Jyrki T. Kuikka

Striatal dopamine transporter density in major depression.

Rationale: There are no previous data available regarding [123I]β-CIT binding to the dopamine transporter sites in the basal ganglia in depressed patients. Objective: The present study tested the hypothesis that the brain DAT density in depressed patients is lower than that in matched healthy controls. Methods: Fifteen drug-naive outpatients with major depression and 18 healthy controls were investigated using single photon emission computerized tomography (SPECT) with a high-affinity dopamine transporter specific radioligand, 123I-labeled β-CIT (2β-carbomethoxy-3β-(4-iodophenyl)-tropane). Results: We found a significantly higher [123I]β-CIT uptake in both sides of the basal ganglia in patients with major depression than in the controls (Mann-Whitney U-test, P = 0.002 on the right and P = 0.003 on the left). Conclusions: The radioligand uptake reflecting the DAT density was significantly higher among the patients than in the controls. This finding is unexpected, since it is generally believed that monoaminergic neurotransmission is lower in depression, and therefore it could be assumed that a reduction in dopamine transmission would lead to secondary down-regulation of DAT density. However, it is possible that up-regulation of the DAT may be the primary alteration, which leads to lower intrasynaptic dopamine concentration and to lower dopamine neural transmission.

Single-photon emission tomography imaging of monoamine transporters in impulsive violent behaviour

Abstract.Several studies have shown that impulsive violent and suicidal behaviour is associated with a central serotonin deficit, but until now it has not been possible to use laboratory tests with high sensitivity and specificity to study this kind of deficit or to localize the sites of serotonergic abnormalities in the living human brain. The aim of this study was to test the hypothesis that monoamine transporter density in brain is decreased in subjects with impulsive violent behaviour. We studied serotonin (5-HT) and dopamine (DA) transporter specific binding in 52 subjects (21 impulsive violent offenders, 21 age- and sex-matched healthy controls, and ten non-violent alcoholic controls) with single-photon emission tomography (SPET) using iodine-123-labelled 2β-carbomethoxy-3β(4-iodophenyl)tropane ([123I]β-CIT) as the tracer. The blind quantitative analysis revealed that the 5-HT specific binding of [123I]β-CIT in the midbrain of violent offenders was lower than that in the healthy control subjects (P<0.005; t test) or the non-violent alcoholics (P<0.05). The results imply that habitual impulsive aggressive behaviour in man is associated with a decrease in the 5-HT transporter density.

Noninvasive Detection of Cardiac Sympathetic Nervous Dysfunction in Diabetic Patients Using [123I]Metaiodobenzylguanidine

The association between clinical autonomic dysfunction and myocardial MIBG accumulation was investigated. The study groups comprised 6 male diabetic patients with autonomic neuropathy (ANP+ group), 6 male diabetic patients without autonomic neuropathy (ANP- group), and 6 male nondiabetic control subjects. The mean age was comparable in all groups, and the subjects had no evidence of coronary heart disease. Reduced heart-rate variation in a deep-breathing test was used as a criterion for autonomic neuropathy. Immediately after injection, the peak net influx rate of MIBG to myocardium was significantly (P < 0.05) reduced in both diabetic groups. At 6 hr after MIBG injection, the MIBG uptake of the myocardium was significantly (P < 0.05) smaller in the ANP+ group than in the control group. In the ANP- group, the MIBG uptake of the myocardium was between that of the ANP+ group and that of the control group. Our data show that reduced myocardial MIBG accumulation is associated with autonomic dysfunction in diabetic patients, but it can occur to a lesser extent also in diabetic patients without apparent autonomic neuropathy. The measurement of the myocardial MIBG accumulation is a promising new method to detect cardiac sympathetic nervous dysfunction in diabetic patients.

SPECT and MRI analysis in Alzheimer's disease: relation to apolipoprotein E epsilon 4 allele.

OBJECTIVES--The epsilon 4 allele of apolipoprotein E (ApoE) is a risk factor for late onset Alzheimers disease. ApoE is present in senile plaques, neurofibrillary tangles, and cerebrovascular amyloid, and it is implicated in synaptogenesis. The effect of ApoE polymorphism on the volumes of hippocampus, amygdala, and frontal lobe was studied. The hypothesis was that the patients with Alzheimers disease carrying the epsilon 4 allele have more pronounced atrophy. The relation of ApoE and cerebral blood flow on cortical areas was also assessed. METHODS--Fifty eight patients with Alzheimers disease at the early stage of the disease and 34 control subjects were studied. Patients with Alzheimers disease were divided into subgroups according to the number of the epsilon 4 alleles. Volumes were measured by MRI and regional cerebral blood flow ratios referred to the cerebellum were examined by 99mTc-HMPAO SPECT. ApoE genotypes were determined by digestion of ApoE polymerase chain reaction products with the restriction enzyme Hha1. RESULTS--patients with Alzheimers disease had smaller volumes of hippocampi and amygdala compared with control subjects, and the patients with Alzheimers disease homozygous for the epsilon 4 allele had the most prominent volume loss in the medial temporal lobe structures. The frontal lobe volumes did not differ significantly. All patients with Alzheimers disease had bilateral temporoparietal hypoperfusion and the subgroups with one or no epsilon 4 alleles also had frontal hypoperfusion compared with control subjects. The occipital perfusion ratios tended to decrease with increasing number of epsilon 4 alleles. CONCLUSIONS--Patients with Alzheimers disease homozygous for the epsilon 4 allele seem to have severe damage in the medial temporal lobe structures early in the disease process and differ from the patients with Alzheimers disease with one or no epsilon 4 alleles.

Increase in cerebral blood flow of right prefrontal cortex in man during orgasm

The functional anatomy of human emotional responses has remained poorly understood, mainly because invasive experiments in humans are unacceptable due to ethical reasons. The new functional imaging techniques such as positron emission tomography and single photon emission computed tomography have made it possible to study the neurophysiology of living humans noninvasively. We studied the regional cerebral blood flow with semi-quantitative 99mTc-HMPAO single photon emission computed tomography in eight healthy right-handed heterosexual males during organism. The results showed decrease of cerebral blood flow during orgasm in all other cortical areas except in right prefrontal cortex, where the cerebral blood flow increased significantly (P < 0.005).

Serotonin and dopamine transporter binding in children with autism determined by SPECT

Disturbances in the serotonergic system have been recognized in autism. To investigate the association between serotonin and dopamine transporters and autism, we studied 15 children (14 males, one female; mean age 8y 8mo [SD 3y 10mo]) with autism and 10 non‐autistic comparison children (five males, five females; mean age 9y 10mo [SD 2y 8mo]) using single‐photon emission computed tomography (SPECT) with [123I] nor‐β‐CIT. The children, with autism were studied during light sedation. They showed reduced serotonin transporter (SERT) binding capacity in the medial frontal cortex, midbrain, and temporal lobe areas. However, after correction due to the estimated effect of sedation, the difference remained significant only in the medial frontal cortex area (p=0.002). In the individuals with autism dopamine transporter (DAT) binding did not differ from that of the comparison group. The results indicate that SERT binding capacity is disturbed in autism. The reduction is more evident in adolescence than in earlier childhood. The low SERT binding reported here and the low serotonin synthesis capacity shown elsewhere may indicate maturation of a lesser number of serotonergic nerve terminals in individuals with autism.

Regional cerebral blood flow during exposure to food in obese binge eating women.

Cerebral responses elicited by the sight of food were evaluated in eight obese binge eating, 11 obese and 12 normal-weight non-binge eating women. Regional cerebral blood flow (rCBF) was mapped while the subjects were looking at a picture of a landscape (control) or at a portion of food (food exposure), and was measured by [99mTc]ethyl-cysteine-dimer and single photon emission computed tomography. Exposure to food was associated with different changes in the cerebral blood flow (normalized to mean cerebellar counts) of the right and left hemispheres in the obese binge eating than in the obese or normal-weight non-binge eating women. As compared with the non-binge eating groups, the obese binge eating women had, due to food exposure, a greater increase in the cerebral blood flow in the left than right hemisphere, especially in the frontal and pre-frontal regions. In addition, strong linear correlations were observed in this group between the rCBF of the left frontal and pre-frontal regions and the increase in the feeling of hunger during the exposure to food. Left hemisphere and its frontal and pre-frontal regions could thus play a role in binge eating behavior in humans.

Reduced serotonin transporter binding in binge eating women

Abstract. Rationale: There is evidence that abnormalities in brain dopamine, norepinephrine and serotonin metabolism may play an important role in binge eating. Serotonin-active antidepressant drugs have also been found to decrease binge eating. Objective: We investigated serotonin transporter binding in obese binge-eating women. Eleven obese binge-eating and seven obese control women participated in the study. The subjects were not taking any medication known to affect serotonin (5-HT) transporters. Methods: We used single-photon emission tomography (SPECT) with the radioligand 123I-labelled nor-β-CIT, which specifically labels 5-HT transporters. Results: Obese binge-eating women showed significantly decreased 5-HT transporter binding in the mid-brain compared with obese controls (2.1±0.5 versus 2.9±0.5, respectively). Conclusions: SPECT imaging with a ligand specific for 5-HT transporters can be used to assess altered serotonin transporter binding in the living human brain. The results tentatively suggest that 5-HT transporter binding is decreased in binge-eating women.

Dopamine transporter and D2-receptor density in late-onset alcoholism

Abstract Rationale: Late onset type 1 alcoholism has been suggested to be associated with an underlying dopaminergic defect. Therefore, it is relevant to study both postsynaptic D2-receptor and presynaptic dopamine transporter (DAT) densities among alcoholics. Objective: We investigated DAT densities, along with striatal and extrastriatal dopamine D2-receptor densities, in nine non-violent late-onset male alcoholics, who had no major mental disorder nor antisocial personality disorder (ASPD), and nine healthy controls. Methods: [123I]PE2I and [123I]epidepride were used in SPECT imaging. Results: DAT occupancy ratios (striatum/cerebellum) were significantly lower among alcoholics than in controls. Extrastriatal D2-receptor occupancy ratios (temporal pole/cerebellum) were not significantly different between the groups. Conclusions: Striatal presynaptic DAT densities are decreased among type 1 alcoholics, and this finding is not associated with recent alcohol abuse.

Cerebral Hemodynamics in Human Acute Ischemic Stroke: A Study with Diffusion- and Perfusion-Weighted Magnetic Resonance Imaging and SPECT

Nineteen patients with acute ischemic stroke (<24 hours) underwent diffusion-weighted and perfusion-weighted (PWI) magnetic resonance imaging at the acute stage and 1 week later. Eleven patients also underwent technetium-99m ethyl cysteinate dimer single-photon emission computed tomography (SPECT) at the acute stage. Relative (ischemic vs. contralateral control) cerebral blood flow (relCBF), relative cerebral blood volume, and relative mean transit time were measured in the ischemic core, in the area of infarct growth, and in the eventually viable ischemic tissue on PWI maps. The relCBF was also measured from SPECT. There was a curvilinear relationship between the relCBF measured from PWI and SPECT (r = 0.854; P < 0.001). The tissue proceeding to infarction during the follow-up had significantly lower initial CBF and cerebral blood volume values on PWI maps (P < 0.001) than the eventually viable ischemic tissue had. The best value for discriminating the area of infarct growth from the eventually viable ischemic tissue was 48% for PWI relCBF and 87% for PWI relative cerebral blood volume. Combined diffusion and perfusion-weighted imaging enables one to detect hemodynamically different subregions inside the initial perfusion abnormality. Tissue survival may be different in these subregions and may be predicted.