Hannu Koponen

Meta-analysis of Paternal Age and Schizophrenia Risk in Male Versus Female Offspring

INTRODUCTION Advanced paternal age (APA) is a reported risk factor for schizophrenia in the offspring. We performed a meta-analysis of this association, considering the effect of gender and study design. METHODS We identified articles by searching Pub Med, PsychInfo, ISI, and EMBASE, and the reference lists of identified studies. Previously unpublished data from the Northern Finland 1966 Birth Cohort (NFBC 1966) study were also included. RESULTS There were 6 cohort studies and 6 case-control studies that met the inclusion criteria. In both study designs, there was a significant increase in risk of schizophrenia in the offspring of older fathers (≥30) compared to a reference paternal age of 25-29, with no gender differences. The relative risk (RR) in the oldest fathers (≥50) was 1.66 [95% confidence interval (95% CI): 1.46-1.89, P < 0.01]. A significant increase in risk was also found for younger fathers (<25) in males (RR = 1.08, 95% CI: 1.02-1.14, P = 0.01) but not females (RR = 1.04, 95% CI: 0.97-1.14, P = 0.28). The population attributable risk percentage (PAR%) was 10% for paternal age ≥30 and 5% for paternal age <25. DISCUSSION Both APA (≥30) and younger paternal age (<25) increase the risk of schizophrenia; younger paternal age may be associated with an increased risk in males but not females. This risk factor increases the risk of schizophrenia as much as any single candidate gene of risk. The mechanism of these associations is not known and may differ for older and younger fathers.

Negative symptoms in schizophrenia—A review

Negative symptoms refer to the weakening or lack of normal thoughts, emotions or behaviour in schizophrenia patients. Their prevalence in first-episode psychosis is high, 50–90%, and 20–40% of schizophrenia patients have persisting negative symptoms. Severe negative symptoms during the early stages of treatment predict poor prognosis. The aim of the study was to review the current literature on the negative symptoms of schizophrenia. In June 2007, the following databases were searched: Web of Science, PubMed, PsycINFO, Medline (Ovid) and Scopus. The search included articles written in English and no time limit was determined. The studies were manually screened by one of the authors according to the title and abstract. About one in three schizophrenia patients suffer from significant negative symptoms. In these patients, negative symptoms constitute a key element of overall symptoms, weakening their ability to cope with everyday activities, affecting their quality of life and their ability to manage without significant outside help. About one in three schizophrenia patients suffer from significant negative symptoms. Attention should be focused on negative symptoms during the early phase of treatment, because they cause significant impairment to patients’ quality of life. So far, no treatment appears to substantially improve negative symptoms narrowly defined. However, according to clinical experience, when treating negative symptoms, the best effect is achieved by optimizing the dose of medication and by complementing it with psychosocial therapies.

Childhood central nervous system infections and risk for schizophrenia

Abstract.Central nervous system (CNS) viral infections have been suggested to increase the risk of schizophrenia, although most of the evidence is indirect and comes from rather few studies on exposure to various infections in general. In the Northern Finland 1966 Birth Cohort the association between schizophrenia and other psychoses and childhood CNS infections has been analysed, and in this paper we present the follow-up results up to the end of 1994 and 1997.Data regarding the infections were collected prospectively between 1966–1980 and data on psychoses from 1982. The registered psychiatric diagnoses were validated using the DSM-III-R classification. Out of the 11017 subjects (96% of all births in that year) 145 had suffered a CNS infection during childhood, which in 102 cases was a viral infection. In the follow-up to the end of 1994, 76 had schizophrenia, and their number increased to 100 to the end of 1997. In addition, up to the end of 1994, 52 patients had a non-schizophrenic psychosis.Four cases in the schizophrenia patient group and none of the patients with other psychosis had suffered a viral CNS infection. None of the schizophrenia cases and two of the patients with other psychosis had had a bacterial infection. The adjusted odds ratio for schizophrenia after a viral CNS infection was 4.8 (95% confidence intervals [CI] 1.6–14.0) in the follow-up to the end of 1994 and 2.5 (0.9–7.0) in the follow-up to the end of 1997. The clinical course variables did not differ between the schizophrenia patients with or without CNS infection.Our results suggest that viral CNS infections during childhood may have a role as a risk factor for schizophrenia. Their role may be modest at the population level due to their relative rareness.

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.

Depressive symptoms predispose females to metabolic syndrome: a 7-year follow-up study

Objective:  To evaluate the risk for developing metabolic syndrome when having depressive symptoms.

Prevalence of alcohol use disorders in schizophrenia – a systematic review and meta-analysis

Objective:  Our aim was to present recent studies of alcohol use disorders (AUDs) in patients with schizophrenia, estimate overall prevalence and characteristics affecting the prevalence of AUDs.

Schizophrenia and sudden cardiac death—A review

Schizophrenia is a devastating mental disorder, which is often associated with severe loss of functioning and shortened life expectancy. Suicides and accidents are well-known causes of the excess mortality, but patients with schizophrenia have also been reported to be three times as likely to experience sudden unexpected death as individuals from the general population. This review is aimed to offer an update of the prevalence and mechanisms for sudden cardiac death in schizophrenia. The PubMed database was searched from 1966 up to May 2007 with key words schizophrenia AND “ sudden cardiac death” OR “autonomic dysfunction” OR “torsades de pointes”. Part of the high death rates may be explained by long-lasting negative health habits, disease- and treatment-related metabolic disorders, and consequent increased frequencies of cardiovascular diseases. The antipsychotic medications may also increase the risk as some antipsychotics may cause prolongation of QT-time, serious ventricular arrhythmias and predispose to sudden death. Autonomic dysfunction seen as low heart rate variability and decreased baroreflex sensitivity may also contribute via malignant arrhythmias. Due to the complex interaction of various risk factors for sudden death, the patients need a comprehensive follow-up of their physical health. In addition, more studies on the role and prevalence of autonomic dysfunction in psychotic patients are needed.

Citalopram in the treatment of obsessive-compulsive disorder: an open pilot study

Obsessive‐compulsive disorder (OCD) is a common anxiety disorder, which often causes significant impairment of the affected individuals social, occupational or interpersonal functioning. Previous reports suggest that the disorder may be treated with the tricyclic antidepressant clomipramine, and also with the more recently introduced selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, fluvoxamine, sertraline and paroxetine. The present 24‐week open pilot study was designed to examine the efficacy, appropriate dose range, side‐effects and clinical usefulness of citalopram in OCD. A total of 29 OCD patients were included in the study, of whom 76% showed alleviation of symptoms as evaluated by various self‐and observer‐rated scales, such as the Yale‐Brown Obsessive Compulsive Scale. In most cases the citalopram doses used were in most cases 40 or 60 mg daily, and the treatment was well tolerated. The most commonly experienced adverse events during the study were nausea, vomiting, increased dreaming and decreased sleep. Diminished sexual desire and orgasmic dysfunction were also reported. Despite having the limitations of an open study, our results suggest that citalopram may be effective in the treatment of obsessive‐compulsive disorder.

Computed tomography findings in delirium

Computerized tomography of the head was carried out on 69 elderly patients who met the DSM-III criteria for delirium and 31 neurological controls in order to evaluate the focal changes and generalized brain atrophy associated with delirium. Neither the difference between the mean ages nor the sex distribution in these groups was statistically significant. The delirious patients differed from the controls significantly in ventricular dilatation and cortical atrophy, and there was a statistically significant correlation between the width of the sylvian fissure and Mini-Mental State Examination score. Focal changes were also statistically more common in the delirious patients, and these changes tended to concentrate in the high-order association areas of the right hemisphere. Results suggest a marked predisposing role for the structural brain diseases (primary degenerative and multi-infarct type dementias, parkinsonism) in the development of delirium in elderly patients.

Longitudinal changes in total brain volume in schizophrenia: relation to symptom severity, cognition and antipsychotic medication.

Studies show evidence of longitudinal brain volume decreases in schizophrenia. We studied brain volume changes and their relation to symptom severity, level of function, cognition, and antipsychotic medication in participants with schizophrenia and control participants from a general population based birth cohort sample in a relatively long follow-up period of almost a decade. All members of the Northern Finland Birth Cohort 1966 with any psychotic disorder and a random sample not having psychosis were invited for a MRI brain scan, and clinical and cognitive assessment during 1999–2001 at the age of 33–35 years. A follow-up was conducted 9 years later during 2008–2010. Brain scans at both time points were obtained from 33 participants with schizophrenia and 71 control participants. Regression models were used to examine whether brain volume changes predicted clinical and cognitive changes over time, and whether antipsychotic medication predicted brain volume changes. The mean annual whole brain volume reduction was 0.69% in schizophrenia, and 0.49% in controls (p = 0.003, adjusted for gender, educational level, alcohol use and weight gain). The brain volume reduction in schizophrenia patients was found especially in the temporal lobe and periventricular area. Symptom severity, functioning level, and decline in cognition were not associated with brain volume reduction in schizophrenia. The amount of antipsychotic medication (dose years of equivalent to 100 mg daily chlorpromazine) over the follow-up period predicted brain volume loss (p = 0.003 adjusted for symptom level, alcohol use and weight gain). In this population based sample, brain volume reduction continues in schizophrenia patients after the onset of illness, and antipsychotic medications may contribute to these reductions.