Astrocytic expression of ZIP14 (SLC39A14) is part of the inflammatory reaction in chronic neurodegeneration with iron overload.

Neurodegeneration is associated with inflammation and mismanaged iron homeostasis, leading to increased concentration of non-transferrin-bound iron (NTBI) in the brain. NTBI can be taken up by cells expressing Zrt-, Irt-like protein-14 (ZIP14), which is regulated by iron overload and pro-inflammatory cytokines, for example, interleukin-1ß (IL-1ß) and IL-6. Here, we focus on the astrocytic involvement and regulation of ZIP14 in an experimental model of chronic neurodegeneration with inflammation and iron overload. Rats were unilaterally injected with ibotenic acid in striatum resulting in excitotoxicity-induced neuronal loss in substantia nigra pars reticulata (SNpr). ZIP14 expression was measured in SNpr using immunohistochemistry, western blotting, and RT-qPCR. Cultures of primary astrocytes were examined for Zip14 mRNA expression after stimulation with ferric ammonium citrate (FAC), IL-6, or IL-1ß. To study the involvement of ZIP14 in astrocytic iron uptake, uptake of 59 Fe was investigated after treatment with IL-1ß and siRNA-mediated ZIP14 knockdown. In the lesioned SNpr, reactive astrocytes, but not microglia, revealed increased ZIP14 expression with a main confinement to cell bodies and cellular processes. In astrocyte cultures, FAC and IL-1ß stimulation increased Zip14 expression and IL-1ß stimulation increased uptake of 59 Fe. Increased 59 Fe uptake was also observed after siRNA-mediated ZIP14 knockdown suggesting that lowering of ZIP14 impaired the balance between astrocytic uptake and export of iron. We conclude that astrocytes increase ZIP14 expression in response to inflammation and iron exposure and that ZIP14 seems pertinent for iron uptake in astrocytes and plays a role for a balanced astrocytic iron homeostasis.

A New Perspective on the Anti-Suicide Effects With Ketamine Treatment: A Procognitive Effect.

Available evidence indicates that a single, low-dose administration of ketamine is a robust, rapid-onset intervention capable of mitigating depressive symptoms in adults with treatment-resistant mood disorders. Additional evidence also suggests that ketamine may offer antisuicide effects. Herein, we propose that the antidepressant effects reported with ketamine administration are mediated, in part, by targeting neural circuits that subserve cognitive processing relevant to executive function and cognitive emotional processing. Empirical support for the conceptual framework of the cognitive domain as a critical target of ketamine's action is the additional observation that pretreatment cognitive function predicts treatment outcomes with ketamine administration. The proposal that beneficial effects on cognitive function may be, in some individuals, the proximate mechanism mitigating symptom relief in mood disorders exists alongside the well-established deleterious effect of ketamine on cognitive function. During the past 5 years, there have been several reviews and meta-analyses concluding that ketamine has possible clinical benefits in refractory mood disorders. We introduce the conceptual framework that ketamine's salutary effects, notably in suicidality, may in part be via procognitive mechanisms.

Anhedonia and cognitive function in adults with MDD: results from the International Mood Disorders Collaborative Project.

BACKGROUND: Cognitive dysfunction is common in major depressive disorder (MDD) and a critical determinant of health outcome. Anhedonia is a criterion item toward the diagnosis of a major depressive episode (MDE) and a well-characterized domain in MDD. We sought to determine the extent to which variability in self-reported cognitive function correlates with anhedonia. METHOD: A post hoc analysis was conducted using data from (N=369) participants with a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR)-defined diagnosis of MDD who were enrolled in the International Mood Disorders Collaborative Project (IMDCP) between January 2008 and July 2013. The IMDCP is a collaborative research platform at the Mood Disorders Psychopharmacology Unit, University of Toronto, Toronto, Canada, and the Cleveland Clinic, Cleveland, Ohio. Measures of cognitive function, anhedonia, and depression severity were analyzed using linear regression equations. RESULTS: A total of 369 adults with DSM-IV-TR-defined MDD were included in this analysis. Self-rated cognitive impairment [ie, as measured by the Adult ADHD Self-Report Scale (ASRS)] was significantly correlated with a proxy measure of anhedonia (r=0.131, p=0.012). Moreover, total depression symptom severity, as measured by the total Montgomery-Åsberg Depression Rating Scale (MADRS) score, was also significantly correlated with self-rated measures of cognitive dysfunction (r=0.147, p=0.005). The association between anhedonia and self-rated cognitive dysfunction remained significant after adjusting for illness severity (r=0.162, p=0.007). CONCLUSIONS: These preliminary results provide empirical data for the testable hypothesis that anhedonia and self-reported cognitive function in MDD are correlated yet dissociable domains. The foregoing observation supports the hypothesis of overlapping yet discrete neurobiological substrates for these domains.

Intercropping of Narrow-Leafed Lupin (Lupinus angustifolius L.) and Barley (Hordeum vulgare L.) Affects the Flavonoid Composition of Both Crops.

Barley (Hordeum vulgare L.) is a common cereal crop in agricultural production and is often included in legume-cereal intercropping. Flavonoids, a major class of secondary metabolites found in barley, are involved in plant defense and protection. However, the effect of intercropping on barley flavonoids remains unknown. Herein, an intercropping system involving barley and lupin (Lupinus angustifolius L.) was studied. Intercropping increased the level of luteolin in lupin roots. Lupin-barley intercropping considerably increased genistein, rutin, and apigenin in barley shoots. Genistein and apigenin were also detected in intercropped barley roots and rhizosphere soil. The three flavonoids have been reported as defense compounds, suggesting that lupin triggers a defense response in barley to strengthen its survival ability.

Birth dimensions, severe mental illness and risk of type 2 diabetes in a cohort of Danish men born in 1953.

BACKGROUND: Birth dimensions have been associated with increased risk of both, severe mental illness and type 2 diabetes in adulthood, however, any influence on their co-occurrence has never been examined. This cohort study examine whether birth weight/ponderal index explain or modify the later association between severe mental illness and risk of type 2 diabetes. METHODS: The Metropolit cohort included 10,863 Danish men born in 1953 with information from age at conscription (between1971-84) until February 15th, 2018. Severe mental illness was defined as the exposure and information was retrieved from the national Danish health registries. Information on type 2 diabetes diagnosis or oral antidiabetic prescriptions was also obtained, as they were the outcome of interest. Information on birth weight/ponderal index was available from birth certificates. Cox proportional hazards regression models were used to estimate the associations and interactions were tested. RESULTS: After 47.1 years of follow-up, 848 (7.8%) and 1320 (12.2%) men developed a severe mental illness or diabetes, respectively. Men with severe mental illness presented higher risk of subsequent diabetes (HR = 1.92; 95%CI, 1.61-2.30). This association was stronger in severe mental ill men with low birth weight (HR = 3.58; 95%CI, 2.11-6.07), than in those normal birth weight (HR = 1.79; 95%CI, 1.45-2.20). This effect modification was most evident for men diagnosed with schizophrenia. CONCLUSIONS: Birth information on birth weight/ponderal index could be of interest in diabetes screening on severe mental ill populations (especially in schizophrenia) since they might play a critical role in the increased risk of type 2 diabetes following severe mental illness.

Incidence of Depression After Stroke, and Associated Risk Factors and Mortality Outcomes, in a Large Cohort of Danish Patients.

IMPORTANCE: More than 30 million people live with a stroke diagnosis worldwide. Depression after stroke is frequent, and greater knowledge of associated risk factors and outcomes is needed to understand the etiology and implications of this disabling complication. OBJECTIVES: To examine whether the incidence of and risk factors for depression differ between patients with stroke and a reference population without stroke and to assess how depression influences mortality. DESIGN, SETTING, AND PARTICIPANTS: Register-based cohort study in Denmark. Participants were all individuals 15 years or older with a first-time hospitalization for stroke between January 1, 2001, and December 31, 2011 (n = 157 243), and a reference population (n = 160 236) matched on age, sex, and municipality. The data were analyzed between January and March 2016. MAIN OUTCOMES AND MEASURES: The incidence of depression and mortality outcomes of depression (defined by hospital discharge diagnoses or antidepressant medication use) were examined using Cox proportional hazards regression analyses. RESULTS: In total, 34 346 patients (25.4%) with stroke and 11 330 (7.8%) in the reference population experienced depression within 2 years after study entry. Compared with the reference population, patients with stroke had a higher incidence of depression during the first 3 months after hospitalization (hazard ratio for stroke vs the reference population, 8.99; 95% CI, 8.61-9.39), which declined during the second year of follow-up (hazard ratio for stroke vs the reference population, 1.93; 95% CI, 1.85-2.08). Significant risk factors for depression for patients with stroke and the reference population included older age, female sex, single cohabitation status, basic educational attainment, diabetes, high level of somatic comorbidity, history of depression, and stroke severity (in patients with stroke). The associations were strongest for the reference population. In both populations, depressed individuals, especially those with new onset, had increased all-cause mortality (hazard ratio for new-onset depression, 1.89 [95% CI, 1.83-1.95] for patients with stroke and 3.75 [95% CI, 3.51-4.00] for the reference population) after adjustment for confounders. Similar patterns were found for natural and unnatural causes of death. In most models, the depression-related relative mortality was approximately twice as high in the reference population vs the stroke population. CONCLUSIONS AND RELEVANCE: Depression is common in patients with stroke during the first year after diagnosis, and those with prior depression or severe stroke are especially at risk. Because a large number of deaths can be attributable to depression after stroke, clinicians should be aware of this risk.

Binge eating in adults with mood disorders: Results from the International Mood Disorders Collaborative Project.

A post hoc analysis was conducted using data from participants (N=631) with a DSM-IV-TR defined diagnosis of major depressive disorder (MDD) or bipolar disorder (BD) who were enrolled in the International Mood Disorders Collaborative Project (IMDCP) between January 2008 and July 2013. It was determined that 20.6% of adults with mood disorders as part of the IMDCP fulfilled criteria for binge eating behaviour (BE). A higher percentage of individuals with BD met criteria for BE when compared to MDD (25.4% vs. 16%; p=0.004) Univariate analyses indicated that individuals with a mood disorder (i.e., MDD or BD) and BE had greater scores on measures of anxiety severity (p=0.013) and higher rates of lifetime and current substance dependence, lifetime alcohol abuse (p=0.007, p=0.006, and p=0.015, respectively), Attention Deficit Hyperactivity Disorder (ADHD) (p=0.018) and measures of neuroticism (p=0.019). Individuals with a mood disorder and concurrent BE had lower scores on measures of conscientiousness (p=0.019). Individuals meeting criteria for BE were also significantly more likely to be obese (i.e., BMI≥30kg/m2) (50% vs. 25.5%; p<0.001). Binge eating is common amongst adults utilising tertiary care services principally for a mood disorder. The presence of BE identifies a subset of adults with mood disorders who have greater illness complexity as evidenced by course of illness variables and comorbidity. Screening for BE amongst individuals with mood disorders is warranted; parsing neurobiological substrates subserving non-homeostatic eating behaviour amongst individuals with mood disorders is a future research vista.