Hair cortisol in patients with a depressive episode treated with electroconvulsive therapy.

BACKGROUND: There is substantial evidence showing changes in hypothalamic pituitary adrenal (HPA)-axis activity in patients with major depressive disorder (MDD). Also, there seem to be differences in HPA-axis functioning between MDD subgroups. It is however unclear whether hair cortisol concentrations (HCC), which are a stable marker of long-term cortisol levels, are suitable as a biomarker for identifying subgroups in MDD. METHODS: We were able to attain valid HCC from a scalp hair sample of sixty-two patients with a major depressive episode right before electroconvulsive therapy (ECT). HCC were our main biological outcome measure. We created subgroups using depression severity as defined by the Hamilton Depression Rating Scale, the presence/absence of psychotic symptoms, the presence of melancholia as defined by the CORE and catatonia as defined by the Bush-Francis Catatonia Rating Scale. RESULTS: Our analyses of the total group showed a median HCC of 4.4 pg/mg. We found patients with catatonia (N = 10) to have substantially higher median HCC (8.3 pg/mg) than patients without catatonia (3.8 pg/mg). Although presence of melancholia and depression severity were not significantly associated with HCC, more severe psychomotor agitation was associated with higher HCC. Pre-treatment HCC was not associated with ECT outcome. STRENGTHS AND LIMITATIONS: A complicating factor in interpretation of our results was the large variability in HCC. This could be related to potential confounders such as cardiometabolic and other comorbidities, that were however addressed to the extent possible. CONCLUSIONS: HCC is a potential biomarker for MDD patients with severe agitation and/or catatonia. CLINICALTRIALS.GOV: Identifier: NCT02562846.

TPF plus cetuximab induction chemotherapy followed by biochemoradiation with weekly cetuximab plus weekly cisplatin or carboplatin: a randomized phase II EORTC trial.

BACKGROUND: Our aim was to test the safety of cetuximab added to chemoradiation with either cisplatin or carboplatin after prior induction chemotherapy. METHODS: Patients with stage III/IV unresectable, squamous cell carcinoma of the head and neck received up to four cycles of TPF-E (cisplatin and docetaxel 75 mg/m2 on day 1 followed by 5-FU 750 mg/m2/day as a continuous infusion on days 1-5 plus cetuximab at a loading dose of 400 mg/m2 followed by a weekly dose of 250 mg/m2), with prophylactic antibiotics but no growth factors. Patients not progressing after four cycles of TPF-E were randomly assigned to radiotherapy (70 Gy over 7 weeks in 2 Gy fractions) and weekly cetuximab with either weekly cisplatin 40 mg/m2 or carboplatin, AUC of 1.5 mg/ml/min. Primary endpoint was feasibility. RESULTS: Forty-seven patients were recruited. One patient did not start TPF (hypersensitivity reaction during the cetuximab loading dose). Induction TPF-E was discontinued in 12 patients due to toxicity (6 patients), medical decision (2), death (1), patient refusal (1), protocol violation (1), co-morbidity (1). Three further patients were not randomized [progressive disease (1), protocol violation (1), toxicity and co-morbidity (1)]. Of particular interest are three patients who suffered from bowel perforation, one patient who died as results of pneumonia and septic shock, and a second patient who was found dead at home 12 days after starting TPF-E (cause of death unknown). Weekly cisplatin and carboplatin was stopped early in seven and four patients, respectively. Radiotherapy was stopped in two patients with cisplatin and interrupted in one patient with cisplatin and four patients with carboplatin. CONCLUSIONS: The addition of cetuximab to full dose TPF induction chemotherapy led to unacceptable complications and premature closing of the study. Only 34 out of 46 patients completed four cycles of TPF-E and only 30 started biochemoradiation.

Impact of one HF-rTMS session on fine motor function in right-handed healthy female subjects: a comparison of stimulation over the left versus the right dorsolateral prefrontal cortex.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive tool to investigate neural conduction in motor processes. Most rTMS research has been conducted by targeting the primary motor cortex. Several studies have also found increased psychomotor speed after rTMS of the dorsolateral prefrontal cortex (DLPFC). However, these studies were mainly performed in psychiatric patients, only targeting the left DLPFC, and often without sham control. Moreover, psychomotor speed is mostly measured based on tasks that also require higher executive functions. METHODS: Here, we examined the lateralized effect of one sham-controlled high-frequency rTMS session applied to the left or right DLPFC on fine motor function in 36 healthy right-handed females, using the Fitts' paradigm. RESULTS: We found a significant improvement in psychomotor speed only after actively stimulating the right DLPFC. CONCLUSION: Our results support the assumption of a right prefrontal neural network implicated in visuomotor behavior and performance processes, and that the improvement in psychomotor speed is not a secondary effect of decreased mood.