Serotonergic modulation of orbitofrontal activity and its relevance for decision making and impulsivity.

BACKGROUND: The orbitofrontal cortex seems to play a crucial role in reward-guided learning and decision making, especially for impulsive choice procedures including delayed reward discounting. The central serotonergic system is closely involved in the regulation of impulsivity, but how the serotonergic firing rate and release, best investigated by the loudness dependence of auditory evoked potentials (LDAEP), interact with orbitofrontal activity is still unknown. METHODS: Twenty healthy volunteers (11 males, 9 females, 31.3 ± 10.6 years old) were studied in a 3T MRI scanner (Philips, Hamburg, Germany) during a delay discounting task, after their LDAEP was recorded using a 32 electrodes EEG machine (Brain Products, Munich, Germany). RESULTS: Significant positive correlations were only found between the LDAEP and the medial orbitofrontal part of the superior frontal gyrus (SFG/MO) [Δ immediate reward - delayed reward] for the right (r = 0.519; P = 0.019) and left side (r = 0.478; P = 0.033). This relationship was stronger for females compared with males. Orbitofrontal activity was also related to the Barratt Impulsivity Scale. CONCLUSIONS: This study revealed that low serotonergic activity as measured by a strong LDAEP was related to a high fMRI signal intensity of SFG/MO during immediate reward behavior which is related to impulsivity. Since this relationship was only found for the infralimbic medial and not for the middle or lateral part of the orbitofrontal cortex, an exclusive projection tract of the serotonergic system to this cortical region can be assumed to regulate impulsive reward-orientated decision making. Hum Brain Mapp 38:1507-1517, 2017. © 2016 Wiley Periodicals, Inc.

The loudness dependence of auditory evoked potentials and effects of psychopathology and psychopharmacotherapy in psychiatric inpatients.

OBJECTIVE: Many studies have provided evidence for the loudness dependence of auditory evoked potentials (LDAEP) as a marker for central serotonergic activity but remained inconclusive for its suitability in clinical use. METHODS: A cross-sectional sample of 162 psychiatric inpatients (major depression N = 86, bipolar disorder N = 12, schizophrenia N = 50, and schizoaffective disorder N = 14) and 40 healthy subjects was retrospectively examined for LDAEP and effects of psychopathology and psychopharmacology. RESULTS: The LDAEP was weaker in patients with affective disorders than in healthy subjects but did not differentiate between the total patient sample and healthy controls. LDAEP correlated significantly with dimensions of the Brief Symptom Inventory in the total patient sample (depression, paranoid ideation, psychoticism, Global Symptom Index, and Positive Symptom Distress Index), in patients with affective disorders (depression) and with schizophrenia spectrum disorders (depression, psychoticism, Global Symptom Index, and Positive Symptom Distress Index). Similar correlations were found in depressed patients with a single noradrenergic and specific serotonergic antidepressant or serotonin-norepinephrine reuptake inhibitor. There was a negative correlation between dosage of typical antipsychotics and LDAEP. Hypnotics generally led to a lower LDAEP. CONCLUSION: The LDAEP in patients is related to severity of psychopathologic syndromes irrespective of diagnosis. Chronic psychopharmacologic treatment may also differentially modulate the LDAEP, but longitudinal studies are needed.

Serum myeloperoxidase in cystic fibrosis patients receiving systemic antibiotics.

Serial serum myeloperoxidase was determined in 27 cystic fibrosis patients with chronic endobronchial Pseudomonas aeruginosa infection over the course of 1 y. The effect of repeated courses of antibiotic therapy on mean serum myeloperoxidase levels was significant (p = 0.034). Serial serum myeloperoxidase may help to guide therapy for pulmonary exacerbations.

Lung deposition after electronically breath-controlled inhalation and manually triggered conventional inhalation in cystic fibrosis patients.

The present work aimed to investigate whether lung deposition can be improved by using a device that optimizes the breathing pattern through electronic control. The relative lung deposition was estimated by inhalation of the marker substance, sodium cromoglycate (SCG), and measurement of urinary excretion of SCG. Thirteen cystic fibrosis (CF) patients (aged 8-20 years) received 20 mg of SCG as nebulizer solution by means of (a) conventional inhalation (Parimaster + Pari LC Star nebulizer, manual interrupter) and (b) electronically breath-controlled inhalation (AKITA + Pari LC Star nebulizer). Inhalations were trained and supervised by a physiotherapist. Patients were asked to provide answers to a questionnaire about the convenience of electronically breath-controlled inhalation. Urine was collected in five fractions until 12 h p.a., and the excreted SCG was determined by means of high-performance liquid chromatography (HPLC). Following breath-controlled inhalation, the amount of SCG excreted in urine was significantly greater than after conventional inhalation (2.22 +/- 0.61 mg vs. 1.63 +/- 0.59 mg, p < 0.001). The absorption half-life for SCG following breath-controlled inhalation was significantly shorter when compared with conventional inhalation (78 +/- 23 min vs. 107 +/- 29 min; p < 0.01), suggestive of a more peripheral deposition for the former. Ninety-two percent of the patients judged that the electronically breath-controlled inhalation was good or very good. In conclusion, inhalation with an electronically optimized breathing pattern yields a greater and more peripheral lung deposition of SCG compared with the manually triggered conventional nebulizer technique in CF patients with several years of aerosol inhalation experience.

Does wearing a noseclip during inhalation improve lung deposition?

Using nebulization, only a small proportion of the dose reaches the lungs, while the remainder is swallowed, exhaled into the atmosphere, or remains in the nebulizer. It was the purpose of this study to investigate whether wearing a noseclip during inhalation can improve lung deposition. Relative lung deposition was compared by inhalation of the marker substance, sodium cromoglycate (SCG), and measurement of urinary excretion of SCG. The SCG absorption half-life allows one to differentiate indirectly between a more or less peripheral deposition. Ten CF patients (9-18 years old) inhaled, under routine conditions, a solution containing 20 mg of SCG in a randomized crossover design through a mouthpiece, without and with a noseclip being worn. Following inhalation without and with a noseclip, no statistically significant difference was seen in the amount of SCG excreted in urine (0.9 +/- 0.4 mg vs. 1.0 +/- 0.5 mg; p = 0.402) and absorption half-life (93 +/- 25 min vs. 113 +/- 36 min; p = 0.083). In conclusion, wearing a noseclip during inhalation under conditions relevant to practice does not increase the amount deposited into the lungs of CF patients and, also, there has been no indication of a more peripheral lung deposition.

Lung deposition in cystic fibrosis patients using an ultrasonic or a jet nebulizer.

This study was conducted to compare pulmonary deposition following inhalation with an ultrasonic and a jet nebulizer in CF patients under conditions relevant to practice. The marker substance used to estimate the relative lung bioavailability was sodium cromoglycate (SCG), which is poorly absorbed from the gastrointestinal tract, but is completely absorbed from the lungs. Ten CF patients (aged 9-21 years) used an ultrasonic nebulizer (Multisonic compact 2.4 MHz) and a jet nebulizer (Parimaster, LC Plus Turbo) in a crossover design to inhale a solution containing 20 mg of SCG and a beta(2)-agonist. Urine was collected in five fractions until 12 h p. a., and the excreted SCG was determined by means of HPLC. Prior to each inhalation, the patients' pulmonary function was measured employing a Pneumoscope. Using the ultrasonic nebulizer, the amount of SCG excreted in urine was significantly greater than that after inhalation with the jet nebulizer (1.43 +/- 0.47 mg vs. 1.04 +/- 0.47 mg; p = 0.002), despite the larger residual volume in the ultrasonic nebulizer. The absorption half-life for SCG following ultrasonic nebulization was significantly shorter when compared with jet nebulization (84 +/- 14 min vs. 101 +/- 19 min; p = 0.005), being suggestive of a more peripheral deposition. Furthermore, an inverse relationship was found between absorption half-life and FEV(1) (% pred.) (r = -0.655, p = 0.04) or MMEF(75/25) (% pred.) (r = -0.844, p = 0.031), but only with the ultrasonic nebulizer. In conclusion, the ultrasonic nebulizer tested when used for inhalation in CF patients was found to be at least equivalent to the jet nebulizer.