The (Poly)Pharmacology of Cannabidiol in Neurological and Neuropsychiatric Disorders: Molecular Mechanisms and Targets

Cannabidiol (CBD), the major nonpsychoactive Cannabis constituent, has been proposed for the treatment of a wide panel of neurological and neuropsychiatric disorders, including anxiety, schizophrenia, epilepsy and drug addiction due to the ability of its versatile scaffold to interact with diverse molecular targets that are not restricted to the endocannabinoid system. Albeit the molecular mechanisms responsible for the therapeutic effects of CBD have yet to be fully elucidated, many efforts have been devoted in the last decades to shed light on its complex pharmacological profile. In particular, an ever-increasing number of molecular targets linked to those disorders have been identified for this phytocannabinoid, along with the modulatory effects of CBD on their cascade signaling. In this view, here we will try to provide a comprehensive and up-to-date overview of the molecular basis underlying the therapeutic effects of CBD involved in the treatment of neurological and neuropsychiatric disorders.     

Mitochondrial and Autophagic Regulation of Adult Neurogenesis in the Healthy and Diseased Brain

Adult neurogenesis is a highly regulated process during which new neurons are generated from neural stem cells in two discrete regions of the adult brain: the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus in the hippocampus. Defects of adult hippocampal neurogenesis have been linked to cognitive decline and dysfunction during natural aging and in neurodegenerative diseases, as well as psychological stress-induced mood disorders. Understanding the mechanisms and pathways that regulate adult neurogenesis is crucial to improving preventative measures and therapies for these conditions. Accumulating evidence shows that mitochondria directly regulate various steps and phases of adult neurogenesis. This review summarizes recent findings on how mitochondrial metabolism, dynamics, and reactive oxygen species control several aspects of adult neural stem cell function and their differentiation to newborn neurons. It also discusses the importance of autophagy for adult neurogenesis, and how mitochondrial and autophagic dysfunction may contribute to cognitive defects and stress-induced mood disorders by compromising adult neurogenesis. Finally, I suggest possible ways to target mitochondrial function as a strategy for stem cell-based interventions and treatments for cognitive and mood disorders.     

Risk of slaughterhouse workers developing work-related musculoskeletal disorders in different organizational working conditions

Job rotation is defined as workers rotating between tasks with different exposure levels and occupational demands. The aim of the present study was to analyze the risk factors for the development of upper-limb work-related musculoskeletal disorders (UL-WMSDs) in poultry slaughterhouse workers as well as compare the score of the OCRA Checklist in different organizational working conditions. In this cross-sectional study, 118 workers were involved, 68 women (32.3 ± 10.7 years) and 50 men (29.5 ± 10.5 years). Three organizational configurations (“without job rotation”, “with job rotation – tasks >1h” and “with job rotation - tasks <1h”) were evaluated using the OCRA Checklist method, totaling 36 tasks and 28 job rotation schemes composed of 2–3 tasks. The OCRA score of the right upper limbs (17.8 ± 3.2) was significantly higher (p = 0.046) relative to the left upper limbs (16.4 ± 3.6). The median score was significantly lower in the “with job rotation - tasks <1h” condition (18.6) when compared to the “job rotation – tasks >1h” (19.4) (p < 0.001) and the “without job rotation” (19.0) (p = 0.038) conditions. However, there was no significant difference between the condition “with job rotation - tasks >1h” and “without job rotation” (p = 0.155). Thus, job rotations with intervals <1h reduced the risk of developing UL-WMSDs. Job rotations with <1 h intervals in poultry slaughterhouses are recommended along with further studies to verify the effectiveness of rotations with more than two tasks, involving mild or non-repetitive tasks.     

Sleep Disorders Reduce Health-Related Quality of Life in Multiple Sclerosis (Nottingham Health Profile Data in Patients with Multiple Sclerosis)

Quality of Life (QoL) is decreased in multiple sclerosis (MS), but studies about the impact of sleep disorders (SD) on health-related quality of Life (HRQoL) are lacking. From our original cohort, a cross-sectional polysomnographic (PSG) study in consecutive MS patients, we retrospectively analysed the previously unpublished data of the Nottingham Health Profile (NHP). Those MS patients suffering from sleep disorders (n = 49) showed significantly lower HRQoL compared to MS patients without sleep disorders (n = 17). Subsequently, we classified the patients into four subgroups: insomnia (n = 17), restless-legs syndrome, periodic limb movement disorder and SD due to leg pain (n = 24), obstructive sleep apnea (n = 8) and patients without sleep disorder (n = 17). OSA and insomnia patients showed significantly higher NHP values and decreased HRQoL not only for the sleep subscale but also for the “energy” and “emotional” area of the NHP. In addition, OSA patients also showed increased NHP values in the “physical abilities” area. Interestingly, we did not find a correlation between the objective PSG parameters and the subjective sleep items of the NHP. However, this study demonstrates that sleep disorders can reduce HRQoL in MS patients and should be considered as an important confounder in all studies investigating HRQoL in MS.     

Extracellular Vesicles in CNS Developmental Disorders

The central nervous system (CNS) is the most complex structure in the body, consisting of multiple cell types with distinct morphology and function. Development of the neuronal circuit and its function rely on a continuous crosstalk between neurons and non-neural cells. It has been widely accepted that extracellular vesicles (EVs), mainly exosomes, are effective entities responsible for intercellular CNS communication. They contain membrane and cytoplasmic proteins, lipids, non-coding RNAs, microRNAs and mRNAs. Their cargo modulates gene and protein expression in recipient cells. Several lines of evidence indicate that EVs play a role in modifying signal transduction with subsequent physiological changes in neurogenesis, gliogenesis, synaptogenesis and network circuit formation and activity, as well as synaptic pruning and myelination. Several studies demonstrate that neural and non-neural EVs play an important role in physiological and pathological neurodevelopment. The present review discusses the role of EVs in various neurodevelopmental disorders and the prospects of using EVs as disease biomarkers and therapeutics.     

Improving storability,physiological disorders,and antioxidant properties of ‘Bartlett’ and ‘d’Anjou’ pears (Pyrus communis L.) by pre-harvest 1-methylcyclopropene spraying

Ethylene continues to be a major factor influencing quality of European pears during storage. Although research has been done on the effect of pre-harvest 1-methylcyclopropene (1-MCP) on physiological characteristics in pears, a full understanding of cultivar response and antioxidant metabolism remains elusive. Spraying 1-MCP on ‘Bartlett’ and ‘d’Anjou’ pears was studied with respect to physiology, storage and eating quality, disorders, and antioxidant properties at two harvest date (H1 and H2) during storage and ripening. Treatment with 1-MCP extended the harvest window of ‘Bartlett’ and ‘d’Anjou’ pears 3 and 4 days, respectively, without reducing storage or eating quality. Treatment with 1-MCP reduced ethylene production (EPR) and respiration rates (RR), maintained fruit firmness and green colour during storage and retarded development of desirable melting texture in both cultivars. Additionally, 1-MCP lowered the incidence of disorders by alleviating membrane lipid peroxidation, retaining high total flavonoids (TF) and antioxidant capacity, and enhancing superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) activity in both cultivars. Overall, pre-harvest 1-MCP applications could extend storage time of ‘Bartlett’ and ‘d’Anjou’ pears to 5 and 6 months, respectively, at −1.1 ± 0.5 °C, by reducing ethylene synthesis and enhancing antioxidant metabolism.     

Recension des écrits sur l'impact des contacts sexuels précoces sur les hommes.

A review of the literature on the impact of sexual contacts between adults and boys reveals the existence of two principal outcomes: 1) some participants develop various disorders once in adulthood, such as behavioural problems, sexual disorders, or personality problems; 2) some participants do not present with any major disorders in the long run. These different outcomes may be associated with several moderating variables related to the sexual contacts, such as the level of coercion at the time of these contacts, the bond between the child and the adult, or the context of the sexual relation. However, the conclusions relating to the relations between early sexual contacts with adults and subsequent problems of adaptation in adulthood are difficult to determine. This is because of various methodological problems associated with relevant studies (i.e., definition of these contacts, nature of the sample, method evaluation, statistical analyses). In this article, we propose certain avenues of research that may help clarify this problem. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

L'accessibilité à des traitements pour les troubles anxieux au Canada: Un commentaire.

Responds to Gauthier (see record 2004-17185-003) who commented on the two articles by Koerner et al (see record 2004-17185-001) and by Roberge et al (see record 2004-17185-002. The purpose of this response is to discuss the issue of limited availability of mental health services for anxiety disorders in Canada. From a public health perspective, the authors emphasize the importance of gathering Canadian empirical data on the organization of mental health services for anxiety disorders. Specifically more research is needed on care requirements, and the financial and structural barriers that restrict access to mental health services at the regional, provincial and national levels. The authors also discuss the role of psychologists in improving mental health care in Canada. Cost-effectiveness studies conducted in interdisciplinary practice environments could demonstrate the value added by psychology in the organization of mental health care for anxiety disorders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A goal-striving life event and the onset of hypomanic and depressive episodes and symptoms: Perspective from the Behavioral Approach System (BAS) dysregulation theory.

On the basis of the behavioral approach system (BAS) dysregulation theory of bipolar disorder, this study examined the relation between occurrence of a BAS activation-relevant life event--goal striving--and onset of hypomanic and depressive episodes and symptoms. In particular, the authors examined the relation between preparing for and completing final exams (a goal-striving event) and onset of bipolar spectrum episodes and symptoms in college students with bipolar II disorder or cyclothymia (i.e., "soft" bipolar spectrum conditions). One hundred fifty-nine individuals with either a bipolar spectrum disorder (n=68) or no major affective psychopathology (controls; n=91) were further classified on the basis of whether they were college students (i.e., completed final exams). Consistent with the BAS dysregulation theory, preparing for and completing final exams was associated with an increase in hypomanic but not depressive episodes and symptoms in individuals with a soft bipolar spectrum diagnosis. Furthermore, self-reported BAS sensitivity moderated the presence of certain hypomanic symptoms during final exams. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modeling language acquisition in atypical phenotypes.

An increasing number of connectionist models have been proposed to explain behavioral deficits in developmental disorders. These simulations motivate serious consideration of the theoretical implications of the claim that a developmental disorder fits within the parameter space of a particular computational model of normal development. The authors examine these issues in depth with respect to a series of new simulations investigating past-tense formation in Williams syndrome. This syndrome and the past-tense domain are highly relevant because both have been used to make strong theoretical claims about the processes underlying normal language acquisition. The authors conclude that computational models have great potential to advance psychologists' understanding of developmental deficits because they focus on the developmental process itself as a pivotal causal factor in producing atypical phenotypic outcomes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)