Disrupted hippocampal neuregulin-1/ErbB3 signaling and dentate gyrus granule cell alterations in suicide.

This corrects the article DOI: 10.1038/tp.2017.132.

Disrupted hippocampal neuregulin-1/ErbB3 signaling and dentate gyrus granule cell alterations in suicide.

Neuregulin-1 (NRG1) and ErbB receptors have been associated with psychopathology, and NRG1-ErbB3 signaling has been shown to increase hippocampal neurogenesis and induce antidepressant-like effects. In this study, we aimed to determine whether deficits in NRG1 or ErbBs might be present in the hippocampus of suicide completers. In well-characterized postmortem hippocampal samples from suicides and matched sudden-death controls, we assessed gene expression and methylation using qRT-PCR and EpiTYPER, respectively. Moreover, in hippocampal tissues stained with cresyl violet, stereology was used to quantify numbers of granule cells and of glia. Granule cell body size was examined with a nucleator probe, and granule cell layer volume with a Cavalieri probe. Unmedicated suicides showed sharply decreased hippocampal ErbB3 expression and decreased numbers of ErbB3-expressing granule cell neurons in the anterior dentate gyrus; a phenomenon seemingly reversed by antidepressant treatment. Furthermore, we found ErbB3 expression to be significantly decreased in the dentate gyrus of adult mice exposed to chronic social defeat stress. Taken together, these results reveal novel suicidal endophenotypes in the hippocampus, as well as a putative etiological mechanism underlying suicidality, and suggest that antidepressant or NRG1 treatment may reverse a potential deficit in anterior dentate gyrus granule cell neurons in individuals at risk of dying by suicide.

dcc orchestrates the development of the prefrontal cortex during adolescence and is altered in psychiatric patients.

Adolescence is a period of heightened susceptibility to psychiatric disorders of medial prefrontal cortex (mPFC) dysfunction and cognitive impairment. mPFC dopamine (DA) projections reach maturity only in early adulthood, when their control over cognition becomes fully functional. The mechanisms governing this protracted and unique development are unknown. Here we identify dcc as the first DA neuron gene to regulate mPFC connectivity during adolescence and dissect the mechanisms involved. Reduction or loss of dcc from DA neurons by Cre-lox recombination increased mPFC DA innervation. Underlying this was the presence of ectopic DA fibers that normally innervate non-cortical targets. Altered DA input changed the anatomy and electrophysiology of mPFC circuits, leading to enhanced cognitive flexibility. All phenotypes only emerged in adulthood. Using viral Cre, we demonstrated that dcc organizes mPFC wiring specifically during adolescence. Variations in DCC may determine differential predisposition to mPFC disorders in humans. Indeed, DCC expression is elevated in brains of antidepressant-free subjects who committed suicide.

Fast-tracking (bypassing the PACU) does not reduce nursing workload after ambulatory surgery.

BACKGROUND: Postoperative day-case patients are usually allowed to recover from anaesthesia in a postanaesthesia care unit (PACU) before transfer back to the day surgical unit (DSU). Bypassing the PACU can decrease recovery time after day surgery. Cost savings may result from a reduced nursing workload associated with the decreased recovery time. This study was designed to evaluate the effects of bypassing the PACU on patient recovery time and nursing workload and costs. METHODS: Two hundred and seven consenting outpatients undergoing day surgery procedures were enrolled. Anaesthesia was induced and maintained with a standardized technique and the electroencephalographic bispectral index was monitored and maintained at 40-60 during anaesthetic maintenance. At the end of surgery, patients were randomly assigned to either a routine or fast-tracking (FT) group. Patients in the FT group were transferred from the operating room to the DSU (i.e. bypassing the PACU) if they achieved the FT criteria. All other patients were transferred to the PACU and then to the DSU. Nursing workload was evaluated using a patient care hour chart based on the type and frequency of nursing interventions in the PACU and DSU. A cost associated with the nursing workload was calculated. RESULTS: The overall time from end of anaesthesia to discharge home was significantly decreased in the fast-tracking group. However, overall patient care hours and costs were similar in the two recovery groups. CONCLUSION: Bypassing the PACU after these short outpatient procedures significantly decreases recovery time without compromising patient satisfaction. However, the overall nursing workload and the associated cost were not significantly affected.

Evaluation of postural stability after low-dose droperidol in outpatients undergoing gynaecological dilatation and curettage procedure.

BACKGROUND: Low-dose droperidol is suggested to be cost-effective in preventing nausea and vomiting after ambulatory surgery. This clinical study evaluated patient postural stability using a computerized force platform after an i.v. dose of droperidol 0.625 mg in outpatients undergoing gynaecological dilatation and curettage procedures. METHODS: After institutional approval and informed consent, 120 females were randomly assigned to receive either 0.9% saline (placebo) or droperidol 0.625 mg i.v. before surgery. Anaesthesia was induced with propofol 2-2.5 mg kg-1 and fentanyl 50-100 micrograms, and was maintained with intermittent boluses of propofol 25-50 mg and fentanyl 25-50 micrograms i.v. After operation, the Post-Anaesthesia Discharge Score (PADS), patient self-assessment scores for pain, nausea, drowsiness and dizziness, and extrapyramidal symptoms were recorded. Body sway velocity was measured while the patient was standing on a firm surface with eyes open then closed vs standing on a foam surface with eyes open then closed, at the time of arrival in the operation holding area (baseline), on achieving a PADS of 9 after surgery and on discharge home. RESULTS: At the time of achieving a PADS of 9, body sway was significantly greater in the droperidol group than in the placebo group (overall 61% vs 33% above baseline). There were no differences between groups with respect to scores for pain, nausea, drowsiness and dizziness. Three patients (5%) in the droperidol group reported nervousness and restlessness postoperatively (not significant). CONCLUSION: Low-dose droperidol 0.625 mg i.v. for anti-emetic prophylaxis can cause balance disturbances in females after gynaecological dilatation and curettage procedures.

Compliance with postoperative instructions: a telephone survey of 750 day surgery patients.

Patients undergoing day surgical procedures are given postoperative instructions not to drink alcohol, drive vehicles or make important decisions for 24 h. They are also advised to have a responsible adult stay with them at home overnight. Seven hundred and fifty patients were telephoned at 24 h postoperatively to determine their compliance with these instructions. Four per cent of patients drove vehicles, 1.8% consumed alcohol, while one patient made an important decision. A higher proportion of patients (5%) drove after general anaesthesia than regional anaesthesia or intravenous sedation (2.4%). The percentage of patients consuming alcohol was similar in both groups (1.8% vs. 1.9%). Four per cent of patients had no one staying with them overnight despite being accompanied out of the hospital. Patient compliance with instructions to not drink alcohol, drive or make important decisions may be improved by physician reinforcement of instructions and patient education.

Music increases satisfaction in elderly outpatients undergoing cataract surgery.

PURPOSE: Music has long been known to reduce anxiety, minimize the need for sedatives, and make patients feel more at ease. The purpose of the study was to evaluate the effect of music in elderly outpatients undergoing elective cataract surgery with retrobulbar block and monitored anaesthetic care using fentanyl or alfentanil and midazolam. METHODS: One hundred and twenty one patients were prospectively and randomly assigned to hear: relaxing suggestions, white noise, operating room noise or relaxing music via audio-cassette headphones. Vital signs were documented before and after retrobulbar block and every 15 min thereafter. Anxiety was assessed using the State-Trait Anxiety Inventory (STAI) before and after surgery. Visual analogue scales (VAS) were used to assess anxiety and patient satisfaction postoperatively with a standardized questionnaire. Between group comparisons were made using Chi-Square, or ANOVA, where appropriate. RESULTS: There were no differences between groups in STAI or anxiety VAS scores at any time. Differences were noted in systolic blood pressure, but not in other vital signs. Patients' ratings of the whole operative experience, satisfaction with the tape played, general level of relaxation and preference for the chosen tape for subsequent surgery were different (music > relaxing suggestions > white noise and OR noise, P < 0.05). CONCLUSIONS: Elderly patients undergoing cataract surgery under retrobulbar block were more satisfied with their experience if they heard relaxing music, rather than relaxing suggestions or white noise or OR noise. The type of auditory stimuli to which the patients were exposed did not influence the level of anxiety.

A prospective randomized double-blinded study of the effect of intravenous fluid therapy on adverse outcomes on outpatient surgery.

This study investigated the impact of perioperative fluid status on adverse clinical outcomes in ambulatory surgery. Two hundred ASA grade I-III ambulatory surgical patients were prospectively randomized into two groups to receive high (20 mL/kg) or low (2 mL/kg) infusions of isotonic electrolyte solution over 30 min preoperatively. A standardized balanced anesthetic was used. A minimal amount of fluid was given during the intraoperative and postoperative periods. Adverse outcomes were assessed by an investigator blinded to the fluid treatment group at 30 and 60 min after surgery, at discharge, and the first postoperative day. The incidence of thirst, drowsiness, and dizziness was significantly lower in the high-infusion group at all intervals. We recommend perioperative hydration of 20 mL/kg for patients undergoing general anesthesia for short ambulatory surgery.