Many factors are involved in the pathogenesis of depression. This article provides an overview of... more Many factors are involved in the pathogenesis of depression. This article provides an overview of the results given in the thesis entitled 'Linking Depression', in which some putative underlying neurobiological and genetic mechanisms of depression are examined. To gain more insight in brain activity as endophenotype for depression. As part of the Netherlands Study of Depression and Anxiety (nesda), 301 people, including patients with depression and/or anxiety and healthy volunteers, underwent functional magnetic resonance imaging (fmri) and genotyping. During the processing of negative emotions, patients with depression showed a pattern of heightened limbic activation but less prefrontal activation. The same pattern, but in reverse, was seen during the processing of positive emotions. We showed that the disc1, comt and npy genes were associated with brain activation patterns comparable to those seen in patients with depression. In addition, in cases of depression, there was ...
Genetic variation in the catechol-O-methyltransferase (COMT) Val158Met polymorphism has been show... more Genetic variation in the catechol-O-methyltransferase (COMT) Val158Met polymorphism has been shown to influence performance on cognitive and emotional tasks. Specifically, it has been suggested that the Met allele might be less advantageous than the Val allele with respect to emotional processing. This study addresses the question whether the presence of the Met allele is directly related to both lower emotional verbalizing proficiency and differences in brain activation during emotional processing. Specifically, we investigated whether COMT genotype would be associated with differences in activation in cortical midline structures during valence evaluation of words. Forty participants ranging from low to high on the verbalizing subscale of the Bermond-Vorst Alexithymia Questionnaire (BVAQ) were genotyped for the COMT Val158Met polymorphism. During fMRI, they evaluated the valence of emotional words. Met homozygotes reported more difficulties in verbalizing their feelings. In additio...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2005
While searching for a PET method to determine the density and occupancy of the dopamine D(3) rece... more While searching for a PET method to determine the density and occupancy of the dopamine D(3) receptor, we found evidence that suggested that the dopamine D(3) antagonist GR218231 could be a substrate of the P-glycoprotein efflux pump. P-glycoprotein protects the brain against toxic substances and xenobiotics, but it also hampers the delivery of various drugs into the brain. In this study, we aimed to explore whether radiolabeled GR218231 could be applied as a PET tracer for monitoring P-glycoprotein activity in the blood-brain barrier. Such an imaging technique could be useful for the development of new drugs and novel strategies to deliver drugs to the brain and for identification of undesirable drug-drug interactions. As a potential PET tracer, GR218231 was labeled with (11)C by reaction of the newly synthesized desmethyl precursor with (11)C-methyl triflate. The biodistribution of (11)C-GR218231 was determined in rats. To assess specific binding to the dopamine D(3) receptor, blo...
Microtesla transcranial magnetic stimulation (microTMS) protocols use time series identical or si... more Microtesla transcranial magnetic stimulation (microTMS) protocols use time series identical or similar to biological signals. Such protocols have a relatively high potency and a pioneering paper reports an analgesic effect in humans after 30 minutes stimulation at 0.2 mT. We aimed to investigate dose-effect relationships, duration of the effect and the mechanism of TMS action. Twenty healthy volunteers participated in this placebo controlled, double blind, balanced, cross over clinical trial. Thirty minutes of microTMS or sham was applied and after one week the other treatment was given. Primary outcomes were measured with thermal quantitative sensory testing (tQST). Secondary outcomes were cognition, emotion and motor behaviour. There were no adverse events. ANOVA indicated a significant microTMS effect on heat pain threshold (effect size: 0.9 to 1.0 degrees centigrade within the first session) that was was still present at one week post-treatment. All other outcomes were unaltered...
E very organism that is alive today is a direct descendant of one or two ancestors: one in the ca... more E very organism that is alive today is a direct descendant of one or two ancestors: one in the case of asexual reproduction and two in the case of sexual reproduction. This self-evident truth tells us two things about those ancestors: (i) they reached sexual maturity in a su ciently healthy state and (ii) they actually replicated. These two achieve-ments, individual survival and species survival, are essential for the continuity of life and, as a result, any trait that increases the ability to execute them is favored by natural selection. It is tempting to call these achievements the goals of life, but apparent goals is a safer term to use. Dawkins (1976) remarked that the two apparent goals of life can easily be simpli ed by regarding the gene as the "atom" of natural selection and replication. Two seemingly rivaling apparent goals of life now become one: individual survival and species survival can both be seen as two di erent expression forms of the conservation of an o...
Neuropeptide Y (NPY) has been associated with stress reactivity in affective disorders and is mos... more Neuropeptide Y (NPY) has been associated with stress reactivity in affective disorders and is most densely expressed in the amygdala. An important stressor associated with affective disorders is the experience of childhood emotional maltreatment (CEM). We investigated whether the interaction of NPY risk genotype and CEM would affect brain activation. From The Netherlands Study of Depression and Anxiety, 33 healthy controls and 85 patients with affective disorders were scanned with functional magnetic resonance imaging while making gender decisions of emotional facial expressions. Results showed interactions between genotype and CEM, within carriers of the risk genotype, CEM was associated with higher amygdala activation, whereas CEM did not influence activation in non-risk carriers. In the posterior cingulate cortex (PCC), less activation was seen in those with CEM and the risk genotype, whereas genotype did not influence PCC activation in those without CEM. In addition, those carrying the risk genotype and with experience of CEM made a faster gender decision than those without CEM. Thus, the combined effect of carrying NPY risk genotype and a history of CEM affected amygdala and PCC reactivity, areas related to emotion, self-relevance processing and autobiographical memory. These results are consistent with the notion that the combination of risk genotype and CEM may cause hypervigilance.
Depression has been associated with limbic hyperactivation and frontal hypoactivation in response... more Depression has been associated with limbic hyperactivation and frontal hypoactivation in response to negative facial stimuli. Anxiety disorders have also been associated with increased activation of emotional structures such as the amygdala and insula. This study examined to what extent activation of brain regions involved in perception of emotional faces is specific to depression and anxiety disorders in a large community-based sample of out-patients. An event-related functional magnetic resonance imaging (fMRI) paradigm was used including angry, fearful, sad, happy and neutral facial expressions. One hundred and eighty-two out-patients (59 depressed, 57 anxiety and 66 co-morbid depression-anxiety) and 56 healthy controls selected from the Netherlands Study of Depression and Anxiety (NESDA) were included in the present study. Whole-brain analyses were conducted. The temporal profile of amygdala activation was also investigated. Facial expressions activated the amygdala and fusiform gyrus in depressed patients with or without anxiety and in healthy controls, relative to scrambled faces, but this was less evident in patients with anxiety disorders. The response shape of the amygdala did not differ between groups. Depressed patients showed dorsolateral prefrontal cortex (PFC) hyperactivation in response to happy faces compared to healthy controls. We suggest that stronger frontal activation to happy faces in depressed patients may reflect increased demands on effortful emotion regulation processes triggered by mood-incongruent stimuli. The lack of strong differences in neural activation to negative emotional faces, relative to healthy controls, may be characteristic of the mild-to-moderate severity of illness in this sample and may be indicative of a certain cognitive-emotional processing reserve.
Many factors are involved in the pathogenesis of depression. This article provides an overview of... more Many factors are involved in the pathogenesis of depression. This article provides an overview of the results given in the thesis entitled 'Linking Depression', in which some putative underlying neurobiological and genetic mechanisms of depression are examined. To gain more insight in brain activity as endophenotype for depression. As part of the Netherlands Study of Depression and Anxiety (nesda), 301 people, including patients with depression and/or anxiety and healthy volunteers, underwent functional magnetic resonance imaging (fmri) and genotyping. During the processing of negative emotions, patients with depression showed a pattern of heightened limbic activation but less prefrontal activation. The same pattern, but in reverse, was seen during the processing of positive emotions. We showed that the disc1, comt and npy genes were associated with brain activation patterns comparable to those seen in patients with depression. In addition, in cases of depression, there was ...
Genetic variation in the catechol-O-methyltransferase (COMT) Val158Met polymorphism has been show... more Genetic variation in the catechol-O-methyltransferase (COMT) Val158Met polymorphism has been shown to influence performance on cognitive and emotional tasks. Specifically, it has been suggested that the Met allele might be less advantageous than the Val allele with respect to emotional processing. This study addresses the question whether the presence of the Met allele is directly related to both lower emotional verbalizing proficiency and differences in brain activation during emotional processing. Specifically, we investigated whether COMT genotype would be associated with differences in activation in cortical midline structures during valence evaluation of words. Forty participants ranging from low to high on the verbalizing subscale of the Bermond-Vorst Alexithymia Questionnaire (BVAQ) were genotyped for the COMT Val158Met polymorphism. During fMRI, they evaluated the valence of emotional words. Met homozygotes reported more difficulties in verbalizing their feelings. In additio...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2005
While searching for a PET method to determine the density and occupancy of the dopamine D(3) rece... more While searching for a PET method to determine the density and occupancy of the dopamine D(3) receptor, we found evidence that suggested that the dopamine D(3) antagonist GR218231 could be a substrate of the P-glycoprotein efflux pump. P-glycoprotein protects the brain against toxic substances and xenobiotics, but it also hampers the delivery of various drugs into the brain. In this study, we aimed to explore whether radiolabeled GR218231 could be applied as a PET tracer for monitoring P-glycoprotein activity in the blood-brain barrier. Such an imaging technique could be useful for the development of new drugs and novel strategies to deliver drugs to the brain and for identification of undesirable drug-drug interactions. As a potential PET tracer, GR218231 was labeled with (11)C by reaction of the newly synthesized desmethyl precursor with (11)C-methyl triflate. The biodistribution of (11)C-GR218231 was determined in rats. To assess specific binding to the dopamine D(3) receptor, blo...
Microtesla transcranial magnetic stimulation (microTMS) protocols use time series identical or si... more Microtesla transcranial magnetic stimulation (microTMS) protocols use time series identical or similar to biological signals. Such protocols have a relatively high potency and a pioneering paper reports an analgesic effect in humans after 30 minutes stimulation at 0.2 mT. We aimed to investigate dose-effect relationships, duration of the effect and the mechanism of TMS action. Twenty healthy volunteers participated in this placebo controlled, double blind, balanced, cross over clinical trial. Thirty minutes of microTMS or sham was applied and after one week the other treatment was given. Primary outcomes were measured with thermal quantitative sensory testing (tQST). Secondary outcomes were cognition, emotion and motor behaviour. There were no adverse events. ANOVA indicated a significant microTMS effect on heat pain threshold (effect size: 0.9 to 1.0 degrees centigrade within the first session) that was was still present at one week post-treatment. All other outcomes were unaltered...
E very organism that is alive today is a direct descendant of one or two ancestors: one in the ca... more E very organism that is alive today is a direct descendant of one or two ancestors: one in the case of asexual reproduction and two in the case of sexual reproduction. This self-evident truth tells us two things about those ancestors: (i) they reached sexual maturity in a su ciently healthy state and (ii) they actually replicated. These two achieve-ments, individual survival and species survival, are essential for the continuity of life and, as a result, any trait that increases the ability to execute them is favored by natural selection. It is tempting to call these achievements the goals of life, but apparent goals is a safer term to use. Dawkins (1976) remarked that the two apparent goals of life can easily be simpli ed by regarding the gene as the "atom" of natural selection and replication. Two seemingly rivaling apparent goals of life now become one: individual survival and species survival can both be seen as two di erent expression forms of the conservation of an o...
Neuropeptide Y (NPY) has been associated with stress reactivity in affective disorders and is mos... more Neuropeptide Y (NPY) has been associated with stress reactivity in affective disorders and is most densely expressed in the amygdala. An important stressor associated with affective disorders is the experience of childhood emotional maltreatment (CEM). We investigated whether the interaction of NPY risk genotype and CEM would affect brain activation. From The Netherlands Study of Depression and Anxiety, 33 healthy controls and 85 patients with affective disorders were scanned with functional magnetic resonance imaging while making gender decisions of emotional facial expressions. Results showed interactions between genotype and CEM, within carriers of the risk genotype, CEM was associated with higher amygdala activation, whereas CEM did not influence activation in non-risk carriers. In the posterior cingulate cortex (PCC), less activation was seen in those with CEM and the risk genotype, whereas genotype did not influence PCC activation in those without CEM. In addition, those carrying the risk genotype and with experience of CEM made a faster gender decision than those without CEM. Thus, the combined effect of carrying NPY risk genotype and a history of CEM affected amygdala and PCC reactivity, areas related to emotion, self-relevance processing and autobiographical memory. These results are consistent with the notion that the combination of risk genotype and CEM may cause hypervigilance.
Depression has been associated with limbic hyperactivation and frontal hypoactivation in response... more Depression has been associated with limbic hyperactivation and frontal hypoactivation in response to negative facial stimuli. Anxiety disorders have also been associated with increased activation of emotional structures such as the amygdala and insula. This study examined to what extent activation of brain regions involved in perception of emotional faces is specific to depression and anxiety disorders in a large community-based sample of out-patients. An event-related functional magnetic resonance imaging (fMRI) paradigm was used including angry, fearful, sad, happy and neutral facial expressions. One hundred and eighty-two out-patients (59 depressed, 57 anxiety and 66 co-morbid depression-anxiety) and 56 healthy controls selected from the Netherlands Study of Depression and Anxiety (NESDA) were included in the present study. Whole-brain analyses were conducted. The temporal profile of amygdala activation was also investigated. Facial expressions activated the amygdala and fusiform gyrus in depressed patients with or without anxiety and in healthy controls, relative to scrambled faces, but this was less evident in patients with anxiety disorders. The response shape of the amygdala did not differ between groups. Depressed patients showed dorsolateral prefrontal cortex (PFC) hyperactivation in response to happy faces compared to healthy controls. We suggest that stronger frontal activation to happy faces in depressed patients may reflect increased demands on effortful emotion regulation processes triggered by mood-incongruent stimuli. The lack of strong differences in neural activation to negative emotional faces, relative to healthy controls, may be characteristic of the mild-to-moderate severity of illness in this sample and may be indicative of a certain cognitive-emotional processing reserve.
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Papers by Rudie Kortekaas