Lack of evidence for elevated obstetric complications in childhood onset schizophrenia.

BACKGROUND: Pre-, peri-, and postnatal obstetric complications (OC) are reported to be more frequent in adult patients with schizophrenia and have been linked to both greater severity and to "earlier" age of onset (before either age 18 or 22) in studies of adult patients. We hypothesized that by extrapolation, patients with childhood-onset schizophrenia (COS), with very early onset and very severe illness, would have had more numerous or more salient OC compared with their healthy siblings. METHODS: We compared the obstetric records of 60 COS children and 48 healthy siblings using the Columbia Obstetrics Complication Scale, a comprehensive measurement scale consisting of 37 variables having included a separate scale for fetal hypoxia. RESULTS: Patients with COS did not have a higher incidence of OC than the healthy sibling control group with the exception of increased incidence of maternal vomiting. CONCLUSIONS: Obstetric complications, with the possible exception of maternal vomiting, are unlikely to play a major role in the etiopathogenesis of childhood-onset schizophrenia.     

Effects of antipsychotic drugs on memory functions of schizophrenic patients.

In this research we investigated the effects of 4 antipsychotic drugs with different anticholinergic components on different memory functions of schizophrenic patients. Drugs were administered in cumulative doses and memory was tested 90 min after each drug was administered. The results show that chlorpromazine and thioridazine impaired short-term verbal memory after 6 h of sequential administration. Trifluoperazine and haloperidol improved short-term verbal memory from the third to the fifth administration. Immediate memory, long-term memory and visual short-term memory were not impaired by any drug.     

Pseudoakathisia and negative symptoms in schizophrenic subjects.

The characteristics of schizophrenic subjects with pseudoakathisia were compared with those without. Those with pseudoakathisia displayed significantly more negative symptoms. This survived correction for other coexisting movement disorders.     

Influence of cannabis abuse on schizophrenic psychopathology.

A study was carried out on a group of 95 schizophrenic patients (DSM-III-R criteria) under the age of 35, 23 of whom were cannabis abusers in the past year. The objective of the study was to evaluate the effect of cannabis on positive and negative schizophrenic symptoms, evaluated using Andreasen's Scales for the Assessment of Positive and Negative Symptoms (SAPS and SANS). There were no statistically significant differences between the groups on the SAPS; the group of cannabis abusers had higher scores except for the delusions subscale. On the SANS nonabusers scored higher, with a significant difference on the alogia subscale. The results suggest that the consumption of cannabis by schizophrenic patients could attenuate negative symptoms, which would support the self-medication hypothesis of cannabis abuse.     

Obstetric complications and autoantibodies in schizophrenia

Our hypothesis stated that patients with schizophrenia who had obstetric complications (OC) were more likely to have autoimmune abnormalities than those without OC. OC were rated using a checklist. Anti-brain autoantibodies were measured in serum using an enzyme immunoassay. Autoantibodies to non-CNS tissues were detected using serological procedures. There were no significant differences between the two groups with respect to anti-brain antibodies, but patients with OC (n= 24) had a significantly higher prevalence of autoantibodies to non-CNS tissues than patients without OC (n= 25). Both groups were receiving neuroleptic drugs. OC may contribute to autoimmune abnormalities among patients with schizophrenia.     

Correlations between obstetric complications and neurological soft signs in Tunisian patients with schizophrenia

The objective of this study was to examine the correlations between a history of obstetric complications (OC) and neurological soft signs (NSS) in Tunisian patients with schizophrenia. Forty‐six patients were assessed using the Krebs et al. NSS scale. History of OC was obtained from the patients' mothers using the McNeil–Sjöström scale. Although there was no significant difference in NSS between patients with and without OC, there were negative correlations between OC total score and motor coordination and integration sub‐scores. These negative correlations suggest that OC could enhance the effects of genetic risk factors for schizophrenia.     

Prenatal underdevelopment and schizophrenia: a case report of monozygotic twins

A case is described herein of monozygotic twins discordant for schizophrenia that illustrates possible causal events of prenatal underdevelopment, morphological changes in the brain, poor premorbid functioning, and the development of schizophrenia. The affected twin was born with a birthweight of 1620 g, whereas the unaffected twin weighed 2300 g at birth. Marked differences in sociability and intelligence were observed between the twins from early childhood. Magnetic resonance imaging of the brain revealed high-intensity signals in the white matter and enlarged ventricles in the affected twin, while no such abnormality was detected in the well twin. This twin pair suggests a possibility that hypoxic brain damage associated with prenatal underdevelopment may be a causal factor for abnormalities in psychosocial development and subsequent schizophrenia.     

Light exposure patterns in schizophrenia.

Spontaneous light exposure patterns were studied in 10 chronic schizophrenic patients. Half of our schizophrenic patients exposed themselves to bright light exceeding ordinary indoor illumination. There was a significant positive correlation between the percentage of exposure to bright light and the Brief Psychiatric Rating Scale subscore anergia and a significant negative correlation with depression.     

Gene-environment interaction and covariation in schizophrenia: the role of obstetric complications

While genetic factors account for a significant proportion of liability to schizophrenia, a body of evidence attests to a significant environmental contribution. Understanding the mechanisms through which genetic and environmental factors coalesce in influencing schizophrenia is critical for elucidating the pathways underlying psychotic illness and for developing primary prevention strategies. Although obstetric complications (OCs) remain among the most well-documented environmental indicators of risk for schizophrenia, the pathogenic role they play in the etiology of schizophrenia continues to remain poorly understood. A question of major importance is do these factors result from a genetic diathesis to schizophrenia (as in gene-environment covariation), act additively or interactively with predisposing genes for the disorder in influencing disease risk, or independently cause disease onset? In this review, we evaluate 3 classes of OCs commonly related to schizophrenia including hypoxia-associated OCs, maternal infection during pregnancy, and maternal stress during pregnancy. In addition, we discuss several mechanisms by which OCs impact on genetically susceptible brain regions, increasing constitutional vulnerability to neuromaturational events and stressors later in life (ie, adolescence), which may in turn contribute to triggering psychosis.     

Olfactory impairment in monozygotic twins discordant for schizophrenia

Objective Several studies demonstrated olfactory dysfunction in patients with schizophrenia, some reported deficient olfaction in unaffected relatives of schizophrenics as well. This study differentially assessed olfactory acuity as well as smell identification and smell discrimination in monozygotic twins discordant for schizophrenia and healthy, monozygotic control twins, to determine the genetic basis of different olfactory modalities and their association to schizophrenia. Method The SniffinSticks test,a comprehensive and standardized olfactory test, was employed to assess the olfactory function of 10 monozygotic twin pairs discordant for schizophrenia versus 10 age- and sexmatched healthy,monozygotic twin pairs. Results Olfaction of affected monozygotic twins was globally impaired. Partial olfactory impairment of their unaffected co–twins may point to a genetic cause of olfactory impairment in schizophrenia. The influence of genetic factors was most evident for olfactory acuity and least evident for smell identification. All olfactory functions declined with duration of illness. Side of stimulus presentation did not influence olfactory performance. Conclusions Genetic factors associated with olfactory dysfunction may contribute to schizophrenia. The degree of the genetic influence on olfaction depends on the olfactory domain under examination.     

Influence of genetic loading,obstetric complications and premorbid adjustment on brain morphology in schizophrenia: a MRI study

Cerebrospinal fluid (CSF) space enlargement in schizophrenia is a prominent finding. This study was initiated to examine the influence of genetic loading, obstetric complications and premorbid adjustment on the extent of this enlargement. The sample of this MRI study consisted of 40 schizophrenic patients, 24 psychiatric and 40 healthy family members from 10 uniaffected and 19 multiple affected families with schizophrenia, such as 27 control subjects from non-affected families. The ventricle-to-brain-ratio (VBR), and the areas of the third ventricle, sylvian fissure, temporal horn and interhemispheric fissure at the slice where these structures reached their maximum were examined relatively to the corresponding total brain areas. The sum of CSF areas was calculated as a parameter for global atrophy. From MANCOVA adjusted for intervening variables the right VBR and the sum of CSF areas revealed significant differences between diagnostic groups. For these areas schizophrenic patients showed an increase compared to control subjects and family members with psychiatric disorder. Genetic loading influenced the interhemispheric fissure, enlarged in multiple affected compared to uniaffected families, and the temporal horn asymmetry, which was right sided (right > left) in control subjects and multiple affected families, but inverted in uniaffected families. Neonatal obstetric complications influenced only the size of the VBR, while premorbid adjustment predicted various CSF areas. In conclusion, schizophrenic subjects from multiple and uniaffected families showed a global atrophy, which was most pronounced in the VBR. Genetic loading seems to have an impact on frontal regions as the interhemispheric fissure and on the temporal horn. Received: 14 February 2002 / Accepted: 17 February 2003 Correspondence to Peter Falkai, MD     

Simple schizophrenia: an investigation of Bleuler's criteria based on the major twin studies of schizophrenia.

Schizophrenics fulfilling Bleuler's criteria for simple schizophrenia--no evidence of hallucinations, delusions, and catatonic behavior--were similar to schizophrenics with more typical forms of the disorder with respect to negative symptoms, premorbid social adjustment, and age at onset. These results support the validity of the simple schizophrenia subtype by providing evidence that schizophrenics without conspicuous positive symptoms are similar to those with such symptoms on these core features of the disorder.     

Neurologic complications in liver transplantation

A retrospective review is presented of neurologic complications in our first 143 consecutive adult patients (208 liver transplants in 143 adults and 18 children) undergoing liver transplantation. Nineteen (13.2%) of the 143 patients developed neurologic complications in the postoperative period. Immunosuppression was initiated intraoperatively with steroids with the addition of azathioprine on Day 1 and cyclosporine, adjusted by RIA to a level of 400-600 ng/ml, on Day 2 post-transplantation. Azathioprine is discontinued in the third month. Fourteen of the 19 patients (73.6%) presented with CNS complications characterized by: diffuse multifactorial encephalopathy (5 patients); leukoencephalopathy (2 patients) which required temporary (1 case) or permanent (1 case) discontinuation of cyclosporine A; hemorrhage (in 2 cases due to arterial hypertension and coagulopathy and another due to unknown causes); ischemic/anoxic injury secondary to cardiorespiratory arrest (2 patients) or arteriothrombosis (1 patient); and myelopathy (1 patient) due to vertebral compression (T10-T11) secondary to osteoporosis. The diagnostic studies most often employed were computed tomographic (CT) (85.7%) and electroencephalography (EEG) (42.8%). Five of 19 patients (26.3%) suffered peripheral nervous system (PNS) complications: 1 patient with reversible Claude-Bernard-Horner Syndrome caused by central venous catheterization during anesthesia: 2 patients with peroneal nerve palsy due to compression below the knees by operating room table supports; 1 patient with an irreversible lesion of the right recurrent laryngeal nerve secondary to prolonged intubation and central venous catheterization; and 1 patient with a reversible lesion of the left brachial plexus secondary to inadvertant hyperextension of the upper extremity on the O.R. table due to the need for dialysis and catheterization of the axillary vein for veno-venous bypass. Nine of fourteen (9/14, 64.2%) of patients with CNS lesion died. In five of the nine patients (55.5%) who died with CNS lesion, the neurologic lesions (CNS hemorrhage and anoxic-isquemic injury) were directly or indirectly responsable for death. Strict control of patient positioning in the operating room, arterial hypertension and coagulation disturbance in the immediate postoperative period and serum cyclosporine A levels would eliminate the majority of neurologic complications in patients undergoing liver transplantation.     

Psychopathological and social status of patients with affective, schizophrenic and schizoaffective disorders after long-term course

A total of 106 affective, 101 schizoaffective and 148 schizophrenic disorders were investigated after a long-term course of illness (mean follow-up period 25.1 years), employing narrow definitions and using reliable international instruments of evaluation. In addition, the social consequences of the illness were evaluated (upward and downward social and occupational drift, premature retirement and achievement of the expected social development). Considering all aspects of outcome, schizophrenic patients (narrow defined, slightly modified DSM-III criteria) had persistent alterations in several aspects of social life, communication and cognitive functions, in some cases to a very high degree. Although the outcome of affective disorders is not always favourable, it is significantly more favourable than that of schizophrenia. Schizoaffective disorders occupy a position between affective and schizophrenic disorders regarding outcome, but with more similarities to that of affective than to that of schizophrenic disorders.     

A controlled study of brain structure in monozygotic twins concordant and discordant for schizophrenia.

BACKGROUND: We examined monozygotic twins concordant and discordant for schizophrenia to clarify the role of genetic and environmental factors in determining brain abnormalities. METHODS: Magnetic resonance imaging brain scans were obtained from 14 monozygotic twin pairs concordant and 10 monozygotic pairs discordant for schizophrenia, as well as 17 pairs of monozygotic control twins. Twenty-two discordant sibling-pairs and 56 pairs of unrelated control subjects were included to assess the extent of genetic control over these structures. RESULTS: Within-pair similarities for whole brain volume increased as pair members were more closely related genetically (monozygotic twins > siblings > unrelated control subjects). Schizophrenic twins, whether from concordant or discordant pairs, had smaller whole brain volumes than control twins. The probands of discordant pairs showed more abnormalities in hippocampal, third and lateral ventricular volumes than concordant twins. CONCLUSIONS: Whole brain volume is under high genetic control and smaller whole brain volume is a reflection of the genetic liability to develop schizophrenia. The variation in hippocampal and ventricular volumes within discordant monozygotic pairs indicates a role for environmental factors in determining these volume abnormalities in schizophrenia. Such factors may also underlie the more extensive morphometric deviations in patients from monozygotic discordant twins than in their counterparts from concordant twins.     

Family burden and coping strategies in schizophrenia: are key relatives really different to other relatives?

Subjective and objective burden, psychiatric symptoms and coping strategies in a sample of 90 key relatives and other relatives of patients with schizophrenia, living in two European countries, were explored by means of well-validated questionnaires. The levels of burden on key relatives did not differ significantly from those on other relatives. Moreover, the risk of developing psychiatric symptoms was similar in the two subject groups at both centres. Significant correlations were found between key relatives and other relatives concerning the adoption of emotion-focused coping strategies. These data contrast with the current belief that family burden in schizophrenia is mainly a burden of key relatives, and they emphasize the need to provide supportive interventions for as many relatives as possible.     

Maternal anxiety and obstetric complications.

The association between maternal anxiety in the third trimester of pregnancy and obstetric complications was studied in 146 patients using the IPAT Anxiety Self-Analysis Form. It was found that the incidence of pre-eclampsia, forceps delivery, prolonged and precipitate labour, primary post-partum haemorrhage, manual removal of the placenta and clinical foetal distress were all significantly higher amongst the high anxiety group.     

Diagnostic and demographic correlates of substance abuse in schizophrenia and major affective disorder.

The relationship between history of specific types of substance abuse (alcohol, stimulants, cannabis, hallucinogens, narcotics) and demographic and diagnostic variables was evaluated in a large (n = 263) sample of schizophrenic, schizoaffective, major depression and bipolar disorder patients. Prevalence rates were also compared with rates observed in a previous study (1983-1986) conducted using the same methods. Demographic characteristics (gender, age, race, educational level) were strong predictors of type of substance abuse. Patients with a history of cocaine abuse had fewer prior hospitalizations, suggesting that less impaired psychiatric patients may be more prone to illicit substance abuse. Diagnoses were not related to most types of substance abuse, although there was a trend for bipolar patients to have a history of alcohol abuse. The results demonstrate the importance of matching groups on demographic characteristics when exploring diagnostic differences in preference to abuse specific types of substances.     

"Panic attacks" in Parkinson's disease

A series of 31 Parkinson's disease (PD) patients suffering from panic attacks (PA), late in the evolution of their disease, was analyzed from a group of 131 levodopa-treated PD patients. We found that many of motor, sensory, and vegetative symptoms, previously described as complicating phenomena in PD, constituted some of the symptoms of panic disorders. Comparing PA series with the series of PD patients who did not complain of PA, we discovered a clear-cut relationship of PA with the presence of standing/gait troubles (p<0.001), depression (p<0.001), and dyskinesias/fluctuations (p<0.001). The patients of the PA series also presented a more precocious age of PD onset, were put on levodopa therapy earlier, and needed to be treated with higher doses of levodopa than the patients without PA. Finally, we hypothesize that PA could be considered to be a sort of abstinence syndrome from levodopa, because they appears mostly (90.3%) in the OFF phase of fluctuations, and are relieved administering new doses of levodopa or dopaminergic agonists. Nevertheless, we suggest PA are not directly related to the pharmacological properties of levodopa, but to alterations of the noradrenergic systems in the CNS.     

A comparison of obstetric and neonatal complications between children with autistic disorder and their siblings

Sixty-one children had a diagnosis of autistic disorder according to the DSM3-R criteria in a population based study of mentally retarded children between the ages of 5 and 19 years in the Aberdeen city area of Scotland. Obstetric case records were traced for 36 out of these 61 autistic children. The obstetric case records of siblings of 30 of these autistic children were also traced. Modified versions of Prechtl's obstetric optimality scale along with that of Pamas were used to score pre-, peri-and neonatal obsteric complications in the autistic group and their normal sibling controls. A Spearman's correlation coefficient test between the scores of the Childhood Autism Rating Scale (CARS) and the Obstetric and Neonatal Complication (ONC) scores of all autistic children did not reveal any significant correlation. However, among the 20 severe autistic children, Spearman's test showed significant correlation between the scores of CARS and some ONC scores. Overall, no statistically significant difference between the autistic children and their siblings in the scores of obstetric optimality was detected by using the Wilcoxon test.