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Abstract Background Smartphone addiction, as with other behavioral addictions, is associated with social, physical, and mental health issues. In this article, we investigated the prevalence of smartphone addiction among postgraduate students and evaluated its correlation with social demographics, depression, attention-deficit/hyperactivity disorder (ADHD), and nicotine dependence. Objectives The objective of this study was to investigate the prevalence of smartphone addiction among Middle Eastern postgraduate students, determine the factors associated with smartphone addiction, and estimate the incidence rate of major depressive disorder (MDD), ADHD, insomnia, and nicotine addiction among postgraduate students with smartphone addiction. Methods As part of a cross-sectional online survey, participants were given a self-questionnaire divided into six sections: Socio-demographics, Smartphone Addiction Scale (SAS), Patient Health Questionnaire (PHQ9) for Depression, Athens Insomnia Scale (AIS), the Fagerström Test for Cigarette Dependence Questionnaire (FTCd), and the adult ADHD Self-Report Scale (ASRS-v1.1). Results Of the 506 patients, 51.0% of the participants demonstrated smartphone addiction. A significant association was also observed between extensive smartphone use and MDD (P = 0.001). Of the smokers in this study, 41.5% were addicted to smartphones (P = 0.039). Smartphone addicts had approximately two times the chance of having insomnia (OR = 2.113) (P = 0.013). In addition, they showcased more ADHD symptoms (OR = 2.712) (P

Background: The impact of the COVID-19 pandemic on populations’ mental health has started to emerge. Objectives: To describe the mental health trends of the risk of major depressive disorder (MDD) and generalized anxiety disorder (GAD) between May and August 2020. It also compares the results with pre-COVID-19 results and identifies risk factors associated with increased likelihood of being at risk of MDD and GAD. Method: This study utilizes repeated cross-sectional design, at national-level coverage of mental health screenings via computer-assisted phone interviews conducted in four waves monthly (between May and August 2020). Arabic-speaking adults from Saudi Arabia were recruited via a random phone list. The questionnaire includes the Arabic version of the Patient Health Questionnaire (PHQ-9) and the General Anxiety Disorder-7 (GAD-7). Pre-COVID-19 comparison was done using the PHQ-2 score to allow for comparison with a previous and similar national study conducted in 2018. Results: Across the four waves, 16,513 participants completed the interviews, with an overall response rate of 81.3%. The weighted national prevalence of people at risk of MDD was 14.9% overall, and 13.8%, 13.6%, 16.8%, and 15.3% in Waves 1, 2, 3, and 4, respectively. The weighted national prevalence of people at risk of GAD was 11.4%, overall, and 10.9%, 10.7%, 12.4%, and 11.7% in Waves 1, 2, 3, and 4, respectively. The weighted national proportion of individuals who were at risk of MDD and GAD at the same time was 7.4% overall. The risk of MDD on PHQ-2 increased by 71.2%, from 12.5% in 2018 to 21.4% in 2020. Conclusions: The risks of MDD and GAD in this study are relatively high. These results can help decision makers to understand the impact of the COVID-19 pandemic on the population’s mental health and the most-impacted subgroups.

Olanzapine is an atypical antipsychotic medication, previously expected to be safe in terms of hematological side effects and considered an alternative choice to clozapine in patients who develop hematotoxicities. However, since olanzapine was introduced to the market many case reports have been published revealing that it could cause hematoxicity. Some of these reports also indicated that olanzapine induced agranulocytosis. Therefore, we conducted a systemic review to explore and address this issue. Electronic database searches from 1998 to 2015 yielded 35 case reports of olanzapine-induced leukopenia and three related systematic reviews. The onset of leukopenia for the majority of these case reports followed in the first month of administration of olanzapine. Moreover, more than two third of these cases never developed drug-related leukopenia before the use of olanzapine. The ages of affected individuals were 16 to 83 years old and their races were African, Caucasian, Asian, Jewish and Mediterranean. The doses of olanzapine ranged from 2.5 to 30 mg. Interestingly, olanzapine was associated with third highest incidence of neutropenia among antipsychotics. The mechanism of olanzapine-induced neutropenia is still unknown, but could be similar to clozapine because of similar chemical composition. Therefore we recommend that the guidelines regarding olanzapine need to be reconsidered and closely monitored with patients being treated with olanzapine for hematological side effects.

Orexins are neuropeptides that are postulated to play a central role in the regulation of the sleep-wake cycle, appetite, affect, and reward circuitry. The objectives of the current review are to comprehensively evaluate (1) the potential role of orexins in the pathophysiology of major depressive disorders (MDD) and (2) the orexin system as a novel target in the treatment of MDD. Dysfunction of the sleep-wake cycle is observed as a central feature of MDD pathophysiology. Orexin system disturbances produce sleep-wake dysfunction, as observed in MDD. Orexin antagonists have been shown to treat insomnia effectively without disrupting normal sleep architecture in both preclinical (e.g., animal models) and clinical studies. Orexin antagonists are generally safe, well-tolerated, and associated with an acceptable long-term adverse effect profile with relatively low propensity for tolerance or dependence. Orexin antagonists have also been shown to possess antidepressant-like properties in some animal models of MDD. Extant evidence indicates that orexin-modulating treatments exert pleiotropic effects on multiple neural systems implicated in the phenomenology of mood disorders and suggests orexins as a promising target for investigation and intervention in mood disorders. To date, no human clinical trials evaluating the antidepressant effects of orexin antagonists in MDD have been completed. Given the promising results from preclinical studies, clinical trials are merited to evaluate the antidepressant effects of orexin antagonists in MDD., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The aim of this study was to examine the role of perceived sleep quality in predicting subjective as well as objective cognitive function in adults with major depressive disorder (MDD)., Methods: Adults with recurrent MDD (n = 100) experiencing a major depressive episode of at least moderate severity and age-, sex-, and education-matched healthy controls (HC) (n = 100) were recruited to participate in a clinical trial validating the THINC-integrated tool (THINC-it; NCT02508493) for cognitive function. The THINC-it includes subjective and objective measures of cognitive function. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI)., Results: Compared with HC, individuals with MDD reported significantly poorer sleep quality, as assessed by domain and global PSQI scores (all P values <.05). Both perceived sleep quality ( P < .001) and depression severity (P = .002) were found to independently predict impairments in subjective cognitive performance. Only perceived sleep quality predicted objective cognitive impairments (P = .017). Exploratory mediation analysis revealed depression severity to be a partial mediator of the relationship between perceived sleep quality and subjective cognitive performance (95% confidence interval [CI]: -0.56, -0.33)., Conclusions: The results indicate that the subjective and objective cognitive impairments are differentially related to perceived sleep quality and depression severity and emphasize the importance of treating sleep disturbances in MDD.

Background and Objectives: This study evaluated the association between self-reported anxiety and objective/subjective measures of cognitive performance in adults with Major Depressive Disorder (MDD)., Methods: Acutely depressed subjects with recurrent MDD (n = 100) and age-, sex-, and education-matched healthy controls (HC; n = 100) between the ages of 18 and 65 completed the cross-sectional validation study of the THINC-integrated tool (THINC-it; ClinicalTrials.gov: NCT02508493). Objective cognitive performance was assessed using the THINC-it, and subjective cognitive impairment with the Perceived Deficits Questionnaire for Depression-5-item. Subjects also completed the Generalized Anxiety Disorder-7-item (GAD-7) questionnaire., Results: Subjects with MDD reported significantly more anxiety symptoms, as assessed by the GAD-7, compared to HC (p < 0.001). Linear regression analysis determined that anxiety symptoms significantly accounted for 70.4% of the variability in subjective cognitive impairment, adjusting for depression severity. Moreover, subjects' ratings of the difficulties caused by their anxiety were reported as significantly more severe among subjects with MDD when compared to HC (p < 0.001). Likewise, greater self-reported difficulties with anxiety significantly predicted 57.8% of the variability in subjective cognitive impairment, adjusting for depression severity. Neither anxiety symptoms nor impairment due to anxiety symptoms predicted objective cognitive performance., Limitations: Subjects were not prospectively verified to have a clinical diagnosis of GAD. Rather, this study examined the relationships between symptoms of generalized anxiety, assessed using a brief screening tool, and subjective and objective cognitive function., Conclusions: Results from the current study indicate that adults with MDD and high levels of self-reported anxiety are significantly more likely to report experiencing subjective cognitive dysfunction., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Learning Objectives: After participating in this activity, learners should be better able to:• Characterize cognitive dysfunction in patients with major depressive disorder.• Evaluate approaches to treating cognitive dysfunction in patients with major depressive disorder., Abstract: Cognitive dysfunction is a core psychopathological domain in major depressive disorder (MDD) and is no longer considered to be a pseudo-specific phenomenon. Cognitive dysfunction in MDD is a principal determinant of patient-reported outcomes, which, hitherto, have been insufficiently targeted with existing multimodal treatments for MDD. The neural structures and substructures subserving cognitive function in MDD overlap with, yet are discrete from, those subserving emotion processing and affect regulation. Several modifiable factors influence the presence and extent of cognitive dysfunction in MDD, including clinical features (e.g., episode frequency and illness duration), comorbidity (e.g., obesity and diabetes), and iatrogenic artefact. Screening and measurement tools that comport with the clinical ecosystem are available to detect and measure cognitive function in MDD. Notwithstanding the availability of select antidepressants capable of exerting procognitive effects, most have not been sufficiently studied or rigorously evaluated. Promising pharmacological avenues, as well as psychosocial, behavioral, chronotherapeutic, and complementary alternative approaches, are currently being investigated.

Sirtuins are NAD + -dependent histone deacetylases that play essential roles in cell survival, energy metabolism, inflammation, and aging; therefore, sirtuins are potential therapeutic targets in the treatment of type 2 diabetes, cancer, inflammatory and metabolic disorders, and neurodegenerative diseases. Available evidence provides the basis for hypothesizing that sirtuins 1, 2, and 3 (SIRT1, SIRT2, and SIRT3) may have a mechanistic role subserving mood disorders (i.e. downregulation) and associated co-morbidity (e.g. metabolic disorders). Specifically, the domains of general cognitive processes, as well as cognitive emotional processing may be particularly relevant to sirtuin physiology. Given the role of sirtuins in the perpetuation of circadian rhythmicity, and evidence of dysfunctional circadian cycling in mood disorders, sirtuins may be an underlying etiological factor that links circadian rhythm functionality with mood disorders. Caloric restriction, and caloric restriction mimetics (e.g. resveratrol) are all capable of upregulating sirtuin isoforms implicated in stress response syndromes. Repurposing existing treatments and/or discovery of novel agents capable of modulating sirtuin physiology may represent genuinely novel approaches for trans-diagnostic domains affected in mood disorders and other brain-based illnesses., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: To determine, via narrative, non-systematic review of pre-clinical and clinical studies, whether the effect of cannabis on hepatic biotransformation pathways would be predicted to result in clinically significant drug-drug interactions (DDIs) with commonly prescribed psychotropic agents., Areas Covered: A non-systematic literature search was conducted using the following databases: PubMed, PsycInfo, and Scopus from inception to January 2017. The search term cannabis was cross-referenced with the terms drug interactions, cytochrome, cannabinoids, cannabidiol, and medical marijuana. Pharmacological, molecular, and physiologic studies evaluating the pharmacokinetics of Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and cannabidiol (CBD), both in vitro and in vivo, were included. Bibliographies were also manually searched for additional citations that were relevant to the overarching aim of this paper., Expert Opinion: Δ 9 -Tetrahydrocannabinol and CBD are substrates and inhibitors of cytochrome P450 enzymatic pathways relevant to the biotransformation of commonly prescribed psychotropic agents. The high frequency and increasing use of cannabis invites the need for healthcare providers to familiarize themselves with potential DDIs in persons receiving select psychotropic agents, and additionally consuming medical marijuana and/or recreational marijuana.

Objectives: To examine the role of pain on cognitive function in adults with major depressive disorder (MDD)., Methods: Adults (18-65) with a Diagnostic and Statistical Manual - Fifth Edition (DSM-5)-defined diagnosis of MDD experiencing a current major depressive episode (MDE) were enrolled (n MDD =100). All subjects with MDD were matched in age, sex, and years of education to healthy controls (HC) (n HC =100) for comparison. Cognitive function was assessed using the recently validated THINC-integrated tool (THINC-it), which comprises variants of the choice reaction time (i.e., THINC-it: Spotter), One-Back (i.e., THINC-it: Symbol Check), Digit Symbol Substitution Test (i.e., THINC-it: Codebreaker), Trail Making Test - Part B (i.e., THINC-it: Trails), as well as the Perceived Deficits Questionnaire for Depression - 5-item (i.e., THINC-it: PDQ-5-D). A global index of objective cognitive function was computed using objective measures from the THINC-it, while self-rated cognitive deficits were measured using the PDQ-5-D. Pain was measured using a Visual Analogue Scale (VAS). Regression analyses evaluated the role of pain in predicting objective and subjective cognitive function., Results: A significant between-group differences on the VAS was observed (p<0.001), with individuals with MDD reporting higher pain severity as evidenced by higher scores on the VAS than HC. Significant interaction effects were observed between self -rated cognitive deficits and pain ratings (p<0.001) on objective cognitive performance (after adjusting for MADRS total score), suggesting that pain moderates the association between self-rated and objective cognitive function., Conclusions: Results indicated that pain is associated with increased self-rated and objective cognitive deficits in adults with MDD., Implications: The study herein provides preliminary evidence demonstrating that adults with MDD reporting pain symptomatology and poorer subjective cognitive function is predictive of poorer objective cognitive performance. THINC-it is capable of detecting cognitive dysfunction amongst adults with MDD and pain., (Copyright © 2017 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)