Unwanted pregnancy as a risk factor for offspring schizophrenia-spectrum and affective disorders in adulthood: a prospective high-risk study.

BACKGROUND: This study investigated whether 'unwanted pregnancy' (i.e. a negative or ambivalent attitude towards the pregnancy/reproduction) is associated with schizophrenia-spectrum and affective disorders in the offspring in adulthood, and if so, whether other pregnancy, perinatal, childhood or genetic-risk factors account for this association. METHOD: In a prospective study beginning during pregnancy, unwanted pregnancy (in combination with other early life risk factors) was studied in relation to adult mental disorders in 75 genetic high-risk (HR) and 91 normal-risk (NR) offspring, defined through maternal psychosis history. Early life risk factors were studied through personal interviews, observations and medical records, and offspring mental disorders were independently diagnosed through follow-up examination at about 22 years of age. RESULTS: Unwanted pregnancy by itself was significantly related to adult offspring schizophrenia-spectrum disorders in both the total sample and the HR subgroup, but the effect was found to be limited to the HR group and occurred in interaction with genetic risk. Other co-temporaneous pregnancy stressors and later perinatal complications, malformations and early childhood environmental stressors could not explain this relationship. Unwanted pregnancy also interacted with genetic-risk status in relating to affective disorders in the offspring. CONCLUSIONS: Unwanted pregnancy, when occurring together with genetic risk for psychosis, was found to be related to both adult schizophrenia-spectrum and affective mental disorders in the offspring. Although the effect of unwanted pregnancy could be mediated by other yet-unidentified factors, unwanted pregnancy might be a functional, discrete environmental psychosocial factor with its own deleterious impact on offspring mental development, when co-occurring with genetic risk.

A prospective study of offspring of women with psychosis: visual dysfunction in early childhood predicts schizophrenia-spectrum disorders in adulthood.

OBJECTIVE: Children with visual dysfunction have perinatal, neurological, visual-perceptual and cognitive abnormalities, similar to schizophrenia patients. We prospectively investigated whether visual dysfunction in childhood selectively predicts adult schizophrenia-spectrum disorders, and is related to childhood neurological abnormality. METHOD: Offspring of mothers with and without a history of psychosis were prospectively assessed with vision tests at 4 years, neurological examinations at 6 years, and interviews for psychiatric disorders at follow-up (93% effective, n=166) at 22 years. RESULTS: In the total sample and high-risk (HR) offspring, visual dysfunction at 4 years, and its severity, were associated only with schizophrenia-spectrum disorders in adulthood, and with neurological abnormality at 6 years. CONCLUSION: Visual dysfunction at 4 years of age selectively predicts schizophrenia-spectrum disorders in adulthood among HR offspring, this likely reflecting disturbed neurological development.

Craniofacial dysmorphology in Swedish schizophrenia patients.

OBJECTIVE: To perform detailed assessments of craniofacial dysmorphology in individuals with schizophrenia and controls in Sweden, in order to further elucidate the neurodevelopmental origins of schizophrenia. METHOD: We performed detailed, anthropometric assessments of craniofacial dysmorphology in male patients with schizophrenia (n=24), healthy controls (n=16), and patients' siblings with schizophrenia (n=2) in Sweden, while remaining as blind as possible to schizophrenia/control status. RESULTS: Individuals with schizophrenia evidenced significantly more craniofacial dysmorphology than controls, especially in the ears and mouth. At a group level, there was a dose-response type relationship between total dysmorphology score and patient/control status. CONCLUSION: The consistency of results across multiple studies supports the hypothesis that individuals with schizophrenia have increased rates of prenatal developmental disturbances. The presence of a dose-response type relationship between total dysmorphology score and patient/control status supports the importance of neurodevelopmental disturbance as a contributory cause of schizophrenia.

Obstetrical complications, parenting practices and risk of criminal behaviour among persons who develop major mental disorders.

OBJECTIVE: The present study examined whether socio-economic status (SES) of the family of origin, inadequate parenting, and pre and perinatal factors are antecedents of criminality among men and women who develop a major mental disorder. METHOD: The sample included the 82 men and 79 women from the 1953 Stockholm birth cohort who developed a major mental disorder by age 30. Information was extracted from obstetric files, health, social and work records and official criminal records. RESULTS: Among males, neonatal complications increased the risk of offending two-fold, the risk of violent offending 2.5 times, and the risk of early start offending 3 times. Neither pregnancy or birth complications, inadequate parenting, or SES of the family of origin increased the risk for offending. Among females, none of the factors that were examined were associated with offending. CONCLUSION: Complications in the neonatal period are associated with offending among men who develop major mental disorders.

Obstetric complications, parenting, and risk of criminal behavior.

BACKGROUND: The results of studies that have examined the relationship between prenatal and perinatal complications and adult criminality and violence are contradictory. Supporting evidence for this relationship comes from studies of samples drawn from a single cohort. The present study was designed to examine the associations between prenatal and perinatal complications and criminality, defining more precisely than past investigations subject characteristics and the types of offenses. METHODS: The cohort includes the 15 117 persons born in Stockholm, Sweden, in 1953 and followed up to age 30 years. Information was extracted from obstetric files, health, social, work, and criminal records. Obstetric complications were defined as deviations from normal development occurring at any point from conception through the neonatal period. Inadequate parenting was indexed by social intervention. RESULTS: Inadequate parenting was experienced by 19.1% of the men and 18.1% of the women, and was shown to increase the risk of offending (men, 1.39 times [95% confidence interval [CI], 1.28-1.50]; women, 2.09 [95% CI, 1.70-2.56]) and of violent offending (men, 2.02 times [95% CI, 1.67-2.44]; women, 2.09 [95% CI, 1.70-2.56]). Obstetric complications in the absence of family problems did not increase the risk of offending. A combination of pregnancy complications and inadequate parenting affected 3.1% of the men and 4.0% of the women, and increased the risk of offending (1.64 times [95% CI, 1.43-1.89]; 1.79 times [95% CI, 1.16-2.75], respectively) and violent offending (2.86 times [95% CI, 2.09-3.91]; 1.81 times [95% CI, 0.57-5.79]). CONCLUSIONS: A combination of pregnancy complications and inadequate parenting increased the risk of violent and nonviolent offending only slightly more than inadequate parenting alone. However, inadequate parenting was experienced by 5 times more cohort members than was the combination of inadequate parenting and pregnancy complications.

Increased rates of psychosis among immigrants to Sweden: is migration a risk factor for psychosis?

BACKGROUND: Previous studies have shown high rates of psychosis among Afro-Caribbean immigrants to the UK and immigrants to the Netherlands. Rates of schizophrenia-like psychoses (SLP), i.e. schizophrenia or other non-affective psychosis, among the native-born and immigrant populations were assessed in Malmö, the city in Sweden with the highest proportion of immigrants. METHODS: All adult patients admitted for in-patient psychiatric treatment in Malmö during the course of a 1-year period (N = 1162) were studied with regard to ethnicity and SLP diagnosis. A smaller sample consisting only of first-onset SLP cases (regardless of in- or out-patient status) was also studied (N = 56). Risks for admission and first-onset were calculated on the basis of current background population figures for Malmö. RESULTS: Compared with those who were native-born, immigrants had increased risk for admission for SLP, with a similar tendency for increased risk for first-onset of SLP. Relative risk for SLP admission was most markedly increased in immigrants from East-Africa. Background factors specifically associated with migration (e.g. extreme duress) did not appear to contribute strongly to SLP in immigrants. CONCLUSION: While the current results add to the growing body of evidence showing increased risk for psychosis in immigrants, vulnerability to psychosis may have been determined by factors other than the migration process.

Substance abuse in schizophrenia: a review of the literature and a study of correlates in Sweden.

The purpose of the current study is twofold: (a) to provide an overall synthesis of recent research on substance abuse in schizophrenia and (b) to present findings in a Swedish patient sample. Studies conducted since 1990 have found a wide range of abuse prevalence rates, with male gender and younger age as primary correlates. Less certainty exists regarding substance abuse as an independent risk factor for schizophrenia and its further impact on illness course. In a sample of 87 patients attending a psychiatric clinic in Malmö, lifetime prevalence of substance abuse was 48.3%, with abuse debut primarily preceding first contact for psychotic symptoms. Significant correlates of abuse were male gender, family history of substance abuse, and increased rates of hospitalization and criminality, with poorer outcome found in previous as well as current abusers. Alcohol abuse, either solely or in combination with other substances, was the main type of substance abuse. Although the specific factors (social, behavioural, genetic) that predispose schizophrenic patients to substance abuse remain unclear, the predominantly male profile of abusers might suggest a link between substance abuse and the poorer clinical outcome frequently observed, especially in male schizophrenic patients.

Neurodevelopmental origins of tardivelike dyskinesia in schizophrenia patients and their siblings.

The question of whether dyskinesia of the type found in tardive dyskinesia (TD) related to schizophrenia has a neurodevelopmental background was studied in a sample of 60 younger schizophrenia patients (mean age 38 years) and 21 of their non-ill siblings. TD-like dyskinesia was studied in relation to selected risk factors in the patients, and to neurological abnormality and parkinsonism in both patients and siblings. One or more signs of TD-like dyskinesia in patients were predicted by male gender, a history of obstetric complications, shorter illness duration, and shorter neuroleptic exposure. One or more signs of TD-like dyskinesia were found in 28.5 percent of the siblings and tended to be associated with neurological abnormality. Little co-occurrence of TD-like dyskinesia was found in the sibling and the patient in the same family. Patients' TD-like dyskinesia was significantly associated with hard neurological signs (independent of involuntary movements) but not with soft signs or primitive reflexes per se. TD-like dyskinesia showed a significant positive relationship to parkinsonism in patients. TD-like dyskinesia in younger schizophrenia patients appears to have neurodevelopmental antecedents and seems to represent one aspect of the total neurological abnormality associated with schizophrenia.

Minor physical anomalies and obstetric complications in schizophrenia.

OBJECTIVE: To evaluate the possibility of using congenital minor physical anomalies (MPA) and obstetric complications (OC) as individual-orientated, early life markers signalling increased risk for schizophrenia. METHOD: Previous findings using Waldrop and colleagues' MPA scale (and additional items) and systematic study of OC history are summarised concerning schizophrenia patients and individuals at heightened genetic risk for schizophrenia. RESULTS: Significantly increased rates of both MPA and OC are consistently found in patients with schizophrenia. Minor physical anomalies are stable characteristics over time and can be studied efficiently from early childhood onward. Minor physical anomalies predict a variety of mental disorders in normal-risk children, but the predictive efficiency of MPA for schizophrenia in genetic high-risk samples and in the general population is unknown. Obstetric complications predict serious mental disturbance and neurodisorder in genetic high-risk cases, as well as doubling or tripling the individual's risk for schizophrenia in the general population. Obstetric complication results are sensitive to methodology and are best investigated using prospectively recorded information and an efficient OC scale for scoring the information. CONCLUSIONS: Both MPA and OC should be included in batteries of methods for identifying individuals at an increased risk for schizophrenia. However, increased rates of MPA and OC are not pathognomonic for schizophrenia, but rather characterise individuals at risk of a much broader range of mental and physical abnormality, as well as normality. Minor physical anomalies and OC are not in themselves stigmatising, but their possible identification as markers for 'increased risk for schizophrenia' should be used judiciously. Further research is recommended regarding the MPA and OC patterns related to schizophrenia.

Neuromotor markers of risk for schizophrenia.

OBJECTIVE: To evaluate the possibility of using neuromotor deviation (NMD) as an individual-orientated, early life marker for increased risk for schizophrenia. METHOD: Previous findings based on systematic examination of NMD are summarised concerning schizophrenia patients and individuals at heightened genetic risk for schizophrenia. RESULTS: Significantly increased rates of NMD are found in patients with schizophrenia, both after and long before disease onset. Neuromotor deviation can be efficiently studied at all ages from infancy to adulthood, and is typically not in itself stigmatising. Neuromotor deviation may represent an unstable characteristic of individuals from infancy to middle-to-late childhood, possibly attaining greater stability thereafter. Neuromotor deviation may also be more stable over time in the high-risk offspring of parents with schizophrenia than in other children. Neuromotor deviation in childhood predicts subsequent serious mental disturbance in genetic high-risk children. The efficiency of NMD for predicting schizophrenia in unselected samples is unknown, as is the optimal age(s) for assessing NMD to predict schizophrenia in high-risk and normal-risk groups. Neuromotor deviation is also found in the well relatives of schizophrenia patients, individuals developing a broad range of mental and physical disorders, and mentally normal individuals in the general population. CONCLUSIONS: Neuromotor deviation should definitely be included in batteries of methods for identifying individuals with notably heightened risk of schizophrenia. However, NMD is not pathognomonic for schizophrenia, and the investigation of NMD during childhood and adolescence must thus be used judiciously in order to avoid possible stigmatisation. Further research should be done concerning the specific forms and developmental timing of NMD as related to schizophrenia.

Labour and delivery complications at birth and later mania. An Irish case register study.

BACKGROUND: Several reports postulate that manic depression and schizophrenia share environmental risk factors. Although obstetric adversity has been suggested as a risk factor for schizophrenia, few studies have examined its relationship to bipolar affective disorder. AIMS: To assess the rate of obstetric complications incurred by patients with mania compared with controls. METHOD: From the Dublin Psychiatric Case Register we identified individuals with a discharge diagnosis of mania and traced their birth records. Each case was matched with a control of the same gender, born in the same hospital, in the same year, matched for maternal age, parity and social class. Two obstetric complications scales were used to make blind evaluations of labour and delivery data. RESULTS: Patients with mania did not experience a greater frequency or severity of labour and delivery complications than their matched controls. Rates of obstetric adversity were unrelated to the presence or absence of family history of psychiatric disorder. Obstetric adversity was unrelated to the age at first diagnosis. CONCLUSIONS: These findings suggest that obstetric adversity is not a risk factor for later mania.

Are neurological abnormalities in schizophrenic patients and their siblings the result of perinatal trauma?

OBJECTIVE: Previous findings of increased neurological abnormalities in schizophrenic patients and their non-psychotic siblings raise the question of possible causes. The purpose of the present study was to examine the role of perinatal trauma in the aetiology of neurological abnormality. METHOD: Obstetric information obtained from hospital records for 55 schizophrenic patients and 19 non-psychotic siblings was scored blindly and separately from a neurological assessment of hard and soft signs. RESULTS: Obstetric complications (OCs) were significantly increased in patients but not in siblings compared to their respective neonatal control groups. Neurological abnormalities were related to OCs in siblings but not in patients. Neurological abnormalities in patients were negatively related to reduced neonatal head circumference. CONCLUSION: Early somatic trauma may increase the probability of neurological abnormality in individuals who are genetically 'at risk'.

Obstetric complications and congenital malformation in schizophrenia.

Recent years have witnessed increasingly intense research activity concerning early life somatic trauma and dysmorphogenesis which are associated with the later development of schizophrenia. The two somatic factors that have received the most extensive scientific attention as antecedents of schizophrenia are obstetric complications (OCs) and the congenital malformations termed 'minor physical anomalies' (MPAs). Head circumference (HC) at birth has also been studied as a measure of prenatal cerebral development. A great number of studies indicate clearly that schizophrenia patients have a significantly increased history of OCs, representing many different OCs from pregnancy, labor-delivery and the neonatal period. The probable common denominator of these OCs is oxygen deprivation. Especially labor-delivery OCs relate strongly to brain structure abnormality in ill twins from monozygotic pairs discordant for schizophrenia. Schizophrenia patients very consistently have evidenced an increased frequency of MPAs in the global head, eyes, mouth, ears, hands, feet and limbs. Specific MPAs occur with considerable frequency even among normal comparison subjects, but combination models for specific MPAs efficiently discriminate most patients from comparison subjects. Schizophrenia patients also have significantly reduced HC at birth, independently of gestational age, suggesting a disturbance in prenatal cerebral development, and most frequently observed in female patients. Evidence has thus accumulated, increasingly, for the role of various forms of early trauma and dysmorphogenesis in subsequent schizophrenia, and efforts continue to determine the manner in which these early trauma influence both the early developing brain and the brain of the adult patient with manifest schizophrenia.

Minor physical anomalies in schizophrenia: cognitive, neurological and other clinical correlates.

Minor physical anomalies (MPAs) are minor congenital malformations which are found with significantly increased frequency among both patients with schizophrenia and their siblings, suggesting the effect of early developmental disturbance in their families. The aim of this study was to explore the relationship between these signs of early dysmorphogenesis and cognitive and neurological dysfunction in the patients and their siblings as well as the clinical characteristics of the patients. Sixty patients with schizophrenia, 21 nonpsychotic siblings and 75 normal comparison subjects were studied. Increased rates of cognitive and neurological dysfunction and high MPA scores were found in both the patients and their siblings. High rates of MPAs were not significantly related to cognitive or neurological dysfunction in the patients or siblings, or to premorbid history or other characteristics of the clinical disease process in the patients. These results suggest that MPAs are possibly markers of general early neuromaldevelopment rather than markers of a specific cognitive/neurological or clinical subtype of schizophrenia.

Relationship of obstetric complications and differences in size of brain structures in monozygotic twin pairs discordant for schizophrenia.

OBJECTIVE: The aim of the study was to determine whether a history of obstetric complications and congenital minor physical anomalies are related to differences in the characteristics of brain structures observed within monozygotic twin pairs discordant for schizophrenia. METHOD: The size of the bilateral hippocampi and cerebral ventricles was studied by magnetic resonance imaging in 22 monozygotic twin pairs discordant for schizophrenia. Obstetric complications and minor physical anomalies were independently assessed through parental report and examination, respectively. RESULTS: Compared with the well co-twins, the ill twins consistently had smaller left and right hippocampi as well as larger left lateral ventricles and third ventricles. Relatively small left and right hippocampi were each significantly related to labor-delivery complications and to prolonged labor per se. Relatively large right lateral ventricle size and large total ventricle size were significantly related to labor-delivery complications, prolonged labor, neonatal complications, and total complications for the entire reproductive sequence. In contrast, these brain size differences were not significantly associated with pregnancy complications or minor physical anomalies. CONCLUSIONS: Trauma at the time of labor and delivery and especially prolonged labor appear to be of importance for brain structure anomalies associated with schizophrenia.

Schizophrenia and complications of pregnancy and labor: an individual patient data meta-analysis.

Several epidemiological studies have reported an association between complications of pregnancy and delivery and schizophrenia, but none have had sufficient power to examine specific complications that, individually, are of low prevalence. We, therefore, performed an individual patient meta-analysis using the raw data from case control studies that used the Lewis-Murray scale. Data were obtained from 12 studies on 700 schizophrenia subjects and 835 controls. There were significant associations between schizophrenia and premature rupture of membranes, gestational age shorter than 37 weeks, and use of resuscitation or incubator. There were associations of borderline significance between schizophrenia and birthweight lower than 2,500 g and forceps delivery. There was no significant interaction between these complications and sex. We conclude that some abnormalities of pregnancy and delivery may be associated with development of schizophrenia. The pathophysiology may involve hypoxia and so future studies should focus on the accurate measurement of this exposure.

Does preexisting abnormality cause labor-delivery complications in fetuses who will develop schizophrenia?

Many authors have suggested that theoretically the labor-delivery complications (LDCs) that frequently appear in the histories of individuals with schizophrenia represent the secondary consequence of preexistent abnormality in the fetus. The question of whether LDCs are systematically associated with prenatal complications and fetal abnormality was studied in 70 singleton schizophrenia patients, in 23 monozygotic twin pairs discordant and 10 pairs concordant for schizophrenia, and in 33 individuals with inferred genetic risk for schizophrenia. Schizophrenia cases with signs of prenatal abnormality (reduced head size, increased minor physical anomalies, greater within-twin-pair birthweight differences) did not have more LDCs than other schizophrenia cases. LDCs were not more frequent in genetic-risk cases with congenital malformations than in genetic-risk cases without malformations. Instead, individuals with schizophrenia who had a history of abnormal length of labor had significantly fewer pregnancy complications and minor physical anomalies than did other individuals with schizophrenia. No support was found for suggestions that LDCs among individuals who have not yet developed schizophrenia are the result of identifiable preexistent fetal abnormality.

Reproductive choices of haemophilia carriers.

The actual reproductive choices made by slightly over a quarter of all the carriers of severe or moderate haemophilia in Sweden were investigated and compared with those of a randomly selected age-matched group of women who were not carriers of haemophilia. In general, the 105 carriers had the same number of children as other women of similar age. However, carriers who did not choose prenatal diagnosis (PD) often abstained from further pregnancies after the birth of a haemophilic child, and they had significantly fewer children than the remainder of the carriers, as well as fewer children than women in the control group. Logistic regression analysis showed choice of PD to be correlated to a positive attitude towards abortion following PD and a family history of haemophilia. Carriers who have experienced the complications of haemophilia or its treatment appear to be more in favour of PD than women whose haemophilic children have received modern treatment without complications.

Maternal distress and congenital malformations: do mothers of malformed fetuses have more problems?

As compared with 580 randomly chosen pregnant women without malformed offspring. 161 women with malformed offspring at the index pregnancy had a more frequent history of previous multiple offspring deaths and somewhat increased maternal age but were not different on social class, marital or cohabitation status or parity. As compared with demographically similar reproducing women (n = 54) interviewed, malformation cases (n = 98) reported having had significantly more strong stress before identification of the malformation, as well as a clear tendency toward less appropriate timing of the pregnancy. Women with malformed offspring represent a psychosocially vulnerable group and should receive special clinical and personal support.

Long-term psychological effects of carrier testing and prenatal diagnosis of haemophilia: comparison with a control group.

The long-term psychological effects resulting from carrier testing and prenatal diagnosis (PD) of haemophilia were evaluated by comparing mental symptomatology scores (Symptom Check List, SCL-90) for 50 carriers of haemophilia who had undergone PD about five years earlier, 55 carriers who had not undergone PD and 262 control women who were not carriers. All of the women had children. Carrier testing for haemophilia per se and in combination with PD does not appear to have negative long-term psychological effects. A low tendency for somatization seems to be a factor characteristic of carriers considering PD for haemophilia and it was particularly salient when carriers had to consider the more invasive late PD procedures (amniocentesis and fetal blood sampling). Women who performed late PD appeared to represent a positive selection of carriers for whom a good sense of coherence and social support protected them from negative long-term psychological effects. It is reassuring that early PD by CVS, which is the current method of choice for PD for haemophilia, did not appear to have negative long-term psychological effects, even for women who had had an early abortion following PD.