Effects of cannabidiol on fear conditioning in anxiety disorders: decreased threat expectation during retention, but no enhanced fear re-extinction.

RATIONALE: Preclinical research suggests that pharmacologically elevating cannabinoid levels may attenuate fear memory expression and enhance fear extinction. OBJECTIVES: We studied the effects of cannabidiol (CBD) on fear memory expression and fear re-extinction in 69 patients with panic disorder with agoraphobia or with social anxiety disorder. Moderation by sex, diagnosis, and serotonergic antidepressant (AD) use was explored. METHODS: A cued fear conditioning paradigm was applied before the first treatment session with 300 mg CBD/placebo augmented exposure therapy. Study medication was administered orally preceding 8 weekly sessions. Fear acquisition and suboptimal extinction took place prior to the first medication ingestion (T0). After the first medication ingestion (T1), we investigated effects on fear memory expression at retention and fear re-extinction. Subjective fear, shock expectancy, skin conductance, and startle responses to conditioned (CS+) and safety stimulus (CS-) were measured. RESULTS: Across the sample, CBD reduced shock expectancy at retention under low and ambiguous threat of shock, but fear re-extinction at T1 was unaffected by CBD. However, in AD users, re-extinction of subjective fear was impaired in the CBD condition compared to placebo. In female AD users, CBD interfered with safety learning measured with fear-potentiated startle. CONCLUSIONS: The current findings provide no evidence for enhanced fear re-extinction by CBD. However, CBD acutely decreased threat expectation at retention, without affecting other indices of fear. More studies are needed to elucidate possible interactions with AD use and sex, as well as potential effects of CBD on threat expectancies.

Discontinuity in Equilibrium Wave-Current Ripple Size and Shape and Deep Cleaning Associated With Cohesive Sand-Clay Beds.

Mixtures of cohesive clay and noncohesive sand are widespread in many aquatic environments. Ripple dynamics in sand-clay mixtures have been studied under current-alone and wave-alone conditions but not combined wave-current conditions, despite their prevalence in estuaries and the coastal zone. The present flume experiments examine the effect of initial clay content, C 0, on ripples by considering a single wave-current condition and, for the first time, quantify how changing clay content of substrate impacts ripple dimensions during development. The results show inverse relationships between C 0 and ripple growth rates and clay winnowing transport rates out of the bed, which reduce as the ripples develop toward equilibrium. For C 0 ≤ 10.6%, higher winnowing rates lead to clay loss, and thus the presence of clean sand, far below the base of equilibrium ripples. This hitherto unquantified "deep-cleaning" of clay does not occur for C 0 > 10.6%, where clay-loss rates are much lower. The clay-loss behavior is associated with two distinct types of equilibrium combined flow ripples: (a) Large asymmetric ripples with dimensions and plan geometries comparable to their clean-sand counterparts for C 0 ≤ 10.6% and (b) small, flat ripples for C 0 > 10.6%. The 10.6% threshold, which may be specific to the experimental conditions, corresponds to a more general 8% threshold found beneath the ripple base, suggesting that clay content here must be <8% for clean-sand-like ripples to develop in sand-clay beds. This ripple-type discontinuity comprises a threefold reduction in ripple height, with notable implications for bed roughness.

[Dental anxiety and alexithymia; research on anxiety acquisition]. / Behandelangst en alexithymie, onderzoek naar angstleerprocessen.

People with alexithymia have difficulty identifying and describing feelings, have little imagination and mental processes largely orientated towards facts and less towards inner experience. It occurs in about 1 in 10 people and therefore in the dental office, too. A positive association has been found between alexithymia and the development of dental anxiety. With the help of an anxiety-conditioning experiment, the acquisition and the extinction of anxiety can be studied. To gain more knowledge about these processes of acquisition in people with alexithymia, such an experiment was conducted among 32 people with severe dental anxiety, 13 of whom with (possible) alexithymia. Relatively little anxiety conditioning occurred during the experiment. This may be explained by the aversive stimulus and the context in which the experiment was conducted. However, it emerged that for people with alexithymia, a physical outcome measure may be a better indicator of anxiety than a subjective score on a visual analogue scale.

The Role of the Endocannabinoids 2-AG and Anandamide in Clinical Symptoms and Treatment Outcome in Veterans with PTSD.

Background: Although current treatments for Post-Traumatic Stress Disorder (PTSD) in war veterans are effective, unfortunately 30-50% still do not benefit from these treatments. Trauma-focused therapies, eg exposure therapy, are primarily based on extinction processes in which the endocannabinoid system (ECS) plays a significant role. Therefore, it can be hypothesized that poor treatment response on trauma-focused therapy due to extinction deficits may be associated with a poorly functioning ECS. The present study examined whether the endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2-AG) are associated with post-treatment symptom reduction. Methods: Blood plasma levels of AEA and 2-AG were determined in war veterans with a PTSD diagnosis (n = 54) and combat controls (n = 26) before and after a 6-8 month interval. During this period veterans with PTSD received trauma-focused therapy (eg cognitive behavioral therapy with exposure or eye-movement desensitization and reprocessing). Clinical symptoms were assessed before and after therapy with the Clinician Administered PTSD Scale (CAPS), State-Trait Anxiety Inventory (STAI) and Mood and Anxiety Symptom Questionnaire (MASQ). Results: Regression analysis demonstrated that pretreatment endocannabinoid levels were not predictive of PTSD symptom reduction. Additionally, baseline endocannabinoid levels did not differ between either PTSD and combat controls or between combat controls, treatment responders, and non-responders. Only cortisol levels significantly decreased over time from pre- to posttreatment (p = .041). Endocannabinoid levels were significantly lower in individuals who reported cannabis use during their lifetime, independent of PTSD diagnosis. Furthermore, correlation analysis revealed that pretreatment 2-AG levels in PTSD were positively correlated with anxious arousal (r = .354, p = .015) and negatively with avoidance symptoms (r = -.271, p = .048). Both posttreatment AEA and 2-AG were positively correlated with trait anxiety (AEA r = .459, p = .003; 2-AG r = .423, p = .006), anxious arousal (AEA r = .351, p = .024; 2-AG r = .311, p = .048) and general distress depression symptoms (AEA r = .414, p = .007; 2-AG r = .374, p = .016). Conclusion: Since endocannabinoids are mainly generated 'on demand', future work could benefit by investigating endocannabinoid circulation under both baseline and stressful conditions. In line with previous research cannabis use was associated with lower endocannabinoid levels. The correlation analysis between pre- and posttreatment endocannabinoid levels and pre- and posttreatment clinical symptomatology were exploratory analysis and should be replicated in future research.

Trajectories of fear learning in healthy participants are able to distinguish groups that differ in individual characteristics, chronicity of fear and intrusions.

BACKGROUND AND OBJECTIVES: Studies on the development and treatment of anxiety disorders mostly focus on the comparison of predefined groups. An alternative approach is to use data-driven latent class growth analyses (LCGA) to determine differentiation between groups based on particular mechanistic factors. This study validated the use of LCGA on responses in a compact fear conditioning task and whether specific characteristics are associated with maladaptive fear learning trajectories. METHODS: Healthy subjects (N = 300) completed a fear conditioning task that included uninstructed and instructed acquisition and extinction phases. Subjective fearfulness and US expectancy were used as outcome measures. Latent classes in the responses to the CS+ (coupled with a scream) and the CS- (control stimulus) were determined based on trajectories across the experimental phases. State and trait anxiety were measured during testing, and return of fear and intrusions were measured one and six weeks later. RESULTS: Fear learning trajectories of poor extinction in responding to the CS+ and generalization of fear to the CS- were associated with higher state and trait anxiety. Individuals belonging to these trajectories reported more intrusions, fear and had higher US expectancy ratings after 1 week. LIMITATIONS: Only 56% of participants completed the six weeks follow-up measures. CONCLUSION: Fear learning trajectories are associated with individual characteristics, return of fear and intrusions. Next, this task will be implemented in clinical practice to assess its predictive power for the extent to which patients benefit from exposure treatments.

Pharmacokinetics and safety of panitumumab in a patient with chronic kidney disease.

PURPOSE: Data on panitumumab dosing in cancer patients with renal insufficiency are lacking. Here, we report a 63-year-old metastatic colorectal cancer patient with chronic kidney injury with a glomerular filtration rate of approximately 11 mL/min. METHODS: Pharmacokinetic parameters, including dose-normalized area under the curve, clearance and elimination half-life (T 1/2) after the 11th and 12th infusions were estimated using trapezoidal non-compartmental methods. Data were compared to previous reported pharmacokinetic data from studies in patients with normal renal function. RESULTS: The results show that the pharmacokinetic data in this patient with kidney failure are comparable to those in patients with adequate renal function. Moreover the treatment was well tolerated in this patient. CONCLUSION: This study suggests that panitumumab can be safely used in cancer patients with renal impairment without dose adjustment.

A fatal case of metastatic squamous cell carcinoma in a patient with myositis ossificans traumatica.

Myositis ossificans traumatica is a rare disease associated with chronic wounds and fistulae. Chronic ulcers, fistulae and wounds can transform into squamous cell carcinoma, the so-called Marjolin's ulcer. We describe a rapid, progressive and fulminant course of a metastatic squamous cell carcinoma arising from a chronic wound in a patient with myositis ossificans traumatica.

Extending standard testing period in honeybees to predict lifespan impacts of pesticides and heavy metals using dynamic energy budget modelling.

Concern over reported honeybee (Apis mellifera spp.) losses has highlighted chemical exposure as a risk. Current laboratory oral toxicity tests in A. mellifera spp. use short-term, maximum 96 hour, exposures which may not necessarily account for chronic and cumulative toxicity. Here, we use extended 240 hour (10 day) exposures to examine seven agrochemicals and trace environmental pollutant toxicities for adult honeybees. Data were used to parameterise a dynamic energy budget model (DEBtox) to further examine potential survival effects up to 30 day and 90 day summer and winter worker lifespans. Honeybees were most sensitive to insecticides (clothianidin > dimethoate ≫ tau-fluvalinate), then trace metals/metalloids (cadmium, arsenic), followed by the fungicide propiconazole and herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). LC50s calculated from DEBtox parameters indicated a 27 fold change comparing exposure from 48 to 720 hours (summer worker lifespan) for cadmium, as the most time-dependent chemical as driven by slow toxicokinetics. Clothianidin and dimethoate exhibited more rapid toxicokinetics with 48 to 720 hour LC50s changes of <4 fold. As effects from long-term exposure may exceed those measured in short-term tests, future regulatory tests should extend to 96 hours as standard, with extension to 240 hour exposures further improving realism.

Human fear acquisition deficits in relation to genetic variants of the corticotropin-releasing hormone receptor 1 and the serotonin transporter--revisited.

We recently showed that a genetic polymorphism (rs878886) in the human corticotropin-releasing hormone receptor 1 (CRHR1) is associated with reduced fear-conditioned responses to a threat cue. This is a potentially important finding considering that the failure to acquire fear contingencies can leave an individual in a maladaptive state of more generalized anxiety. Consistent with that idea, the CRHR1-dependent fear acquisition deficit translated into heightened contextual anxiety when taking genetic variability within the serotonin transporter long polymorphic region (5-HTTLPR) into account. To replicate our previous findings, we conducted a replication study in 224 healthy medication-free human subjects using the exact same cue and context virtual reality fear-conditioning procedure as in study by Heitland et al. (2013). In the replication study, consistent with the original findings, CRHR1 rs878886 G-allele carriers showed reduced acquisition of cue-specific fear-conditioned responses compared with C/C homozygotes. Also, in this larger sample the cue acquisition deficit of G-allele carriers translated into heightened contextual anxiety, even independent of 5-HTT gene variation. In contrast to our earlier findings, there was an additional interaction effect of CRHR1 rs878886 and the triallelic 5-HTTLPR/rs25531 variant on cued fear acquisition. In summary, this study replicated the initially reported association of the CRHR1 rs878886 G-allele with cued fear acquisition deficits, albeit with a different pattern of results regarding the interaction with 5-HTT variation. This further supports the notion that the human corticotropin-releasing hormone plays a role in the acquisition of fears.

Safety and efficacy of the addition of simvastatin to cetuximab in previously treated KRAS mutant metastatic colorectal cancer patients.

INTRODUCTION: Cetuximab is registered for use in colorectal cancer (CRC) patients with RAS wild-type tumours only. Simvastatin blocks the mevalonate pathway and thereby interferes with the post-translational modification (prenylation) of KRAS. We hypothesize that the activated KRAS pathway in KRAS mutant tumors can be inhibited by simvastatin rendering these tumors sensitive to the EGFR inhibitor cetuximab. METHODS: A Simon two-stage, single-arm, phase II study was performed to test the efficacy and safety of the addition of simvastatin to cetuximab in patients with a KRAS mutation in their CRC tumour who were previously treated with fluoropyrimidine, oxaliplatin and irinotecan based regimens. The primary endpoint was to test the percentage of patients alive and free from progression 12.5 weeks after the first administration of cetuximab. Our hypothesis was that at least 40% was free from progression, comparable to, though slightly lower than in KRAS wild-type patients. RESULTS: Four of 18 included patients (22.2%) were free from progression at the primary endpoint time. The time to progression in these 4 patients ranged from 20.3 to 47 weeks. CONCLUSION: Based on the current study we conclude that the theoretical concept of KRAS modulation with simvastatin was not applicable in the clinic, as we were not able to restore sensitivity to cetuximab in CRC patients harbouring a somatic KRAS mutation.

A simple mechanistic model to interpret the effects of narcotics.

In this research we will show the advantages of using a time-independent dose metric in a mechanistic model to evaluate toxic effects for different narcotic compounds on different species. We will show how different already existing QSARs can be combined within a mechanistic framework to 1) make predictions of lethal thresholds; 2) show some limitations in the use of existing QSARs; 3) show how a mechanistic framework solves some conceptual problems in current approaches and 4) show how such a framework can be used to be of aid in an experimental setup in predicting the outcome of a survival experiment. The approach we chose is based on the simplest mechanistic model available, a scaled one-compartment model to describe uptake and elimination and hazard model to link the exposure to effects on survival. Within this theoretical framework a prediction for an internal threshold for effects on survival of 3 mmol/kg bw can be made, which should be similar for different species and independent of the partitioning characteristics of the toxicant. To demonstrate this, a threshold for 51 different species was derived, which indeed appeared to lie in a relatively small range, typically between 1 and 10 mmol/kg bw.

Genetic variability in the human cannabinoid receptor 1 is associated with resting state EEG theta power in humans.

It has long been postulated that exogenous cannabinoids have a profound effect on human cognitive functioning. These cannabinoid effects are thought to depend, at least in parts, on alterations of phase-locking of local field potential neuronal firing. The latter can be measured as activity in the theta frequency band (4-7Hz) by electroencephalogram. Theta oscillations are supposed to serve as a mechanism in neural representations of behaviorally relevant information. However, it remains unknown whether variability in endogenous cannabinoid activity is involved in theta rhythms and therefore, may serve as an individual differences index of human cognitive functioning. To clarify this issue, we recorded resting state EEG activity in 164 healthy human subjects and extracted EEG power across frequency bands (δ, θ, α, and ß). To assess variability in the endocannabinoid system, two genetic polymorphisms (rs1049353, rs2180619) within the cannabinoid receptor 1 (CB1) were determined in all participants. As expected, we observed significant effects of rs1049353 on EEG power in the theta band at frontal, central and parietal electrode regions. Crucially, these effects were specific for the theta band, with no effects on activity in the other frequency bands. Rs2180619 showed no significant associations with theta power after Bonferroni correction. Taken together, we provide novel evidence in humans showing that genetic variability in the cannabinoid receptor 1 is associated with resting state EEG power in the theta frequency band. This extends prior findings of exogenous cannabinoid effects on theta power to the endogenous cannabinoid system.

Pharmacokinetics and safety of cetuximab in a patient with renal dysfunction.

INTRODUCTION: In the literature, data on the effect of renal impairment on the pharmacokinetics of anticancer drugs are scarce. Here, we report a 68-year-old metastatic osteosarcoma patient with impaired renal function due to prior chemotherapy, who was treated on compassionate use basis with 400 mg/m(2) cetuximab. MATERIAL AND METHODS: Pharmacokinetic parameters after the first dose, including dose-normalised AUC from time zero to day 7, clearance, elimination half-life (t(1/2)), were estimated using trapezoidal non-compartmental methods and compared to pharmacokinetic data from a study population with normal kidney function. RESULTS: The results showed that the pharmacokinetics of cetuximab in this patient with renal failure was similar to that with adequate renal function. CONCLUSION: This study suggests that cetuximab can be safely used in cancer patients with renal impairment without dose adjustment.

Pharmacokinetics of panitumumab in a patient with liver dysfunction: a case report.

PURPOSE: Panitumumab is used for the treatment for metastatic RAS wild-type colorectal cancer (mCRC). It is likely that many of these patients will present with liver metastases and some with liver dysfunction. The pharmacokinetics in patients with hepatic impairment has not been investigated, and dosage adjustments are undetermined. Here, we present a case of a patient with progressive mCRC and liver dysfunction. METHODS: A heavily pretreated KRAS wild-type mCRC patient with liver disease Child-Pugh class B was treated with 2-weekly intravenous panitumumab (6 mg/kg). The patient received 2 doses of 490 mg i.v. panitumumab after which progressive disease was documented. Toxicities were graded using CTCAEv4.0. Serum samples were collected, and panitumumab concentrations were determined using a validated immunoassay. Pharmacokinetic parameters after the first dose, including dose-normalized AUC from time zero-day 14, clearance (CL), and elimination half-life (T1/2), were estimated via trapezoidal noncompartmental methods. Data were compared to historical data from a population with adequate liver function, as reported by Stephenson (Clin Colorectal Cancer, 8:29-37, 2009). Values within the range of the mean ±1 standard deviation (SD) were considered not deviant. RESULTS: Calculated AUC after the first dose of 6 mg/kg panitumumab in this patient with hepatic dysfunction was 877 µg day/mL (Stephenson's cohort 1: 744 ± 195 µg day/mL). Estimated T1/2 was 3.58 days (5.28 ± 1.90 days), and CL was 6.9 mL/day/kg (8.21 ± 3.79 mL/day/kg). Estimated PK parameters during the first cycle were inside reported mean ±1 SD of historical controls without liver dysfunction. No toxicity was reported during treatment; particularly, no diarrhea and skin toxicity were noticed. CONCLUSIONS: The pharmacokinetics of panitumumab in this patient suffering from metastatic colorectal cancer with liver dysfunction Child-Pugh class B was similar compared to patients with adequate liver function. Moreover, no substantial toxicity was detected. The here-presented data may help clinical decision making in real-life practice. Two-weekly panitumumab monotherapy seems to be safely applicable in patients with KRAS wild-type mCRC and hepatic dysfunction, without the need for any dose adjustments.

Auditory event-related potentials (P3a, P3b) and genetic variants within the dopamine and serotonin system in healthy females.

The late positive components of the human event-related brain potential comprise electrocortical reflections of stimulus-driven attentional capture (the anteriorly distributed P3a) and top-down control detection of relevant events (the posteriorly distributed P3b). As of yet, the neuropharmacologic and neurogenetic origin of the P3a and P3b is not fully understood. In this study, we address the contribution of dopaminergic and serotoninergic mechanisms. Sixty healthy females completed an active auditory novelty oddball paradigm while EEG was recorded. In all subjects, genetic polymorphisms within the dopamine system (dopamine transporter [DAT1], catecholamine-O-methyltransferase val158met [COMT val158met]) and the serotonin system (serotonin transporter [5HTTLPR]) were assessed. Across genotypes, novels (relative to standards) elicited a fronto-centrally distributed P3a, and targets (relative to standards) a parieto-centrally distributed P3b. Genotypes effects were observed for both P3a (COMT, 5HTTPLR) and P3b (DAT1, COMT, 5HTTLPR) only at prefrontal electrode location (Fz). Specifically, the frontal P3a was enhanced in COMT met/met homozygotes, but not in DAT1 9R. The target-related P3b was enhanced in COMT met/met and DAT1 9R relative to its genetic counterparts, but only at frontal electrodes. This 'anteriorized' enhancement may reflect either an additional frontal component in the target-related P3 dependent on dopamine, or a more subtle shift in the neural ensemble that generates the target-related P3. Results for 5HTTLPR short allele homozygotes mimicked those in COMT met/met homozygotes. In all, the present findings suggest involvement of frontal-cortical dopaminergic and serotoninergic mechanisms in bottom-up attentional capture (COMT val158met, 5HTTLPR), with an additional top-down component sensitive to striatal signals (DAT1).

[Hindering the immune system by tumours in the head and neck area]. / Remming van het immuunsysteem door tumoren in het hoofd-halsgebied.

Head and neck tumours possess several mechanisms to hinder an appropriate immune response against the tumour cell. In the first place, the tumour cells attempt to suppress the presentation of tumour-associated antigens to the cells of the immune system. Tumours also have a negative effect on the surface structures of the efferent blood vessel epithelium, thereby inhibiting the recruitment of immune cells. In addition, proteins are secreted capable of inactivating immune cells. These immunosuppressive activities of the tumour result in a deterioration of life expectancy. Several experimental methods to improve the immune response of the patient against tumour cells are currently being explored.

No positive effect of Acid etching or plasma cleaning on osseointegration of titanium implants in a canine femoral condyle press-fit model.

PURPOSE: Implant surface treatments that improve early osseointegration may prove useful in long-term survival of uncemented implants. We investigated Acid Etching and Plasma Cleaning on titanium implants. METHODS: In a randomized, paired animal study, four porous coated Ti implants were inserted into the femurs of each of ten dogs. PC (Porous Coating; control)PC+PSHA (Plasma Sprayed Hydroxyapatite; positive control)PC+ET (Acid Etch)PC+ET+PLCN (Plasma Cleaning) After four weeks mechanical fixation was evaluated by push-out test and osseointegration by histomorphometry. RESULTS: The PSHA-coated implants were better osseointegrated than the three other groups on outer surface implant porosity (p<0.05) while there was no statistical difference in deep surface implant porosity when compared with nontreated implant. Within the deep surface implant porosity, there was more newly formed bone in the control group compared to the ET and ET+PCLN groups (p<0.05). In all compared groups, there was no statistical difference in any biomechanical parameter. CONCLUSIONS: In terms of osseointegration on outer surface implant porosity PC+PSHA was superior to the other three groups. Neither the acid etching nor the plasma cleaning offered any advantage in terms of implant osseointegration. There was no statistical difference in any of the biomechanical parameters among all groups in the press-fit model at 4 weeks of evaluation time.

Failure to extinguish fear and genetic variability in the human cannabinoid receptor 1.

Failure to extinguish fear can lead to persevering anxiety and has been postulated as an important mechanism in the pathogenesis of human anxiety disorders. In animals, it is well documented that the endogenous cannabinoid system has a pivotal role in the successful extinction of fear, most importantly through the cannabinoid receptor 1. However, no human studies have reported a translation of this preclinical evidence yet. Healthy medication-free human subjects (N=150) underwent a fear conditioning and extinction procedure in a virtual reality environment. Fear potentiation of the eyeblink startle reflex was measured to assess fear-conditioned responding, and subjective fear ratings were collected. Participants were genotyped for two polymorphisms located within the promoter region (rs2180619) and the coding region (rs1049353) of cannabinoid receptor 1. As predicted from the preclinical literature, acquisition and expression of conditioned fear did not differ between genotypes. Crucially, whereas both homozygote (G/G, N=23) and heterozygote (A/G, N=68) G-allele carriers of rs2180619 displayed robust extinction of fear, extinction of fear-potentiated startle was absent in A/A homozygotes (N=51). Additionally, this resistance to extinguish fear left A/A carriers of rs2180619 with significantly higher levels of fear-potentiated startle at the end of the extinction training. No effects of rs1049353 genotype were observed regarding fear acquisition and extinction. These results suggest for the first time involvement of the human endocannabinoid system in fear extinction. Implications are that genetic variability in this system may underlie individual differences in anxiety, rendering cannabinoid receptor 1 a potential target for novel pharmacological treatments of anxiety disorders.

Genetic polymorphisms of the dopamine and serotonin systems modulate the neurophysiological response to feedback and risk taking in healthy humans.

Genetic differences in the dopamine and serotonin systems have been suggested as potential factors underlying interindividual variability in risk taking and in brain activation during the processing of feedback. Here, we studied the effects of dopaminergic (dopamine transporter [DAT1], catecholamine-O-methyltransferase val158met [COMT]) and serotonergic (serotonin transporter [5HTTLPR]) polymorphisms on risk taking and brain responses following feedback in 60 healthy female subjects. The subjects completed a well-established experimental gambling paradigm while an electroencephalogram was recorded. During the task, risk-taking behavior and prefrontal brain responses (feedback-related negativity [FRN]) following monetary gains and losses were assessed. FRN amplitudes were enhanced for nine-repeat-allele carriers of the DAT1 and short-allele carriers of 5HTTLPR, which are both presumably linked to less transporter activity and higher neurotransmitter levels. Moreover, nine-repeat DAT1 carriers displayed a trend toward increased risk taking in general, whereas 5HTTLPR short-allele carriers showed decreased risk taking following gains. COMT val158met genotype was unrelated to FRN amplitude and average risk taking. However, COMT met/met carriers showed a pronounced feedback P3 amplitude independent of valence, and a gradual increase in risk taking during the gambling task. In sum, the present findings underline the importance of genetic variability in the dopamine and serotonin systems regarding the neurophysiology of feedback processing.

SUVmax during 18FDG-PET scanning in small cell lung cancer: similar information as in non-small cell lung cancer?

In patients with non-small cell lung carcinoma (NSCLC) fluorine-18 fluorodeoxyglucose positron emission tomography (18FDG-PET)-scanning is shown to be of prognostic value. Small cell lung cancer (SCLC) is an aggressive tumor with poor prognosis. Limited results on the prognostic and predictive value of the maximum standard uptake values (SUVmax) obtained during 18FDG-PET scanning in SCLC are available. An observational study in 75 chemonaive patients diagnosed with SCLC who underwent a 18FDG-PET scan was performed. SUVmax values of the primary tumor were related to the overall survival (OS) and the progression free survival (PFS). Significant lower SUVmax values of the primary tumor were observed in patients with stage I-III disease compared to stage IV disease. SUVmax did not discriminate for either OS or PFS in the whole group of patients. In patients with stage IV disease and treatment with chemotherapy, OS and PFS were significantly higher in patients with a high SUVmax. (p-value 0.005 and 0.002 respectively) compared to patients with a low SUVmax value. In patients with SCLC metabolic activity determined using 18FDG-PET (SUVmax) differed between stage I-III and stage IV diseases. Compared to NSCLC, the relationship between SUVmax) and prognosis seems more complex.