Polymorphisms in genes related to the hypothalamic-pituitary-adrenal axis and antidepressant response – systematic review

ObjectiveAround 50% of depressed patients do not respond to antidepressants. Evidence from familial studies suggests a genetic component to this. This study investigated whether patients with polymorphisms in genes related to the hypothalamic-pituitary-adrenal (HPA) axis were less likely to respond to antidepressants.MethodEMBASE, MEDLINE, PsycINFO, and the Cochrane Library were searched. Inclusionary criteria were: 1) patients with depression, 2) study of HPA axis-related candidate genes, 3) at least four weeks of antidepressants, and 4) assessment of depressive symptoms dividing patients into non-responders and responders.ResultsNineteen studies were identified. Non-responders and responders did not differ in single nucleotide polymorphisms (SNPs) in genes encoding arginine vasopressin. Findings were equivocal regarding genes encoding the FK506 binding protein 5 and glucocorticoid and mineralocorticoid receptors. Specific SNPs and haplotypes within genes related to corticotropin-releasing hormone (CRHBP, CRHR1) and melanocortins (POMC) predicted non-responder status.ConclusionsReplication studies and additional investigations exploring gene x environment and drug x environment interactions are necessary before pharmacological treatments may be adjusted based on a patient’s genetic profile

Non-traditional platinum compounds for improved accumulation, oral bioavailability, and tumor targeting

The five platinum anticancer compounds currently in clinical use conform to structure–activity relationships formulated (M. J. Cleare and J. D. Hoeschele, Bioinorg. Chem., 1973, 2, 187–210) shortly after the discovery that cis-diamminedichloroplatinum(II), cisplatin, has antitumor activity in mice. These compounds are neutral platinum(II) species with two am(m)ine ligands or one bidentate chelating diamine and two additional ligands that can be replaced by water through aquation reactions. The resulting cations ultimately form bifunctional adducts on DNA. Information about the chemistry of these platinum compounds and correlations of their structures with anticancer activity have provided guidance for the design of novel anticancer drug candidates based on the proposed mechanisms of action. This article discusses advances in the synthesis and evaluation of such non-traditional platinum compounds, including cationic and tumor-targeting constructs.National Cancer Institute (U.S.) (Grant CA34992

Antitumor Pentamethylcyclopentadienyl Rhodium Complexes of Maltol and Allomaltol: Synthesis, Solution Speciation and Bioactivity

The reaction of the dimer [RhIII(pentamethylcyclopentadienyl)(m-Cl)Cl]2 ([RhIII(Cp*)(m- Cl)Cl]2) with the hydroxypyrone ligands maltol and allomaltol affords complexes of the general formula [RhIII(Cp*)(L)Cl] under standard and microwave conditions. The organometallic compounds were characterized by standard analytical methods and in the case of the allomaltol derivative in the solid state by single-crystal X-ray diffraction analysis. The complexes showed similar cytotoxicity profiles and were proved to be moderately active against various human cancer cell lines. The stoichiometry and stability of these complexes were determined in aqueous solution by pH-potentiometry, 1H NMR spectroscopy and UVvisible spectrophotometry. Speciation was studied in the presence and in the absence of chloride ions. Hydrolysis of [RhIII(Cp*)(H2O)3]2+ gave dimeric mixed hydroxido species [(RhIII(Cp*))2(m-OH)3]+ and [(RhIII(Cp*))2(m-OH)2Z2] (Z = H2O/Cl‒). Formation of the mononuclear complexes [RhIII(Cp*)(L)Z] of maltol and allomaltol with similar and moderate stability was found. These species predominate at physiological pH and decompose only partially at micromolar concentrations. In addition, hydrolysis of the aqua complex or the chlorido/hydroxido co-ligand exchange resulted in the formation of the mixed-hydroxido species [RhIII(Cp*)(L)(OH)] in the basic pH range. Replacement of the chlorido by an aqua ligand in the complex [RhIII(Cp*)(L)Cl] was monitored and with the help of the equilibrium constants the extent of aquation at various chloride concentrations of the extra- and intracellular milieu can be predicted. Complexation of these RhIII complexes was compared to analogous [RuII(h6-p-cymene)] species and higher conditional stabilities were found in the case of the RhIII compounds at pH 7.4

A narrative review on the similarities and dissimilarities between myalgic encephalomyelitis/chronic fatigue syndrome (me/cfs) and sickness behavior

It is of importance whether myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a variant of sickness behavior. The latter is induced by acute infections/injury being principally mediated through proinflammatory cytokines. Sickness is a beneficial behavioral response that serves to enhance recovery, conserves energy and plays a role in the resolution of inflammation. There are behavioral/symptomatic similarities (for example, fatigue, malaise, hyperalgesia) and dissimilarities (gastrointestinal symptoms, anorexia and weight loss) between sickness and ME/CFS. While sickness is an adaptive response induced by proinflammatory cytokines, ME/CFS is a chronic, disabling disorder, where the pathophysiology is related to activation of immunoinflammatory and oxidative pathways and autoimmune responses. While sickness behavior is a state of energy conservation, which plays a role in combating pathogens, ME/CFS is a chronic disease underpinned by a state of energy depletion. While sickness is an acute response to infection/injury, the trigger factors in ME/CFS are less well defined and encompass acute and chronic infections, as well as inflammatory or autoimmune diseases. It is concluded that sickness behavior and ME/CFS are two different conditions

Development of Parkinsonism following exposure to aripiprazole: two case reports

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Introduction: Aripiprazole is a novel atypical neuroleptic used in the treatment of psychosis. A few recent studies have demonstrated an association between the use of aripiprazole and an exacerbation of Parkinsonism, although this relationship is poorly defined. To our knowledge, this is the first case series describing an onset of Parkinsonism in patients without prior history of Parkinson’s diseas

Suicide attempts and non-suicidal self-harm: national prevalence study of young adults

Background: There are few prevalence studies of suicide attempts and non-suicidal self-harm (NSSH). Aims: We aimed to estimate the prevalence of thoughts of NSSH, suicidal thoughts, NSSH and suicide attempts among 18- to 34-year-olds in Scotland. Method: We interviewed a representative sample of young adults from across Scotland. Results: We interviewed 3508 young people; 11.3 and 16.2% reported a lifetime history of suicide attempts and NSSH, respectively. The first episode of NSSH tended to precede the first suicide attempt by about 2 years. Age at onset of NSSH and suicide attempt was younger in females. Earlier age at onset was associated with more frequent NSSH/suicide attempts. Women are significantly more likely to report NSSH and suicide attempts compared with men. Conclusions: One in nine young people has attempted suicide and one in six has engaged in NSSH. Clinicians should be vigilant, as suicide attempts and NSSH are relatively common

High cocoa polyphenol rich chocolate may reduce the burden of the symptoms in chronic fatigue syndrome

<p>Abstract</p> <p>Background</p> <p>Chocolate is rich in flavonoids that have been shown to be of benefit in disparate conditions including cardiovascular disease and cancer. The effect of polyphenol rich chocolate in subjects with chronic fatigue syndrome (CFS) has not been studied previously.</p> <p>Methods</p> <p>We conducted a double blinded, randomised, clinical pilot crossover study comparing high cocoa liquor/polyphenol rich chocolate (HCL/PR) in comparison to simulated iso-calorific chocolate (cocoa liquor free/low polyphenols(CLF/LP)) on fatigue and residual function in subjects with chronic fatigue syndrome. Subjects with CFS having severe fatigue of at least 10 out of 11 on the Chalder Fatigue Scale were enrolled. Subjects had either 8 weeks of intervention in the form of HCL/PR or CLF/LP, with a 2 week wash out period followed by 8 weeks of intervention with the other chocolate.</p> <p>Results</p> <p>Ten subjects were enrolled in the study. The Chalder Fatigue Scale score improved significantly after 8 weeks of the HCL/PR chocolate arm [median (range) Exact Sig. (2-tailed)] [33 (25 - 38) vs. 21.5 (6 - 35) 0.01], but that deteriorated significantly when subjects were given simulated iso-calorific chocolate (CLF/CP) [ 28.5 (17 - 20) vs. 34.5 (13-26) 0.03]. The residual function, as assessed by the London Handicap scale, also improved significantly after the HCL/PR arm [0.49 (0.33 - 0.62) vs. 0.64 (0.44 - 0.83) 0.01] and deteriorated after iso-calorific chocolate [00.44 (0.43 - 0.68) vs. 0.36 (0.33 - 0.62)0.03]. Likewise the Hospital Anxiety and Depression score also improved after the HCL/PR arm, but deteriorated after CLF/CP. Mean weight remained unchanged throughout the trial.</p> <p>Conclusion</p> <p>This study suggests that HCL/PR chocolate may improve symptoms in subjects with chronic fatigue syndrome.</p

Information seeking, mental health and loneliness: Longitudinal analyses of adults in the UK COVID-19 mental health and wellbeing study

Information seeking has generally been seen as an adaptive response to the COVID-19 pandemic. However, it may also result in negative outcomes on mental health. The present study tests whether reporting COVID-related information seeking throughout the pandemic is associated with subsequently poorer mental health outcomes. A quota-based, non-probability-sampling methodology was used to recruit a nationally representative sample. COVID-related information seeking was assessed at six waves along with symptoms of depression, anxiety, mental wellbeing and loneliness (N = 1945). Hierarchical linear modelling was used to assess the relationship between COVID-related information seeking and mental health outcomes. Information seeking was found to reduce over time. Overall, women, older and higher socioeconomic group individuals reported higher levels of information seeking. At waves 1-4 (March-June 2020) the majority of participants reported that they sought information on Covid 1-5 times per day, this decreased to less than once per day in waves 5 and 6 (July-November 2020). Higher levels of information seeking were associated with poorer mental health outcomes, particularly clinically significant levels of anxiety. Use of a non-probability sampling method may have been a study limitation, nevertheless, reducing or managing information seeking behaviour may be one method to reduce anxiety during pandemics and other public health crises

Measurement invariance of the 4-item entrapment scale short-form (E-SF): a transnational examination across race/ethnicity, sexual orientation, and suicide attempt history among minoritized adults

Feelings of entrapment—posited to arise when attempts to escape from defeating or humiliating circumstances are blocked—may confer increased risk for psychopathology and suicidal thoughts and behaviors (STB), particularly among minoritized individuals who often have more frequent exposure to such experiences. Including entrapment in empirical models may aid research efforts in further exploring its role in minority mental health. The Entrapment Scale Short-Form (E-SF), a brief version of the 16-item Entrapment Scale, is one tool that may be utilized towards this end; however, to do so meaningfully, its psychometric properties and measurement invariance must be evaluated in diverse samples. The current study aimed to examine the factor structure, measurement invariance, and convergent validity of the E-SF across race/ethnicity and sexual orientation in a combined transnational sample of minoritized adults (total N = 1194). Results supported a one-factor model of the E-SF that was invariant across samples, race/ethnicity, sexual orientation, and history of suicide attempt. Further, significant positive correlations observed between theoretically relevant constructs of anxiety, depression, and posttraumatic stress disorder symptoms supported its convergent validity. Implications include disproportionate levels of entrapment experienced by minoritized individuals— particularly by sexual minorities—which likely reflect the discrimination frequently endured by these individuals