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J Tiihonen

Publications and source records attributed to J Tiihonen.

At least 37 records · Page 2Linked to original sources
PubMed2001

Dopamine D(2)/D(3)-receptor and transporter densities in nucleus accumbens and amygdala of type 1 and 2 alcoholics.

Alcohol acts through mechanisms involving the brain neurotransmitter dopamine (DA) with the nucleus accumbens as the key zone for mediating these effects. We evaluated the densities of DA D(2)/D(3) receptors and transporters in the nucleus accumbens and amygdala of post-mortem human brains by using [(125)l]epidepride and [(125)I]PE2I as radioligands in whole hemispheric autoradiography of Cloninger type 1 and 2 alcoholics and healthy controls. When compared with controls, the mean binding of [(125)I]epidepride to DA D(2)/D(3) receptors was 20% lower in the nucleus accumbens and 41% lower in the amygdala, and [(125)I]PE2I binding to DA transporters in the nucleus accumbens was 39% lower in type 1 alcoholics. These data indicate that dopaminergic functions in these limbic areas may be impaired among type 1 alcoholics, due to the substantially lower number of receptor sites. Our results suggest that such a reduction may result in the chronic overuse of alcohol as an attempt to stimulate DA function.

Adult↗
PubMed2001

Dopamine transporter density and novelty seeking among alcoholics.

OBJECTIVE: The aim of this study was to investigate a putative association between the personality trait of novelty seeking (NS) and dopaminergic neuronal activity in the human brain. METHOD: We studied the striatal dopamine transporter (DAT) density of 30 (18 early and 12 late-onset) alcoholics and 26 healthy controls with beta-CIT ([123I]-2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane) and SPET (Single Photon Emission Tomography); personality traits were assessed with the Tridimensional Personality Questionnaire (TPQ). RESULTS: DAT density correlated significantly with both NS (r = 0.46, p = 0.011) and age (r = -0.50, p = 0.005) in the alcoholics, generally. NS scores were higher in alcoholics with antisocial personality disorder (p = 0.004) than among other alcoholics. CONCLUSION: Among alcoholics, NS correlated positively with DAT density, which is in line with Cloninger's theory concerning personality and character.

Adult↗
PubMed2001

Dopamine transporter in vitro binding and in vivo imaging in the brain.

Much research interest has lately been focused on the dopamine transporter function in brain. Recent findings indicate that dopamine reuptake is more like a highly regulated than a constitutive determinant of dopamine clearance. Positron emission tomography (PET) and single-photon emission tomography (SPET) offer unique methods to study dopamine transporter function. Results from in vivo PET and SPET studies correspond well with in vitro studies performed on post mortem human brain tissue. Considering some of the variances between in vitro and in vivo receptor binding phenomena it may be that the role of a compound to alter binding to monoamine uptake sites in vitro does not indicate its potential to affect monoamine transporters after administration in vivo. This discrepancy may be better understood taking into account recent studies indicating the possibility of a rapid regulation of transporter function and surface expression. Furthermore, the dopamine transporter is a fruitful target for CNS drug discovery. Fundamental nature of drug actions in vivo may be studied using demonstrated in vitro and in vivo imaging methods.

Brain↗
PubMed2000

In vivo voltammetry with removable carbon fibre electrodes in freely-moving mice: dopamine release during intracranial self-stimulation.

The advantages of in vivo voltammetry at carbon fibre electrodes cannot be fully realised without the registration of neurotransmitter release in freely moving animals. Here we describe an approach to record electrically evoked dopamine release in freely-moving mice. A description of a simple in-house made micromanipulator (0.4 g) and preamplifier (0.6 g) is given. This system was used to record electrochemical signal in the nucleus accumbens four to eight times during 2 weeks following intracranial self-stimulation (ICSS) of the median forebrain bundle. High-speed chronoamperometry was found to be the best choice for recording. The most efficient parameters of electrical stimulation for training and self-stimulation (50 Hz, 0.2 s, 60 microA) were insufficient to induce a measurable voltammetric signal. Increasing the strength of stimulation (0.5 s, 160 microA) significantly decreased the rate of self-stimulation and allowed the registration of separate peaks of dopamine overflow on each stimulation and a tonic increase of electrochemical signal following higher rates of ICSS. Due to exhaustion of the readily releasable dopamine pool, the length of recording the electrochemical signal depended on the rate of self-stimulation. A fixed ratio schedule of ICSS decreased the rate of electrical stimulation and permitted the maintenance of stable peaks of dopamine overflow at a high rate of nose-poking.

Animals↗
PubMed2000

Patterns of dopamine overflow in mouse nucleus accumbens during intracranial self-stimulation.

Dopamine (DA) overflow in the mouse nucleus accumbens during intracranial self-stimulation (ICSS) of the median forebrain bundle was estimated by chronoamperometry with removable carbon fibre electrodes. The specificity of the voltammetric signal was confirmed pharmacologically. The parameters of stimulation (50 Hz, 0.5 s train length) allowed us to obtain measurable DA release and to maintain ICSS. Continuous (CR) and fixed-ratio (FR8) schedule of reinforcement showed differing correspondence of the patterns of DA release with the patterns of stimulation/nose-poking. The CR schedule induced a high rate nose-poking and tonic increase in dopamine overflow, which became decreased following the first periods of self-stimulations. The FR schedule induced stable peaks of DA overflow during the entire period of ICSS. We conclude that the availability of a readily-releasable pool of DA in presynaptic terminals determined the pattern of dopamine overflow in the nucleus accumbens during ICSS in mice.

Animals↗
PubMed2000

Specific binding and laterality of human extrastriatal dopamine D2/D3 receptors in late onset type 1 alcoholic patients.

Late onset type 1 alcoholism has been suggested to be associated with decreased dopaminergic transmission. Our hypothesis was that late onset type 1 alcoholics have also abnormal extrastriatal dopamine D(2)/D(3) receptor distribution. We performed binding, heterogeneity and laterality analysis of extrastriatal and striatal dopamine D(2)/D(3) receptors in nine late onset male alcoholics and in 12 age-matched healthy males. A radioligand, [(123)I]epidepride was used in high resolution single-photon emission tomography (SPET). Specific binding of epidepride in the left temporal pole was significantly (P<0.05) lower in type 1 alcoholics (0.74+/-0.14 ml/ml) than in controls (0.89+/-0.14 ml/ml). In alcoholics, there was no normal left-to-right asymmetry of the temporal cortical heterogeneity of epidepride distribution observed in control males (0.89+/-0.19 vs. 1.10+/-0.19; P<0.05). The results suggest that the specific binding of dopamine D(2)/D(3) receptors in late type 1 alcoholics is decreased and its laterality in the temporal brain is altered from normal.

Adult↗
PubMed2000

Ethanol modulates evoked dopamine release in mouse nucleus accumbens: dependence on social stress and dose.

Ethanol may modulate the activity of presynaptic terminals to increase extracellular dopamine release in the nucleus accumbens though conflicting results have been published. It has been suggested that the stress of social defeat might be a factor influencing the effects of ethanol. We investigated the effects of ethanol on the evoked dopamine overflow in the nucleus accumbens in anaesthetised mice by in vivo voltammetry. Dominant animals, subordinates which had been defeated following eight intruder-resident encounters, and subordinate nondefeated mice were used. The overflow was evoked by electrical stimulation of the median forebrain bundle (100 pulses) at low (20 Hz) and high (50 Hz) frequencies of stimulation. Ethanol at 0.1 and 2 g/kg had no effects on evoked dopamine overflow in aggressive and nondefeated mice. Ethanol increased dopamine release at 0.1 g/kg and decreased release at 2 g/kg following high frequency stimulation in defeated mice. These data suggest that the stress of social defeat may have sensitised the machinery involved in dopamine release to ethanol, a process that may increase the reinforcing properties of this compound.

Aggression↗
PubMed2000

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.

Adult↗
PubMed2000

Lack of association between the functional variant of the catechol-o-methyltransferase (COMT) gene and early-onset alcoholism associated with severe antisocial behavior.

Addictive drugs, including ethanol, increase the brain's dopaminergic transmission, and catechol-o-methyltransferase (COMT) enzyme has a crucial role in dopamine inactivation. A common functional polymorphism in the COMT gene results in a three- to four-fold variation in enzyme activity. In a previous study, we found an association between type 1 (with late-onset but without prominent antisocial behavior) alcoholism and the low activity allele of the COMT gene. In this work we analyzed whether the COMT polymorphism has any effect on the development of type 2 (with early-onset and habitual impulsive violent behavior) alcoholism. The COMT genotype was determined in 62 impulsive violent recidivist offenders with early-onset (type 2) alcoholism, 123 late-onset nonviolent (type 1) alcoholics, and 267 race and gender-matched controls. The allele and genotype frequencies of these groups were compared with each other and also with previously published data from 3,140 Finnish blood donors. The type 2 alcoholics did not differ from either the blood donors or the controls. The low activity (L) allele frequency was higher among type 1 alcoholics (chi(2) = 4.98, P = 0.026) when compared with type 2 cases. The odds ratio for type 1 alcoholism as compared with type 2 alcoholism for those subjects with the LL genotype versus the HH genotype was 3.0 (95% confidence interval 1.1-8.4, P = 0.017). The results suggest that COMT genotype has no major role in the development of early-onset alcoholism with severe antisocial behavior.

Adult↗
PubMed2000

Dopamine-transporter density in nucleus accumbens of type-1 alcoholics.

We have shown that alcoholic patients have a lower number of dopamine transporters in the nucleus accumbens, which mediates the rewarding effects of addictive drugs. Thus, certain dopaminergic agents may be beneficial in the treatment of alcohol withdrawal and in the long-term treatment of alcoholism with selective use.

Alcoholism↗
PubMed2000

Metabolism of [123I]epidepride may affect brain dopamine D2 receptor imaging with single-photon emission tomography.

Iodine-123 labelled epidepride is a novel radiopharmaceutical for the study of cerebral dopamine D2 receptors using single-photon emission tomography (SPET). A lipophilic labelled metabolite of [123I]epidepride which may enter the brain and hamper the quantitation of receptors has been observed in human plasma. In the present study, gradient high-performance liquid chromatography (HPLC) was used to investigate the plasma concentration of the lipophilic labelled metabolite and its correlation to SPET imaging of striatal dopamine D2 receptors. A linear regression fit showed a negative correlation between the amount of the lipophilic labelled metabolite and the striatum to cerebellum ratio (n=16, R=-0.58, P<0.02), suggesting that plasma metabolite analysis is essential when imaging dopamine D2 receptors with SPET using [123I]epidepride.

Adult↗
PubMed2000

A volumetric MRI study of the hippocampus in type 1 and 2 alcoholism.

In recent years, magnetic resonance imaging (MRI) of the hippocampus has been extensively studied on neurological and psychiatric disorders. Particularly in studies on schizophrenia and mood disorders, findings regarding the hippocampal involvement have been most controversial. Previously, minor volume loss of the hippocampus in alcoholism, a major comorbidity alongside psychiatric disorders, has been reported but no data exist on the hippocampal volumes in subtypes of alcoholism. In this study, MRI was used to measure volumes of the hippocampus in late-onset type 1 alcoholics and early-onset type 2 alcoholics. The type 2 alcoholic subjects were also violent offenders with antisocial personality disorder, derived from a forensic psychiatric sample. All were non-psychotic and legally competent. Normal volunteers, representing a wide age range, served as a controls group. Compared to the controls, the right, but not left, hippocampi were significantly smaller in both alcoholic groups. While there was no correlation between the hippocampal volumes with age in the control subjects, there was tendency towards decreased volumes with aging and also with the duration of alcoholism in the type 1 alcoholic subjects. Surprisingly, there was a significant positive correlation between the right hippocampal volume and age in the type 2 alcoholics. This study provides further in vivo evidence that type 1 alcoholism, in general, is associated with a minor loss in hippocampal volume. It is suggested that type 2 alcoholism, in general, similarly displays a minor decrease in hippocampal volume, but this decrease is unevenly distributed within the type 2 category, being weighted towards the younger subjects. These effects suggest differences between the two alcoholic groups, and raise the possibility that the observed effects within the type 2 category are due to other factors than the cumulative acquired effects related to alcohol abuse, such as primary personality psychopathology.

Adult↗
PubMed2000

Quantitative MRI of the hippocampus and amygdala in severe depression.

BACKGROUND: There is little evidence to support possible structural changes in the amygdala and hippocampus of patients with severe depression. METHODS: Quantitative MRI of the amygdala and hippocampus, as well as proton spectroscopy (MRS) of mesial temporal structures were studied in 34 drug-resistant in-patients with major depression and compared with 17 age-matched controls. Volumetric MRI data were normalized for brain size. RESULTS: The volume of the left hippocampus was significantly smaller in the patients compared with the controls. Both groups exhibited similar significant hippocampal asymmetry (left smaller than right). The patients, but not the controls, had significant asymmetry of the amygdalar volumes (right smaller than left). No differences were observed between the patients and controls in the T2 relaxation times for the hippocampus and amygdala. Mesial temporal lobe MRS revealed a significantly elevated choline/creatine ratio in the patients compared with the controls. CONCLUSIONS: This quantitative MRI study provides support for a possible association between structural and biochemical substrates and severe drug-resistant major depression.

Adult↗
PubMed2000

Suicidal behavior in patients with schizophrenia is related to COMT polymorphism.

A common functional polymorphism that results in a three- to four-fold difference in catechol-O-methyltransferase (COMT) enzyme activity has been related to psychiatric disorders such as ultra-ultra rapid cycling bipolar disorder, drug abuse and alcoholism (Lachman et al., 1996a; Karayiorgou et al., 1997; Vandenbergh et al., 1997; Papolos et al., 1998; Tiihonen et al., 1999). Several studies have also reported associations between the allele encoding the low enzyme activity COMT variant (L allele) and other-directed aggression (Strous et al., 1997; Lachman et al., 1998; Kotler et al., 1999) in schizophrenic and schizoaffective patients. The current study investigated whether the COMT L allele is also associated with suicide attempts in schizophrenic and schizoaffective patients. COMT genotypes were determined and history of suicide attempts was retrospectively investigated in a Finnish sample (n = 94) and a US sample (n = 54). Significant associations were observed between COMT genotype and suicide; specifically, history of violent suicide attempts. The COMT L allele was more frequent in subjects who had attempted suicide by violent means. These associations were significant in males but not females. These findings support a common neurobiological substrate for self- and other-directed aggression, and suggest that catecholaminergic alterations may contribute to these behaviors in schizophrenic and schizoaffective patients.

Adult↗
PubMed2000

Association between the functional polymorphism of catechol-O-methyltransferase gene and alcohol consumption among social drinkers.

BACKGROUND: A common functional genetic polymorphism in the catechol-O-methyltransferase (COMT) gene (Val158 Met) results in 3- to 4-fold differences in COMT enzyme activity and dopamine inactivation rate. Previous studies have shown that type I alcoholism is more common among subjects with low activity COMT genotype (LL), compared with high activity (HH) or heterozygotic (LH) genotypes. METHODS: We studied alcohol consumption and the COMT genotype in middle-aged Finnish men (n 896), who represented an unselected ethnically homogenous population sample and reported using alcohol during the past year. Average alcohol use in pure ethanol (grams per week) was compared between subjects with LL genotype and subjects with LH or HH genotypes. RESULTS: Men with LL genotype (30% of all subjects) reported 27% higher weekly alcohol consumption compared with the two other genotype groups (p < 0.05). The difference remained statistically significant after a multivariate adjustment for sociodemographic factors and prior or existing diseases (p = 0.031). CONCLUSIONS: The results indicate that COMT polymorphism may contribute significantly to alcohol intake not only in alcoholics but also in a general male population.

Adult↗
PubMed2000

Aging and homicide rates.

There are no published studies concerning the effect of mortality rate on the rate of homicide by habitually violent offenders. On the basis of nation-wide statistics in Finland, the frequency of homicide is 61% lower among 50-year old males than among 30-year old males. However, when the 4.9-fold mortality of habitually violent offenders is taken into account, the homicide rate is only 43% lower among 50-year old males than among 30-year old males. This is an important issue in forensic psychiatry and that requires further attention, as age is used a predictive factor when assessing the risk of violent behavior.

Adult↗