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H Naukkarinen

Publications and source records attributed to H Naukkarinen.

At least 19 recordsLinked to original sources
PubMed2002

Decrease of energy expenditure causes weight increase in olanzapine treatment - a case study.

The aim of this study was to evaluate the mechanisms underlying weight gain induced by the atypical antipsychotic, olanzapine. We performed euglycemic, hyperinsulinemic clamp combined with indirect calorimetry on a 48-year-old male with antisocial personality disorder, alcohol dependence and paranoid ideation before and after one month of olanzapine (10 - 15 mg/day) therapy. The patient gave his informed, written consent for this study. The results were a weight gain of 6 kg and a decrease in both basal (from 1673 to 1613 kcal/24 h) and 3-hour (from 22.8 to 20.2 cal/kg fat free mass/min) energy expenditure. Serum thyroid hormone and high-density lipoprotein cholesterol levels decreased, and the triglyceride and low-density lipoprotein cholesterol levels increased. Insulin sensitivity did not change. We conclude that decreased basal energy expenditure may contribute to weight gain in olanzapine treatment.

Antipsychotic Agents↗
PubMed2001

No association of CCK and CCK(B) receptor polymorphisms with alcohol dependence.

Cholecystokinin (CCK) is the most widely distributed neuropeptide in the central nervous system. One of its several functions is to modulate the release of dopamine in brain areas involved in reinforcement and reward behavior. The aim of this study was to investigate the association of CCK system genes (CCK, CCK(A) and CCK(B) receptor genes) with alcohol dependence using single nucleotide polymorphisms (SNPs) as genetic markers. A total of 257 psychiatrically interviewed Finns were genotyped for CCK (-45C>T), CCK(A) (Val365Ile) and CCK(B) (Val125Ile) receptor polymorphisms. Allele frequencies were compared between 150 unrelated healthy Finnish controls and 107 unrelated alcohol-dependent subjects (DSM-III-R criteria), who were also criminal offenders. The frequency of the CCK -45T allele was not significantly different between controls [0.07] and alcoholics [0.09]. The CCK(B) receptor polymorphism Val125Ile was also not associated with alcoholism and the Ile125 allele frequencies were 0.05 in controls vs. 0.06 in alcohol-dependent subjects. A CCK(A) receptor marker, Val365Ile, was uninformative in this Finnish dataset; all subjects were Val365/Val365 homozygous. The results suggest that CCK -45C>T and CCKBR Val125Ile polymorphisms do not have a major role in alcohol dependence in the population studied. The role of the CCK(A) the receptor in alcohol dependence remains open until additional DNA sequence variants for this gene become available.

Alcoholism↗
PubMed2001

Reduced serotonin transporter binding in binge eating women.

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-beta-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.

Adult↗
PubMed2000

An abundant proneurotensin polymorphism, 479A>G, and a test of its association with alcohol dependence in a Finnish population.

BACKGROUND: Neurotensin is a 13-amino acid neuropeptide that endogenously modulates dopamine release in the central nervous system. In substance dependence, the mesolimbic dopamine system has been postulated to be a central structure that mediates rewarding and reinforcing effects. Neurotensin receptors in the neurons of the ventral tegmental area facilitate dopamine release, making the neurotensin gene an excellent candidate gene for alcohol dependence and for other behaviors that involve reinforcement. METHODS: A total of 639 psychiatrically interviewed Finns were genotyped for proneurotensin 479A>G polymorphism. We used the polymorphism as a marker to study the association between proneurotensin gene and alcohol dependence by comparing 229 unrelated Finnish healthy controls to 134 unrelated alcohol-dependent (DSM-III-R criteria) subjects who were also criminal offenders. In addition, 276 relatives of the alcohol-dependent and control subjects were genotyped. RESULTS: The frequencies of the genotypes in the whole sample (n = 639) were 0.84 for 479A/A, 0.16 for 479A/G, and 0.003 for 479G/G. The frequency of the rarer 479G allele was 0.07 and 0.06 in controls and alcohol-dependent subjects, respectively, and this difference was not statistically significant (chi2 = 0.264, df = 1, p = 0.61, controls vs. alcohol-dependent subjects). CONCLUSIONS: The results of the comparison between psychiatrically interviewed controls and alcoholics from a relatively well defined population indicate that the proneurotensin 479A>G polymorphism is not strongly associated with alcohol dependence. The results do not rule out a role for this gene in the pathogenesis of alcoholism or in differential vulnerability.

Alcoholism↗
PubMed1999

Blood concentrations of vasopressin, neuropeptide FF and prolactin are increased by high-dose right unilateral ECT.

Electroconvulsive therapy (ECT) is known to stimulate subcortical brain regions and release hormones from the anterior and the posterior pituitary. To enhance the subcortical effect of ECT and the neuroendocrinological response we used high dose right unilateral ECT (RUL-ECT) in 11 depressive patients and studied its effect on the release of vasopressin, prolactin and neuropeptide FF. The RUL ECT stimulus for all studied patients was 5 times the individual seizure threshold and it led to immediate release of vasopressin in all studied patients. The release of prolactin was less uniform however in accordance with results from earlier studies. The ECT also stimulated a NPFF secretion peak that came approximately 5 min after ECT stimulus and preceded the prolactin peak. The maximal elevations in circulating vasopressin and prolactin concentrations were 680% and 950%, respectively. The neuropeptide FF concentration increased by 100% after ECT. There was a second rise in NPFF concentration at 25 min after the ECT treatment. The increases in all peptide concentrations were significant, but were not correlated with each other. The neuropeptide FF concentration returned to baseline level at 10 min and the vasopressin concentration at 25 min after ECT. The prolactin concentration remained increased during the 30 min follow up period. Our results complete earlier finding on ECT stimulated vasopressin and prolactin release and show that high intensity RUL-ECT releases neuropeptide FF into human blood. The modest rise of circulating NFFF most likely represents leakage from the CNS.

Adult↗
PubMed1998

Mutation screening of the 5-hydroxytryptamine7 receptor gene among Finnish alcoholics and controls.

Impaired central serotonin neurotransmission has been associated with increased aggression, impaired impulse control and diurnal activity rhythm disturbances among humans. Neuroanatomic distribution and pharmacological properties of the serotonin 5-HT7 receptor suggest that it may play a role in psychiatric disorders and in circadian rhythm regulation. In this study a point mutation causing proline279 --> leucine amino acid substitution in the 5-hydroxytryptamine7 (5-HT7) receptor gene was discovered. This 5-HT7Leu279 variant was observed in six of 825 individuals, all of whom are heterozygous for the substitution. Three of them are alcoholic offenders (3/255), two are relatives of an offender without the 5-HT7Leu279 allele (2/255) and one is a healthy control without any psychiatric diagnosis (1/248). The allele frequency of the 5-HT7Leu279 variant is 0.004 (6/758) among Finns. Although the 5-HT7Leu279 variant is approximately three times more common among alcoholic offenders than among healthy controls, it is not significantly associated with alcoholism or impulsivity in the present study. The 5-HT7Leu279 allele may, however, be a predisposing allele in a subgroup of alcoholic offenders with multiple behavioral problems.

Adult↗
PubMed1998

Role of the serotonin transporter promoter polymorphism in anxiety-related traits.

BACKGROUND: The heritability of interindividual variation in anxiety and other aspects of personality establishes that variants of genes influence these traits. A functional polymorphism in the promoter of the human serotonin transporter gene (SLC6A4*C) was identified and found to be linked to an anxiety-related personality trait, Neuroticism. The polymorphism affects gene transcription and, ultimately, gene function. We have attempted to confirm the role of SLC6A4*C in anxiety-related personality traits by sibpair analysis and association studies. METHODS: Sibpair linkage analysis and association study were performed in 655 Finns. The index cases were 182 alcoholic criminal offenders, through which 258 relatives were ascertained to obtain 366 sibpairs. In addition, 215 unrelated population controls were collected. Each individual was psychiatrically interviewed, blind-rated for DSM-III-R diagnoses, and assessed with the Tridimensional Personality Questionnaire. RESULTS: The sibpair analysis revealed a positive linkage between SLC6A4*C and the 2 anxiety-related subdimensions of Harm Avoidance: HA1 (Anticipatory Worry) and HA2 (Fear of Uncertainty) (P = .003). However, there was no consistent association between SLC6A4*C and any Tridimensional Personality Questionnaire trait. CONCLUSIONS: In the present study we replicated the relationship of SLC6A4*C to anxiety by sibpair linkage analysis but found no evidence of association, raising the question of whether SLC6A4*C locus is itself affecting anxiety or is linked to another still unknown functional variant.

Alcoholism↗
PubMed1998

Linkage of antisocial alcoholism to the serotonin 5-HT1B receptor gene in 2 populations.

BACKGROUND: In mice, quantitative trait locus studies and behavioral evaluation of animals deleted for 5-HT1B have implicated this serotonin autoreceptor in alcohol consumption and aggressive behavior. We therefore investigated whether the 5-HT1B gene (HTR1B) is linked to alcoholism with aggressive and impulsive behavior in the human, as represented by 2 psychiatric diagnoses: antisocial personality disorder and intermittent explosive disorder comorbid with alcoholism. METHODS: Linkage was first tested in 640 Finnish subjects, including 166 alcoholic criminal offenders, 261 relatives, and 213 healthy controls. This was followed by a study in a large multigenerational family derived from a Southwestern American Indian tribe (n=418) with a high rate of alcoholism. All subjects were psychiatrically interviewed, blind-rated for psychiatric diagnoses, and typed for a HTR1B G861C polymorphism and for a closely linked short-tandem repeat locus, D6S284. Linkage was evaluated in sib pairs, and by using an association approach in which pedigree randomization corrects for nonindependence of observations on related subjects. RESULTS: In Finnish sib pairs, antisocial alcoholism showed significant evidence of linkage to HTR1B G861C (P=.04) and weak evidence with D6S284 (P=.06). By association analysis, the 183 Finnish antisocial alcoholics had a significantly higher HTR1B-861C allele frequency than the other 457 Finns we studied (P=.005). In the Southwestern American Indian tribe, significant sib pair linkage of antisocial alcoholism to HTR1B G861C (P=.01) was again observed, and there was also significant linkage to D6S284 (P=.01). CONCLUSION: These results suggest that a locus predisposing to antisocial alcoholism may be linked to HTR1B at 6q13-15.

Adolescent↗
PubMed1998

Fluoxetine normalizes increased cardiac vagal tone in bulimia nervosa.

Patients with bulimia nervosa have been reported to respond to treatment with the serotonin uptake inhibitor fluoxetine. In a preliminary study, which had a small sample size, women with bulimia nervosa were reported to have elevated cardiac vagal tone. We investigated cardiac vagal tone in women with bulimia nervosa before and after treatment with fluoxetine. At baseline, resting cardiac vagal tone, deduced from the respiratory component of heart rate variability, was quantified in 41 healthy volunteer women and in 25 women with bulimia nervosa. The bulimic women received in a parallel-group design, double blind, either placebo or fluoxetine 60 mg/24 hr for 8 weeks. All patients participated in behavioral therapy. Resting cardiac vagal tone was measured again at the end of the treatment. Women with bulimia nervosa had higher cardiac vagal tone than age-matched healthy volunteer women. Placebo had no effect on cardiac vagal tone. Fluoxetine reduced cardiac vagal tone among the women with bulimia nervosa to a level similar to the healthy volunteer women. Women with bulimia nervosa have elevated resting cardiac vagal tone. Fluoxetine normalized the elevated resting cardiac vagal tone among the women with bulimia nervosa. At both the central and peripheral levels, vagal neurons are endowed with serotonin-3 receptors. In vitro, fluoxetine desensitizes or blocks serotonin-3 receptors. A controlled trial of serotonin-3 receptor blockers is warranted in bulimia nervosa.

Adult↗
PubMed1998

Identification of new sequence variants in the leptin gene.

The leptin gene (LEP) has been linked to extreme obesity. However, no common obesity-related gene variants have been found to exist in the LEP. The present study was designed to investigate the LEP for variants by screening both the putative promoter and the coding region of this gene in obese Finnish subjects (n = 200; body mass index, > 27 kg/m2). PCR-amplified DNA samples were subjected to single strand conformation analysis. A G144A substitution in codon 48 and a G328A substitution in codon 110 were identified in two obese subjects, both of whom had very low serum leptin levels. A rare silent C538T polymorphism was detected 33 bp downstream of the translation stop codon (TGA). A common polymorphism A19G was identified in the untranslated exon 1. This polymorphism was not associated with traits of obesity; in agreement, the allele frequencies were similar between 64 normal weight and 141 obese Finns. In summary, this study failed to find a common gene variant in the LEP associated with obesity, but introduces 2 rare mutations associated with very low serum leptin concentrations in 2 obese subjects.

Adult↗
PubMed1995

Urinary excretion of bufotenin (N,N-dimethyl-5-hydroxytryptamine) is increased in suspicious violent offenders: a confirmatory study.

We previously reported that violent offenders with paranoid symptoms or whose violent actions had been directed against family members had higher urinary levels of bufotenin than other violent offenders. In the present study, patients were evaluated with the Karolinska Scales of Personality (KSP), and urinary levels of bufotenin were determined by mass spectrometry. In drug-free patients suspiciousness was positively correlated, and socialization was negatively correlated, with urinary bufotenin excretion. These two personality variables were strongly interdependent. In drug users, bufotenin excretion was correlated positively with social desirability and negatively with irritability, but not with suspiciousness. Bufotenin excretion was not found to be associated with violence toward family members in the present study. The results are in keeping with the earlier finding that violent offenders with paranoid personality traits have higher urinary levels of bufotenin than other violent offenders.

Adult↗
PubMed1994

Capsaicin-induced central facilitation of a sympathetic vasoconstrictor response to painful stimulation in humans.

The effect of capsaicin, a compound selectively activating nociceptive primary afferent fibers, on a centrally mediated autonomic (sympathetic) vasoconstriction response to painful peripheral stimulation was studied in healthy human volunteers. Capsaicin (1%) was applied topically to the dorsal forearm and the threshold for eliciting a vasoconstriction response in the contralateral forefinger to painful electrical or thermal stimulation of the forearm skin adjacent to or remote from the capsaicin-treated region was determined with Laser Doppler flowmetry. Capsaicin produced a significant decrease of the threshold for the vasoconstriction response to painful electrical stimulation of the area of central allodynia; i.e., the skin area located adjacent to the capsaicin-treated region in which a light touch evoked an unpleasant sensation. Capsaicin did not change the threshold for the vasoconstriction response to painful heat stimuli applied to the area of central allodynia or to painful electric stimulation applied outside the borders of the allodynic area. Heart rate, blood pressure and heart vagal tone were not modified by capsaicin. It is concluded that a selective activation of nociceptive primary afferent fibers of the skin by capsaicin produces a central submodality-dependent facilitation of an autonomic vasoconstriction response to noxious stimulation in humans. This central facilitation can be explained by segmental excitability changes of afferent interneurons at the spinal cord level.

Adult↗
PubMed1993

The use of clozapine in treatment-refractory schizophrenia.

The effects of clozapine on positive and negative symptoms were studied in 103 patients with treatment-refractory schizophrenia. The evaluation of symptom profile was made before and after clozapine treatment. Overt psychopathology did not vary significantly before clozapine treatment. Significant decreases in positive and negative symptoms were noted by the third month on clozapine. No further significant progress could be observed after 6 months of treatment. No fatal cases were observed, although two patients developed agranulocytosis during clozapine treatment.

Adult↗
PubMed1993

Interferon-alpha as adjuvant treatment in chronic schizophrenia.

The therapeutic use of interferon (IFN)-alpha administered as adjuvant medication in chronic schizophrenia was investigated. Natural leukocyte IFN-alpha was given to 9 long-term hospitalized chronic schizophrenic patients daily as subcutaneous injection of 3 million units 5 times a week. The trial followed a placebo-controlled double-blind crossover design. Each treatment period lasted for 8 weeks with a 2-week washout period in between. IFN-alpha did not prove to be beneficial for the total group of patients. Yet, 3 patients improved during the IFN-alpha drug period. The clinical improvement was seen as better social competence and less affective tension in the ward surroundings.

Adult↗
PubMed1992

Modified activity of the human auditory cortex during auditory hallucinations.

Previous reports have shown abnormalities in brain metabolism and evoked responses of schizophrenic patients with hallucinations. The authors recorded electric and magnetic auditory responses during transitory auditory hallucinations in two patients. Small but replicable response delays occurred during hallucinations. The results suggest that the effect of hallucinations on auditory cortex activity is similar to the effect of real sounds.

Acoustic Stimulation↗
PubMed1990

Remoxipride and haloperidol in schizophrenia: a double-blind multicentre study.

Ninety-two patients with schizophrenia were included in a double-blind multicentre parallel-group trial comparing remoxipride and haloperidol. The mean daily dose during the last week of treatment was 316 mg (range, 150-600 mg) in the remoxipride group and 8.7 mg (range, 5-20 mg) in the haloperidol group. The study period was six weeks with at least one day of washout. Both Clinical Global Impression (CGI) rating, and Brief Psychiatric Rating Scale (BPRS) total scores declined at the end of the trial compared with pretreatment values in both groups. No significant differences were found between the remoxipride and haloperidol groups with regard to the treatment outcome. Treatment-emergent extrapyramidal symptoms were statistically more frequent and more severe during haloperidol than during remoxipride treatment. Haloperidol-treated patients reported also significantly more concentration difficulties. Severe extrapyramidal side effects in the haloperidol group and clinical ineffectiveness in the remoxipride group were the most frequent reasons for premature discontinuation of treatment.

Adolescent↗