Genetic background of extreme violent behavior.

In developed countries, the majority of all violent crime is committed by a small group of antisocial recidivistic offenders, but no genes have been shown to contribute to recidivistic violent offending or severe violent behavior, such as homicide. Our results, from two independent cohorts of Finnish prisoners, revealed that a monoamine oxidase A (MAOA) low-activity genotype (contributing to low dopamine turnover rate) as well as the CDH13 gene (coding for neuronal membrane adhesion protein) are associated with extremely violent behavior (at least 10 committed homicides, attempted homicides or batteries). No substantial signal was observed for either MAOA or CDH13 among non-violent offenders, indicating that findings were specific for violent offending, and not largely attributable to substance abuse or antisocial personality disorder. These results indicate both low monoamine metabolism and neuronal membrane dysfunction as plausible factors in the etiology of extreme criminal violent behavior, and imply that at least about 5-10% of all severe violent crime in Finland is attributable to the aforementioned MAOA and CDH13 genotypes.

Double-blind study of mirtazapine and placebo in hospitalized patients with major depression.

The purpose of the present 6-week multicenter dose finding study was to compare the efficacy and tolerability of mirtazapine (preferentially presynaptic alpha 2-adrenergic receptor blocker) to placebo in hospitalized patients with major depression. The clinical efficacy was evaluated with the Hamilton Depression Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), Beck Self-Rating Depression Scale, Global Assessment Scale (GAS), and Brief Psychiatric Rating Scale (BPRS). The side effects were recorded on a checklist of emergent symptoms (ROSE) and physical examinations, ECG, clinical chemistry, and hematology tests were carried out. The dosages of mirtazapine were gradually raised from 15 mg to 50 mg. One hundred and fourteen patients were included. Twenty-two patients (37%) in mirtazapine group and 24 (44%) in the placebo group were prematurely withdrawn from the study mainly due to inadequate efficacy. The decrease in HAM-D and MADRS was generally more pronounced in the mirtazapine group than in the placebo group. Minor side effects were reported in less than 15% of the patients in both groups. Only fatigue and faintness were slightly more pronounced in the mirtazapine group than in the placebo group. No significant changes were found in laboratory parameters. Because of methodological flaws like combining a dose finding study with a placebo controlled study, further conclusions should not be made on the efficacy of mirtazapine when treating depressive patients.

Zuclopenthixol and haloperidol in patients with acute psychotic states. A double-blind, multi-centre study.

A double-blind, multi-centre study was carried out in 49 hospitalized patients with an acute psychosis or an exacerbation of a chronic psychosis to compare the wanted and unwanted effects of the neuroleptics, zuclopenthixol and haloperidol. Patients were allocated at random to receive treatment with one or other of the trial drugs for 8 weeks or until discharge. Five patients on zuclopenthixol and 6 on haloperidol were excluded from the efficacy analyses because they did not complete a minimum of 4-weeks' treatment. Dosage was chosen and adjusted to the individual patient's condition and response. The average daily doses in Week 4 were 33.5 mg and 10.3 mg, respectively. Clinical assessments, including CGI, BPRS and the UKU side-effect scale, were done at baseline, and after 1, 2, 4, 6 and 8 weeks of treatment or at discharge if the patient was discharged earlier than Week 8. Both treatments caused a significant reduction in scores with no between-group differences. More patients in the zuclopenthixol group were discharged early indicating slightly more rapid onset of action. Zuclopenthixol caused a significantly greater improvement in 'anxious-depression' factor score than haloperidol. The most frequent unwanted effects were extrapyramidal symptoms and there were no significant differences between the groups. The extrapyramidal symptoms tended to be transient in the zuclopenthixol group, but not in the haloperidol group. The study confirmed that both zuclopenthixol and haloperidol were effective drugs in the treatment of acute, psychotic patients. There was a trend towards a slightly more rapid onset of effect and a somewhat stronger anxiolytic-antidepressant effect by zuclopenthixol compared to haloperidol.

Psychosocial factors, female fertility and pregnancy: a prospective study--Part I: Fertility.

The aim of the study was to determine prospectively whether psychosocial, personality-related or stress factors have influence on fertility. Initially 191 healthy nulliparas without a history of infertility who were planning to have children were studied gynecologically and by psychiatric examination. Life changes and changes in psychosocial stress were monitored throughout the study period of 6 months at regular intervals. The following factors turned out to be associated with higher than average fertility in the final follow-up sample of 180 women: looking younger than one's actual age, no fluctuation in body weight before pregnancy, low consumption of coffee, low score of psychosomatic symptoms, being the youngest sibling, low number of negative life changes, younger than spouse, having phobic traits, and customarily religious. There was no clearcut association between low fertility and deviations in personality factors.

Psychosocial factors, female fertility and pregnancy: a prospective study--Part II: Pregnancy.

The aim of the study was to determine whether psychosocial factors have an influence on the progress and outcome of pregnancy and whether personality-related or stress factors are significant in this respect. One hundred and ninety-one nulliparas without a history of infertility were prospectively studied gynecologically and psychiatrically. Life changes and changes in stress factors were monitored throughout the study period and obstetric complications were registered. By the end of the study period 120 (63%) of the subjects had given birth, 38 (19%) had abortion, 22 (12%) did not conceive and the remaining 11 (6%) discontinued. Certain psychosocial factors (e.g. life changes, anxiety, subjectively estimated physically and mentally stressful work) were associated with complications of pregnancy. In the logistic regression analysis the psychosocial stress factors were more strongly associated with the outcome of pregnancy than the factors related to personality. Adjusting for the stress-buffering factors (personality, coping methods and social support) did not reduce the original association.

Risk of homicidal behavior among discharged forensic psychiatric patients.

We studied the risk of homicidal behavior among 281 released male forensic psychiatric patients during the 14-year period 1978-1991. Released patients were about 300 times more likely to commit a homicide than the general male population during the first year outside hospital, and the corresponding risk was 53-fold during a mean follow-up period of 7.8 years. The odds ratio for committing a homicide among all Finnish schizophrenics during the 12-year period 1980-1991 was 9.7, which indicates that previous criminality associated with schizophrenia also increases the risk of homicidal behavior remarkably when compared with schizophrenia per se. We believe that this kind of epidemiological approach is a useful method of identifying and classifying factors associated with very high risk of homicidal behavior and preventing homicidal behavior among high-risk populations.

Hepatitis A, B, C and HIV infections among Finnish female prisoners--young females a risk group.

OBJECTIVES: Previous prison studies have shown that the female gender is associated with higher hepatitis C prevalence. However, there are few prison studies of gender differences concerning the risk factors of hepatitis C infections. We studied the prevalence of hepatitis and HIV infections and the risk factors among Finnish female prisoners. METHODS: The material consisted of 88 females and 300 male prisoners as controls. RESULTS: The prevalence of hepatitis C virus antibodies was 52%, hepatitis B surface antigen 0%, hepatitis A virus antibodies 38% and HIV antibodies 1% among women, and 44%, 0.7%, 4% and 0.7% respectively among men. Among women, 71% of the age group 16-24 had HCV. There was no significant association between gender and HCV. Women were more commonly sharing syringes/needles and had unsafe sexual habits. Among women, HCV was associated only with IDU and syringe/needle sharing whereas among men also with tattoos, cumulative years in prison and age. CONCLUSIONS: Especially young females had a high prevalence of HCV. The study showed that the risk factors are differentiated by gender. This should be taken into account when assessing earlier studies which mainly concentrate on men.

Carbamazepine-induced changes in plasma levels of neuroleptics.

We compared the effect of carbamazepine and oxcarbazepine treatment on the plasma levels of clozapine and thioridazine in 12 patients. There was a 47% decrease in the plasma levels of clozapine (p < 0.005, Students two-tailed t-test) during carbamazepine treatment, while the effects on the thioridazine levels were less marked (n.s.). Since carbamazepine is also used in patients receiving concurrent clozapine therapy, it is important to take this marked interaction between these two drugs into account.

Cis(Z)-clopenthixol and haloperidol in chronic schizophrenic patients--a double-blind clinical multicentre investigation.

Sixty-three chronic schizophrenic in-patients were included in the double-blind, double-dummy clinical trial comparing antipsychotic activity and side effects of cis(Z)-clopenthixol and haloperidol. Test treatment was administered at least 8 and in most cases 12 weeks with clinical evaluations including BPRS, NOSIE-30, CGI and single side effects done at weeks 0, 2, 4, 8, and 12. The average end-of-trial doses were 40 mg cis(Z)-clopenthixol and 10 mg haloperidol. Statistically significant improvements of total BPRS-score and Thinking disturbance were registered with both drugs from week 2 onwards. At week 12 when 36 patients were receiving test treatment total BPRS-score was reduced by 31% in the cis(Z)-clopenthixol group and by 17% in the haloperidol group. At week 4 Thinking disturbance was reduced by 32% in the cis(Z)-clopenthixol group and by 16% in the haloperidol group--these findings constituted the only significant difference between test drugs. Compared to the BPRS-results less improvements and no differences between test drugs were registered with NOSIE-30 and CGI. Any trends towards different frequency and severity of side effects were in the favour of cis(Z)-clopenthixol.

The patients' opinions about curative factors in involuntary treatment.

The patients' opinions about their treatment are seldom solicited in psychiatry. We studied the opinions of 225 patients about curative factors in their treatment in a maximum security hospital: 90% answered the questions, which evaluated 38 forms of treatment. The patients received help from free walking in the hospital area in 98% of the patients, holidays in 93%, a personal psychiatric nurse in 91%, trips in 91%, communication in 88%, personnel's support in 87% and a psychiatrist in 86%. Medication was considered helpful in 77% and even restriction or isolation in 36% of the patients. If the patient experienced help from the psychiatrist, the cross-tabulation revealed that she or he also received help from many other treatment forms, even from the isolation. Help from the personal psychiatric nurse and medication depended on many other treatment forms. The most helpful treatment factors experienced were liberties and interactive treatment forms.

A long-term study of remoxipride in chronic schizophrenic patients.

The purpose of this study was to assess the tolerability and efficacy of 150-600 mg remoxipride (predominantly a DA2 receptor antagonist) in an open long-term (1 year) multicentre trial in chronic schizophrenic patients. The mean duration of illness before entering the study was 21 years and the pre-study neuroleptic dosage in chlorpromazine equivalents was 930 mg/day. The clinical efficacy was measured with the Brief Psychiatric Rating Scale and the Clinical Global Impression scale. The adverse events were recorded by a 26-item Adverse Symptom Checklist and by the Abnormal Involuntary Movements Scale. Forty-five patients were included in the study. The mean daily dose of remoxipride during the last week of treatment was 378 mg. Eighty percent (36 patients) withdrew prematurely (< 1 year). The main reasons for withdrawal were: ineffectiveness (n = 15), treatment refusal (n = 12) and adverse events (n = 8). The most frequently reported adverse events were insomnia (n = 20) and tiredness (n = 7), whereas only a few (n = 6) extrapyramidal symptoms were reported. There was no relationship between remoxipride plasma concentration and clinical efficacy nor was any relationship found between the ratio of pretrial chlorpromazine equivalent to last remoxipride dose and the therapeutic effect. Remoxipride alone seemed to have an insufficient neuroleptic efficacy in these chronic and treatment-resistant schizophrenic patients but was well tolerated.

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.