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We asked if sensation-seeking is linked to premorbid personality characteristics in patients with addictive disorders, or the characteristics follow the sensation-seeking activity. We interpreted the former as a state associated with normal rates of dopamine synthesis, and the latter as a trait of individuals with abnormally high rates of synthesis. We previously determined dopaminergic receptor density in striatum, and we now tested the hypothesis that an elevated dopaminergic condition with increased extracellular dopamine and receptor density follows increased dopamine synthesis capacity in highly sensation-seeking individuals, as measured by positron emission tomography of 18 men with tracer fluorodopa (FDOPA). We detected a site in left caudate nucleus where the volume of distribution of FDOPA-derived metabolites correlated negatively with FDOPA metabolite turnover, consistent with decreased metabolite breakdown in highly sensation-seeking subjects. High rates of sensation-seeking attenuated the dopamine turnover in association with a low rate of dopamine recycling, low dopamine oxidation, and elevated extracellular dopamine and receptors in caudate nucleus. In contrast, low rates of sensation-seeking were associated with rapid dopamine recycling, rapid dopamine oxidation, low extracellular dopamine, and low receptor density. We conclude that the modulation of dopaminergic neurotransmission associated with sensation-seeking is a state of sensation-seeking, rather than a trait of personality following abnormal regulation of dopaminergic neurotransmission.

We asked if sensation-seeking is linked to premorbid personality characteristics in patients with addictive disorders, or the characteristics follow the sensation-seeking activity. We interpreted the former as a state associated with normal rates of dopamine synthesis, and the latter as a trait of individuals with abnormally high rates of synthesis. We previously determined dopaminergic receptor density in striatum, and we now tested the hypothesis that an elevated dopaminergic condition with increased extracellular dopamine and receptor density follows increased dopamine synthesis capacity in highly sensation-seeking individuals, as measured by positron emission tomography of 18 men with tracer fluorodopa (FDOPA). We detected a site in left caudate nucleus where the volume of distribution of FDOPA-derived metabolites correlated negatively with FDOPA metabolite turnover, consistent with decreased metabolite breakdown in highly sensation-seeking subjects. High rates of sensation-seeking attenuated the dopamine turnover in association with a low rate of dopamine recycling, low dopamine oxidation, and elevated extracellular dopamine and receptors in caudate nucleus. In contrast, low rates of sensation-seeking were associated with rapid dopamine recycling, rapid dopamine oxidation, low extracellular dopamine, and low receptor density. We conclude that the modulation of dopaminergic neurotransmission associated with sensation-seeking is a state of sensation-seeking, rather than a trait of personality following abnormal regulation of dopaminergic neurotransmission.

BACKGROUND: Prioritization of acutely ill patients in the Emergency Department remains a challenge. We aimed to evaluate whether routine blood tests can predict mortality in unselected patients in an emergency department and to compare risk prediction with a formalized triage algorithm.METHODS: A prospective observational cohort study of 12,661 consecutive admissions to the Emergency Department of Nordsjælland University Hospital during two separate periods in 2010 (primary cohort, n = 6279) and 2013 (validation cohort, n = 6383). Patients were triaged in five categories by a formalized triage algorithm. All patients with a full routine biochemical screening (albumin, creatinine, c-reactive protein, haemoglobin, lactate dehydrogenase, leukocyte count, potassium, and sodium) taken at triage were included. Information about vital status was collected from the Danish Central Office of Civil registration. Multiple logistic regressions were used to predict 30-day mortality. Validation was performed by applying the regression models on the 2013 validation cohort.RESULTS: Thirty-day mortality was 5.3%. The routine blood tests had a significantly stronger discriminative value on 30-day mortality compared to the formalized triage (AUC 88.1 [85.7;90.5] vs. 63.4 [59.1;67.5], p < 0.01). Risk stratification by routine blood tests was able to identify a larger number of low risk patients (n = 2100, 30-day mortality 0.1% [95% CI 0.0;0.3%]) compared to formalized triage (n = 1591, 2.8% [95% CI 2.0;3.6%]), p < 0.01.CONCLUSIONS: Routine blood tests were strongly associated with 30-day mortality in acutely ill patients and discriminatory ability was significantly higher than with a formalized triage algorithm. Thus routine blood tests allowed an improved risk stratification of patients presenting in an emergency department.

BACKGROUND: Prioritization of acutely ill patients in the Emergency Department remains a challenge. We aimed to evaluate whether routine blood tests can predict mortality in unselected patients in an emergency department and to compare risk prediction with a formalized triage algorithm.METHODS: A prospective observational cohort study of 12,661 consecutive admissions to the Emergency Department of Nordsjælland University Hospital during two separate periods in 2010 (primary cohort, n = 6279) and 2013 (validation cohort, n = 6383). Patients were triaged in five categories by a formalized triage algorithm. All patients with a full routine biochemical screening (albumin, creatinine, c-reactive protein, haemoglobin, lactate dehydrogenase, leukocyte count, potassium, and sodium) taken at triage were included. Information about vital status was collected from the Danish Central Office of Civil registration. Multiple logistic regressions were used to predict 30-day mortality. Validation was performed by applying the regression models on the 2013 validation cohort.RESULTS: Thirty-day mortality was 5.3%. The routine blood tests had a significantly stronger discriminative value on 30-day mortality compared to the formalized triage (AUC 88.1 [85.7;90.5] vs. 63.4 [59.1;67.5], p < 0.01). Risk stratification by routine blood tests was able to identify a larger number of low risk patients (n = 2100, 30-day mortality 0.1% [95% CI 0.0;0.3%]) compared to formalized triage (n = 1591, 2.8% [95% CI 2.0;3.6%]), p < 0.01.CONCLUSIONS: Routine blood tests were strongly associated with 30-day mortality in acutely ill patients and discriminatory ability was significantly higher than with a formalized triage algorithm. Thus routine blood tests allowed an improved risk stratification of patients presenting in an emergency department.

Dopaminergic medication for motor symptoms in Parkinson's disease (PD) recently has been linked with impulse control disorders, including pathological gambling (PG), which affects up to 8% of patients. PG often is considered a behavioral addiction associated with disinhibition, risky decision-making, and altered striatal dopaminergic neurotransmission. Using [(11)C]raclopride with positron emission tomography, we assessed dopaminergic neurotransmission during Iowa Gambling Task performance. Here we present data from a single patient with PD and concomitant PG. We noted a marked decrease in [(11)C]raclopride binding in the left ventral striatum upon gambling, indicating a gambling-induced dopamine release. The results imply that PG in PD is associated with a high dose of dopaminergic medication, pronounced motor symptomatology, young age at disease onset, high propensity for sensation seeking, and risky decision-making. Overall, the findings are consistent with the hypothesis of medication-related PG in PD and underscore the importance of taking clinical variables, such as age and personality, into account when patients with PD are medicated, to reduce the risk of PG.

Dopaminergic medication for motor symptoms in Parkinson's disease (PD) recently has been linked with impulse control disorders, including pathological gambling (PG), which affects up to 8% of patients. PG often is considered a behavioral addiction associated with disinhibition, risky decision-making, and altered striatal dopaminergic neurotransmission. Using [(11)C]raclopride with positron emission tomography, we assessed dopaminergic neurotransmission during Iowa Gambling Task performance. Here we present data from a single patient with PD and concomitant PG. We noted a marked decrease in [(11)C]raclopride binding in the left ventral striatum upon gambling, indicating a gambling-induced dopamine release. The results imply that PG in PD is associated with a high dose of dopaminergic medication, pronounced motor symptomatology, young age at disease onset, high propensity for sensation seeking, and risky decision-making. Overall, the findings are consistent with the hypothesis of medication-related PG in PD and underscore the importance of taking clinical variables, such as age and personality, into account when patients with PD are medicated, to reduce the risk of PG.

Two mechanisms of midbrain and striatal dopaminergic projections may be involved in pathological gambling: hypersensitivity to reward and sustained activation toward uncertainty. The midbrain-striatal dopamine system distinctly codes reward and uncertainty, where dopaminergic activation is a linear function of expected reward and an inverse U-shaped function of uncertainty. In this study, we investigated the dopaminergic coding of reward and uncertainty in 18 pathological gambling sufferers and 16 healthy controls. We used positron emission tomography (PET) with the tracer [(11)C]raclopride to measure dopamine release, and we used performance on the Iowa Gambling Task (IGT) to determine overall reward and uncertainty. We hypothesized that we would find a linear function between dopamine release and IGT performance, if dopamine release coded reward in pathological gambling. If, on the other hand, dopamine release coded uncertainty, we would find an inversely U-shaped function. The data supported an inverse U-shaped relation between striatal dopamine release and IGT performance if the pathological gambling group, but not in the healthy control group. These results are consistent with the hypothesis of dopaminergic sensitivity toward uncertainty, and suggest that dopaminergic sensitivity to uncertainty is pronounced in pathological gambling, but not among non-gambling healthy controls. The findings have implications for understanding dopamine dysfunctions in pathological gambling and addictive behaviors.

Two mechanisms of midbrain and striatal dopaminergic projections may be involved in pathological gambling: hypersensitivity to reward and sustained activation toward uncertainty. The midbrain-striatal dopamine system distinctly codes reward and uncertainty, where dopaminergic activation is a linear function of expected reward and an inverse U-shaped function of uncertainty. In this study, we investigated the dopaminergic coding of reward and uncertainty in 18 pathological gambling sufferers and 16 healthy controls. We used positron emission tomography (PET) with the tracer [(11)C]raclopride to measure dopamine release, and we used performance on the Iowa Gambling Task (IGT) to determine overall reward and uncertainty. We hypothesized that we would find a linear function between dopamine release and IGT performance, if dopamine release coded reward in pathological gambling. If, on the other hand, dopamine release coded uncertainty, we would find an inversely U-shaped function. The data supported an inverse U-shaped relation between striatal dopamine release and IGT performance if the pathological gambling group, but not in the healthy control group. These results are consistent with the hypothesis of dopaminergic sensitivity toward uncertainty, and suggest that dopaminergic sensitivity to uncertainty is pronounced in pathological gambling, but not among non-gambling healthy controls. The findings have implications for understanding dopamine dysfunctions in pathological gambling and addictive behaviors.

Gambling excitement is believed to be associated with biological measures of pathological gambling. Here, we tested the hypothesis that dopamine release would be associated with increased excitement levels in Pathological Gamblers compared with Healthy Controls.

Gambling excitement is believed to be associated with biological measures of pathological gambling. Here, we tested the hypothesis that dopamine release would be associated with increased excitement levels in Pathological Gamblers compared with Healthy Controls.

Gambling excitement is believed to be associated with biological measures of pathological gambling. Here, we tested the hypothesis that dopamine release would be associated with increased excitement levels in Pathological Gamblers compared with Healthy Controls.

Absent Skin Conductance Response (SCR) in pathological gambling (PG) may relate to dopaminergic mechanisms. We recruited equal numbers of PG subjects and healthy control (HC) subjects, and then tested the claim that SCR is less conditioned by dopaminergic activity in PG subjects. During active gambling, SCR differed in PG and HC subjects (P < 0.05), but positron emission tomography revealed the same dopamine receptor availability. However, highly sensation-seeking (HS) PG subjects had lower dopamine receptor availability (P < 0.0001) in the baseline, compared to normal sensation-seeking (NS) PG subjects. We find that HS versus NS controls had the same observation of significant increase of binding potential (BP(ND)) in high compared to normal sensation seekers. In both groups, PG and HC, highly sensation-seeking subjects had significant increase of receptor availability in striatum, compared to normally sensation-seeking subjects, separately (P < 0.05 and P = 0.02, respectively) and together (P < 0.0005). We conclude that SCR is less conditioned by dopaminergic activity in highly sensation-seeking subjects, regardless of PG status

Udgivelsesdato: 2010-Feb-4, Sensation seeking is a core personality trait that declines with age in both men and women, as do also both density and availability of the dopamine D(2/3) receptors in striatum and cortical regions. In contrast, novelty seeking at a given age relates inversely to dopamine receptor availability. The simplest explanation of these findings is an inverted-U-shaped correlation between ratings of sensation seeking on the Zuckerman scale and dopamine D(2/3) receptor availability. To test the claim of an inverted-U-shaped relation between ratings of the sensation-seeking personality and measures of dopamine receptor availability, we used PET to record [(11)C]raclopride binding in striatum of 18 healthy men. Here we report that an inverted-U shape significantly matched the receptor availability as a function of the Zuckerman score, with maximum binding potentials observed in the midrange of the scale. The inverted-U shape is consistent with a negative correlation between sensation seeking and the reactivity ("gain") of dopaminergic neurotransmission to dopamine. The correlation reflects Zuckerman scores that are linearly linked to dopamine receptor densities in the striatum but nonlinearly linked to dopamine concentrations. Higher dopamine occupancy and dopamine concentrations explain the motivation that drives afflicted individuals to seek sensations, in agreement with reduced protection against addictive behavior that is characteristic of individuals with low binding potentials.

Udgivelsesdato: 2010-Aug-2, The dopamine system is believed to affect gambling behavior in pathological gambling. Particularly, dopamine release in the ventral striatum appears to affect decision-making in the disorder. This study investigated dopamine release in the ventral striatum in relation to gambling performance on the Iowa Gambling Task (IGT) in 16 Pathological Gamblers (PG) and 14 Healthy Controls (HC). We used Positron Emission Tomography (PET) to measure the binding potential of [(11)C] raclopride to dopamine D2/3 receptors during a baseline and gambling condition. We hypothesized that decreased raclopride binding potentials in the ventral striatum during gambling (indicating dopamine release) would be associated with higher IGT performance in Healthy Controls, but lower IGT performance in Pathological Gamblers. The results showed that Pathological Gamblers with dopamine release in the ventral striatum had significantly lower IGT performance than Healthy Controls. Furthermore, dopamine release was associated with significantly higher IGT performance in Healthy Controls and significantly lower IGT performance in Pathological Gamblers. The results suggest that dopamine release is involved both in adaptive and maladaptive decision-making. These findings may contribute to a better understanding of dopaminergic dysfunctions in pathological gambling and substance related addictions.

Udgivelsesdato: 2010-Feb-4, Sensation seeking is a core personality trait that declines with age in both men and women, as do also both density and availability of the dopamine D(2/3) receptors in striatum and cortical regions. In contrast, novelty seeking at a given age relates inversely to dopamine receptor availability. The simplest explanation of these findings is an inverted-U-shaped correlation between ratings of sensation seeking on the Zuckerman scale and dopamine D(2/3) receptor availability. To test the claim of an inverted-U-shaped relation between ratings of the sensation-seeking personality and measures of dopamine receptor availability, we used PET to record [(11)C]raclopride binding in striatum of 18 healthy men. Here we report that an inverted-U shape significantly matched the receptor availability as a function of the Zuckerman score, with maximum binding potentials observed in the midrange of the scale. The inverted-U shape is consistent with a negative correlation between sensation seeking and the reactivity ("gain") of dopaminergic neurotransmission to dopamine. The correlation reflects Zuckerman scores that are linearly linked to dopamine receptor densities in the striatum but nonlinearly linked to dopamine concentrations. Higher dopamine occupancy and dopamine concentrations explain the motivation that drives afflicted individuals to seek sensations, in agreement with reduced protection against addictive behavior that is characteristic of individuals with low binding potentials.

Absent Skin Conductance Response (SCR) in pathological gambling (PG) may relate to dopaminergic mechanisms. We recruited equal numbers of PG subjects and healthy control (HC) subjects, and then tested the claim that SCR is less conditioned by dopaminergic activity in PG subjects. During active gambling, SCR differed in PG and HC subjects (P < 0.05), but positron emission tomography revealed the same dopamine receptor availability. However, highly sensation-seeking (HS) PG subjects had lower dopamine receptor availability (P < 0.0001) in the baseline, compared to normal sensation-seeking (NS) PG subjects. We find that HS versus NS controls had the same observation of significant increase of binding potential (BP(ND)) in high compared to normal sensation seekers. In both groups, PG and HC, highly sensation-seeking subjects had significant increase of receptor availability in striatum, compared to normally sensation-seeking subjects, separately (P < 0.05 and P = 0.02, respectively) and together (P < 0.0005). We conclude that SCR is less conditioned by dopaminergic activity in highly sensation-seeking subjects, regardless of PG status

Udgivelsesdato: 2010-Aug-2, The dopamine system is believed to affect gambling behavior in pathological gambling. Particularly, dopamine release in the ventral striatum appears to affect decision-making in the disorder. This study investigated dopamine release in the ventral striatum in relation to gambling performance on the Iowa Gambling Task (IGT) in 16 Pathological Gamblers (PG) and 14 Healthy Controls (HC). We used Positron Emission Tomography (PET) to measure the binding potential of [(11)C] raclopride to dopamine D2/3 receptors during a baseline and gambling condition. We hypothesized that decreased raclopride binding potentials in the ventral striatum during gambling (indicating dopamine release) would be associated with higher IGT performance in Healthy Controls, but lower IGT performance in Pathological Gamblers. The results showed that Pathological Gamblers with dopamine release in the ventral striatum had significantly lower IGT performance than Healthy Controls. Furthermore, dopamine release was associated with significantly higher IGT performance in Healthy Controls and significantly lower IGT performance in Pathological Gamblers. The results suggest that dopamine release is involved both in adaptive and maladaptive decision-making. These findings may contribute to a better understanding of dopaminergic dysfunctions in pathological gambling and substance related addictions.

Background: Dopamine transmission in the striatum and especially the ventral striatum (VST), a structure which includes the nucleus accumbens, ventral caudate, and ventral putamen, plays a critical role in the pathophysiology of psychotic states and the reinforcing effects of virtually all drugs of abuse. Objective/Hypotheses: The sensitivity of the measurement of DA transmission using raclopride as the surrogate marker may be affected by the type of analysis of raclopride binding potential (pB) chosen. Here, we compare striatal pB data obtained using three routine analyses of raclopride data. Methods: Dynamic emission recordings were obtained for 60 minutes after i.v. [11C] raclopride (190-366 MBq) using the ECAT HR tomography for 14 subjects during baseline (no decision making, no possibility to win money). Spatial normalization to a stereotactic atlas was performed using a combination of linear and nonlinear registrations. Regions were extracted using model-based segmentation. Maps of pB were calculated by the Lammertsma Simplified Reference Tissue Method, the Logan method with the slope calculated between 20 and 60 min. post injection and the ERLiBiRD method, using the cerebellum as reference for all three methods. Mean pB were calculated for left and right putamen, caudate and VST. Correlations between the left and right pB were examined for each striatal region. The results of the three methods were also compared. Results: For all three methods, there was a highly significant correlation between the left and right caudate and putamen (p<0.001). There was a significant but lower correlation between the left and right VST (0.01< 0.001), because of a higher standard error in the pB. Conclusions: There were no significant differences among the three methods. The ERLiBiRD method appears to be more robust when the variance in t

Background: Dopamine transmission in the striatum and especially the ventral striatum (VST), a structure which includes the nucleus accumbens, ventral caudate, and ventral putamen, plays a critical role in the pathophysiology of psychotic states and the reinforcing effects of virtually all drugs of abuse. Objective/Hypotheses: The sensitivity of the measurement of DA transmission using raclopride as the surrogate marker may be affected by the type of analysis of raclopride binding potential (pB) chosen. Here, we compare striatal pB data obtained using three routine analyses of raclopride data. Methods: Dynamic emission recordings were obtained for 60 minutes after i.v. [11C] raclopride (190-366 MBq) using the ECAT HR tomography for 14 subjects during baseline (no decision making, no possibility to win money). Spatial normalization to a stereotactic atlas was performed using a combination of linear and nonlinear registrations. Regions were extracted using model-based segmentation. Maps of pB were calculated by the Lammertsma Simplified Reference Tissue Method, the Logan method with the slope calculated between 20 and 60 min. post injection and the ERLiBiRD method, using the cerebellum as reference for all three methods. Mean pB were calculated for left and right putamen, caudate and VST. Correlations between the left and right pB were examined for each striatal region. The results of the three methods were also compared. Results: For all three methods, there was a highly significant correlation between the left and right caudate and putamen (p<0.001). There was a significant but lower correlation between the left and right VST (0.01< 0.001), because of a higher standard error in the pB. Conclusions: There were no significant differences among the three methods. The ERLiBiRD method appears to be more robust when the variance in t

Denne artikel fokuserer på heterogenitetsforholdet i sensationssøgende adfærd. Sensationssøgning er et begreb, som er omgærdet med megen interesse, men som også er kontroversielt i litteraturen. I denne artikel vil jeg anvende eksempler fra ludomaniforskningen til at belyse den heterogene kompleksitet inden for afhængighedstilstandene, samt belyse aspekter af begrebet sensationssøgning. Først introduceres begrebet sensationssøgning med særlig vægt på ludomani. Derefter præsenteres tre nylige eller igangværende studier af sensationssøgning inden for ludomani: 1.) en klinisk undersøgelse af over 300 behandlingssøgende ludomaner, 2.) en neurovidenskablig undersøgelse af sammenhængen mellem sensationssøgning og bindingspotentialet af neurotransmitterstoffet dopamin i hjernen, og 3.) en neuro-kognitiv undersøgelse af sensationssøgning og beslutningsprocesser i spillesituationer blandt ludomane og ikke-ludomane. Endelig diskuteres interaktionen mellem sensationssøgende adfærd og bio-psyko-sociale faktorers betydning for heterogenitetsspørgsmålet inden for ludomani og andre afhængighedstilstande.

Welcome to this special issue of Psyke & Logos, which focuses on addictions. Several journals are dedicated to the issue of addictions (e.g. Addiction, Addictive Behaviors, and Psychology of Addictive Behaviors), yet little attention has been dedicated to the concept of addictions and the addictive component in different types of addictive behavior. Since the 60s and the 70s with the introduction and wide spread use of substances such as cannabis and opiates, there has been an increase in the multitude of substances used for recreational (i.e. non-medical) purposes including the use of cocaine and amphetamine in the 80s and 90s and so-called »designer drugs« such as ecstasy in the new millennium. At the same time, we’ve seen concerns ‘addictive behaviors’, particularly among children, associated with technological developments ranging from the use of comic books in the 60s and 70s, to the use of video films in the 80s, the use of video games in the 90s and the use of the internet and mobile phones in the new millennium. A third development is the efforts of information and reduction of health risking behavior. Most noticeably, probably, is the perceptual and behavioral changes related with tobacco use, which has resulted in a reduction of the total number of smokers as well as a reduction of smoking in public places. Other areas which have received attention in later years is eating disorders (both anorexia nervosa, bulimia, and over eating (binge eating)), as well as the efforts to inform about risk behavior of alcohol consumption among youths. The Psyke & Logos conference held on January 28, 2005 has the focus of comparing different types of addictive behavior in a conglomerate of clinical manifestations. The papers produced from the conference together with the invited papers for this issue, all present different aspects of addictive behavior, and have been chosen to provide the reader with insights into the different types of behaviors as well as different disci