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Biomedical subjects

J Tiihonen

Publications and source records attributed to J Tiihonen.

At least 55 records · Page 3Linked to original sources
PubMed1999

Dopamine transporter availability and depressive symptoms during alcohol withdrawal.

Alcohol-related temporary depressive symptoms are hypothesized to be related to dopaminergic dysfunction. The aim of this study was to investigate whether or not depressive symptoms correlate with reduced dopamine transporter (DAT) availability. We studied the DAT availability in 28 alcoholic subjects with beta-CIT ([123-iodium]-2-betacarbomethoxy-3-beta-(4-iodophenyl)-tropa ne) single photon emission tomography (SPET) and found a reduction in DAT availability during withdrawal that subsequently showed a significant increase during sobriety. The relationship between DAT availability and Montgomery-Asberg Depression Rating scale scores, both during withdrawal and after sobriety, was assessed. The main finding was a statistically significant correlation between DAT variances and depressive symptom scores during both states. The findings indicate a possible dopaminergic etiology for depressive symptoms in alcohol withdrawal, which suggests that dopaminergic antidepressants might be beneficial in the treatment of alcohol withdrawal.

Adult↗
PubMed1999

Mortality among habitually violent offenders.

There are no published studies about mortality among habitually violent offenders, although it would be essential to take into account the possibly higher mortality rate of this population, when the incidence of committing violent offenders is calculated as a function of age. We studied mortality during the age range 30-50 years among 102 habitually violent male offenders, who were considered to be dangerous to the lives of other people, during the 24.5-year period 1971-1995 (in the range 3.5 months-24.5 years, the average prison time was 6 years, 7 months and 11 days). In Finland, the death rate in the group of men aged 30-50 years is 3.7/1000/year, but among these habitually violent male criminals, the mortality rate was observed to be 18.1/1000/year. Therefore, the relative risk for dying in this age group was 4.9-fold when compared with the normal male population aged 30-50 years. A finding of this magnitude has a substantial effect, when the real incidence of committing homicides or other violent offenses is calculated as a function of age. This is an important issue in forensic psychiatry, since it is generally believed that the incidence of committing violent crimes is decreased between the ages of 30 and 50 years, and age is used as one predictive factor when the risk of forthcoming violent behavior is assessed.

Adult↗
PubMed1999

Striatal dopamine transporter density in major depression.

RATIONALE: There are no previous data available regarding [123I]beta-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 beta-CIT (2beta-carbomethoxy-3beta-(4-iodophenyl-tropane). RESULTS: We found a significantly higher [123I]beta-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.

Analysis of Variance↗
PubMed1999

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

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 nonviolent 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.

Adult↗
PubMed1999

Iodine-123 labelled PE2I for dopamine transporter imaging: influence of age in healthy subjects.

The iodine-123 labelled selective ligand N-(3-iodoprop-2E-enyl)-2beta-carbomethoxy-3beta-(4-methylphe nyl)nortr opane ([(123)I]PE2I) has been developed and has been shown to be suitable for single-photon emission tomography imaging of the dopamine transporter. In this study the influence of age on ligand binding was investigated in 16 healthy males with an age range of 23- 75 years. Single-photon emission tomography (SPET) imaging was performed with a triple-headed gamma camera. A simplified reference region model, in which the input function was derived from the non-displaceable cerebellar compartment, was used to calculate the volume of distribution in the striatum. The volume of distribution was shown to decline with age (-0.4%/year; P<0.005). The results were in agreement with in vivo and in vitro findings of a decline in dopamine transporter binding with age. The findings confirm the suitability of [(123)I]PE2I for SPET imaging in clinical routine but emphasize the necessity of using age-matched controls in patient studies.

Adult↗
PubMed1999

Outcome of different types of long-term antidepressant treatments: a 3-year follow-up study of 14182 patients.

BACKGROUND: Antidepressant efficacy studies are rare in large populations for prolonged periods. METHODS: The efficacy of antidepressants was investigated by using disability pensions due to major affective disorders as the efficacy variable from a large Finnish population (n = 14182) during a 3-year follow-up. RESULTS: Of all males, 345 (6.0%) were receiving disability pension due to major affective disorder, and of all females, 498 (5.9%). A logistic regression analysis showed a significantly higher risk (age-adjusted ORs, 1.42-4.09) for disability pension in every antidepressant group except the amitriptyline group when compared with fluoxetine group. Those who used a combination of antidepressive agents (age-adjusted OR 4.09) or moclobemide (age-adjusted OR 2.18) had the highest risks. CONCLUSIONS: In the study population fluoxetine and amitriptyline were the most efficient antidepressants in the long-term treatment of depression.

Adult↗
PubMed1999

Association between the functional variant of the catechol-O-methyltransferase (COMT) gene and type 1 alcoholism.

Catechol-O-methyltransferase (COMT) is an enzyme which has a crucial role in the metabolism of dopamine. It has been suggested that a common functional genetic polymorphism in the COMT gene, which results in 3 to 4-fold difference in COMT enzyme activity, may contribute to the etiology of mental disorders such as bipolar disorder and alcoholism. Since ethanol-induced euphoria is associated with the rapid release of dopamine in limbic areas, it is conceivable that subjects who inherit the allele encoding the low activity COMT variant would have a relatively low dopamine inactivation rate, and therefore would be more vulnerable to the development of ethanol dependence. The aim of this study was to test this hypothesis among type 1 (late-onset) alcoholics. The COMT polymorphism was determined in two independent male late onset (type 1) alcoholic populations in Turku (n = 67) and Kuopio (n = 56). The high (H) and low (L) activity COMT genotype and allele frequencies were compared with previously published data from 3140 Finnish blood donors (general population) and 267 race- and gender-matched controls. The frequency of low activity allele (L) was markedly higher among the patients both in Turku (P = 0.023) and in Kuopio (P = 0.005) when compared with the general population. When all patients were compared with the general population (blood donors), the difference was even more significant (P = 0.0004). When genotypes of all alcoholics (n = 123) were compared with genotypes of matched controls, the odds ratio (OR) for alcoholism for those subjects having the LL genotype vs those with HH genotype was 2.51, 95% CI 1.22-5.19, P = 0.006. Also, L allele frequency was significantly higher among alcoholics when compared with controls (P = 0.009). The estimate for population etiological (attributable) fraction for the LL genotype in alcoholism was 13.3% (95% CI 2.3-25.7%). The results indicate that the COMT polymorphism contributes significantly to the development of late-onset alcoholism.

Adult↗
PubMed1999

Association between low activity serotonin transporter promoter genotype and early onset alcoholism with habitual impulsive violent behavior.

A common 44-base pair insertion/deletion polymorphism in the promoter region of the human serotonin transporter (5-HTT) gene has been observed to be associated with affective illness and anxiety-related traits. This biallelic functional polymorphism, designated long (L) and short (S), affects 5-HTT gene expression since the S promoter is less active than the L promoter. Since there is strong evidence of a disturbance in brain serotonergic transmission among antisocial, impulsive, and violent type 2 alcoholic subjects, we decided to test the hypothesis that the frequency of the S allele, which is associated with reduced 5-HTT gene expression, is higher among habitually violent type 2 alcoholics when compared with race and gender-matched healthy controls and non-violent late-onset (type 1) alcoholics. The 5-HTT promoter genotype was determined by a PCR-based method in 114 late onset (type 1) non-violent alcoholics, 51 impulsive violent recidivistic offenders with early onset alcoholism (type 2), and 54 healthy controls. All index subjects and controls were white Caucasian males of Finnish origin. The S allele frequency was higher among type 2 alcoholics compared with type 1 alcoholics (chi2 = 4.86, P = 0.028) and healthy controls (chi2 = 8.24, P = 0.004). The odds ratio for SS genotype vs LL genotype was 3.90, 95% Cl 1.37-11.11, P = 0.011 when type 2 alcoholics were compared with healthy controls. The results suggest that the 5-HTT 'S' promoter polymorphism is associated with an increased risk for early onset alcoholism associated with antisocial personality disorder and impulsive, habitually violent behavior.

Adult↗
PubMed1999

Altered parallel auditory processing in schizophrenia patients.

Patients with schizophrenia have impaired auditory processing that has been demonstrated by diminished P50 response to paired auditory stimuli in event-related potential (ERP) studies. Cerebral processing can also be studied with magnetoencephalography (MEG). With a whole-head MEG, which enables one to simultaneously measure brain activity in both hemispheres, we investigated whether early parallel auditory processing is impaired in schizophrenia. Sequences of tones were monaurally presented to schizophrenia patients and healthy controls in a passive condition, and the event-related magnetic fields were recorded simultaneously over both auditory cortices. The interhemispheric latency difference of the P50m, but not that of the N100m, was significantly shorter in the patient group in the right-ear but not in the left-ear stimulus condition. Further, the ipsilateral P50m was significantly earlier in schizophrenia patients in the right-ear condition. This result suggests that schizophrenia affects the consecutive preconscious auditory processing in a different manner.

Adult↗
PubMed1999

Mitchell B. Balter Award--1998. Pindolol and major affective disorders: a three-year follow-up study of 30,485 patients.

The role of serotonin autoreceptor antagonism in major depression has been a matter of intense debate in recent years. On the basis of animal experiments, it has been suggested that the blockade of this autoreceptor with pindolol during concomitant treatment with selective serotonin reuptake inhibitors (SSRIs) would result in a rapid and augmented antidepressant effect, but it has also been argued that the possible augmenting effect of pindolol is due to the beta-blocking properties of this drug. Results from the first human studies have also been controversial. We used a national computer-based central register to study the cumulative incidence of the use of beta-adrenergic receptor antagonists and antidepressant drugs, as well as the point prevalence of disability pensions as a result of major affective disorders (296, DSM-III-R; F30-F34, ICD-10) at the end of a 3-year follow-up period. Our results from a very large database (total N = 30,485) indicate that the use of pindolol is associated with a marked reduction (from 29% to 52%) in the prevalence of disability pensions resulting from major affective disorders when compared with the use of other beta-adrenergic receptor antagonists. The use of pindolol was associated with a slightly lower rate of antidepressant use when compared with other beta-adrenergic receptor antagonists and especially when compared with propranolol. The results suggest that long-term therapy with pindolol treatment augments the pharmacologic effect of antidepressant drugs (especially SSRIs) among patients with major affective disorders. The finding that patients receiving pindolol have a lower prevalence of disability pensions resulting from major affective disorders indicates that the prevalence of severe treatment-resistant major affective disorders could be decreased markedly by using pindolol as the first-choice beta-adrenergic receptor antagonist in the treatment of cardiovascular diseases whenever possible among those patients who have experienced at least one depressive episode and are receiving antidepressant treatment.

Adrenergic beta-Antagonists↗
PubMed1999

Serum testosterone levels, mental disorders and criminal behaviour.

OBJECTIVE: Although previous studies have revealed an association between androgens and aggression, there is a lack of knowledge of this issue in different mental disorders. METHOD: The associations between serum testosterone levels and criminal behaviour in different mental disorders were examined using data collected from forensic psychiatric male patients (20 schizophrenics and 42 subjects with personality disorders). RESULTS: Male criminals with personality disorders had significantly higher serum levels of total and free testosterone than criminal schizophrenics. Among schizophrenics, total (P=0.01) and free testosterone (P=0.01) declined significantly more with age compared to healthy controls and patients with personality disorders, and also correlated with duration of neuroleptic drug use (r=-0.60, P=0.000 for total and r=-0.46, P=0.0001 for free testosterone). The recidivists with personality disorder had higher total (P=0.04) and free testosterone (P=0.05) levels than non-recidivists with personality disorder. CONCLUSION: Personality disordered criminals with multiple offences had high serum testosterone levels. The low testosterone concentrations among schizophrenics may be due either to long-term use of neuroleptic agents or to the mental illness itself and its possible inhibition of the pituitary-gonadal axis.

Adult↗
PubMed1999

Maternal smoking during pregnancy and risk of criminal behavior among adult male offspring in the Northern Finland 1966 Birth Cohort.

OBJECTIVE: The goal of this study was to test the hypothesis that maternal smoking during pregnancy is associated with greater risk for criminal behavior of the offspring in adulthood. METHOD: An unselected, general population cohort composed of 11,017 subjects (5,636 men, 5,381 women) was followed up prospectively from the sixth month of pregnancy to age 28 years. Interviews with the mother during the pregnancy, health records, and an assessment of the offspring at age 1 year provided information on risk factors. The Ministry of Justice provided information on criminal offenses for all subjects. RESULTS: Because of the low rate of criminal offenses among women, the present analyses are restricted to men (N = 5,636). Compared to the sons of mothers who did not smoke, the sons of mothers who smoked during pregnancy had more than a twofold risk of having committed a violent crime or having repeatedly committed crimes, even when other biopsychosocial risk factors were controlled. While maternal smoking during pregnancy alone explained 4% of the variance associated with violent offenses among male offspring, it was not significantly associated with nonviolent offenses among male offspring. When maternal smoking during pregnancy was combined with a maternal age of less than 20 years, a single-parent family, an unwanted pregnancy, and a developmental lag in walking or talking, the odds ratios for violent offenses increased up to ninefold and for persistent offenses up to 14-fold. CONCLUSIONS: Maternal smoking during pregnancy is associated with violent offenses and persistent offenses, but not with nonviolent offenses, among male offspring in adulthood.

Adult↗
PubMed1998

Abnormal structure of human striatal dopamine re-uptake sites in habitually violent alcoholic offenders: a fractal analysis.

Both animal and human studies imply that aggressive behaviour is associated with increased dopaminergic transmission. Our hypothesis was that impulsive violent offenders have also higher heterogeneity of the striatal dopamine transporter (DAT) density than controls. We performed a fractal analysis in 21 impulsive violent offenders, 10 non-violent alcoholics and 21 controls to measure the heterogeneity and laterality of the striatal DAT density characterised by [123I]beta-CIT single-photon emission tomography (SPET). The [123I]beta-CIT distribution was significantly more heterogeneous in the right striatum of violent offenders than in healthy controls. In addition, in young violent offenders there was no normal left-to-right asymmetry observed in control subjects of the same age. The normalisation of the left-to-right asymmetry may reflect late neurobiological maturation.

Aggression↗
PubMed1998

Reversal of cerebral asymmetry in schizophrenia measured with magnetoencephalography.

It has been suggested that schizophrenic patients fail to develop left-hemisphere dominance because of an early disturbance in neuronal development. This hypothesis has been supported by some post-mortem. CT and magnetic resonance imaging (MRI) studies, while other in-vivo studies have given contradicting results. We used 122-channel whole-head magnetoencephalography and MRI to locate the sources of auditory evoked responses in 19 schizophrenic patients and in 20 healthy controls. Auditory evoked responses were detected in all subjects. The left-right hemisphere asymmetry of cerebral sources for auditory evoked responses was markedly dispersed among patients when compared with controls. The source locations for left auditory cortex were clearly anterior with respect to the right hemisphere in 32% of the patients, while the corresponding prevalence of this abnormal asymmetry was 0% in controls (p = 0.008. Fisher's exact test). The reversed asymmetry appeared to be associated with a shorter anterior-posterior distance between the auditory cortex and the anterior tip of the temporal lobe in the left side when compared with the right side. The reversed asymmetry was associated with higher PANSS general psychopathological score, and especially with higher guilt feelings and motor retardation scores. The large 2.5-fold standard deviation in the inter-hemispheric anterior posterior difference in the location of the auditory cortex among patients (p 0.001 for the difference in the magnitude of variance between controls and patients) clearly reflects the dispersion of the left right asymmetry into both direction, and three of the patients with 'normal asymmetry' had a greater left-right asymmetry than any of the controls. Markedly greater reversal of hemispheric asymmetry among patients implies that regulation of the development of brain asymmetry is disturbed among schizophrenic patients. Abnormality in the cerebral asymmetry may be a crucial factor in the development of schizophrenic disorder in a substantial proportion of patients. The results suggest that the reversed asymmetry is associated with the higher severity of general psychopathological symptoms.

Adult↗
PubMed1998

Fentanyl decreases beta-CIT binding to the dopamine transporter.

Evidence from animal studies suggest that centrally acting opiates increase synaptic dopamine (DA) concentration. However, the interaction between mu-opioid receptors and the DA system is unclear. We report here an effect of fentanyl on striatal [123I]beta-CIT binding to the DA transporter in a patient and in rats. A female patient underwent [123I]beta-CIT single-photon emission tomography (SPET) study after intrathecal injection of fentanyl for her back pain. After a 2-week drug-free period, the SPET study was repeated. In the experimental study, male Wistar rats were treated with fentanyl either acutely (50 micrograms/kg, i.p.) before imaging study or subacutely for 4 days (10 micrograms/kg, twice a day, i.p.). Brain planar imaging was performed at 3.5 hours after an intravenous injection of [123I]beta-CIT with gamma camera with a pinhole collimator. In a female patient, [123I]beta-CIT binding in the basal ganglia was decreased by 37% during fentanyl as compared to the binding after 2-week drug-free period. Similarly in rats, acute fentanyl treatment decreased [123I]beta-CIT binding to the striatum by 30% as compared to that of with the control rats. After subacute administration of fentanyl, no significant difference was observed compared to the control group. According to the present data, fentanyl decreases [123I]beta-CIT binding in the basal ganglia both in human and rats, suggesting that opiates possibly directly affect DA reuptake.

Adult↗