pavlovian influences on action selection in depression and suggests a potential vulnerability factor for mood disorders. We discuss our findings in the light of the involvement of the neuromodulators serotonin and dopamine.
Drugs of abuse elicit dopamine release in the ventral striatum, possibly biasing dopamine-driven reinforcement learning towards drug-related reward at the expense of non-drug-related reward. Indeed, in alcohol-dependent patients, reactivity in dopaminergic target areas is shifted from non-drug-related stimuli towards drug-related stimuli. Such hijacked' dopamine signals may impair flexible learning from non-drug-related rewards, and thus promote craving for the drug of abuse. Here, we used functional magnetic resonance imaging to measure ventral striatal activation by reward prediction errors (RPEs) during a probabilistic reversal learning task in recently detoxified alcohol-dependent patients and healthy controls (N=27). All participants also underwent 6-[F-18]fluoro-DOPA positron emission tomography to assess ventral striatal dopamine synthesis capacity. Neither ventral striatal activation by RPEs nor striatal dopamine synthesis capacity differed between groups. However, ventral striatal coding of RPEs correlated inversely with craving in patients. Furthermore, we found a negative correlation between ventral striatal coding of RPEs and dopamine synthesis capacity in healthy controls, but not in alcohol-dependent patients. Moderator analyses showed that the magnitude of the association between dopamine synthesis capacity and RPE coding depended on the amount of chronic, habitual alcohol intake. Despite the relatively small sample size, a power analysis supports the reported results. Using a multimodal imaging approach, this study suggests that dopaminergic modulation of neural learning signals is disrupted in alcohol dependence in proportion to long-term alcohol intake of patients. Alcohol intake may perpetuate itself by interfering with dopaminergic modulation of neural learning signals in the ventral striatum, thus increasing craving for habitual drug intake.
Stress plays a key role in modulating addictive behavior and can cause relapse following periods of abstinence. Common effects of stress and alcohol on the dopaminergic system have been suggested, although the precise mechanisms are unclear. Here, we investigated 20 detoxified alcohol-dependent patients and 19 matched healthy controls and assessed striatal D2/D3 availability using [F-18]-fallypride positron emission tomography and stressful life events. We found a strong association between striatal D2/D3 availability and stress in patients, but not in healthy controls. Interestingly, we found increased D2/D3 receptor availability in patients with higher stress levels. This mirrors complex interactions between stress and alcohol intake in animal studies and emphasizes the importance to investigate stress exposure in neurobiological studies of addiction.
We investigated the efficacy of reminiscence therapy (RT) on symptoms of depression in patients with mild to moderate dementia. Out of 227 patients with mild to moderate dementia from a specialized physician’s office, 27 pairs (N = 54; mean age 79.04 ± 6.16 years) who had either received treatment as usual (TAU) or TAU combined with RT, were matched retrospectively according to age as well as cognitive and depressive symptom scores. After controlling for age and sex, symptoms of depression significantly decreased over time in the RT group compared to TAU (F1,52 = 4.36; p < .05). RT is a promising option for the treatment of depression in mild to moderate dementia. Larger randomized-controlled trials are needed.
Background: Infection with human immunodeficiency virus (HIV) affects muscle mass, altering independent activities of people living with HIV (PLWH). Resistance training alone (RT) or combined with aerobic exercise (AE) is linked to improved muscle mass and strength maintenance in PLWH. These exercise benefits have been the focus of different meta-analyses, although only a limited number of studies have been identified up to the year 2013/4. An up-to-date systematic review and meta-analysis concerning the effect of RT alone or combined with AE on strength parameters and hormones is of high value, since more and recent studies dealing with these types of exercise in PLWH have been published. Methods: Randomized controlled trials evaluating the effects of RT alone, AE alone or the combination of both (AERT) on PLWH was performed through five web-databases up to December 2017. Risk of bias and study quality was attained using the PEDro scale. Weighted mean difference (WMD) from baseline to post-intervention changes was calculated. The I2 statistics for heterogeneity was calculated.
Results: Thirteen studies reported strength outcomes. Eight studies presented a low risk of bias. The overall change in upper body strength was 19.3 Kg (95% CI: 9.8±28.8, p< 0.001) after AERT and 17.5 Kg (95% CI: 16±19.1, p< 0.001) for RT. Lower body change was 29.4 Kg (95% CI: 18.1±40.8, p< 0.001) after RT and 10.2 Kg (95% CI: 6.7±13.8, p< 0.001) for AERT. Changes were higher after controlling for the risk of bias in upper and lower body strength and for supervised exercise in lower body strength. A significant change towards lower levels of IL-6 was found (-2.4 ng/dl (95% CI: -2.6, -2.1, p< 0.001). Conclusion: Both resistance training alone and combined with aerobic exercise showed a positive change when studies with low risk of bias and professional supervision were analyzed, improving upper and, more critically, lower body muscle strength. Also, this study found that exercise had a lowering effect on IL-6 levels in PLWH.
Age-related decline in executive functions and postural control due to degenerative processes in the central nervous system have been related to increased fall-risk in old age. Many studies have shown cognitive-postural dual-task interference in old adults, but research on the role of specific executive functions in this context has just begun. In this study, we addressed the question whether postural control is impaired depending on the coordination of concurrent response-selection processes related to the compatibility of input and output modality mappings as compared to impairments related to working-memory load in the comparison of cognitive dual and single tasks. Specifically, we measured total center of pressure (CoP) displacements in healthy female participants aged 19–30 and 66–84 years while they performed different versions of a spatial one-back working memory task during semi-tandem stance on an unstable surface (i.e., balance pad) while standing on a force plate. The specific working-memory tasks comprised: (i) modality compatible single tasks (i.e., visual-manual or auditory-vocal tasks), (ii) modality compatible dual tasks (i.e., visual-manual and auditory-vocal tasks), (iii) modality incompatible single tasks (i.e., visual-vocal or auditory-manual tasks), and (iv) modality incompatible dual tasks (i.e., visual-vocal and auditory-manual tasks). In addition, participants performed the same tasks while sitting. As expected from previous research, old adults showed generally impaired performance under high working-memory load (i.e., dual vs. single one-back task). In addition, modality compatibility affected one-back performance in dual-task but not in single-task conditions with strikingly pronounced impairments in old adults. Notably, the modality incompatible dual task also resulted in a selective increase in total CoP displacements compared to the modality compatible dual task in the old but not in the young participants. These results suggest that in addition to effects of working-memory load, processes related to simultaneously overcoming special linkages between input- and output modalities interfere with postural control in old but not in young female adults. Our preliminary data provide further evidence for the involvement of cognitive control processes in postural tasks.