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M Virkkunen

Publications and source records attributed to M Virkkunen.

At least 55 records · Page 3Linked to original sources
PubMed1996

The association between the dopamine D4 receptor (D4DR) 16 amino acid repeat polymorphism and novelty seeking.

Ebstein and colleagues have recently reported a significant association between the 7-repeat allele of the dopamine D4 receptor (D4DR) 16 amino acid repeat polymorphism and the personality trait of Novelty Seeking (NS) in 124 Israeli subjects. This study, and another study conducted in the US (although with a different personality measure) that observed a similar association, have generated wide interest in the identification of the genes involved in personality variation. We have determined D4DR genotypes in two groups of Finnish subjects; 193 psychiatrically screened normal controls and 138 alcoholic offenders and assessed NS with the Tridimensional Personality Questionnaire (TPQ). In normals, we find no significant association between NS and the 7-repeat allele despite similar allele frequencies and the use of the same personality measure as Ebstein et al. The group of alcoholic offenders have significantly higher NS than normals, however we fail to replicate the previous association in this group and, in fact, find a significant association in the opposite direction as previously observed. These data suggest that D4DR may require re-evaluation as a candidate gene for personality variation.

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↗
PubMed1995

DRD4 dopamine receptor genotype and CSF monoamine metabolites in Finnish alcoholics and controls.

The DRD4 dopamine receptor is thus far unique among neurotransmitter receptors in having a highly polymorphic gene structure that has been reported to produce altered receptor functioning. These allelic variations are caused by a 48-bp segment in exon III of the coding region which may be repeated from 2-10 times. Varying the numbers of repeated segments changes the length, structure, and, possibly, the functional efficiency of the receptor, which makes this gene an intriguing candidate for variations in dopamine-related behaviors, such as alcoholism and drug abuse. Thus far, these DRD4 alleles have been investigated for association with schizophrenia, bipolar disorder, Parkinson's disease, and chronic alcoholism, and all have been largely negative for a direct association. We evaluated the DRD4 genotype in 226 Finish adult males, 113 of whom were alcoholics, many of the early onset type with features of impulsivity and antisocial traits. Genotype frequencies were compared to 113 Finnish controls who were free of alcohol abuse, substance abuse, and major mental illness. In 70 alcoholics and 20 controls, we measured CSF homovanillic acid (HVA), the major metabolite of dopamine, and 5-hydroxyindoleacetic acid (5-HIAA). No association was found between a particular DRD4 dopamine receptor allele and alcoholism. CSF concentrations of the monoamine metabolites showed no significant difference among the DRD4 genotypes. This study of the DRD4 dopamine receptor in alcoholics is the first to be conducted in a clinically and ethnically homogeneous population and to relate the DRD4 genotype to CSF monoamine concentrations. The results indicate that there is no association of the DRD4 receptor with alcoholism.

Adult↗
PubMed1995

Identification, expression, and pharmacology of a Cys23-Ser23 substitution in the human 5-HT2c receptor gene (HTR2C).

The function of brain serotonin-2C (5-HT2C) receptors, including behavioral and neurochemical responses to 5-HT2C agonist challenge, has been suggested to be abnormal in individuals with neuropsychiatric disorders. Thus, it is important to identify polymorphisms and functional variants within this gene. Using SSCP analysis, we identified a Cys23-Ser23 substitution (designated 5-HT2Ccys and 5-HT2Cser) in the first hydrophobic region of the human 5-HT2C receptor. Allele frequencies in unrelated Caucasians were 0.13 and 0.87 for 5-HT2Cser and 5-HT2Ccys, respectively. DNAs from informative CEPH families were typed for this polymorphism and analyzed with respect to 20 linked markers on the X chromosome. Linkage analysis placed the 5-HT2C receptor gene (HTR2C) on Xq24. To evaluate whether this amino acid substitution causes a variant function of this receptor, recombinant human 5-HT2Ccys and 5-HT2Cser receptors were expressed in Xenopus oocytes and tested for responses to 5-HT using electrophysiological techniques. Concentration-response curves for 5-HT were not significantly different in oocytes expressing either form of the receptor, suggesting that the 5-HT2Ccys and 5-HT2Cser receptor proteins may not differ in their responses to serotonin under baseline physiological conditions.

Animals↗
PubMed1995

Mapping of the serotonin 5-HT1D beta autoreceptor gene on chromosome 6 and direct analysis for sequence variants.

Abnormal brain serotonin function may be characteristic of several neuropsychiatric disorders. Thus, it is important to identify polymorphic genes and screen for functional variants at loci coding for genes that control normal serotonin functions. 5-HT1D beta is a terminal serotonin autoreceptor which may play a role in regulating serotonin synthesis and release. Using an SSCP technique we screened for 5-HT1D beta coding sequence variants in psychiatrically interviewed populations, which included controls, alcoholics, and alcoholic arsonists and alcoholic violent offenders with low CSF concentrations of the main serotonin metabolite 5-HIAA. A common polymorphism was identified in the 5-HT1D beta gene with allele frequencies of 0.72 and 0.28. The SSCP variant was caused by a silent G to C substitution at nucleotide 861 of the coding region. This polymorphism could also be detected as a HincII RFLP of amplified DNA. DNAs from informative CEPH families were typed for the HincII RFLP and analyzed with respect to 20 linked markers on chromosome 6. Multipoint analysis placed the 5-HT1D beta receptor gene between markers D6S286 and D6S275. A maximum two-point lod score of 10.90 was obtained to D6S26, which had been previously localized on 6q14-15. Chromosomal aberrations involving this region have been previously shown to cause retinal anomalies, developmental delay, and abnormal brain development. This region also contains the gene for North Carolina-type macular dystrophy.

Alcoholism↗
PubMed1995

Citalopram, a selective serotonin reuptake inhibitor, in the treatment of aggression in schizophrenia.

The aim of this double-blind cross-over study was to investigate whether treatment with the selective serotonin reuptake inhibitor, citalopram reduces aggressiveness in chronically violent schizophrenic inpatients. Initially 19 patients were enrolled into this double-blind cross-over study in which the patients were treated for 24 weeks with placebo and 24 weeks with citalopram (20-60 mg/day) as a supplement to their previous neuroleptic medication. Fourteen patients completed the entire study, but sufficient data on 15 patients could be used in the end-point analysis of efficacy. Psychiatric assessments (Brief Psychiatric Rating Scale, Clinical Global Impression Scale for Severity of Illness, Social Dysfunction and Aggression Scale and the Global Aggression Scale) and side effects (UKU Side Effect Scale) were recorded at baseline and 4 times during both periods. Aggressive incidents (Staff Observation Aggression Scale) were recorded throughout the study. During citalopram treatment, the frequency of aggressive incidents was significantly lower and the mental state did not deteriorate. Patients either experienced no side effects or else side effects were equally mild during both periods.

Adolescent↗
PubMed1995

Low brain serotonin turnover rate (low CSF 5-HIAA) and impulsive violence.

The findings of a series of studies by the authors support the idea that most impulsive offenders who have a tendency to behave aggressively while intoxicated have a low brain serotonin turnover rate. The impulsive violent offenders with the lowest CSF 5-HIAA concentrations have diurnal activity rhythm disturbances, and are also prone to hypoglycemia after an oral glucose challenge. Low CSF 5-HIAA combined with hyoglycemic tendency also predicts future violence under the influence of alcohol. Sons of alcoholic fathers, who have committed violent crimes, have very low CSF 5-HIAA concentrations. Vagal tone does not correlate significantly with CSF 5-HIAA but correlates with enhanced insulin secretion, which is most prominent in subjects with intermittent explosive disorder. A polymorphism of tryptophan hydroxylase (TPH) gene is associated with low CSF 5-HIAA and a history of suicide attempts.

Alcoholism↗
PubMed1994

CSF biochemistries, glucose metabolism, and diurnal activity rhythms in alcoholic, violent offenders, fire setters, and healthy volunteers.

BACKGROUND: There is an extensive literature describing a central serotonin deficit in alcoholic, impulsive, violent offenders and fire setters. In the present study, we investigated biochemical concomitants of impulsivity and aggressiveness, and the physiological consequences of reduced central serotonin turnover. METHODS: Forty-three impulsive and 15 nonimpulsive alcoholic offenders and 21 healthy volunteers were studied in the forensic psychiatry ward of a university psychiatric department. The subjects underwent lumbar punctures and oral glucose and aspartame challenges, and their diurnal activity rhythm was measured with physical activity monitors. Discriminant function analyses were used to investigate psychophysiological and biochemical concomitants of aggressive and impulsive behaviors. RESULTS: Alcoholic, impulsive offenders with antisocial personality disorder had low mean cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) and corticotropin levels and high mean CSF testosterone concentrations. Compared with healthy volunteers, they showed increased physical activity during the daytime. Alcoholic, impulsive offenders with intermittent explosive disorder had a low mean CSF 5-HIAA concentration and blood glucose nadir after an oral glucose challenge, and desynchronized diurnal activity rhythm. Healthy volunteers had mean CSF 5-HIAA concentrations that were intermediate between those of alcoholic, impulsive and nonimpulsive offenders. Alcoholic, nonimpulsive offenders had a significantly higher mean CSF 5-HIAA concentration than all the other groups, including healthy volunteers. CONCLUSIONS: In the present sample, a low CSF 5-HIAA concentration was primarily associated with impulsivity and high CSF testosterone concentration, with aggressiveness or interpersonal violence.

Adrenocorticotropic Hormone↗
PubMed1994

Personality profiles and state aggressiveness in Finnish alcoholic, violent offenders, fire setters, and healthy volunteers.

BACKGROUND: Based on clinical observations in a series of studies on Finnish alcoholic, violent offenders, we asserted that the impulsive offenders represented an extreme group of type 2 alcoholics. We also observed that these subjects were vulnerable to hypoglycemia after the administration of oral glucose load. Furthermore, we believe that while being hypoglycemic, the impulsive offenders are particularly irritable and aggressive. In the present study, we addressed these issues by studying psychological trait and state variables in a new group of violent offenders and fire setters, and age- and sex-matched healthy volunteers. METHODS: Fifty-eight alcoholic, violent offenders and impulsive fire setters and 21 healthy volunteers were administered the Karolinska scales of personality and the Rosenzweig picture frustration test after an oral aspartame and glucose challenge. RESULTS: The psychological test results and the criminal histories of the offenders, together with biochemical measurements, suggest that a low 5-hydroxyindoleacetic acid concentration in cerebrospinal fluid in the alcoholic offenders is associated with irritability and impaired impulse control, and a high free testosterone concentration in cerebrospinal fluid is associated with increased aggressiveness, monotony avoidance, sensation seeking, suspiciousness, and reduced socialization. CONCLUSION: Finnish alcoholic, impulsive offenders have personality profiles characteristic of Scandinavian early-onset male alcoholics with antisocial traits, who have been also referred to as type 2 alcoholics.

Adult↗
PubMed1994

Suicidality and 5-hydroxyindoleacetic acid concentration associated with a tryptophan hydroxylase polymorphism.

BACKGROUND: To examine whether the tryptophan hydroxylase (TPH) gene, which codes for the rate-limiting enzyme in the biosynthesis of serotonin, may be a factor influencing serotonin turnover and behaviors controlled by serotonin. METHODS: Using a polymerase chain reaction-based method, TPH genotype was determined in DNA samples from 56 impulsive and 14 nonimpulsive, alcoholic, violent offenders and 20 healthy volunteers. RESULTS: In the behaviorally extreme impulsive group, we observed a significant association between TPH genotype and cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA) concentration. No association of TPH genotype with impulsive behavior was detected. The polymorphism was also associated with a history of suicide attempts in all violent offenders, independent of impulsivity status and cerebrospinal fluid 5-HIAA concentration. CONCLUSION: In some individuals, a genetic variant of the TPH gene may influence 5-HIAA concentration in the cerebrospinal fluid and predisposition to suicidal behavior.

Adult↗
PubMed1994

Serotonin, violent behavior and alcohol.

At the NIAAA intramural research program, in collaboration with investigators at the Department of Psychiatry, University of Helsinki, we have mounted an extensive research program on early onset male alcoholism. A central serotonergic deficit is common among these patients. This finding has led to behavioral, biochemical, physiological and molecular genetic studies on the serotonin system in early onset, antisocial and violent male alcoholics and in appropriate control populations. The results of the studies completed by the fall of 1993 are summarized in this communication.

Age Factors↗
PubMed1993

Brain serotonin, type II alcoholism and impulsive violence.

There is ample evidence that low CSF 5-HIAA concentration is associated with a tendency to exhibit impulsive violent behavior under the influence of alcohol. This is especially true for subjects who fulfill criteria for psychiatric diagnoses often associated with early onset alcoholism such as antisocial personality disorder and intermittent explosive disorder. Brain serotonin turnover as indicated by CSF 5-HIAA concentration does not correlate with CSF free testosterone concentration. The latter is more strongly associated with outward-directed aggressiveness and lack of socialization than impulsiveness. CSF ACTH concentration on the other hand correlates positively with socialization.

Aggression↗
PubMed1992

Factors associated with recidivism in a criminal population.

The present study is a follow-up of a sample of 348 men convicted of manslaughter, attempted manslaughter, or arson who were released from incarceration. Multiple factors assessed at the time of incarceration, including demographic, behavioral, family history, and biochemical variables, and psychiatric diagnoses were used in an attempt to discriminate between those who became recidivists during the follow-up period and those who did not. Violent recidivism was most strongly associated (sensitivity of 90%) with impulsivity of the original crime in killers and attempted killers; for arsonists, having made a suicide attempt was the strongest predictor (68% sensitivity). For predictive purposes, both single factor associations and multiple entries into discriminant analysis produced too many false-positives, i.e., the high rate of false designation as recidivist remained a problem.

Adolescent↗
PubMed1992

D2 dopamine receptor genotype and cerebrospinal fluid homovanillic acid, 5-hydroxyindoleacetic acid and 3-methoxy-4-hydroxyphenylglycol in alcoholics in Finland and the United States.

If a genetic association between the D2 dopamine receptor genotype and alcoholism is mediated by altered dopamine function, then a stronger association might be found in alcoholics who are deviant in indices of dopamine function and by comparing alcoholics to nonalcoholics matched for ethnic origin. Therefore, we evaluated the D2/TaqI polymorphism in 29 impulsive violent alcoholic Finns, 17 nonimpulsive violent alcoholic Finns and 36 Finnish controls free of mental disorders, alcoholism and substance abuse. In 37 of the alcoholics, we measured cerebrospinal fluid (CSF) homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol. There was no relationship between D2/Taq 1 genotype and concentrations of these monoamine metabolites in this group, which exhibits lower CSF HVA and 5-HIAA as compared to controls. There was also no genotypic difference between Finnish alcoholics and nonalcoholic controls. The lack of relationship between D2/Taq1 genotype and HVA concentration was replicated in 24 Caucasian alcoholics in the United States.

Adult↗