Genetic variation in the glucocorticoid receptor and psychopathology after dexamethasone administration in cardiac surgery patients.

The glucocorticoid receptor (GR) agonist dexamethasone is frequently used for its anti-inflammatory properties. We recently showed that a single high-dose of dexamethasone had long-lasting protective effects on the development of psychopathology after cardiac surgery and postoperative intensive care unit stay. In this study, we investigated whether common genetic variation in the hypothalamic-pituitary-adrenal (HPA)-axis would influence the susceptibility for PTSD and depression after dexamethasone administration. Participants (n = 996) of the Dexamethasone for Cardiac Surgery (DECS) randomized clinical trial were followed after receiving a single high intraoperative dose of dexamethasone (1 mg/kg), a GR agonist, or placebo. PTSD and depressive symptoms were assessed up to four years after cardiac surgery. We focused primarily on five common single nucleotide polymorphisms (SNPs) in the glucocorticoid receptor (GR). Secondarily, we comprehensively assessed common genetic variation in the FK506 binding protein (FKBP5) and the mineralocorticoid receptor (MR). The protective effects of dexamethasone on postoperative PTSD symptoms were dependent on the GR polymorphisms rs41423247 (p = .009), rs10052957 (p = .003), and rs6189 (p = .002), but not on rs6195 (p = .025) or rs6198, (p = .026) after Bonferroni correction. No genotype-dependent effects were found for postoperative depressive symptoms. Also, no associations of FKBP5 and MR polymorphisms were found on PTSD and depression outcomes. Protective effects of dexamethasone on PTSD symptoms after cardiac surgery and ICU stay seem to depend on common genetic variation in its target receptor, the GR. These effects indicate that pre-operative genetic screening could potentially help in stratifying patients for their vulnerability for developing PTSD symptoms after surgery.

Comparing episodes of antidepressants use with intermittent episodes of no use: A higher relative risk of suicide attempts but not of suicide at young age.

The Food and Drug Administration has issued a number of advisories regarding a possible causal link between antidepressants and suicide behaviour among young persons. We investigated the age dependency of (fatal) suicide attempts associated with antidepressants (N=232,561). By linking insurance claims with the death register of Statistics Netherlands (2002-2011), rates of (fatal) suicide attempts were estimated during antidepressant use and intermittent episodes without use. The age dependency of the relative risk of attempts and of suicide during episodes with compared with episodes without antidepressants was investigated by testing the {age × episode} interaction.The attempt rate during antidepressant use decreased with increasing age, concurrently with a decrease of the relative risk from 3.62 to 1.86 (p for interaction <0.001). This age dependency was found both at the early (<0.5 year) and at later stages after the first prescription (>5 years). No suicides were found among those aged <18 years, and no age dependency for the relative risk of suicide at ages ⩾ 18 was established (p>0.46). The association between antidepressants and suicide attempts at a young age does not necessarily point to a causal relationship, and, most importantly, did not translate to a similar age dependency for suicide.

Prescription patterns for psychotropic drugs in cancer patients; a large population study in the Netherlands.

BACKGROUND: Psychotropic drugs are commonly prescribed for various psychological complaints in cancer patients. We aim to examine the prescription pattern in cancer patients of three common psychotropic drugs: benzodiazepine, antidepressant and antipsychotic. METHODS: This is a retrospective case-control study. Data were extracted from the Agis Health Database. This insurance database contains the healthcare consumption of 1.3 million inhabitants of the Netherlands. We analyzed the use of psychotropics in cancer patients and an equally sized randomly selected control group of noncancer patients from 2006 to 2008. Odds ratio (OR) were adjusted for age, gender, immigrant status, neighborhood socio-economic status, and premorbid medical condition. Additionally, the numbers of new user in the 3 months after cancer was diagnosed and in the 3 months before death were compared. RESULTS: A total of 113 887 cancer patients and 121 395 control subjects were included. Cancer patients were significantly more often prescribed psychotropic drugs (adjusted OR: benzodiazepines = 1.70, CI = 1.67-1.74; antidepressants = 1.38, CI = 1.34-1.42; and antipsychotics = 1.70, CI = 1.62-1.77). Lower socio-economic status, immigrant, and premorbid chronic medical conditions were significantly associated with higher risk of psychotropic use. Odds for a new prescription for all three psychotropic drugs were significantly less in the first 3 months after cancer diagnosis than the 3 months before death (benzodiazepine, OR = 0.673, CI = 0.647-0.705; antidepressant, OR = 0.592, CI = 0.544-0.644; antipsychotic, OR = 0.177, CI = 0.165-0.190) CONCLUSIONS: Psychotropic drug prescription is common in cancer patients, starts soon after diagnosis, and increases in the terminal stage. Prescription rates were significantly higher in patients from lower socio-economic group, immigrants, or with premorbid chronic medical condition.