Season of birth and obstetrical complications in schizophrenics

Many studies indicate that both obstetrical complications (OCs) and birth in winter or early spring are risk factors for schizophrenia, but few studies have examined how these risk factors covary in the same subjects. We assessed pre- and perinatal OCs, while blind to diagnosis, using medical data recorded at the time of subjects' births, in 29 probands with DSM-III schizophrenia or schizoaffective disorder and 39 of their unaffected adult sibs. Pre- and perinatal OCs were both significantly more common in probands than sibs. Schizophrenics not born during the winter or early spring had significantly more total and perinatal OCs than schizophrenics born in other months, but did not differ for prenatal OCs. Results indicate that OCs increase risk for schizophrenia, but also suggest the possibility that the impact of OCs on this risk may be affected by season of birth.     

Winter birth and biological family history in adopted schizophrenics

To investigate relationships between birth season and biological family history in schizophrenia, this study used a sample of schizophrenics that had the advantages of (a) particularly thorough diagnostic assessments of schizophrenics' relatives, including information from direct interviews as well as chart reviews, and (b) schizophrenic probands who were adopted at early age, mitigating the usual confounding of genetic and postnatal environmental influences of the family. Adopted schizophrenics with no biological family history of schizophrenia-spectrum disorders were significantly more likely to be born in winter months than were either (a) their own biological relatives, including their sibs and half-sibs, (b) schizophrenics with a positive family history for schizophrenia-spectrum disorders, or (c) people in the general population. Family-history-positive schizophrenics and their schizophrenic relatives were, in turn, significantly less likely than their own non-schizophrenic biological relatives to be born in the winter; schizophrenics in these families tended to be born in the milder-weather seasons, particularly the spring and fall. Results suggest that environmental factors associated with winter birth may be etiologically important in schizophrenia, particularly for cases in which familial liability factors are weak. By contrast, a familial, probably genetic, liability factor may be especially important in schizophrenics born in mild weather.     

Month of birth and schizophrenia in Alberta

Numerous studies have demonstrated that a greater than expected number of schizophrenics are born during the winter months. The present investigation examined this phenomenon in Alberta. The study population consisted of 1,101 schizophrenic patients admitted to either of the two provincial mental hospitals during 1976-1983 and who were born in Canada. After controlling for year of birth, no seasonality effect was found.     

Relationship between impairment of prenatal brain growth and family history of psychosis in schizophrenia

Recently McNeil et al. (1993b), showed that schizophrenics had smaller head circumference (HC) at birth than controls. This small head size at birth was observed more commonly among schizophrenics without a family history of psychosis than among familial schizophrenics, suggesting that some prenatal environmental factors, rather than genetic factors, are related to the impaired brain growth in utero. We attempted to replicate this finding in 100 Japanese schizophrenics (DSM-III-R), using contemporaneous data on body measures at birth. Conversely, in the current study, HC at birth was found to be significantly smaller in schizophrenics with a family history of psychosis (N = 19) than those without (N = 81). A multiple regression analysis, controlling for gender, gestational age, maternal age, birth order and year of birth, yielded an overall reduction of about 1 cm in HC at birth among familial schizophrenics compared with non-familial schizophrenics. When HC at birth in family history positive and negative groups was compared separately with the local population norms with adjustment for gender and gestational age, familial and non-familial schizophrenics were both found to have significantly smaller HC at birth, although the difference was less marked for the latter. These results suggest that schizophrenics have delayed cerebral development in utero, and that genes which operate on prenatal neurodevelopment may play an important role in the aetiology of schizophrenia, although it is possible that some environmental factors may also be involved in the impaired brain growth.     

Seasonality effects on schizophrenic births in multiplex families in a tropical island

Many studies have found that individuals with schizophrenia have been born in winter months in disproportionately high numbers. Temperature and weather effects, such as hot summers or cold winters, have been among the suggested explanations for this seasonality effect. We studied the relationship between schizophrenia and season of birth in Puerto Rico, a tropical island with mild seasonal variation of temperature and virtually no cold periods. Our sample consisted of 132 subjects (57 with schizophrenia, 75 without) from 24 multiplex families. Schizophrenic family members were significantly more likely to be born during the winter months (21/57; 36.8%) than their unaffected relatives (16/75; 21.3%). These results suggest that extreme temperatures are not a sufficient explanation for the seasonality effect and that other factors associated with seasonality may have an effect on the later development of schizophrenia. The fact that a seasonality effect was found in a group likely to have an increased genetic loading for schizophrenia suggests that seasonality may be associated with a second, environmental "hit" in a "two-hit hypothesis" of schizophrenia.     

Season of birth of schizophrenics in Mississippi, USA.

Prior reviews indicate that schizophrenics tend to be born in the winter, relative to non-psychiatric controls. This conclusion has been criticized, however, as the association between birth seasonality and schizophrenia may be the result of a statistical artifact, the age-incidence effect. To examine this possibility, we studied the birth seasonality of 2892 schizophrenics, controlling for the age-incidence effect. Both before and after instituting these controls, we found excesses for the months of December and March. We conclude that the age-incidence hypothesis does not provide any general explanation of the season-of-birth effect in schizophrenia.     

Birthrates of schizophrenics following relatively warm versus relatively cool summers.

Schizophrenics have consistently been found to be born with unusually high frequency in the early months of the calendar year. A previous study found significantly more schizophrenics to be born following warmer as contrasted with cooler summers, thus suggesting that summer temperature or a correlate of summer temperature may be an effective factor in the season of birth schizophrenia relationship. The current study re-tested the warmer vs. cooler summer finding, using both a local sample (N = 301) and a nationwide sample of Swedish schizophrenics (N = 13,440), each sample showing increased frequency of births in the early months of the year. In order to localize the possible effects of temperature to a more specific gestational period, the schizophrenics in each sample were further divided into sub-groups based upon which trimester of gestation likely occurred during the summer prior to the birth. The 71 years (1876-1946) during which the patients were born rank-ordered by mean summer temperature at representative geographical locations, and the rank-orders of years were divided into temperature quartiles. The rates of births for the total patient groups and the trimester sub-groups among both samples showed no positive linear or systematic relationship to temperature during the previous summer. Even the warmest among the 71 years were not followed by increased rates of births of schizophrenics. The results of the study did not corroborate the earlier finding.     

Season of birth and inflammatory response system in schizophrenia

Infective agents (e.g., viruses) together with functional alterations of the immune system have been hypothesized to be implicated in the multifactorial pathogenesis of schizophrenia. The viral hypothesis of schizophrenia has been supported by the observation of birth peaks in winter seasons, prenatal exposure to virus epidemics and specific geographic patterns. On the other hand, not all the data published have shown consistent results supporting the immune hypothesis. Thus, it is likely that immune response factors may play a role in the pathogenesis of the disease only in specific subgroups of patients. The aim of the study was to investigate for the presence of differences of IL-6, IL-6R, gp130 and CC16 among four groups of chronic schizophrenic patients categorized according to the season of birth. We hypothesized that patients born in winter and spring would have had increased values of these cytokines. No significant differences were found among the four groups in any of the measures considered. These preliminary results appear to exclude a major role of the season of birth in determining reported interleukins system alterations in chronic schizophrenia.     

Seasons of birth and psychiatry. A retrospective inpatients study

Births of schizophrenics tend to occur more often than expected during the first months of the year. This phenomenon has been repeatedly demonstrated in large samples of patients, but data from France are not yet available. METHOD. Medical records of 2,215 inpatients born in France, have been studied with DSM III-R. Admissions were unduplicated. Inpatient population is described table I. The 230 schizophrenic patients were also classified into three groups according with family history for psychotic diseases (Positive, Negative and Unknown). The year was divided in quarters, but also in two climatic half-years (Cold and Warm). Two different populations were used as controls: first, the live births data in France collected by the INSEE; and second, the 1726 non psychotic inpatients hospitalised in the same unit as the psychotics, during the same period. RESULTS. The season of birth effect can be demonstrated from our sample. When the whole schizophrenic group is compared to the INSEE data, a significant excess of births is found for the winter quarter (p less than .04) and for the cold half-year (p less than .01). In the DSM III-R disorganized patients the seasonal variation becomes significant at a level of p less than .001. The other subtypes of schizophrenia do not show significant seasonal variations (table II). The pattern of birth of the other DSM III-R diagnoses, does not significantly differ from INSEE control data (table III). Schizophrenic patients without psychiatrically ill relatives show a slight, non significant excess of births in winter which become significant for the cold half-year (p less than .03). Subjects with possible family history do not show any trend suggesting a seasonal effect (table IV). DISCUSSION. Few reports include an entire inpatient population as we have done. Such data in our study offers an element of useful comparison with the schizophrenics. Clinic data: Most of seasonal studies have used ICD-8, ICD-9 or Tsuang and Winokur criteria, to compare only paranoid and non paranoid subjects, and some of them found a very small excess of paranoid births in winter. The discrepancies between these studies and ours, can reflect both variability among environmental factors and variability in the diagnostic criteria. Control data: Most of the subjects were born between 1920 and 1960. All live births in France for the same years could be used as controls, but unfortunately INSEE data were not available by months or quarters before 1949. But since in western and southern European general population, the season of birth appears to be relatively uniform and stable over time, it seemed possible to use the posterior INSEE data to compare with our anterior inpatients data. Familial data: We found a birth excess in the cold season, only for schizophrenics without any family history. This finding is consistent with various other reports. CONCLUSION. In conclusion, our findings are consistent with the suggestion that the season of birth is important in the aetiology of the disorganized subgroup of schizophrenic aetiology of the disorganized subgroups of schizophrenic patients. Moreover, the excess of winter births is only observed in the "negative family history" group.     

Schizophrenia and season of birth: further southern hemisphere studies.

Studies in the northern hemisphere and an equatorial region have suggested that schizophrenics have a greater likelihood of being born in the coldest three months of the year. Two further southern hemisphere studies, performed in New Zealand and Tasmania, are reported in this paper. Results from these and other studies suggest that support for a link between schizophrenia and winter birth in the southern hemisphere is slight and inconsistent.     

Season of birth and schizophrenia - an equatorial study

Studies in the northern and southern hemisphers have generally demonstrated an association between schizophrenia and winter birth. No provious study has been performed in an equatorial region. The present study investigated the distribution of births of 3,508 schizophrenic patients born in the Philippines. A 15% excess above expectation was found for patients born in the coldest 3-month period of the year (December-February). An excess of births in that period was found in both sexes and in each decade of birth examined. The hypothesis that schizophrenics have a greater sensitivity to those physiological factors which determine conception in the general population is not supported.     

Seasonality and infectious disease in schizophrenia: the birth hypothesis revisited

Research literature supports the notion that more people diagnosed with schizophrenia are born during the winter months than other seasons [O'Hare A, Walsh D, Torrey F. Seasonality of schizophrenia births in Ireland. Br J Psychiatry 1980;137:74 7; Pulver AE, Stewart W, Carpenter WT, Jr., Childs B. Risk factors in schizophrenia: season of birth in Maryland, USA. Br J Psychiatry 1983;143:389-96.]. Researchers have postulated that this surge in winter-birth schizophrenia may be related to increases in viral infectious such as influenza and measles [Watson CG, Kucala T, Tilleskjor C, Jacobs L. Schizophrenic birth seasonality in relation to incidence of infectious diseases and temperature extremes. Arch Gen Psychiatry 1984:41:85-90; Mednick SA, Machon RA, Huttunen MO, Bonnett D. Adult schizophrenia following prenatal exposure to an influenza epidemic. Arch Gen Psychiatry 1988;45:189-92.]. However, data supporting significant relationships between infectious disease and schizophrenia incidence has been equivocal [Kendell R, Kemp I. Maternal influenza in the etiology of schizophrenia. Arch Gen Psychiatry 1989;46:878-82; McGrath J, Castle D. Does influenza cause schizophrenia? A five year review. Aust N Z J Psychiatry 1995;29:23-31.]. The purpose of this study was to replicate and expand previous studies by examining seasonal and infectious disease influences on schizophrenia prevalence. It was hypothesized that: (1) there would be an increase in schizophrenia prevalence during the winter months; and (2) that a significant amount of variability in schizophrenia birthrates would be accounted for by rates of influenza and measles. A Georgia Medicaid database (N = 746,615) and statewide infectious disease tables were used to identify correlations. Medicaid recipients were divided into schizophrenia (n = 11,736) and non-schizophrenia (n = 734,879) groups. A ratio of schizophrenic recipients to non-schizophrenic recipients was calculated for each birth cohort represented by each month of the year from 1948-1965. Multiple regression analyses indicated a significant relationship between winter season and schizophrenia incidence. However, neither influenza nor measles was predictive of schizophrenia prevalence. These findings were made using one of the largest sample of schizophrenic individuals in the literature to date. Limitations of the study are discussed, including the use of seasonal and prevalence correlations without data on patient linked maternal infections.     

Perinatal distress and infectious disease as risk factors for catatonia

A retrospective case control study was performed using the records of 60 catatonics, 189 noncatatonic schizophrenics, 262 schizophreniform disorder cases, 122 manics, 203 depressives and 134 surgical controls. This study suggests that perinatal distress and a history of severe infectious disease in childhood are more common among subjects with catatonia. Rheumatic fever is particularly common among the histories of catatonic patients. Although these findings did not occur in all cases of catatonia in the study, they may indicate a risk factor for some types of catatonia.     

Increased frequency of dentate granule cells with basal dendrites in the hippocampal formation of schizophrenics

In the hippocampal formation of schizophrenics, the detailed morphology of Golgi-impregnated granule cells was examined. These granule cells of the dentate gyrus are interposed between the rostral entorhinal cortex and the hippocampus proper. In these limbic regions significant cytoarchitectural alterations in schizophrenics are reported, giving rise to the concept of a prenatal limbic maldevelopment in schizophrenia. Compared to controls, the frequency of dentate granule cells with basal dendrites was significantly increased in schizophrenics [43% (+/-3)] vs. [22% (+/-2) in the control group]. In epilepsy, dentate granule cells of epileptic patients also develop basal dendrites, which is explained as an adaptive process of plasticity. Similarly, the hippocampal alterations described in schizophrenics could be the sequela of primary entorhinal cytoarchitectural alterations. Since the increase in basal dendrites seems to reflect a process of continuous plasticity, suggesting an increased rate of postnatal granule cell generation, the synthesis of a prenatal limbic maldevelopment with an ongoing process of plasticity might, therefore, supersede the hypothesis of a neurodegeneration in schizophrenia.     

The problem of birth control in schizophrenic patients

A study was made of 250 sterilized schizophrenics (50 men and 200 women) who had been hospitalized between 1972-1983. All had been diagnosed by more than 2 physicians as being schizophrenic for at least 5 years, and had used at least 1 kind of birth control since becoming ill. 258 healthy subjects were chosen as a control group. The marriage rate of schizophrenics is between 32.8-45.6% for males, and 57.6-67.9% for females. The subjects ranged in age from 26-50 years, 40.5% of whom were between 31-40 years. Length of illness was between 5-21 years, averaging 11.8 years. Prior to sterilization, subjects had an average of 2.7 children. Following the 1980 directive of having 1 child per couple, the schizophrenic 1 child rate was 1/8-1/4--that of the control group. 56.8% of the subjects started birth control 6-12 years after the onset of illness, and 3/5 used contraceptives for sterilization. 42.4% of the subjects' children were born after 1 of the parents had become ill; 2/3 of these children were conceived during the illness. The rate of complication from the birth control operation was similar to that of healthy persons. The rate of effectiveness in birth control was lower among schizophrenics, especially the women, than in healthy people, as evidenced by the fact 15.2% of the subjects' children were born after the subjects had taken birth control measures. It is concluded that female schizophrenics be given priority and that sterilization be the foremost method of birth control.     

Elevated Plasma Dopamine Concentrations in Unmedicated Acute Schizophrenics

Abstract: The authors studied the concentrations of plasma catecholamines in 23 acute schizophrenics, 28 healthy controls, 20 chronic schizophrenics, and 26 otherwise diagnosed psychiatric cases. Blood samples were taken from the consecutively admitted acute schizophrenics before the administration of antipsychotic drugs and catecholamines were assayed with a high performance liquid chromatography and electrochemical detector. Plasma adrenaline in the acute schizophrenics and the other psychiatric patients was significantly elevated in comparison with the healthy controls. There were no significant differences in the noradrenaline concentrations among the four groups. The plasma dopamine concentrations in the acute schizophrenics were also higher than those in the healthy controls. It is unlikely that physical exercise caused the elevation of dopamine in the acute schizophrenics. There was no significant correlation between plasma catecholamines and BPRS scores in the acute schizophrenics.     

Elevated plasma dopamine concentrations in unmedicated acute schizophrenics

The authors studied the concentrations of plasma catecholamines in 23 acute schizophrenics, 28 healthy controls, 20 chronic schizophrenics, and 26 otherwise diagnosed psychiatric cases. Blood samples were taken from the consecutively admitted acute schizophrenics before the administration of antipsychotic drugs and catecholamines were assayed with a high performance liquid chromatography and electrochemical detector. Plasma adrenaline in the acute schizophrenics and the other psychiatric patients was significantly elevated in comparison with the healthy controls. There were no significant differences in the noradrenaline concentrations among the four groups. The plasma dopamine concentrations in the acute schizophrenics were also higher than those in the healthy controls. It is unlikely that physical exercise caused the elevation of dopamine in the acute schizophrenics. There was no significant correlation between plasma catecholamines and BPRS scores in the acute schizophrenics.     

Season of birth, gender and negative symptoms in schizophrenia.

The aim of this study was to ascertain whether the symptom profile distinguishes between schizophrenic patients born in the winter and early spring and those born in other seasons. The sample consisted of 204 patients with a DSM-III-R diagnosis of schizophrenia who had been hospitalized for acute psychotic decompensation. Symptom ratings were based on the Positive and Negative Syndrome Scale (PANSS). The use of demographic and anamnestic data as dependent variables did not detect any season-of-birth effect. In contrast, clear gender-specific differences emerged from the comparison focusing on symptom dimensions and clinical subtype. Female patients born in the winter and early spring had higher scores on the PANSS negative scale and anergia factor whereas male patients born in other seasons had higher scores on the PANSS anergia factor. In addition, we found a gender-specific association between season of birth and clinical subtype. Most paranoid female patients were born in the non-winter months whereas, among men, a slightly higher percentage of paranoid patients were born in winter months. These results suggest that gender plays a role in modulating the effect of the season of birth on symptoms of schizophrenia.     

Schizophrenia and 1957 Pandemic of Influenza: Meta-analysis

Maternal influenza during pregnancy is a controversial risk factor for schizophrenia in the child. We conducted a meta-analysis to examine whether birth during the 9-month period after the pandemic of 1957 was a risk factor for schizophrenia. Studies that compared the risk of schizophrenia among subjects born after the pandemic with that among those born in corresponding time periods in surrounding years were divided into those conducted in the United States, Europe, or Australia (type A studies, n = 8) and those from Japan, where the epidemic came in 2 waves (type B studies, n = 3). Other studies examined the risk among subjects born to mothers who were pregnant during the pandemic and reported having had influenza (type C studies, n = 2). Relative risks (RRs) were extracted or calculated for each month and/or trimester of possible exposure by 2 independent authors. All analyses were performed using a fixed-effects model. The weighted results of the type A studies did not indicate a significantly increased risk of schizophrenia among children exposed during any trimester or month of prenatal life. Not a single study found a significant first- or second-trimester effect. The mean weighted RR for subjects who were in their first, second, or third trimester of prenatal life during the pandemic (8 effect sizes) was 0.91 (95% confidence interval [CI]: 0.85–0.98), 1.00 (95% CI: 0.93–1.07), and 1.05 (95% CI: 0.98–1.12), respectively. The pooled results of the type B and type C studies were also negative. Given high infection rates during the pandemic (about 50%), these results do not support the maternal influenza hypothesis.     

Depressive symptoms predict exaggerated inflammatory responses to an in vivo immune challenge among pregnant women

ObjectiveStress and depressive symptoms predict exaggerated inflammatory responses to a biological challenge in nonpregnant humans and animals. The extent to which these findings generalize to pregnancy is unknown because the immune system exhibits substantial changes to support pregnancy. Notably, inflammatory responses to infectious agents play a causal role in the development of gestational hypertension as well as risk for preterm birth. Thus, depressive symptoms may increase susceptibility to these outcomes via sensitization of inflammatory processes. The current study was designed to test the hypothesis that depressive symptoms would predict an exaggerated proinflammatory response to an in vivo antigen challenge, influenza virus vaccination, among pregnant women.MethodTwenty-two pregnant women completed two study visits: baseline and 1 week after receiving influenza virus vaccination. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression Scale (CES-D) at baseline. Serum levels of macrophage migration inhibitory factor (MIF) were determined using a high sensitivity immunoassay at both study visits.OutcomesAnalyses demonstrated that, as compared to those in the lowest tertile of CES-D scores, those in the highest tertile exhibited significantly higher levels of MIF 1 week after influenza virus vaccination (p = .035).ConclusionsDepressive symptoms predicted exaggerated MIF production following influenza virus vaccination during pregnancy. These data support the hypothesis that depressive symptoms are associated with sensitization of the inflammatory response during pregnancy. Thus, women with greater depressive symptoms may be more vulnerable to negative sequelae of infectious illness during pregnancy.