The effect on cerebral blood flow of acute diazoxide-induced hypotension was studied in rats with... more The effect on cerebral blood flow of acute diazoxide-induced hypotension was studied in rats with renal and spontaneous hypertension. Diazoxide (5 mg/kg, i.v. bolus), caused arterial pressure to fall rapidly to that of normotensive rats, i.e. c. 75 mmHg. There was a concomitant fall in cerebral blood flow of about 35% (P < 0-01) in renal hypertensive rats and 25% (P < 0.05) in spontaneously hypertensive rats; the greater fall in flow in the former corresponded to a greater drop in pressure. Flow remained at these reduced levels during a 2 h observation period.
Enhanced expression of the immediate early gene c-fos has been used as a marker of cellular activ... more Enhanced expression of the immediate early gene c-fos has been used as a marker of cellular activation in many different neuronal pathways. We wished to determine the neurochemical content and the connectivity of neurons, in which expression of c-fos is induced.
Gamma-Aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the brain. A defic... more Gamma-Aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the brain. A deficiency of GABAergic inhibition mediated via the GABAA receptor complex has for a long time been suspected to be a central factor in epileptogenesis. Status epilepticus is a condition of sustained and prolonged excitation of neuronal circuits, as detected by epileptiform discharges in the electroencephalogram (EEG). Reduction of GABAA receptor-mediated hippocampal inhibition has been implicated in the development of status epilepticus. The present study provides direct evidence of a link between the GABAA receptor and epilepsy. We show that selective inhibition of the expression of the GABAA receptor gamma2 subunit in the rat hippocampus by means of antisense oligonucleotides leads to spontaneous electrographic seizures that evolve into profound limbic status epilepticus, ultimately resulting in severe neurodegenerative changes. Concurrent treatment with diazepam prevents the development of status epilepticus and markedly reduces neuronal cell loss. These findings strongly support the hypothesis that the GABAA receptor is critically involved in the pathogenesis of seizures and status epilepticus.
The purpose of the present study was to relate the number of platelet serotonin transporters in u... more The purpose of the present study was to relate the number of platelet serotonin transporters in unipolar and bipolar patients and in control subjects to two polymorphisms in the serotonin transporter gene: a VNTR in intron 2 and a deletion/insertion in the promoter region. Density of platelet serotonin transporters was determined by radioligand binding analysis. Genotyping was performed by PCR amplification of polymorphic regions followed by size determination of the obtained fragments. The control subjects and the two groups of patients were similar with respect to the genotype and allele distribution belonging to the two polymorphisms in the serotonin transporter gene for. An interaction between status (control, unipolar- or bipolar patient) and VNTR genotype regarding the number of platelet serotonin transporters was observed; unipolar patients with the genotype 12/10 had more platelet serotonin transporters than bipolar patients and controls with this genotype. No association re...
A case report and a review of the literature concerning electroconvulsive therapy (ECT) in the tr... more A case report and a review of the literature concerning electroconvulsive therapy (ECT) in the treatment of Parkinson's disease with special reference to the therapy of "on-off" phenomena is given. The first report of positive effect appeared in 1959 and, with a single exception, all published articles on this topic point to a positive outcome of ECT. There seems to be a specific anti-Parkinsonian effect alongside the well-known effect on various psychotic conditions. ECT thus must be considered a valuable intervention when drug therapy is insufficient, when prolonged medication leads to decreased efficacy, or when patients develop neuro-psychiatric manifestations. A short review of the pathophysiological mechanisms which may underly the effect of ECT in Parkinson's disease is given.
Psykoanalyse er en psykoterapeutisk disciplin, udviklet af Sigmund Freud i 1890'erne. Den omfatte... more Psykoanalyse er en psykoterapeutisk disciplin, udviklet af Sigmund Freud i 1890'erne. Den omfatter dels en terapeutisk teknik til behandling af neuroser og andre psykiske lidelser, dels en metode til analyse af kulturfaenomener, og endelig en almen psykologisk teori. Den terapeutiske teknik baserer sig på en terapeutisk samtale mellem den terapeut der forestår behandlingen, psykoanalytikeren, og den der bliver analyseret, analysanden. I den klassiske udgave af psykoanalyse ligger analysanden udstrakt på en sofa, mens analytikeren som en forholdsvis tavs tilhører sidder i ene laenestol udenfor analysandens synsfelt. Analysanden opfordres til at meddele alle tanker og associationer uanset hvor ligegyldige de kan forekomme, ligesom indholdet af drømme bidrager til det materiale der ved siden af dagligdags oplevelser, erindringer og reflektioner, der bliver tema for samtalerne. Analysandens følelsesmaessige overføring på analytikeren spiller en vaesentlig rolle for hvordan analytikeren fortolker materialet. Fortolkningerne har til formål at åbne det ubevidste og bringe uløste eller fejlagtigt løste konflikter for dagen med henblik på en ny og bedre løsning. Den psykoanalytiske tilgangsmåde kendes generelt på, at de i grundlaget tilstedevaerende konflikter og selvmodsigelser søges blotlagt.
The generation of new neurons in the adult mammalian brain has been documented in numerous recent... more The generation of new neurons in the adult mammalian brain has been documented in numerous recent reports. Studies undertaken so far indicate that adult hippocampal neurogenesis is related in a number of ways to hippocampal function.Here, we report that subjecting adult rats to fractionated brain irradiation blocked the formation of new neurons in the dentate gyrus of the hippocampus. At different time points after the termination of the irradiation procedure, the animals were tested in two tests of short-term memory that differ with respect to their dependence on hippocampal function. Eight and 21 days after irradiation, the animals with blocked neurogenesis performed poorer than controls in a hippocampus-dependent place-recognition task, indicating that the presence of newly generated neurons may be necessary for the normal function of this brain area. The animals were never impaired in a hippocampus-independent object-recognition task. These results are in line with other reports...
The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), 2002
Several neuroimaging studies of patients with OCD have pointed to basal ganglia and the frontal c... more Several neuroimaging studies of patients with OCD have pointed to basal ganglia and the frontal cortical regions being relevant for an understanding of the pathophysiology and therapy of OCD. In a search for the neural substrate underlying the therapeutic action of paroxetine in the therapy of OCD we measured regional glucose metabolism in a PET study of 20 OCD patients before and after at least 3 months of treatment. We used 18-fluoro-deoxyglucose PET-scanning to measure regional cerebral glucose metabolic rate (rCMRglc) in 20 non-depressed patients fulfilling DSM-IV criteria for OCD. Patients were studied before and after 12-20 wk of treatment with the serotonin re-uptake inhibitor paroxetine. Clinical assessment rating with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was performed before the first and after the second study. The PET data was analysed regionally using statistical parametric mapping (SPM-96). A clinical improvement was indicated by a mean decrease of 55% in ...
Positron emission tomography (PET) is a method for quantitative imaging of regional physiological... more Positron emission tomography (PET) is a method for quantitative imaging of regional physiological and biochemical parameters. Positron emitting radioactive isotopes can be produced by a cyclotron, eg. the biologically important carbon (11C), oxygen (15O), and nitrogen (13N) elements. With the tomographic principle of the PET scanner the quantitative distribution of the administered isotopes can be determined and images can be provided as well as dynamic information on blood flow, metabolism and receptor function. In neurology PET has been used for investigations on numerous physiological processes in the brain: circulation, metabolism and receptor studies. In Parkinson&#39;s disease PET studies have been able to localize the pathology specifically, and in early stroke PET technique can outline focal areas with living but non-functioning cells, and this could make it possible to intervene in this early state. With positron emission tomography a quantitative evaluation of myocardial blood flow, glucose and fatty acid metabolism can be made as well as combined assessments of blood flow and metabolism. Combined studies of blood flow and metabolism can determine whether myocardial segments with abnormal motility consist of necrotic or viable tissue, thereby delineating effects of revascularisation. In the future it will probably be possible to characterize the myocardial receptor status in different cardiac diseases. The PET technique is used in oncology for clinical as well as more basic research on tumor perfusion and metabolism. Further, tumor uptake of positron labelled cytotoxic drugs might predict the clinical benefit of treatment.
The aim of the study was to examine the occurrence of psychiatric disorders in epilepsy patients ... more The aim of the study was to examine the occurrence of psychiatric disorders in epilepsy patients who had received surgical treatment, especially amygdalohippocampectomy (AHE), for the relief of medically intractable seizures. Forty-seven subjects, treated during the period 1987-1991 in the Danish epilepsy surgery programme (EPIKIR), entered a retrospective interview study. Of these, 37 had undergone AHE. Preoperative psychiatric morbidity was assessed through interview and available case notes, including a routine psychiatric interview. Postoperative psychiatric morbidity was assessed by the use of the Present State Examination. A total of six subjects (five AHE subjects) developed depressive disorders of various duration and severity after operation. In three subjects this occurred "de novo". No paranoid-hallucinatory psychoses developed within the follow-up period (a minimum of one year), and the presence of psychiatric disorders could not be associated with either later...
The International Journal of Neuropsychopharmacology, 2005
The pharmacological efficacy of serotonergic-acting drugs suggest that patients with obsessive-co... more The pharmacological efficacy of serotonergic-acting drugs suggest that patients with obsessive-compulsive disorder (OCD) may have alterations in their cerebral serotonergic (5-HT) receptor system, and previous neuroimaging studies of OCD patients have shown abnormalities in several fronto-subcortical regions. In this study we investigated cerebral 5-HT(2A) receptor binding in 15 untreated OCD patients and in 15 age- and gender-matched healthy volunteers by magnetic resonance imaging and [(18)F]altanserin positron emission tomography (PET). Eleven of the patients were rescanned with PET after receiving treatment with a selective serotonin reuptake inhibitor (SSRI). The distribution volumes of specific tracer binding (DV(3)&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;) were calculated for 12 brain regions, and comparisons were made between: (1) healthy volunteers vs. untreated OCD patients, (2) healthy volunteers vs. treated OCD patients, and (3) OCD patients before and during treatment. When comparing the distribution volume for specific fronto-subcortical brain regions, significantly higher values were recorded in the caudate nuclei in OCD patients (DV(3)&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;: 0.24+/-0.14) compared to the healthy control group (DV(3)&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;: 0.15+/-0.13) (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05, Wilcoxon matched-pairs test). This difference between groups was not present after treatment with SSRIs. There was no correlation between the severity of OCD symptoms and 5-HT(2A )receptor binding. An increase in 5-HT(2A) receptor binding is found in the caudate nuclei of untreated patients with OCD. The up-regulation in 5-HT(2A) receptors might be compensatory for a lack of serotonin in the feedback loop between the thalamus and orbito-frontal cortex, the caudate nuclei, and the globus pallidus.
The International Journal of Neuropsychopharmacology, 2007
Evidence implies a role for corticotropin-releasing hormone (CRH) and tachykinins, e.g. substance... more Evidence implies a role for corticotropin-releasing hormone (CRH) and tachykinins, e.g. substance P (SP) and neurokinin A (NKA) in the pathophysiology of depression. We have previously shown that SP-and NKA-like immunoreactivity (-LI) concentrations were altered in the frontal cortex and striatum of the congenitally ' depressed ' Flinders Sensitive Line (FSL) compared to the Flinders Resistant Line (FRL) control rats. It is also known that environmental stress may affect brain levels of tachykinins. In view of these results we decided to superimpose maternal deprivation, an early life environmental stressor, onto the genetically predisposed ' depressed' FSL rats and the FRL control rats and use this paradigm as a model of gene-environment interaction. The adult animals were sacrificed, adrenal glands and brains dissected out and SP-, NKA-and CRH-LI levels were determined in ten discrete brain regions. Maternal deprivation led to a marked increase in SP-LI and NKA-LI levels in the periaqueductal grey (PAG) and entorhinal cortex of the 'depressed' FSL strain while it had no significant effect in the FRL controls. Furthermore, specific strain differences in peptide-LI content were confirmed. No difference was found in relative adrenal gland weight, which is consistent with the finding that CRH-LI levels in the hypothalamus were similar across strains, and insensitive to stress in either strain. Taken together, these data are in line with behavioural experiments showing ameliorating effects of NK 1 and NK 2 receptor antagonists against anxiety and depression-like symptoms in rodents, and therefore further implicate the tachykinin systems in the pathophysiology of depression and adult life psychopathology.
International Journal of Neuropsychopharmacology, 2007
Experimental and clinical data have suggested that abnormalities in the serotonergic neurotransmi... more Experimental and clinical data have suggested that abnormalities in the serotonergic neurotransmissions in frontal-subcortical circuits are involved in Tourette&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome. To test the hypothesis that the brain&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s 5-HT2A receptor binding is increased in patients with Tourette&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome, PET imaging was performed. Twenty adults with Tourette&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome and 20 healthy control subjects were investigated with PET-[18F]altanserin using a bolus-infusion protocol. Regions of interest were delineated automatically on co-registered MRI images, and partial volume-corrected binding parameters were extracted from the PET images. Comparison between control subjects and Tourette&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome patients showed increased specific [18F]altanserin binding, not only in the a-priori selected brain regions hypothesized to be involved in Tourette&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome, but also post-hoc analysis showed a global up-regulation when testing for a overall difference with a randomization test (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.03). Increased 5-HT2A receptor binding was found not only in regions closely related to subcortical regions in patients with Tourette&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome, but also in most other brain regions. Our data suggest that the serotonergic transmitter system is pathophysiologically involved in Tourette&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome and that a clinical trial with 5-HT2A receptor antagonists may be justified.
The effect on cerebral blood flow of acute diazoxide-induced hypotension was studied in rats with... more The effect on cerebral blood flow of acute diazoxide-induced hypotension was studied in rats with renal and spontaneous hypertension. Diazoxide (5 mg/kg, i.v. bolus), caused arterial pressure to fall rapidly to that of normotensive rats, i.e. c. 75 mmHg. There was a concomitant fall in cerebral blood flow of about 35% (P < 0-01) in renal hypertensive rats and 25% (P < 0.05) in spontaneously hypertensive rats; the greater fall in flow in the former corresponded to a greater drop in pressure. Flow remained at these reduced levels during a 2 h observation period.
Enhanced expression of the immediate early gene c-fos has been used as a marker of cellular activ... more Enhanced expression of the immediate early gene c-fos has been used as a marker of cellular activation in many different neuronal pathways. We wished to determine the neurochemical content and the connectivity of neurons, in which expression of c-fos is induced.
Gamma-Aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the brain. A defic... more Gamma-Aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the brain. A deficiency of GABAergic inhibition mediated via the GABAA receptor complex has for a long time been suspected to be a central factor in epileptogenesis. Status epilepticus is a condition of sustained and prolonged excitation of neuronal circuits, as detected by epileptiform discharges in the electroencephalogram (EEG). Reduction of GABAA receptor-mediated hippocampal inhibition has been implicated in the development of status epilepticus. The present study provides direct evidence of a link between the GABAA receptor and epilepsy. We show that selective inhibition of the expression of the GABAA receptor gamma2 subunit in the rat hippocampus by means of antisense oligonucleotides leads to spontaneous electrographic seizures that evolve into profound limbic status epilepticus, ultimately resulting in severe neurodegenerative changes. Concurrent treatment with diazepam prevents the development of status epilepticus and markedly reduces neuronal cell loss. These findings strongly support the hypothesis that the GABAA receptor is critically involved in the pathogenesis of seizures and status epilepticus.
The purpose of the present study was to relate the number of platelet serotonin transporters in u... more The purpose of the present study was to relate the number of platelet serotonin transporters in unipolar and bipolar patients and in control subjects to two polymorphisms in the serotonin transporter gene: a VNTR in intron 2 and a deletion/insertion in the promoter region. Density of platelet serotonin transporters was determined by radioligand binding analysis. Genotyping was performed by PCR amplification of polymorphic regions followed by size determination of the obtained fragments. The control subjects and the two groups of patients were similar with respect to the genotype and allele distribution belonging to the two polymorphisms in the serotonin transporter gene for. An interaction between status (control, unipolar- or bipolar patient) and VNTR genotype regarding the number of platelet serotonin transporters was observed; unipolar patients with the genotype 12/10 had more platelet serotonin transporters than bipolar patients and controls with this genotype. No association re...
A case report and a review of the literature concerning electroconvulsive therapy (ECT) in the tr... more A case report and a review of the literature concerning electroconvulsive therapy (ECT) in the treatment of Parkinson's disease with special reference to the therapy of "on-off" phenomena is given. The first report of positive effect appeared in 1959 and, with a single exception, all published articles on this topic point to a positive outcome of ECT. There seems to be a specific anti-Parkinsonian effect alongside the well-known effect on various psychotic conditions. ECT thus must be considered a valuable intervention when drug therapy is insufficient, when prolonged medication leads to decreased efficacy, or when patients develop neuro-psychiatric manifestations. A short review of the pathophysiological mechanisms which may underly the effect of ECT in Parkinson's disease is given.
Psykoanalyse er en psykoterapeutisk disciplin, udviklet af Sigmund Freud i 1890'erne. Den omfatte... more Psykoanalyse er en psykoterapeutisk disciplin, udviklet af Sigmund Freud i 1890'erne. Den omfatter dels en terapeutisk teknik til behandling af neuroser og andre psykiske lidelser, dels en metode til analyse af kulturfaenomener, og endelig en almen psykologisk teori. Den terapeutiske teknik baserer sig på en terapeutisk samtale mellem den terapeut der forestår behandlingen, psykoanalytikeren, og den der bliver analyseret, analysanden. I den klassiske udgave af psykoanalyse ligger analysanden udstrakt på en sofa, mens analytikeren som en forholdsvis tavs tilhører sidder i ene laenestol udenfor analysandens synsfelt. Analysanden opfordres til at meddele alle tanker og associationer uanset hvor ligegyldige de kan forekomme, ligesom indholdet af drømme bidrager til det materiale der ved siden af dagligdags oplevelser, erindringer og reflektioner, der bliver tema for samtalerne. Analysandens følelsesmaessige overføring på analytikeren spiller en vaesentlig rolle for hvordan analytikeren fortolker materialet. Fortolkningerne har til formål at åbne det ubevidste og bringe uløste eller fejlagtigt løste konflikter for dagen med henblik på en ny og bedre løsning. Den psykoanalytiske tilgangsmåde kendes generelt på, at de i grundlaget tilstedevaerende konflikter og selvmodsigelser søges blotlagt.
The generation of new neurons in the adult mammalian brain has been documented in numerous recent... more The generation of new neurons in the adult mammalian brain has been documented in numerous recent reports. Studies undertaken so far indicate that adult hippocampal neurogenesis is related in a number of ways to hippocampal function.Here, we report that subjecting adult rats to fractionated brain irradiation blocked the formation of new neurons in the dentate gyrus of the hippocampus. At different time points after the termination of the irradiation procedure, the animals were tested in two tests of short-term memory that differ with respect to their dependence on hippocampal function. Eight and 21 days after irradiation, the animals with blocked neurogenesis performed poorer than controls in a hippocampus-dependent place-recognition task, indicating that the presence of newly generated neurons may be necessary for the normal function of this brain area. The animals were never impaired in a hippocampus-independent object-recognition task. These results are in line with other reports...
The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), 2002
Several neuroimaging studies of patients with OCD have pointed to basal ganglia and the frontal c... more Several neuroimaging studies of patients with OCD have pointed to basal ganglia and the frontal cortical regions being relevant for an understanding of the pathophysiology and therapy of OCD. In a search for the neural substrate underlying the therapeutic action of paroxetine in the therapy of OCD we measured regional glucose metabolism in a PET study of 20 OCD patients before and after at least 3 months of treatment. We used 18-fluoro-deoxyglucose PET-scanning to measure regional cerebral glucose metabolic rate (rCMRglc) in 20 non-depressed patients fulfilling DSM-IV criteria for OCD. Patients were studied before and after 12-20 wk of treatment with the serotonin re-uptake inhibitor paroxetine. Clinical assessment rating with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was performed before the first and after the second study. The PET data was analysed regionally using statistical parametric mapping (SPM-96). A clinical improvement was indicated by a mean decrease of 55% in ...
Positron emission tomography (PET) is a method for quantitative imaging of regional physiological... more Positron emission tomography (PET) is a method for quantitative imaging of regional physiological and biochemical parameters. Positron emitting radioactive isotopes can be produced by a cyclotron, eg. the biologically important carbon (11C), oxygen (15O), and nitrogen (13N) elements. With the tomographic principle of the PET scanner the quantitative distribution of the administered isotopes can be determined and images can be provided as well as dynamic information on blood flow, metabolism and receptor function. In neurology PET has been used for investigations on numerous physiological processes in the brain: circulation, metabolism and receptor studies. In Parkinson&#39;s disease PET studies have been able to localize the pathology specifically, and in early stroke PET technique can outline focal areas with living but non-functioning cells, and this could make it possible to intervene in this early state. With positron emission tomography a quantitative evaluation of myocardial blood flow, glucose and fatty acid metabolism can be made as well as combined assessments of blood flow and metabolism. Combined studies of blood flow and metabolism can determine whether myocardial segments with abnormal motility consist of necrotic or viable tissue, thereby delineating effects of revascularisation. In the future it will probably be possible to characterize the myocardial receptor status in different cardiac diseases. The PET technique is used in oncology for clinical as well as more basic research on tumor perfusion and metabolism. Further, tumor uptake of positron labelled cytotoxic drugs might predict the clinical benefit of treatment.
The aim of the study was to examine the occurrence of psychiatric disorders in epilepsy patients ... more The aim of the study was to examine the occurrence of psychiatric disorders in epilepsy patients who had received surgical treatment, especially amygdalohippocampectomy (AHE), for the relief of medically intractable seizures. Forty-seven subjects, treated during the period 1987-1991 in the Danish epilepsy surgery programme (EPIKIR), entered a retrospective interview study. Of these, 37 had undergone AHE. Preoperative psychiatric morbidity was assessed through interview and available case notes, including a routine psychiatric interview. Postoperative psychiatric morbidity was assessed by the use of the Present State Examination. A total of six subjects (five AHE subjects) developed depressive disorders of various duration and severity after operation. In three subjects this occurred "de novo". No paranoid-hallucinatory psychoses developed within the follow-up period (a minimum of one year), and the presence of psychiatric disorders could not be associated with either later...
The International Journal of Neuropsychopharmacology, 2005
The pharmacological efficacy of serotonergic-acting drugs suggest that patients with obsessive-co... more The pharmacological efficacy of serotonergic-acting drugs suggest that patients with obsessive-compulsive disorder (OCD) may have alterations in their cerebral serotonergic (5-HT) receptor system, and previous neuroimaging studies of OCD patients have shown abnormalities in several fronto-subcortical regions. In this study we investigated cerebral 5-HT(2A) receptor binding in 15 untreated OCD patients and in 15 age- and gender-matched healthy volunteers by magnetic resonance imaging and [(18)F]altanserin positron emission tomography (PET). Eleven of the patients were rescanned with PET after receiving treatment with a selective serotonin reuptake inhibitor (SSRI). The distribution volumes of specific tracer binding (DV(3)&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;) were calculated for 12 brain regions, and comparisons were made between: (1) healthy volunteers vs. untreated OCD patients, (2) healthy volunteers vs. treated OCD patients, and (3) OCD patients before and during treatment. When comparing the distribution volume for specific fronto-subcortical brain regions, significantly higher values were recorded in the caudate nuclei in OCD patients (DV(3)&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;: 0.24+/-0.14) compared to the healthy control group (DV(3)&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;: 0.15+/-0.13) (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05, Wilcoxon matched-pairs test). This difference between groups was not present after treatment with SSRIs. There was no correlation between the severity of OCD symptoms and 5-HT(2A )receptor binding. An increase in 5-HT(2A) receptor binding is found in the caudate nuclei of untreated patients with OCD. The up-regulation in 5-HT(2A) receptors might be compensatory for a lack of serotonin in the feedback loop between the thalamus and orbito-frontal cortex, the caudate nuclei, and the globus pallidus.
The International Journal of Neuropsychopharmacology, 2007
Evidence implies a role for corticotropin-releasing hormone (CRH) and tachykinins, e.g. substance... more Evidence implies a role for corticotropin-releasing hormone (CRH) and tachykinins, e.g. substance P (SP) and neurokinin A (NKA) in the pathophysiology of depression. We have previously shown that SP-and NKA-like immunoreactivity (-LI) concentrations were altered in the frontal cortex and striatum of the congenitally ' depressed ' Flinders Sensitive Line (FSL) compared to the Flinders Resistant Line (FRL) control rats. It is also known that environmental stress may affect brain levels of tachykinins. In view of these results we decided to superimpose maternal deprivation, an early life environmental stressor, onto the genetically predisposed ' depressed' FSL rats and the FRL control rats and use this paradigm as a model of gene-environment interaction. The adult animals were sacrificed, adrenal glands and brains dissected out and SP-, NKA-and CRH-LI levels were determined in ten discrete brain regions. Maternal deprivation led to a marked increase in SP-LI and NKA-LI levels in the periaqueductal grey (PAG) and entorhinal cortex of the 'depressed' FSL strain while it had no significant effect in the FRL controls. Furthermore, specific strain differences in peptide-LI content were confirmed. No difference was found in relative adrenal gland weight, which is consistent with the finding that CRH-LI levels in the hypothalamus were similar across strains, and insensitive to stress in either strain. Taken together, these data are in line with behavioural experiments showing ameliorating effects of NK 1 and NK 2 receptor antagonists against anxiety and depression-like symptoms in rodents, and therefore further implicate the tachykinin systems in the pathophysiology of depression and adult life psychopathology.
International Journal of Neuropsychopharmacology, 2007
Experimental and clinical data have suggested that abnormalities in the serotonergic neurotransmi... more Experimental and clinical data have suggested that abnormalities in the serotonergic neurotransmissions in frontal-subcortical circuits are involved in Tourette&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome. To test the hypothesis that the brain&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s 5-HT2A receptor binding is increased in patients with Tourette&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome, PET imaging was performed. Twenty adults with Tourette&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome and 20 healthy control subjects were investigated with PET-[18F]altanserin using a bolus-infusion protocol. Regions of interest were delineated automatically on co-registered MRI images, and partial volume-corrected binding parameters were extracted from the PET images. Comparison between control subjects and Tourette&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome patients showed increased specific [18F]altanserin binding, not only in the a-priori selected brain regions hypothesized to be involved in Tourette&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome, but also post-hoc analysis showed a global up-regulation when testing for a overall difference with a randomization test (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.03). Increased 5-HT2A receptor binding was found not only in regions closely related to subcortical regions in patients with Tourette&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome, but also in most other brain regions. Our data suggest that the serotonergic transmitter system is pathophysiologically involved in Tourette&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome and that a clinical trial with 5-HT2A receptor antagonists may be justified.
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