PubMed Health⌕ Search

Biomedical subjects

Matti Virkkunen

Publications and source records attributed to Matti Virkkunen.

At least 19 recordsLinked to original sources
PubMed2006

Sleep architecture in homicidal women with antisocial personality disorder--a preliminary study.

The aim of the present study was to characterize sleep in severely violent women with antisocial personality disorder (ASP) as the primary diagnosis. Participants for this preliminary study were three drug-free female offenders ordered to undergo a forensic mental examination in a maximum security state mental hospital after committing homicide or attempted homicide. Ten healthy age- and gender-matched controls consisted of hospital staff with no history of physical violence. The most striking finding was the increased amount of slow wave sleep, particularly the deepest sleep stage, S4, in women with ASP. This finding is in agreement with previously reported results in habitually violent male criminals with ASP. Severe female aggression seems to be associated with profound changes in sleep architecture. Whether this reflects specific brain pathology, or a delay in the normal development of sleep patterns in the course of aging, needs to be clarified. From the perspective of sleep research, the biological correlates of severe impulsive violence seem to be similar in both sexes.

Adult↗
PubMed2006

Dimensional anxiety mediates linkage of GABRA2 haplotypes with alcoholism.

The GABAAalpha2 receptor gene (GABRA2) modulates anxiety and stress response. Three recent association studies implicate GABRA2 in alcoholism, however in these papers both common, opposite-configuration haplotypes in the region distal to intron3 predict risk. We have now replicated the GABRA2 association with alcoholism in 331 Plains Indian men and women and 461 Finnish Caucasian men. Using a dimensional measure of anxiety, harm avoidance (HA), we also found that the association with alcoholism is mediated, or moderated, by anxiety. Nine SNPs were genotyped revealing two haplotype blocks. Within the previously implicated block 2 region, we identified the two common, opposite-configuration risk haplotypes, A and B. Their frequencies differed markedly in Finns and Plains Indians. In both populations, most block 2 SNPs were significantly associated with alcoholism. The associations were due to increased frequencies of both homozygotes in alcoholics, indicating the possibility of alcoholic subtypes with opposite genotypes. Congruently, there was no significant haplotype association. Using HA as an indicator variable for anxiety, we found haplotype linkage to alcoholism with high and low dimensional anxiety, and to HA itself, in both populations. High HA alcoholics had the highest frequency of the more abundant haplotype (A in Finns, B in Plains Indians); low HA alcoholics had the highest frequency of the less abundant haplotype (B in Finns, A in Plains Indians) (Finns: P = 0.007, OR = 2.1, Plains Indians: P = 0.040, OR = 1.9). Non-alcoholics had intermediate frequencies. Our results suggest that within the distal GABRA2 region is a functional locus or loci that may differ between populations but that alters risk for alcoholism via the mediating action of anxiety.

Adult↗
PubMed2006

Increased deep sleep in a medication-free, detoxified female offender with schizophrenia, alcoholism and a history of attempted homicide: effect of concomitant administration of quetiapine and citalopram.

BACKGROUND: An increased amount of deep sleep has been shown to be associated with antisocial personality disorder. This phenomenon has also been observed in a habitually violent female offender with schizophrenia and alcohol dependence. AIM: To evaluate sleep patterns in this patient and compare them with those of healthy, pro-social women of similar age, and in the same patient over time after treatment. METHOD: Multiple measures of sleep were taken over two consecutive nights with the presenting patient and with three age-matched healthy women. One year after the patient was established on atypical antipsychotic (quetiapine), and antidepressant (SSRI) medication (citalopram) her sleep evaluation was repeated. In each case only the second night's recordings were used in analyses. RESULTS: The patient differed significantly from the three healthy women on most sleep measures. After a year on the medication, the patient's sleep had improved and the non-REM sleep measures had come into the normal range. She had also shown a sustained clinical and behavioural improvement. DISCUSSION AND IMPLICATIONS: The literature suggests that both drugs had a part to play in the improvements in sleep, symptomatology and behaviour. The possibility that improvement in deep sleep is secondary to citalopram and that it is this that was specifically associated with violence reduction seems worthy of further study.

Adult↗
PubMed2005

Looking for pyromania: characteristics of a consecutive sample of Finnish male criminals with histories of recidivist fire-setting between 1973 and 1993.

BACKGROUND: As pyromania is a rare diagnosis with questionable validity, we aimed to describe a forensic psychiatric population of arson recidivists. METHODS: The medical records as well as the forensic psychiatric examination statements of 90 arson recidivists referred for pretrial psychiatric assessment in Helsinki University Hospital Department of Forensic Psychiatry between 1973 and 1993 were reviewed. RESULTS: The most important diagnostic categories of arson recidivists were personality disorders, psychosis and mental retardation, often with comorbid alcoholism. In all, 68% of arsonists were under alcohol intoxication during the index crime. Psychotic as well as mentally retarded persons with repeated fire-setting behaviour were mostly "pure arsonists"--persons guilty only of arsons during their criminal careers. Arson recidivists with personality disorder, in contrast, often exhibited various types of criminal behaviour and arson appeared to be only one expression of a wide range of criminal activity. Comorbid alcoholism was apparently a more rarely observed phenomenon among pure arsonists than in "nonpure arsonists". We found only three subjects fulfilling the present diagnostic criteria for pyromania. CONCLUSION: Using the criteria of the DSM-IV-TR, pyromania must be regarded as an extremely rare phenomenon. Especially the question of substance intoxication as an exclusion criterion for pyromania should be reconsidered.

Adolescent↗
PubMed2005

Quantitative electroencephalographic measures in homicidal men with antisocial personality disorder.

Many symptoms of antisocial personality disorder have been proposed to be related to decreased daytime vigilance. To explore this hypothesis, quantitative analyses were conducted of the electroencephalographic (EEG) activity of drug-free and detoxified homicidal male offenders with antisocial personality disorder as the primary diagnosis. Subjects comprised 16 men recruited from a forensic psychiatric examination in a special ward of a university psychiatric hospital. Fifteen healthy age- and gender-matched controls with no criminal record or history of physical violence consisted of hospital staff and students. An overall reduction of alpha power was observed in the waking EEG of offenders. A bilateral increase in occipital delta and theta power was also found in these individuals. This study provides further support to the growing evidence of brain dysfunction in severe aggressive behavior. Homicidal offenders with antisocial personality disorder seem to have difficulties in maintaining normal daytime arousal. Decreased vigilance, together with social and psychological variables, may explain their aberrant behavior in everyday life. New studies are, however, needed to specify the vigilance problems of this patient group.

Adult↗
PubMed2005

Haplotype-based localization of an alcohol dependence gene to the 5q34 {gamma}-aminobutyric acid type A gene cluster.

CONTEXT: Pharmacobehavioral and pharmacogenetic evidence links gamma-aminobutyric acid type A (GABA(A)) receptors and chromosomal regions containing GABA(A) receptor genes to ethanol-related responses. The GABA(A) gene cluster on chromosome 5q34 is of particular interest in the genetics of alcohol dependence because of the gamma2 subunit requirement for ethanol's modulatory action on GABA(A) receptors, previous linkage findings in mice and humans implicating both GABRA6 and GABRG2, and reported associations of GABRA6, GABRB2, and GABRG2 alleles with alcohol dependence. OBJECTIVE: To determine whether variation at the 5q34 GABA(A) gene cluster is implicated in differential susceptibility to alcohol dependence. METHODS: Two large psychiatrically interviewed samples, a Southwestern Native American population sample (N = 433) and a Finnish sample (N = 511) with alcohol-dependent subjects and unaffected individuals, were genotyped for 6 single nucleotide polymorphisms at the 5q34 GABA(A) gene cluster. In addition to sib-pair linkage and case-control association analyses, linkage disequilibrium mapping with haplotypes was used. RESULTS: Sib-pair linkage of GABRG2 to alcohol dependence was observed in Finns (P = .008). Association of the GABRB2 1412T allele with alcohol dependence was detected in both populations (Finns, P = .01; Southwestern Native Americans, P = .008), and the GABRA6 1519T allele was associated in both Finns (P = .01) and Southwestern Native Americans (P = .03). Linkage disequilibrium mapping with 3-locus haplotypes yielded evidence for an alcohol-dependence locus at the GABA(A) gene cluster region in both populations. The most highly significant signals were at 3-locus haplotypes that included 1 or more GABRA6 polymorphisms, with the peak signal at a GABRA6 3-locus haplotype (Finns, empirical P = .004; Southwestern Native Americans, empirical P = .02). CONCLUSIONS: We detected sib-pair linkage of 5q34 GABA(A) receptor genes to alcohol dependence in Finns and found association both in Finns and in Southwestern Native Americans. In both populations, the haplotype localization implicates the region containing the Pro385Ser GABRA6 polymorphism and 2 other polymorphisms at GABRA6.

Adolescent↗
PubMed2005

Haplotype-based linkage of tryptophan hydroxylase 2 to suicide attempt, major depression, and cerebrospinal fluid 5-hydroxyindoleacetic acid in 4 populations.

CONTEXT: Tryptophan hydroxylase 2 (TPH2) encodes the rate-limiting enzyme for brain serotonin biosynthesis. It was recently reported that the TPH2 haplotype was linked to depression in humans. OBJECTIVE: To determine the association of TPH2 with suicide attempt, major depression, and a neurochemical intermediate phenotype, cerebrospinal fluid 5-hydroxyindoleacetic acid. DESIGN: We resequenced TPH2 coding, 5' promoter, 3'-untranslated region, and splice junction regions in 190 individuals selected for ethnic and clinical diversity, determined haplotype structure using 15 single nucleotide polymorphisms spanning 106 kilobases (kb), and performed linkage analysis in 1798 cases and controls representing 4 populations (657 African Americans, including 104 suicide attempters and 135 with major depression; 513 Finnish whites, including 150 suicide attempters; 146 US whites, including 81 with depression, anxiety disorder, or both; and 482 southwestern American Indians, including 123 suicide attempters and 191 with depression, anxiety disorder, or both) and in 94 Finnish whites for cerebrospinal fluid 5-hydroxyindoleacetic acid levels. RESULTS: Sixteen single nucleotide polymorphisms, including Pro206Ser, were detected. The 15-locus panel defined and maximized information content from 2 haplotype blocks in whites, 3 haplotype blocks in African Americans, and the single haplotype block spanning TPH2 in southwestern American Indians. Among common Block1b haplotypes were 2 in yin and yang (opposite) configuration, indicating ancient origin. The yin haplotype, 212121, was increased in frequency in suicide attempters in both populations tested (Finnish whites and African Americans). It was associated with major depression and anxiety disorders in US whites and with major depression in African Americans. The yin haplotype was moderately predictive of lower cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations in controls but not in cases. CONCLUSION: Haplotype linkage of TPH2 to suicide attempt and major depression and to a mediating phenotype, cerebrospinal fluid 5-hydroxyindoleacetic acid, provides preliminary evidence of a functional locus potentially within a haplotype block at least 52 kb in size.

Adult↗
PubMed2005

Thr105Ile, a functional polymorphism of histamine N-methyltransferase, is associated with alcoholism in two independent populations.

BACKGROUND: Histamine is expressed in cortical and limbic areas that are involved in emotion and cognition and modulates these behaviors. H1 receptor antagonists are sedative. Histamine N-methyltransferase (HNMT) catalyzes the Ntau methylation of histamine, the sole pathway for termination of the neurotransmitter action of histamine in mammalian brain. A common and functionally significant polymorphism, a C314T transition in exon 4 of the HNMT gene results in a Thr105Ile substitution of the protein encoded. The Thr105 allele is associated with approximately 2-fold higher enzyme activity, leading to the prediction that it might be associated with diminished histamine levels, resulting in differences in anxiety, cognition, and sedation that play important roles in alcoholism. In two ethnically distinct populations, we tested whether the Thr105Ile polymorphism was associated with alcoholism and with harm avoidance, a dimensional measure of anxious personality. METHODS: A 5' exonuclease assay (TaqMan) was used to genotype Thr105Ile in psychiatrically interviewed Finnish Caucasian (n = 218) and Plains American Indian (n = 186) alcoholics, along with ethnically matched, psychiatrically interviewed, controls (Finns: n = 313, Plains Indian: n = 140). RESULTS: Ile105 allele frequencies were significantly lower in alcoholics compared with nonalcoholics in both populations (Finns: 0.12 vs. 0.17, chi(2) = 6, p = 0.015; Plains Indians: 0.03 vs. 0.08, chi(2) = 5, p = 0.023). Genotype distributions also differed significantly. In Finns, Ile105 showed borderline significance for an association with lower harm avoidance (p = 0.070) after correcting for alcoholism diagnosis. CONCLUSIONS: Decreased levels of brain histamine consequent to the Thr105 allele may result in higher levels of anxiety and, as a consequence, vulnerability to alcoholism.

Adult↗
PubMed2004

Increased deep sleep in a medication-free, detoxified female offender with schizophrenia, alcoholism and a history of attempted homicide: case report.

BACKGROUND: Psychiatric sleep research has attempted to identify diagnostically sensitive and specific sleep patterns associated with particular disorders. Both schizophrenia and alcoholism are typically characterized by a severe sleep disturbance associated with decreased amounts of slow wave sleep, the physiologically significant, refreshing part of the sleep. Antisocial behaviour with severe aggression, on the contrary, has been reported to associate with increased deep sleep reflecting either specific brain pathology or a delay in the normal development of sleep patterns. The authors are not aware of previous sleep studies in patients with both schizophrenia and antisocial personality disorder. CASE PRESENTATION: The aim of the present case-study was to characterize the sleep architecture of a violent, medication-free and detoxified female offender with schizophrenia, alcoholism and features of antisocial personality disorder using polysomnography. The controls consisted of three healthy, age-matched women with no history of physical violence. The offender's sleep architecture was otherwise very typical for patients with schizophrenia and/or alcoholism, but an extremely high amount of deep sleep was observed in her sleep recording. CONCLUSIONS: The finding strengthens the view that severe aggression is related to an abnormal sleep pattern with increased deep sleep. The authors were able to observe this phenomenon in an antisocially behaving, violent female offender with schizophrenia and alcohol dependence, the latter disorders previously reported to be associated with low levels of slow wave sleep. New studies are, however, needed to confirm and explain this preliminary finding.

Adult↗
PubMed2004

Neurological soft signs in homicidal men with antisocial personality disorder.

Neurological soft signs (NSS) are characterized by abnormalities in motor, sensory, and integrative functions. NSS have been regarded as a result of neurodevelopmental dysfunction, and as evidence of a central nervous system defect, resulting in considerable sociopsychological dysfunction. During the last decade there has been growing evidence of brain dysfunction in severe aggressive behavior. As a symptom, aggression overlaps a number of psychiatric disorders, but it is commonly associated with antisocial personality disorder. The aim of the present study was to examine NSS in an adult criminal population using the scale by Rossi et al. [29]. Subjects comprised 14 homicidal men with antisocial personality disorder recruited from a forensic psychiatric examination. Ten age- and gender-matched healthy volunteers as well as eight patients with schizophrenia, but no history of physical aggression, served as controls. The NSS scores of antisocial offenders were significantly increased compared with those of the healthy controls, whereas no significant differences were observed between the scores of offenders and those of patients with schizophrenia. It can be speculated that NSS indicate a nonspecific vulnerability factor in several psychiatric syndromes, which are further influenced by a variety of genetic and environmental components. One of these syndromes may be antisocial personality disorder with severe aggression.

Adult↗
PubMed2004

Failure to detect DUP25 in lymphoblastoid cells derived from patients with panic disorder and control individuals representing European and American populations.

Investigation of the co-occurrence of panic and phobic disorders with joint laxity led to the identification of interstitial duplications involving human chromosome 15q24-26 (named 'DUP25') in a Spanish population. DUP25 was observed in 97% of patients and in 7% of control individuals. In the present study, we used two different methods to detect DUP25: high-throughput molecular gene dosage analysis and fluorescence in situ hybridization (FISH). We evaluated 56 lymphoblastoid cell lines derived from 26 unrelated patients with panic disorder obtained from several European and American populations and 30 normal controls. We could not find any cell line showing a result consistent with DUP25. These data do not support any association of DUP25 with panic disorder.

Adult↗
PubMed2004

ADHD and sleep in homicidal men with antisocial personality disorder.

A history of attention deficit hyperactivity disorder (ADHD) is commonly found in subjects with antisocial personality disorder (ASP). Besides ASP, childhood ADHD also predicts drug abuse disorders and criminal activity in adulthood. Childhood ADHD and ASP appear to be the only psychiatric disorders reported to be associated with an increase in deep sleep. The aims of the present study were to retrospectively measure the childhood ADHD of habitually violent men with ASP and Cloninger type 2 alcoholism, and to characterize the possible relationship between childhood ADHD and sleep architecture in these men. The subjects of the study consisted of 14 homicidal offenders recruited from a forensic psychiatric examination. Ten age- and gender-matched healthy volunteers served as controls. Childhood ADHD symptoms were measured using the Wender-Utah Rating Scale (WURS). The main findings were that violent offenders with ASP had significantly higher mean WURS scores compared with controls, and both the absolute and percentage amount of stage 4 sleep as well as delta and theta powers in this sleep stage were positively correlated with the WURS scores. The present study supports the idea that childhood ADHD is associated with the abnormal sleep architecture in habitually violent men with ASP. These two disorders seem to share, at least partly, the same central nervous system deficit.

Adolescent↗
PubMed2003

NPY Leu7Pro and alcohol dependence in Finnish and Swedish populations.

BACKGROUND: Neuropeptide Y (NPY) is a modulator of alcohol intake in animal models of alcoholism, and is potentially involved in alcohol dependence. A coding Leu7Pro polymorphism in the signal peptide of preproNPY has been described, and the Pro7 allele has been reported to correlate with increased alcohol consumption in non-dependent Finnish males. Recently, this polymorphism was also reported to be associated with an actual diagnosis of alcohol dependence. METHODS: We compared Pro7 allele frequencies in one Finnish (n = 135) and one Swedish (n = 472) population of alcohol dependent individuals, and ethnically matched controls (Finns: n = 213; Swedes: n = 177) in whom alcohol dependence was established, or any diagnosis of substance disorder was excluded, respectively, through the use of structured face-to-face interviews. RESULTS: Pro7 frequencies in alcoholics were 5.2 and 4.1% in Finns and Swedes, respectively, similar to the 5.0-5.5% recently reported in European Americans in a Yale study. However, corresponding frequencies in the control populations were similar, at 6.1 and 5.9% in Finns and Swedes, respectively, yielding no association, in contrast with the Yale study, where an association was reported based on a 2.0% Pro7 frequency in European American controls. A meta-analysis of available data yields Pro7 frequencies of 4.7% both in Caucasian alcoholics and Caucasian controls. CONCLUSIONS: Pro7 does not seem to be associated with a diagnosis of alcoholism in Caucasian populations.

Alcoholism↗
PubMed2003

Growth hormone-insulin-like growth factor-1 axis, leptin and sleep in anorexia nervosa patients.

The present study characterizes the relationships between severe malnutrition, sleep, growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis, and leptin levels in anorexia nervosa (AN) patients before and after weight gain. Eleven restricting-type anorectic females (mean age = 19.7 years) with severe starvation state [mean body mass index (BMI) = 13.3] were studied using polysomnography and spectral power analysis. The hormone levels were measured in the morning after sleep recording. Eleven normal-weight, age- and gender-matched healthy volunteers without a history of any eating disorder served as controls. After nutritional treatment for about 2 months (65.7 +/- 6.4 days), sleep examinations and blood tests were repeated. At this stage, the study group consisted of 5 patients (mean BMI = 15.6). Higher IGF-1 and leptin levels were associated with longer and deeper sleep among anorectics. The sleep parameters including the percentages of stage 1 sleep and SWS as well as IGF-1 tended to normalize after only limited weight gain. Sleep disturbances in anorectics may be mediated through changes in the levels of the GH-IGF-1 axis hormones, as well as the levels of leptin.

Adolescent↗
PubMed2003

Sleep among habitually violent offenders with antisocial personality disorder.

The aim of the present study was to characterize the subjective and objective sleep and sleep quality in habitually violent offenders with DSM-IV diagnosis of antisocial personality disorder using a sleep questionnaire, actigraphy, polysomnography and power spectral analysis. Subjects for the study were 19 drug-free males (mean age +/- SEM 30.7 +/- 2.58 years) recruited from a forensic psychiatric examination in a special ward of a university psychiatric hospital. The most striking finding was the high amount of slow-wave sleep, particularly the deepest S4 stage (17% as compared with 6% in healthy controls), in males with antisocial personality disorder. Moreover, in the spectral power analysis, both the delta and the theta power were significantly elevated. Whether this increase in persons with antisocial personality disorder reflects a specific brain pathology, or a delay in the normal development of sleep patterns in the course of ageing needs to be clarified with further experiments.

Adult↗
PubMed2003

Risk of repeat offending among violent female offenders with psychotic and personality disorders.

OBJECTIVE: The aim of this study was to examine the rate of criminal recidivism among female homicide offenders evaluated by forensic psychiatrists, to compare this rate with that of other violent female offenders, and to analyze the explanatory variables of recidivism. METHOD: This was a retrospective study of all women (N=132) sent for forensic psychiatric examination after being convicted of homicide or attempted homicide in Finland during 1982-1992; subjects were followed up until mid-1999. Data were collected from the national crime register, the prisoner record, and Statistics Finland. The authors compared the rate of violent repeat offending in this group with that of other violent women and analyzed the explanatory variables of recidivism. RESULTS: During the follow-up period, 23% of the study group committed a repeat offense, 15% of which were violent and 3% of which were homicides. Almost half of all repeat offenses occurred within the first 2 years after the index offense. There was no statistically significant difference in violent recidivism between the study group and other violent female offenders. Of those who committed repeat offenses, 81% were diagnosed with a personality disorder, and 10% were diagnosed with psychosis. Criminality prior to the index event, alcohol or drug dependency, and young age significantly raised the risk and rapidity of further offenses. CONCLUSIONS: The risk of recidivism was high in this study group yet was similar to that of other violent female offenders. The risk was high very early after release. It seems that women and men who are violent and have personality disorders are comparable in their risk of recidivism.

Adult↗