An update on potential pharmacotherapies for cognitive impairment in bipolar disorder.

INTRODUCTION: Cognitive impairment is a core feature of bipolar disorder (BD) that impedes recovery by preventing the return to optimal socio-occupational functioning and reducing quality of life. Presently, there are no efficacious treatments for cognitive impairment in BD, but many pharmacological interventions are being considered as they have the potential to target the underlying pathophysiology of the disorder. AREAS COVERED: This review summarizes the available evidence for pharmacological interventions for cognitive impairment in bipolar disorder. We searched PubMed, MedLine, and PsycInfo from inception to December 1st, 2022. Traditional treatments, such as lithium, anticonvulsants (lamotrigine), antipsychotics (aripiprazole, asenapine, cariprazine, lurasidone, and olanzapine), antidepressants (vortioxetine, fluoxetine, and tianeptine) and psychostimulants (modafinil), and emerging interventions, such as acetylcholinesterase inhibitors (galantamine and donepezil), dopamine agonists (pramipexole), erythropoietin, glucocorticoid receptor antagonists (mifepristone), immune modulators (infliximab, minocycline and doxycycline), ketamine, metabolic agents (insulin, metformin, and liraglutide), probiotic supplements, and Withania somnifera are discussed. EXPERT OPINION: The investigation of interventions for cognitive impairment in BD is a relatively under-researched area. In the past, methodological pitfalls in BD cognition trials have also been a critical limiting factor. Expanding on the existing literature and identifying novel pharmacological and non-pharmacological treatments for cognitive impairment in BD should be a priority.

Patient Functioning, Life Engagement, and Treatment Goals in Schizophrenia.

Unmet needs in the treatment of schizophrenia include nonadherence to treatment, symptom relapse, incomplete functional recovery, and poor quality of life. Incorporating the patient's perspective into the treatment plan and measuring treatment outcomes that are meaningful to patients is an important part of addressing these issues. Goal setting is associated with greater improvements in motivation and role functioning, but clinicians should keep in mind that their goals for treatment may not align with those of their patients. Patients tend to think about their lives more holistically than clinicians, with equal weight given to social and clinical needs, and improved functioning and engagement with life are likely to emerge as priorities, beyond the need for symptom control. In a recent roundtable meeting, a panel of 5 experts discussed life engagement and its relationship to symptoms and functioning in patients with major depressive disorder (MDD) and schizophrenia. This Academic Highlights, part 2 in a series, summarizes the experts' discussion of how life engagement can inform goal-setting and treatment selection in patients with schizophrenia.

Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce.

OBJECTIVES: The therapeutic use of nutrient-based 'nutraceuticals' and plant-based 'phytoceuticals' for the treatment of mental disorders is common; however, despite recent research progress, there have not been any updated global clinical guidelines since 2015. To address this, the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Disorders (CANMAT) convened an international taskforce involving 31 leading academics and clinicians from 15 countries, between 2019 and 2021. These guidelines are aimed at providing a definitive evidence-informed approach to assist clinicians in making decisions around the use of such agents for major psychiatric disorders. We also provide detail on safety and tolerability, and clinical advice regarding prescription (e.g. indications, dosage), in addition to consideration for use in specialised populations. METHODS: The methodology was based on the WFSBP guidelines development process. Evidence was assessed based on the WFSBP grading of evidence (and was modified to focus on Grade A level evidence - meta-analysis or two or more RCTs - due to the breadth of data available across all nutraceuticals and phytoceuticals across major psychiatric disorders). The taskforce assessed both the 'level of evidence' (LoE) (i.e. meta-analyses or RCTs) and the assessment of the direction of the evidence, to determine whether the intervention was 'Recommended' (+++), 'Provisionally Recommended' (++), 'Weakly Recommended' (+), 'Not Currently Recommended' (+/-), or 'Not Recommended' (-) for a particular condition. Due to the number of clinical trials now available in the field, we firstly examined the data from our two meta-reviews of meta-analyses (nutraceuticals conducted in 2019, and phytoceuticals in 2020). We then performed a search of additional relevant RCTs and reported on both these data as the primary drivers supporting our clinical recommendations. Lower levels of evidence, including isolated RCTs, open label studies, case studies, preclinical research, and interventions with only traditional or anecdotal use, were not assessed. RESULTS: Amongst nutraceuticals with Grade A evidence, positive directionality and varying levels of support (recommended, provisionally recommended, or weakly recommended) was found for adjunctive omega-3 fatty acids (+++), vitamin D (+), adjunctive probiotics (++), adjunctive zinc (++), methylfolate (+), and adjunctive s-adenosyl methionine (SAMe) (+) in the treatment of unipolar depression. Monotherapy omega-3 (+/-), folic acid (-), vitamin C (-), tryptophan (+/-), creatine (+/-), inositol (-), magnesium (-), and n-acetyl cysteine (NAC) (+/-) and SAMe (+/-) were not supported for this use. In bipolar disorder, omega-3 had weak support for bipolar depression (+), while NAC was not currently recommended (+/-). NAC was weakly recommended (+) in the treatment of OCD-related disorders; however, no other nutraceutical had sufficient evidence in any anxiety-related disorder. Vitamin D (+), NAC (++), methylfolate (++) were recommended to varying degrees in the treatment of the negative symptoms in schizophrenia, while omega-3 fatty acids were not, although evidence suggests a role for prevention of transition to psychosis in high-risk youth, with potential pre-existing fatty acid deficiency. Micronutrients (+) and vitamin D (+) were weakly supported in the treatment of ADHD, while omega-3 (+/-) and omega-9 fatty acids (-), acetyl L carnitine (-), and zinc (+/-) were not supported. Phytoceuticals with supporting Grade A evidence and positive directionality included St John's wort (+++), saffron (++), curcumin (++), and lavender (+) in the treatment of unipolar depression, while rhodiola use was not supported for use in mood disorders. Ashwagandha (++), galphimia (+), and lavender (++) were modestly supported in the treatment of anxiety disorders, while kava (-) and chamomile (+/-) were not recommended for generalised anxiety disorder. Ginkgo was weakly supported in the adjunctive treatment of negative symptoms of schizophrenia (+), but not supported in the treatment of ADHD (+/-). With respect to safety and tolerability, all interventions were deemed to have varying acceptable levels of safety and tolerability for low-risk over-the-counter use in most circumstances. Quality and standardisation of phytoceuticals was also raised by the taskforce as a key limiting issue for firmer confidence in these agents. Finally, the taskforce noted that such use of nutraceuticals or phytoceuticals be primarily recommended (where supportive evidence exists) adjunctively within a standard medical/health professional care model, especially in cases of more severe mental illness. Some meta-analyses reviewed contained data from heterogenous studies involving poor methodology. Isolated RCTs and other data such as open label or case series were not included, and it is recognised that an absence of data does not imply lack of efficacy. CONCLUSIONS: Based on the current data and clinician input, a range of nutraceuticals and phytoceuticals were given either a supportive recommendation or a provisional recommendation across a range of various psychiatric disorders. However several had only a weak endorsement for potential use; for a few it was not possible to reach a clear recommendation direction, largely due to mixed study findings; while some other agents showed no obvious therapeutic benefit and were clearly not recommended for use. It is the intention of these guidelines to inform psychiatric/medical, and health professional practice globally.

Oxidative Stress Mediates the Association Between Dietary Fat Intake and Cognition in US Older Adults.

OBJECTIVE: Dietary fat intake was considered as a modifiable factor influencing cognitive performance. The objective was to 1) examine the associations between different types of dietary fat intakes and cognitive outcomes among elder adults (≥60 years old); 2) assess whether peripheral oxidative stress and antioxidant biomarkers are potential mediators of dietary fat intake and cognitive impairment relationship. METHODS: Using data from National Health and Nutrition Examination Survey 2011-2014, total fat, saturated fatty acid (SFAT), monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), cholesterol, ω-3 and ω-6 fatty acids were used to evaluate dietary fat intakes. Cognitive outcomes were assessed by word learning and recall modules from the consortium to establish a registry for Alzheimer's Disease (CERAD), animal fluency test, and digit symbol substitution test (DSST). Antioxidant biomarkers were assessed by gamma glutamyl transpeptidase (GGT), bilirubin, uric acid, and vitamin D levels. Linear regression models and causal mediation analysis were applied to quantify the associations. RESULTS: A total of 2,253 elder adults were included in the data analyses. Dietary intake of PUFA and ω-6 fatty acid were positively associated with DSST [ß (95% CI): 0.06 (0.01,0.10), t statistic = 2.39, df= 2238, p = 0.02; ß (95% CI): 0.06 (0.01,0.11), t statistic = 2.54, df= 2238, p = 0.01, respectively]. GGT was negatively associated with DSST [ß (95% CI): -0.04 (-0.07, -0.01), t statistic = -2.73, df= 2239, p = 0.01], whereas uric acid was positively associated with CERAD total score [ß (95% CI): 0.04 (0.00,0.08), t statistic = 2.03, df= 2233, p = 0.04]. The association between dietary intake of PUFA/ω -3/ω -6 and DSST performance was partially mediated by GGT level. CONCLUSION: Our findings support that PUFAs in dietary sources were associated with lower risks for cognitive impairment partially via lowering oxidative stress. Dietary PUFA supplementation may potentially reduce risk of cognitive impairment via antioxidative mechanism.

Molecular Mechanisms of Psilocybin and Implications for the Treatment of Depression.

Therapeutic deficiencies with monoaminergic antidepressants invites the need to identify and develop novel rapid-acting antidepressants. Hitherto, ketamine and esketamine are identified as safe, well-tolerated rapid-acting antidepressants in adults with treatment-resistant depression, and also mitigate measures of suicidality. Psilocybin is a naturally occurring psychoactive alkaloid and non-selective agonist at many serotonin receptors, especially at serotonin 5-HT2A receptors, and is found in the Psilocybe genus of mushrooms. Preliminary studies with psilocybin have shown therapeutic promise across diverse populations including major depressive disorder. The pharmacodynamic mechanisms mediating the antidepressant and psychedelic effects of psilocybin are currently unknown but are thought to involve the modulation of the serotonergic system, primarily through agonism at the 5-HT2A receptors and downstream changes in gene expression. It is also established that indirect effects on dopaminergic and glutamatergic systems are contributory, as well as effects at other lower affinity targets. Along with the direct effects on neurochemical systems, psilocybin alters neural circuitry and key brain regions previously implicated in depression, including the default mode network and amygdala. The aim of this review is to synthesize the current understanding of the receptor pharmacology and neuronal mechanisms underlying the psychedelic and putative antidepressant properties of psilocybin.

Impact of Supplementation and Nutritional Interventions on Pathogenic Processes of Mood Disorders: A Review of the Evidence.

This narrative review was conducted using searches of the PubMed/Medline and Google Scholar databases from inception to November 2019. Clinical trials and relevant articles were identified by cross-referencing major depressive disorder (and/or variants) with the following terms: folate, homocysteine, S-adenosylmethionine (SAMe), L-acetylcarnitine, alpha-lipoic acid, N-acetylcysteine, L-tryptophan, zinc, magnesium, vitamin D, omega-3 fatty acids, coenzyme Q10, and inositol. Manual reviews of references were also performed using article reference lists. Abnormal levels of folate, homocysteine, and SAMe have been shown to be associated with a higher risk of depression. Numerous studies have demonstrated antidepressant activity with L-methylfolate and SAMe supplementation in individuals with depression. Additionally, the amino acids L-acetylcarnitine, alpha-lipoic acid, N-acetylcysteine, and L-tryptophan have been implicated in the development of depression and shown to exert antidepressant effects. Other agents with evidence for improving depressive symptoms include zinc, magnesium, omega-3 fatty acids, and coenzyme Q10. Potential biases and differences in study designs within and amongst the studies and reviews selected may confound results. Augmentation of antidepressant medications with various supplements targeting nutritional and physiological factors can potentiate antidepressant effects. Medical foods, particularly L-methylfolate, and other supplements may play a role in managing depression in patients with inadequate response to antidepressant therapies.

Resting-State Functional Connectivity and Brain Network Abnormalities in Depressive Patients with Suicidal Ideation.

Our study aimed to investigate whether changes in brain function measured with functional magnetic resonance imaging (fMRI) can be detected among individuals with depressive disorders and suicidal ideation. The association between depression severity and brain images is also discussed. Our study recruited 111 participants in three groups: 35 depressive patients with suicidal ideation (SI), 32 depressive patients without suicidal ideation (NS), and 44 healthy controls (HCs). All participants were scanned using 3T MRI to obtain resting-state functional images, and functional connectivity (FC), amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and graph theoretical analysis (GTA) were performed. We found functional activity differences, such as the hippocampus and thalamus, in the SI group compared with the NS group. We also concluded lower activity in the thalamus and cuneus regions were related to suicidal ideation. We also found several functional connectivity of the brain areas, such as hippocampus, cuneus, and frontal regions, in the SI group correlated with Hamilton Depression Rating Scale (HAM-D) and Hospital Anxiety and Depression Scale (HADS). A graph theoretical analysis (GTA) and network-based statistical (NBS) analysis revealed different topological organization and slightly better local segregation of the brain network in healthy participants compared with those in depressive patients with suicidal ideation. We suggest that brain functional connectivity may be affected in depressive patients with suicidal ideation.

A quantitative and qualitative study on the neuropsychiatric sequelae of acutely ill COVID-19 inpatients in isolation facilities.

This study examined the neuropsychiatric sequelae of acutely ill patients with coronavirus disease 2019 (COVID-19) infection who received treatment in hospital isolation wards during the COVID-19 pandemic. Ten COVID-19 patients who received treatment in various hospitals in Chongqing, China; 10 age- and gender-matched psychiatric patients; and 10 healthy control participants residing in the same city were recruited. All participants completed a survey that collected information on demographic data, physical symptoms in the past 14 days and psychological parameters. Face-to-face interviews with COVID-19 patients were also performed using semi-structured questions. Among the COVID-19 patients, 40% had abnormal findings on the chest computed topography scan, 20% had dysosmia, 10% had dysgeusia, and 80% had repeated positivity on COVID-19 reverse-transcription polymerase chain reaction testing. COVID-19 and psychiatric patients were significantly more worried about their health than healthy controls (p = 0.019). A greater proportion of COVID-19 patients experienced impulsivity (p = 0.016) and insomnia (p = 0.039) than psychiatric patients and healthy controls. COVID-19 patients reported a higher psychological impact of the outbreak than psychiatric patients and healthy controls, with half of them having clinically significant symptoms of posttraumatic stress disorder. COVID-19 and psychiatric patients had higher levels of depression, anxiety and stress than healthy controls. Three themes emerged from the interviews with COVID-19 patients: (i) The emotions experienced by patients after COVID-19 infection (i.e., shock, fear, despair, hope, and boredom); (ii) the external factors that affected patients' mood (i.e., discrimination, medical expenses, care by healthcare workers); and (iii) coping and self-help behavior (i.e., distraction, problem-solving and online support). The future direction in COVID-19 management involves the development of a holistic inpatient service to promote immune and psychological resilience.

Do psychiatric patients experience more psychiatric symptoms during COVID-19 pandemic and lockdown? A case-control study with service and research implications for immunopsychiatry.

This study aimed to assess and compare the immediate stress and psychological impact experienced by people with and without psychiatric illnesses during the peak of 2019 coronavirus disease (COVID-19) epidemic with strict lockdown measures. Seventy-six psychiatric patients and 109 healthy control subjects were recruited from Chongqing, China and completed a survey on demographic data, physical symptoms during the past 14 days and a range of psychiatric symptoms using the Impact of Event Scale-Revised (IES-R), Depression, Anxiety and Stress Scale (DASS-21) and Insomnia Severity Index (ISI). IES-R measures PTSD symptoms in survivorship after an event. DASS-21 is based on tripartite model of psychopathology that comprise a general distress construct with distinct characteristics. The mean IES-R, DASS-21 anxiety, depression and stress subscale and ISI scores were higher in psychiatric patients than healthy controls (p < 0.001). Serious worries about their physical health, anger and impulsivity and intense suicidal ideation were significantly higher in psychiatric patients than healthy controls (p < 0.05). More than one-third of psychiatric patients might fulfil the diagnostic criteria post-traumatic stress disorder (PTSD). More than one-quarter of psychiatric patients suffered from moderately severe to severe insomnia. Respondents who reported no change, poor or worse physical health status and had a psychiatric illness were significantly more likely to have higher mean IES-R, DASS depression, anxiety and stress subscale scores and ISI scores (p < 0.05). This study confirms the severity of negative psychological impact on psychiatric patients during the COVID-19 epidemic with strict lockdown measures. Understanding the psychological impact on psychiatric patients during the COVID-19 pandemic has the potential to provide insight into how to develop a new immunopsychiatry service. Further research is required to compare pro-inflammatory cytokines between psychiatric patients and healthy controls during the pandemic.

Is returning to work during the COVID-19 pandemic stressful? A study on immediate mental health status and psychoneuroimmunity prevention measures of Chinese workforce.

This study aimed to quantify the immediate psychological effects and psychoneuroimmunity prevention measures of a workforce returning to work during the COVID-19 epidemic. Workforce returning to work was invited to complete an online questionnaire regarding their attitude toward the COVID-19 epidemic and return-to-work along with psychological parameters including the Impact of Event Scale-Revised, Depression, Anxiety, Stress Scale- 21 (DASS-21) and Insomnia Severity Index (ISI). Psychoneuroimmunity prevention measures include precautions at personal and organization levels. From 673 valid questionnaires, we found that 10.8% of respondents met the diagnosis of post-traumatic stress disorder (PTSD) after returning to work. The respondents reported a low prevalence of anxiety (3.8%), depression (3.7%), stress (1.5%) and insomnia (2.3%). There were no significant differences in the severity of psychiatric symptoms between workers/technicians and executives/managers. >95% reported psychoneuroimmunity prevention measures including good ventilation in the workplace and wore a face mask as protective. Factors that were associated with the severity of psychiatric symptoms in the workforce were marital status, presence of physical symptom, poor physical health and viewing return to work as a health hazard (p < 0.05). In contrast, personal psychoneuroimmunity prevention measures including hand hygiene and wearing face masks as well as organizational measures including significant improvement of workplace hygiene and concerns from the company were associated with less severe psychiatric symptoms (p < 0.05). Contrary to expectations, returning to work had not caused a high level of psychiatric symptoms in the workforce. The low prevalence of psychiatric symptoms could be due to confidence instilled by psychoneuroimmunity prevention measures before the resumption of work. Our findings would provide information for other countries during the COVID-19 pandemic.

Efficacy of omega-3 PUFAs in depression: A meta-analysis.

We conducted this meta-analysis of double-blind randomized placebo-controlled trials to estimate the efficacy of omega-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), in the improvement of depression. We applied a systematic bibliographic search in PubMed and EMBASE for articles published prior to 20 December 2017. This meta-analysis was performed using RevMan 5.3 and R 3.4.3, and means and standard deviations were calculated in fixed- or random-effects models based on the results of the Q-test. A sensitivity analysis was also conducted to evaluate the stability of the results, and publication bias was evaluated by a funnel plot and Egger's linear regression analysis. Our search resulted in 180 articles; we analyzed 26 studies, which included 2160 participants. The meta-analysis showed an overall beneficial effect of omega-3 polyunsaturated fatty acids on depression symptoms (SMD = -0.28, P = 0.004). Compared with placebo, EPA-pure (=100% EPA) and EPA-major formulations (≥60% EPA) demonstrated clinical benefits with an EPA dosage ≤1 g/d (SMD = -0.50, P = 0.003, and SMD = -1.03, P = 0.03, respectively), whereas DHA-pure and DHA-major formulations did not exhibit such benefits.Current evidence supports the finding that omega-3 PUFAs with EPA ≥ 60% at a dosage of ≤1 g/d would have beneficial effects on depression. Further studies are warranted to examine supplementation with omega-3 PUFAs for specific subgroups of subjects with inflammation, severity of depression, and the dose response for both EPA and DHA supplementation.

Indices of Change, Expectations, and Popularity of Biological Treatments for Major Depressive Disorder between 1988 and 2017: A Scientometric Analysis.

BACKGROUND: Major Depressive Disorder (MDD) is the most common psychiatric disorder with high prevalence and disease burden. Biological treatments of MDD over the last several decades include a wide range of antidepressants and neurostimulation therapies. While recent meta-analyses have explored the efficacy and tolerability of antidepressants, the changing trends of biological treatments have not been evaluated. Our study measured the indices of change, expectations, and popularity of biological treatments of MDD between 1988 and 2017. METHODS: We performed a scientometric analysis to identify all relevant publications related to biological treatments of MDD from 1988 to 2017. We searched the Web of Science websites for publications from 1 January 1988 to 31 December 2017. We included publications of fluoxetine, paroxetine, citalopram, sertraline, amitriptyline, fluvoxamine, escitalopram, venlafaxine, duloxetine, milnacipran, desvenlafaxine, levomilnacipran, clomipramine, nortriptyline, bupropion, trazodone, nefazodone, mirtazapine, agomelatine, vortioxetine, vilazodone, electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), vagus nerve stimulation (VNS), deep brain stimulation (DBS), and transcranial direct current stimulation (tDCS). We excluded grey literature, conference proceedings, books/book chapters, and publications with low quality as well as publications not related to medicine or human health. The primary outcomes assessed were indices of change, expectations, and popularity. RESULTS: Of 489,496 publications identified, we included 355,116 publications in this scientometric analysis. For the index of change, fluoxetine, sertraline and ECT demonstrated a positive index of change in 6 consecutive periods. Other neurostimulation therapies including rTMS, VNS, DBS and tDCS had shown a positive index of change since 1998. We calculated the index of change of popularity index (PI), which indicates that from 2013 to 2017, the number of publications on tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) were reduced by 85.0% and 81.3% respectively, as compared with the period 2008-2012. For the index of expectation, fluoxetine and ECT showed the highest index of expectations in six consecutive periods and remained the highest in 2013-2017. For popularity, the three antidepressants with highest PI were fluoxetine (4.01), paroxetine (2.09), and sertraline (1.66); the three antidepressants with lowest PI were desvenlafaxine (0.08), vilazodone (0.04) and levomilnacipran (0.03). Among neurostimulation therapies, ECT has the highest PI (2.55), and tDCS the lowest PI (0.14). The PI of SSRI remained the highest among all biological treatments of MDD in 2013-2017. In contrast, the PI of ECT was reduced by approximately 50% during the period 2008 to2012 than that in the period 2013 to 2017. CONCLUSIONS: This scientometric analysis represents comprehensive evidence on the popularity and change in prospects of biological treatments for MDD from 1988 to 2017. The popularity of SSRI peaked between 1998 and 2002, when their efficacy, tolerability and safety profile allowed them to replace the TCAs and MAOIs. While the newer neurostimulation therapies are gaining momentum, the popularity of ECT has sustained.

Keeping up with the clinical advances: depression.

Major depressive disorder (MDD) is a prevalent and heterogeneous disorder. Although there are many treatment options for MDD, patients with treatment-resistant depression (TRD) remain prevalent, wherein delayed time to response results in inferior chances of achieving remission. Recently, therapeutics have been developed that depart from the traditional monoamine hypothesis of depression and focus instead on the glutamatergic, GABAergic, opioidergic, and inflammatory systems. The literature suggests that the foregoing systems are implicated in the pathophysiology of MDD and preclinical trials have informed the development of pharmaceuticals using these systems as therapeutic targets. Pharmaceuticals that target the glutamatergic system include ketamine, esketamine, and rapastinel; brexanolone and SAGE-217 target the GABAergic system; minocycline targets the inflammatory system; and the combinatory agent buprenorphine + samidorphan targets the opioidergic system. The aforementioned agents have shown efficacy in treating MDD in clinical trials. Of particular clinical relevance are those agents targeting the glutamatergic and GABAergic systems as they exhibit rapid response relative to conventional antidepressants. Rapid response pharmaceuticals have the potential to transform the treatment of MDD, demonstrating reduction in depressive symptoms within 24 hours, as opposed to weeks noted with conventional antidepressants. Novel therapeutics have the potential to improve both patient mood symptomatology and economical productivity, reducing the debased human capital costs associated with MDD. Furthermore, a selection of therapeutic targets provides diverse treatment options which may be beneficial to the patient considering the heterogeneity of MDD.

Risk of Dementia Among Individuals With Psoriasis: A Nationwide Population-Based Cohort Study in Taiwan.

OBJECTIVE: Psoriasis is a chronic inflammatory disease putatively associated with dementia. However, the epidemiologic evidence of the relationship between psoriasis and dementia has been limited. We used a large national sample to investigate this relationship as well as the association between systemic therapy for psoriasis and incident dementia. METHODS: The cases were identified as a first recorded diagnosis of psoriasis (ICD-9-CM codes: 696.0, 696.1, or 696.8) between 1996 and 2013 from Taiwan's National Health Insurance Research Database (NHIRD). Each selected case of psoriasis was compared with 4 sex-, age-, and urbanization-matched comparison subjects. The first diagnosis of dementia (ICD-9-CM codes: 290.0-290.4, 294.1-294.2, 331.0-331.2, or 331.82) that covered vascular and nonvascular subtypes until the end of 2013 was tracked in both groups. Cox regression analyses and a competing risk model were applied to evaluate the risk, adjusting for sex, urbanization, age, hypertension, diabetes, heart disease, hyperlipidemia, stroke, and depression. The association between systemic therapy and incidence of dementia in the psoriasis group was examined in further stratified analyses. RESULTS: Overall, 3,820 patients with psoriasis and 15,280 comparisons were identified. After adjustment, a significantly higher risk of dementia was identified in the psoriasis group than in the comparison group (adjusted hazard ratio [aHR] = 1.23; 95% CI, 1.06-1.42). A significant association between psoriasis and dementia was identified for nonvascular dementia (aHR = 1.25, 95% CI, 1.07-1.45) but not for vascular dementia (aHR = 1.27, 95% CI, 0.83-1.93). Receiving systemic therapy for psoriasis for more than 90 days significantly reduced the risk of developing dementia compared with no systemic therapy (aHR = 0.66; 95% CI, 0.45-0.97). Compared with those who received no systemic therapy, the patients who received disease-modifying antirheumatic drugs and/or biologics had a significantly lower risk of dementia incidence (aHR = 0.69; 95% CI, 0.50-0.97), which was not the case in patients who received only phototherapy. CONCLUSIONS: Individuals with psoriasis have a significantly higher incidence of dementia, particularly the nonvascular type. Systemic therapy might be protective in preventing dementia in patients with psoriasis.

Antidepressant Prescription and Risk of Lung Cancer: A Nationwide Case-Control Study.

INTRODUCTION: In recent decades, concern about safety of antidepressants has been raised but the risk between antidepressants and lung cancer has not yet been established. METHODS: A case-control study was conducted by using a nationwide database in Taiwan. The case groups were new onset lung cancer diagnosis during 1999-2008 and age- and gender-matched controls were selected among those without any cancer. The cumulative exposure dose before the lung cancer diagnosis was added and risks were calculated according to the levels of defined daily dose and classes of antidepressants. RESULTS: A total of 39,001 individuals with lung cancer and 189,906 individuals without lung cancer between 1999 and 2008 were included in the analysis. Antidepressants, of any class, were not associated with elevated risks for lung cancer with the exception of bupropion at high exposure levels (odds ratio=4.81, 95% confidence interval=1.39-16.71). DISCUSSION: Antidepressant prescription was not associated with elevation of lung cancer incidence using a nationally representative sample. The elevated risk for lung cancer with bupropion at high doses may be a bias by indication and warrant longitudinal investigation.

Frequency of use and perceived helpfulness of wellness strategies for bipolar and unipolar depression.

BACKGROUND: The majority of research in mood disorders has focused on pharmacologic, psychotherapeutic, and brain stimulation interventions. Conversely, the utility of less structured interventions, such as lifestyle modifications or wellness strategies, has remained understudied. The objective of the current study is to evaluate the frequency of use and perceived helpfulness of wellness strategies for bipolar and unipolar depression. METHODS: The Depression and Bipolar Support Alliance (DBSA) conducted an online survey asking participants about the use and helpfulness of wellness strategies. RESULTS: In total, 896 participants completed the survey (unipolar depression [n = 447] and bipolar depression [n = 449]). Wellness strategies were used by 62% and 59% of individuals with bipolar and unipolar depression, respectively. Listening to music, socializing, and adequate sleep were commonly reported wellness strategies. The majority of participants reported wellness strategies to be helpful. Use of wellness strategies was associated with greater overall perceived treatment effectiveness (P < .0001) and greater subjective helpfulness of medications (P = .039), psychotherapy (P < .0001), and peer support groups (P < .0001). CONCLUSIONS: Wellness strategies were commonly used by the majority of respondents. These strategies were subjectively helpful for most respondents and were associated with greater overall treatment effectiveness and increased helpfulness of medications, psychotherapy, and peer support groups. As such, wellness strategies should be considered while developing a holistic treatment plan for depression. Further research is needed to evaluate the antidepressant effects of specific wellness strategies to better understand the role of these interventions in the management of depression.

Depressive disorders: Processes leading to neurogeneration and potential novel treatments.

Mood disorders are wide spread with estimates that one in seven of the population are affected at some time in their life (Kessler et al., 2012). Many of those affected with severe depressive disorders have cognitive deficits which may progress to frank neurodegeneration. There are several peripheral markers shown by patients who have cognitive deficits that could represent causative factors and could potentially serve as guides to the prevention or even treatment of neurodegeneration. Circadian rhythm misalignment, immune dysfunction and oxidative stress are key pathologic processes implicated in neurodegeneration and cognitive dysfunction in depressive disorders. Novel treatments targeting these pathways may therefore potentially improve patient outcomes whereby the primary mechanism of action is outside of the monoaminergic system. Moreover, targeting immune dysfunction, oxidative stress and circadian rhythm misalignment (rather than primarily the monoaminergic system) may hold promise for truly disease modifying treatments that may prevent neurodegeneration rather than simply alleviating symptoms with no curative intent. Further research is required to more comprehensively understand the contributions of these pathways to the pathophysiology of depressive disorders to allow for disease modifying treatments to be discovered.

Air pollution, aeroallergens and suicidality: a review of the effects of air pollution and aeroallergens on suicidal behavior and an exploration of possible mechanisms.

OBJECTIVE: Risk factors for suicide can be broadly categorized as sociodemographic, clinical and treatment. There is interest in environmental risk and protection factors for suicide. Emerging evidence suggests a link between environmental factors in the form of air pollution and aeroallergens in relation to suicidality. METHODS: Herein, we conducted a systematic review of 15 articles which have met inclusion criteria on the aforementioned effects. RESULTS: The majority of the reviewed articles reported an increased suicide risk alongside increased air pollutants or aeroallergens (i.e. pollen) increase; however, not all environmental factors were explored equally. In specific, studies that were delimited to evaluating particulate matter (PM) reported a consistent association with suicidality. We also provide a brief description of putative mechanisms (e.g. inflammation and neurotransmitter dysregulation) that may mediate the association between air pollution, aeroallergens and suicidality. CONCLUSION: Available evidence suggests that exposure to harmful air quality may be associated with suicidality. There are significant public health implications which are amplified in regions and countries with greater levels of air pollution and aeroallergens. In addition, those with atopic sensitivity may represent a specific subgroup that is at risk.

Cannabidiol in medical marijuana: Research vistas and potential opportunities.

The high and increasing prevalence of medical marijuana consumption in the general population invites the need for quality evidence regarding its safety and efficacy. Herein, we synthesize extant literature pertaining to the phytocannabinoid cannabidiol (CBD) and its brain effects. The principle phytocannabinoid Δ9-tetrahydrocannabinol (Δ9-THC) and CBD are the major pharmacologically active cannabinoids. The effect of CBD on brain systems as well as on phenomenological measures (e.g. cognitive function) are distinct and in many cases opposite to that of Δ9-THC. Cannabidiol is without euphoriant properties, and exerts antipsychotic, anxiolytic, anti-seizure, as well as anti-inflammatory properties. It is essential to parcellate phytocannabinoids into their constituent moieties as the most abundant cannabinoid have differential effects on physiologic systems in psychopathology measures. Disparate findings and reports related to effects of cannabis consumption reflect differential relative concentration of Δ9-THC and CBD. Existing literature, notwithstanding its deficiencies, provides empirical support for the hypothesis that CBD may exert beneficial effects on brain effector systems/substrates subserving domain-based phenomenology. Interventional studies with purified CBD are warranted with a call to target-engagement proof-of-principle studies using the research domain criteria (RDoC) framework.

Asthma, corticosteroid use and schizophrenia: A nationwide population-based study in Taiwan.

OBJECTIVE: Asthma and corticosteroid use have been implicated as possible risk factors for schizophrenia. The retrospective cohort study herein aimed to investigate the association between asthma, corticosteroid use, and schizophrenia. METHOD: Longitudinal data (2000 to 2007) from adults with asthma (n = 50,046) and without asthma (n = 50,046) were compared on measures of schizophrenia incidence using Taiwan's National Health Insurance Research Database (NHIRD). Incidence of schizophrenia diagnosis (ICD-9 codes 295.XX) between 2000 and 2007 were compared between groups. Competing risk-adjusted Cox regression analyses were conducted, adjusting for sex, age, residence, socioeconomic status, corticosteroid use, outpatient and emergency room visit frequency, Charlson comorbidity index, and total length of hospital stays days for any disorder. RESULTS: Of the 75,069 subjects, 238 received a diagnosis of schizophrenia. The mean (SD) follow-up interval for all subjects was 5.8 (2.3) years. After adjusting for potential confounding factors, asthma was associated with significantly greater hazard ratio for incident schizophrenia 1.40 (95% CI = 1.05, 1.87). Additional factors associated with greater incidence of schizophrenia were rural residence, lower economic status, and poor general health. Older age (i.e. ≥65 years) was negatively associated with schizophrenia incidence. Corticosteroid use was not associated with increased risk for schizophrenia. CONCLUSIONS: Asthma was associated with increased risk for schizophrenia. The results herein suggest that a convergent disturbance in the immune-inflammatory system may contribute to the pathoetiology of asthma and schizophrenia.