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Biomedical subjects

J Tiihonen

Publications and source records attributed to J Tiihonen.

At least 73 records · Page 4Linked to original sources
PubMed1998

Iodine-123 labeled nor-beta-CIT as a potential tracer for serotonin transporter imaging in the human brain with single-photon emission tomography.

Iodine-123 labelled 2beta-carbomethoxy-3beta-(4-iodophenyl) (nor-beta-CIT) is an analogue of beta-CIT, which has high affinity to the serotonin transporter. Initial single-photon emission tomography (SPET) studies with [123I]nor-beta-CIT were performed in five healthy volunteers. In addition, its metabolism in plasma was investigated with gradient high performance liquid chromatography. [123I]nor-beta-CIT was prepared by a method which gave a specific radioactivity of more than 180 GBq/micromol. Unchanged [123I]nor-beta-CIT in plasma accounted for 43% and 19% of total radioactivity after 30 and 180 min, respectively. The dynamic SPET studies demonstrated a high and rapid uptake of radioactivity in the brain (6%/ID at 30 min). Highest accumulation was observed in the striatum, the mid-brain and the thalamus. The specific binding in the mid-brain was 33% higher compared with that of [123I]beta-CIT. The high radioactivity in the mid-brain is assumed to represent the accumulation of [123I]nor-beta-CIT in the serotonin transporter-rich regions, which indicates that [123I]nor-beta-CIT might be a potential tracer for visualization of serotonin transporter sites in the human brain with SPET.

Adult↗
PubMed1998

Pharmacokinetics and dosimetry of iodine-123 labelled PE2I in humans, a radioligand for dopamine transporter imaging.

The iodine-123 labelled selective ligand N-(3-iodoprop-2E-enyl)-2-beta-carbomethoxy-3beta-(4-methylphenyl) nortropane ([123I]PE2I) was evaluated as a probe for in vivo dopamine transporter imaging in the human brain. Six healthy subjects were imaged with a high-resolution single-photon emission tomography scanner. Striatal radioactivity peaked at 1 h after injection. The background radioactivity was low. The volume of distribution in the striatum was 94+/-24 ml/ml. The results were compared with those of [123I]beta-CIT imaging. There was no significant uptake of [123I]PE2I in serotonin-rich regions such as the midbrain, hypothalamus and anterior gingulus, suggesting that in vivo binding is specific for the dopamine transporter. One main polar metabolite of [123I]PE2I was found in plasma, and the parent plasma concentration decayed rapidly. Radiation exposure to the study subject is 0.022+/-0.004 mSv/MBq (effective dose). The preliminary results suggest that [123I]PE2I is a selective SPET ligand for imaging striatal dopamine transporter density.

Adult↗
PubMed1998

The incidence and onset-age of hospitalized bipolar affective disorder in Finland.

BACKGROUND: Some studies have indicated that there are wide variations on incidence and prevalence of bipolar disorder in specific populations. METHODS: The occurrence of bipolar affective disorder and the age at onset was studied in both genders among the hospitalized Finnish population. RESULTS: The annual rate of all hospitalized patients with bipolar disorder was 0.03%. Of these, 2% were under 20 years, 14% under 30 years, 61% under 50 years and 81% under 60 years of age. The 1-year incidence was highest in the age group 50-59 years in males and 40-49 years in females. CONCLUSIONS: The low prevalence and incidence of bipolar disorder in Finland may be due to late onset-age. LIMITATION: The study is based on hospital-treated bipolar disorder patients. CLINICAL RELEVANCE: We have presented previously unreported differences between the age of onset of bipolar disorder in Finland compared with other countries.

Adolescent↗
PubMed1998

Secular trends in the rates and seasonality of violent and nonviolent suicide occurrences in Finland during 1980-95.

BACKGROUND: Because secular trends in seasonality of different types of suicides has not been studied before, we utilized a novel statistical method to evaluate this phenomenon by using national Finnish suicide statistics during 1980-95. METHODS: Rates were analyzed with ordinary linear regression analysis. Secular trends were evaluated using ratio-statistic and its 95% confidence intervals. RESULTS: The rate of violent suicides increased before year 1990 and decreased since that. The nonviolent suicide rate increased continuously. The decreasing tendency of seasonality in nonviolent suicides and a slight decrease in violent suicides are seen within the three successive time periods studied. CONCLUSIONS: Trends in rates and in seasonality of suicides might be related to changes in the health politics in Finland. LIMITATIONS: The short time-series and lack of studying associations of suicides with socioeconomic, environmental or biological factors are limitations of our study. CLINICAL RELEVANCE: Studying the time-dependent changes in rates and in seasonality of suicides provide a novel perspective for the evaluation of the aetiology of suicidal behaviour.

Finland↗
PubMed1998

Increasing homicide rate in Finland accompanied by decreasing seasonality over the period 1957-95.

Homicide is recognized as a global public health problem. Finland has the highest overall homicide rate of the Nordic countries in comparisons over short time periods. Using the 39-year time series of homicide incidents in Finland from 1957-95, we analyzed the trend in homicide rate. In addition, we explored for the first time over the time trend in the seasonal variation of homicide and compared seasonal statistics over eight successive time periods. The present study revealed that there has been steadily increasing trend in homicides in Finland since 1950s. At the same time, the seasonality of homicide has decreased markedly. The peaks in homicide rates occurred commonly during summer and the troughs during winter.

Finland↗
PubMed1998

Striatal presynaptic dopamine function in type 1 alcoholics measured with positron emission tomography.

Recent in vivo studies have shown low dopamine D2 receptor and dopamine transporter densities among late onset (type 1) alcoholics. We have now studied 6-[18F]-FDOPA (FDOPA) uptake in 10 type 1 alcoholics and eight matched controls to test the hypothesis that striatal presynaptic dopamine function is lower among alcoholics. Markedly low FDOPA uptake (Ki) was observed in the left caudate of two alcoholic patients, but the mean striatal uptake values of the patient group were higher than those of the control group. The greatest difference was observed in the mean FDOPA intake in the left putamen, which was 28% higher in the patient group (t = 3.00, P = 0.008, d.f. = 16, independent samples t-test), and in the right caudate (difference 36%, t = 2.87, P = 0.01). The elevated FDOPA uptake in putamen and caudate correlated with poor Wisconsin Card Sorting Test (WCST) performance (error %) among alcoholics (correlation coefficients from 0.49 to 0.56), which suggests that the magnitude of presynaptic dopamine function alteration correlates with the degree of disability to modify one's behavior. The results do not give support to the hypothesis of generally decreased striatal dopamine turnover in type 1 alcoholism, but on the contrary indicate an increased presynaptic dopamine function. This may represent a compensatory mechanism to low postsynaptic DA function. The low presynaptic DA function observed in the left caudate of two patients suggests that type 1 alcoholism may be a heterogeneous disorder.

Adult↗
PubMed1998

Imaging the structure of the striatum: a fractal approach to SPECT image interpretation.

The spatial pattern of striatal dopamine transporter density in the living human brain was tested by duplicate SPECT scans with [123I]PE2I, [123I]beta-CIT or [123I]beta-CIT-FP and striatal phantom measurements. The resolution-dependent spatial variation was calculated by the fractal analysis of SPECT images. This variation, which depends on the size of the region of interest, was described by the spatial dispersion i.e. the standard deviation of the count densities divided by the mean density. In each sub-region, the observed and methodological dispersions were computed, and the resulting spatial dispersion was calculated. The methodological dispersion is caused by the imaging resolution, flood field non-uniformity, count density, scatter, reconstruction errors and partial volume effects, whereas the spatial dispersion is based on the cerebral heterogeneity of the dopamine transporter density. Recognition of the normal variation in heterogeneity is important in evaluation of the striatal dopamine transporter density between controls and patients suffering from various neuropsychiatric disorders.

Adult↗
PubMed1998

Schizophrenia, alcohol abuse, and violent behavior: a 26-year followup study of an unselected birth cohort.

It has been suggested that schizophrenia and alcoholism are associated with violent behavior. But so far there are no published studies from unselected cohorts quantifying the actual risk associated with schizophrenia both with and without comorbid alcoholism. In this study, an unselected birth cohort (n = 11,017) was prospectively followed to the age of 26, and data on psychiatric disorders and crimes were collected from national registers. The odds ratios for violent offenses and recidivism were calculated for each diagnostic group. Men who abused alcohol and were diagnosed with schizophrenia were 25.2 (95% confidence interval (CI) 6.1-97.5) times more likely to commit violent crimes than mentally healthy men. The risk for nonalcoholic patients with schizophrenia was 3.6 (95% CI 0.9-12.3) and for other psychoses, 7.7 (95% CI 2.2-23.9). None of the patients with schizophrenia who did not abuse alcohol were recidivists (> 2 offenses), but the risk for committing more crimes among alcoholic subjects with schizophrenia was 9.5-fold (95% CI 2.7-30.0). This study suggests that to prevent the crimes being committed by people with schizophrenia, it is important that clinicians watch for comorbid alcohol abuse.

Adolescent↗
PubMed1998

Juvenile mortality, mental disturbances and criminality: a prospective study of the Northern Finland 1966 birth cohort.

Mortality, criminality and mental illness among young adults were studied in an unselected birth cohort of 12 058 children born live in Northern Finland during 1966. The cohort members were followed up to the age of 27 years. The total number of all deaths was 117, and 79.5% of these deaths were from unnatural causes. The mortality of males was more than threefold higher than that of females. There was a significantly higher mortality risk in men with schizophrenia (OR, 9.31; 95% CI, 3.14-25.53), other psychoses (OR, 10.28; 95% CI, 2.40-37.02), personality disorders (OR, 4.28; 95% CI, 1.04-14.67) and combined personality disorders and criminality (OR, 3.27, 95% CI, 0.99-9.59). In the group of major mental disorders, 75% of deaths were suicides.

Accidents↗
PubMed1998

Seasonal variation in suicide occurrence in Finland.

The aim of this study was to investigate the age-, gender- and suicide method-related seasonality of suicide occurrence by using the largest database examined so far (n=21,279). The Chi-square test for multinomials was used as the overall measure of deviation. The monthly observed and expected numbers of suicides were calculated and classified by year, month, gender, age groups and suicide methods. To identify the statistically significant peak and trough months, the ratio of observed numbers of suicides to expected numbers with 95% confidence intervals was calculated. For males, there was a suicide peak from April to July, while for females the distribution was bimodal (with peaks in May and October). In elderly people there was a significant excess in the number of suicides in autumn, and the troughs were deeper in winter. For violent suicides there was a unimodal spring peak, but for non-violent suicides the distribution was bimodal. The results indicate that suicides among elderly subjects, as well as non-violent suicides, occur significantly more often during autumn than would be expected.

Adult↗
PubMed1998

Fractal analysis--a new approach in brain receptor imaging.

Improvements in detector technology and the development of radioligands for brain receptor imaging have introduced exiting new insights into the pathophysiology of various neuropsychiatric disorders and have improved the possibilities of optimizing the treatment for patients suffering from them. Positron emission tomography (PET) and single-photon emission tomography (SPET) with tailored radiopharmaceuticals provide information on the topographic physiological chemistry of the living human brain. The different patterns of brain receptor densities and distribution can be imaged and modelled with PET and SPET. The normal receptor distribution in the brain is broadly heterogeneous with different cortical layers, which show receptor densities varying from very low to high. Further exploration of the data shows that human neurophysiology and neural architectures possess fractal properties that may be altered during activation and in different neuropsychiatric disorders. This review highlights recent findings in SPET receptor imaging and the use of fractal analysis in the interpretation of images representing various neuropsychiatric disorders.

Brain↗
PubMed1997

Fractal analysis of striatal dopamine re-uptake sites.

Spatial variation in regional blood flow, metabolism and receptor density within the brain and in other organs is measurable even with a low spatial resolution technique such as emission tomography. It has been previously shown that the observed variance increases with increasing number of subregions in the organ/tissue studied. This resolution-dependent variance can be described by fractal analysis. We studied striatal dopamine re-uptake sites in 39 healthy volunteers with high-resolution single-photon emission tomography using iodine-123 labelled 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([123I]beta-CIT). The mean fractal dimension was 1.15+/-0.07. The results indicate that regional striatal dopamine re-uptake sites involve considerable spatial heterogeneity which is higher than the uniform density (dimension=1.00) but much lower than complete randomness (dimension=1.50). There was a gender difference, with females having a higher heterogeneity in both the left and the right striatum. In addition, we found striatal asymmetry (left-to-right heterogeneity ratio of 1.19+/-0.15; P<0.001), suggesting functional hemispheric lateralization consistent with the control of motor behaviour and integrative functions.

Adult↗
PubMed1997

Striatal and extrastriatal imaging of dopamine D2 receptors in the living human brain with [123I]epidepride single-photon emission tomography.

The iodine-123 labelled ligand benzamide epidepride was evaluated as a probe for in vivo imaging of striatal and extrastriatal dopamine D2 receptor sites in the human brain. Four healthy males were imaged with a high-resolution single-photon emission tomography scanner. Striatal radioactivity peaked at 3 h after injection. The specific binding in the striatum was 0.91+/-0.03 at 3 h and this ratio steadily increased with time. Extrastriatal radioactivity was highest in the thalamus, in the midbrain and in the temporal cortex, and peaked at 45-60 min after injection of tracer. A smaller amount of radioactivity was found in the parietal, frontal and occipital cortices. Two radioactive metabolites were observed, of which one was more lipophilic than the parent compound. The radiation burden to the patient was 0.035 mSv/MBq (effective dose equivalent). The preliminary results showed that [123I]epidepride can be used for imaging striatal and extrastriatal dopamine D2 receptor sites in the living human brain.

Adult↗
PubMed1997

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

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 2beta-carbomethoxy-3beta(4-iodophenyl)tropane ([123I]beta-CIT) as the tracer. The blind quantitative analysis revealed that the 5-HT specific binding of [123I]beta-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.

Adult↗
PubMed1997

Seasonal variation in the occurrence of homicide in Finland.

OBJECTIVE: Although seasonal variation in impulsive aggression related to circannual rhythms of central serotonin neurotransmission is a topic of current interest, there is little firm knowledge on seasonality in the occurrence of homicide. Longitudinal studies on the seasonal rhythms of platelet imipramine binding and L-tryptophan levels have placed the circannual peaks around January and February and the nadirs around May and August. The aim of this study was to test the hypothesis that the number of homicides is the lowest during winter and the highest during spring and summer. A secondary hypothesis was that the seasonal variations in homicides and violent suicides are correlated. METHOD: The largest database on the monthly occurrence of homicide thus far (N = 4,553) was used in this study, in which the monthly occurrence of all murders and manslaughters in Finland during the years 1957-1995 was analyzed. RESULTS: During winter the homicide rate was 6% below the expected rate. Correspondingly, during summer there was a 6% elevation above the expected homicide rate, but no significant peak was observed in spring. There was a significant association between the monthly occurrence of homicides and violent suicides but not between homicides and nonviolent suicides. CONCLUSIONS: The results suggest that a seasonal variation in the occurrence of homicide exists. On the basis of current literature, it could be hypothesized that this seasonal variation and the correlation between the monthly occurrence of homicides and violent suicides are associated with the observed circannual rhythms of serotonin transmission.

Biomarkers↗
PubMed1997

Dopamine reuptake site densities in patients with social phobia.

OBJECTIVE: It has been suggested that social phobia is associated with dysfunction of the noradrenergic and dopaminergic systems, but there are no published anatomic data on the monoaminergic abnormalities found in the brains of phobic patients. The authors studied the density of dopamine reuptake sites in patients with social phobia. METHOD: The study included 11 patients with social phobia and 28 healthy comparison subjects, 11 of whom were age- and gender-matched to the patients for the analyses. Measurement of the density of dopamine reuptake sites was performed by using a 123I-labeled cocaine analogue, [123I]beta-CIT, with single photon emission computed tomography (SPECT). RESULTS: Blind quantitative analysis revealed that striatal dopamine reuptake site densities were markedly lower in the patients with social phobia than in the age- and gender-matched comparison subjects. CONCLUSIONS: The results indicate that social phobia may be associated with a dysfunction of the striatal dopaminergic system.

Adult↗