A family hereditary study of post-partum “psychoses”

Summary A group of 80 women suffering from a severe psychiatric post-partum disorder and hospitalized for the first time in their lives was followed up between 4 and 35 years later. Besides the further evolution of psychic health of the patients, the occurrence of endogenous (i.e., functional) psychoses in first degree relatives was investigated. A global morbidity risk for endogenous psychoses of 10.9% was found, affective psychosis accounting for two-thirds of secondary cases. Subdivision of the sample according to the criterion of absence or presence of further psychotic episodes unrelated to childbirth revealed that first degree relatives of patients with exclusively puerperal decompensations had a low morbidity risk of 2.0%, but relatives of patients with later nonpuerperal episodes of illness one of 15.2%, the difference being statistically significant (P < 0.002). This suggests that severe psychiatric disorders occurring exclusively in the post-partum period are nosologically distinct from those followed by nonpuerperal psychotic episodes of illness. Only the latter seem to be related to the traditionally recognized subgroups of endogenous psychoses.     

On the nosology of severe psychiatric post-partum disorders

Summary A group of 57 women, who had been hospitalised for puerperal psychiatric disorders from 1958 to 1977, were reexamined in 1982. The aim of the study was to determine the proportion of patients who had suffered from nonpuerperal psychotic relapses or other subsequent psychopathology, to define the sample diagnostically, taking into account progress in classification, to characterize the so far relatively neglected later course of illness, and to establish criteria related to relapse and global clinical outcome.Of these patients 65% had at least one nonpuerperal relapse, only 25% remained free of later psychopathology, but the global outcome was favorable or relatively favorable in many cases. Of the patients who had had nonpuerperal relapses 43% were classified as suffering from affective psychosis, as many as 38% from schizoaffective psychosis, and only 19% from schizophrenia. Schizoaffective psychosis seems to be particularly liable to be provoked by childbirth. No major evidence was found that endogenous psychoses with puerperal onset and nonpuerperal relapses have a course of illness different from that of the corresponding diagnostic category in general. Cases with exclusively puerperal decompensations seem to be nosologically independent from the traditionally recognized endogenous psychoses. Characteristics strongly related to nonpuerperal relapses were a family history of psychosis and the occurrence of psychotic episodes before the index episode. Puerperal relapses occurred at a much higher rate in patients who also had nonpuerperal relapses than in patients without.     

Familiality of the puerperal trigger in bipolar disorder: results of a family study

OBJECTIVE: Puerperal psychosis, an episode of mania or psychosis precipitated by childbirth, follows approximately one in 1,000 deliveries. The evidence of clinical, outcome, and genetic studies supports the hypothesis that the majority of puerperal psychotic episodes are manifestations of an affective disorder diathesis with a puerperal trigger. Family studies of puerperal psychosis consistently demonstrate familial aggregation of psychiatric (particularly affective) disorder and suggest a major overlap in the familial factors predisposing to puerperal psychosis and bipolar disorder. The single large study that used direct interview of relatives suggested that familial factors play a role in vulnerability to puerperal triggering itself. The authors' goal was to test this hypothesis further. METHOD: They conducted a study of the occurrence of episodes of puerperal psychosis in families multiply affected with bipolar disorder participating in an ongoing molecular genetic study of bipolar disorder in sibling pairs. RESULTS: Episodes of puerperal psychosis followed 81 (26%) of 313 deliveries to 152 parous women with bipolar disorder, 58 (38%) of whom had at least one puerperal psychotic episode. Puerperal episodes clustered in families. Episodes of puerperal psychosis occurred in 74% (N=20) of the 27 parous women with bipolar disorder who had a family history of puerperal psychosis in a first-degree relative but in only 30% (N=38) of the 125 women with bipolar disorder with no such family history. CONCLUSIONS: These results conclusively demonstrate that familial (probably genetic) factors are implicated in susceptibility to triggering of puerperal episodes in women with bipolar disorder. These findings have implications for future research and will be of use clinically in the management of women with bipolar disorder who are considering pregnancy.     

Cycloid psychoses as atypical manic-depressive disorders. Results of a family study

BACKGROUND: Whereas a growing body of evidence suggests that cycloid psychoses have to be separated from schizophrenic psychoses, their relations to bipolar affective disorder are less clear. PATIENTS AND METHODS: In a controlled family study, we recruited 46 patients with cycloid psychosis (CP), 33 with manic-depressive illness (MDI), and 27 controls. Three hundred fifty-six of 389 living first-degree relatives were personally examined by experienced psychiatrists blinded to the diagnosis of the index proband. RESULTS: The relatives of CP patients showed significantly lower morbidity risk of functional psychoses than relatives of patients with MDI in Kaplan-Meier life table calculation. The morbidity risk for functional psychoses in relatives of patients with CP did not differ significantly from that in relatives of controls. CONCLUSION: These results suggest that CP are etiologically different from bipolar affective psychoses and cannot be integrated into the spectrum of bipolar affective disorders. The findings provide further evidence for a nosological independence of CP.     

A prospective study of postpartum psychoses in a high-risk group. 3. Relationship to mental health characteristics during pregnancy

Within a sample of 88 pregnant women with a history of nonorganic psychosis, mental health characteristics during pregnancy, assessed prospectively through interviews and psychiatric records, were studied in relationship to the development of 25 postpartum psychotic episodes (PPPs) occurring during the first 6 months postpartum. Cases with PPP onset within 3 weeks of delivery (mostly affective or cycloid psychoses) evidenced more frequent tension-anxiety and excitement at interviews during pregnancy than did diagnostically comparable cases not developing PPPs. Cases with PPP onset later than 3 weeks postpartum (mostly schizophrenic-like psychoses) were not more frequently disturbed than were diagnostically comparable cases not developing PPPs. An absence of both affective symptoms and common fears represented a sign of increased PPP-risk in these later onset cases. The subsample of actively disturbed cases who were in contact with a psychiatrist during pregnancy were at notably increased risk for a PPP during the total 6-month period.     

Incidence of hospitalization for postpartum psychotic and bipolar episodes in women with and without prior prepregnancy or prenatal psychiatric hospitalizations

CONTEXT: Postpartum psychosis occurs in 1 to 2 cases per 1000 live births. Most studies have not distinguished postpartum psychosis from bipolar disorder or the proportion of the incidence attributable to prepregnancy psychiatric morbidity. OBJECTIVE: To determine the incidence of postpartum psychosis and bipolar disorder attributable to previous psychiatric hospitalization. DESIGN: Population-based study using linked registry data to determine postpartum onset of psychotic and bipolar episodes within 90 days after the first birth, by women with and without prepregnancy or prenatal psychiatric hospitalization. We assessed the type, number, and recency of previous hospitalizations on the incidence of hospitalization for postpartum psychotic and bipolar episodes. SETTING: Nationwide Swedish Hospital Discharge and Medical Birth registers. PATIENTS: Swedish women delivering a first live infant between January 1, 1987, and December 31, 2001. MAIN OUTCOME MEASURES: Postpartum hospitalization for psychosis or bipolar disorder. RESULTS: The cumulative incidences for postpartum psychotic and bipolar episodes (adjusted for age at first birth) were 0.07% and 0.03%, respectively. The incidence of psychiatric hospitalizations for postpartum psychotic or bipolar episodes among women without previous psychiatric hospitalizations was 0.04% and 0.01% of first births, respectively; for women with any psychiatric hospitalization before delivery, the incidence was 9.24% and 4.48%, respectively. For postpartum psychotic and bipolar episodes, the risk increased significantly with the recency of prepregnancy hospitalizations, number of previous hospitalizations, and length of most recent hospitalization. More than 40% of women hospitalized during the prenatal period for a bipolar or a psychotic condition were hospitalized again during the postpartum period. Approximately 90% of all postpartum psychotic and bipolar episodes occurred within the first 4 weeks after delivery. CONCLUSIONS: Almost 10% of women hospitalized for psychiatric morbidity before delivery develop postpartum psychosis after their first birth. This underscores the need for obstetricians to assess history of psychiatric symptoms and, with pediatric and psychiatric colleagues, to optimize the treatment of mothers with psychiatric diagnoses through childbirth.     

The relationship between postpartum psychosis and bipolar disorder: a review

BACKGROUND: The evidence for a spectrum of bipolar disorders is mounting. Of particular interest and importance is the evolution and recurrence of bipolar disorder in the postpartum period and its relationship to postpartum psychosis. Understanding whether such a phenomenological link exists has diagnostic, prognostic, and treatment implications. OBJECTIVES: A comprehensive review of (1) the literature regarding the relationships between postpartum psychosis and bipolar affective disorder, (2) the data regarding prophylactic treatment and acute management of postpartum psychosis and bipolar disorder in the puerperium, and (3) critical areas for future research. STUDY DESIGN: MEDLINE and PubMed (1966-2002) databases were searched for English-language articles using the keywords postpartum/puerperal depression, puerperal/postpartum psychosis, bipolar disorder, lithium, anticonvulsants, antipsychotics, and breastfeeding. RESULTS: Evidence from studies of women with a history of bipolar disorder, longitudinal studies of women with puerperal episodes of psychosis, and family studies support a link between postpartum psychosis and bipolar disorder. CONCLUSIONS: Understanding the relationship between postpartum psychosis and bipolar disorder has implications for perinatal and long-term treatment. Prophylactic treatment of women with bipolar disorder and/or a history of postpartum psychosis may be indicated. Epidemiological, genetic, and pharmacologic research must be completed to understand, prevent, and adequately treat postpartum psychosis.     

A controlled family study of chronic psychoses. Schizophrenia and schizoaffective disorder

Two hundred thirty-seven relatives of 48 patients with chronic psychosis, diagnosed as either schizophrenia or schizoaffective disorder, along with 380 relatives of psychiatrically normal controls, were studied using systematic diagnostic interviews, information from relatives, and review of medical records where appropriate. A variety of nonbipolar psychotic disorders was found in the relatives of the patients. Comparing relatives of patients with schizophrenia with relatives of patients with schizoaffective disorder, there was no tendency for schizoaffective diagnosis or acute psychoses to aggregate separately from schizophrenia. Increased incidence of bipolar disorder was found in relatives of patients with schizoaffective disorder but not in relatives of patients with schizophrenia. Incidence of major affective disorder (bipolar and unipolar) was increased in relatives of probands with both types of psychoses. If we subdivide the ill probands according to whether or not they had a history of substance abuse, relatives of probands with substance abuse had greater frequency of affective disorder and substance abuse, but there were not significant differences in the number of relatives with nonbipolar psychoses.     

No association between two polymorphisms at the 5HT2A gene and bipolar affective puerperal psychosis

OBJECTIVE: To examine whether variation at two common polymorphisms, T102C and -1438AG, of the serotonin 2A gene (5HT2A) are involved in the puerperal triggering mechanism of bipolar affective puerperal psychosis. METHOD: A total of 242 parous women diagnosed with bipolar disorder were genotyped for the two polymorphisms. Of these, 165 women had experienced a manic or psychotic episode, according to DSM-IV criteria, within 6 weeks of childbirth (the puerperal psychosis group). The comparison group comprised of 77 parous women who had not experienced psychiatric disturbance following childbirth. RESULTS: No significant differences between genotype or allelic frequencies were found between the two groups for either polymorphism. CONCLUSION: The results indicate that variation at two common polymorphisms of the 5HT2A gene does not appear to play a major role in the development of bipolar affective puerperal psychosis.     

Genetic factors in puerperal affective psychoses

The hypothesis that puerperal affective psychosis (PAP) is genetically related to maniodepressive disorder was tested by comparing the morbidity risks for puerperal and non-puerperal affective disorders in the relatives of 17 PAP subjects and 20 parous manic-depressives (PMD) with no history of puerperal illness. The risk for affective disorder (mania, depression or suicide) and puerperal affective disorder was the same in the two groups of relatives and the test hypothesis was accepted, although the sample size was small. The fre-quencies of HLA-A, B and C locus antigens, nine blood group antigens and 10 red blood cell isoenzymes were not significantly different in the PAP and PMD subjects, showing that in this series genetic markers do not distinguish puerperal from non-puerperal affective psychoses.     

Differenzierte Diagnostik, Verlauf und Ausgang postpartaler Psychosen Eine katamnestische Untersuchung

In a polydiagnostic study, a systematically recruited collective of 34 women with a first-episode postpartum psychosis was reexamined after a period of 6-26 years (averaging 12.6 years) in order to establish lifetime-diagnoses according to ICD-10 and Leonhard's classification, and to determine course and outcome. According to ICD-10, unipolar depressive disorders (32%) and acute polymorphous psychotic disorders (28%) represented the most frequent diagnoses. Applying Leonhard's classification revealed a marked predominance of cycloid psychoses (62%) with the subform of motility psychosis being the most frequent diagnosis (38%). Schizophrenias occurred rarely according to both classifications. Investigating the long-term course, we found in 59% multiphasic disorders. The mean number of episodes per patient was 2.5 (range 2-6) with a mean duration of 9.8 weeks (SD = 5.2). 6 patients (18%) had undergone a monophasic course, in 4 cases (12%) the course was not determinable. 17 women (50%) had 19 further deliveries during the follow-up period. The frequency of relapses in connection with a further delivery was 47%. Administering the Strauss-Carpenter-Outcome-Scale revealed a favourable outcome with a mean value of 14.1 (SD = 2.83) for our total sample. Only 4 patients (12%) had never recovered fully since the onset of the illness. Our findings suggest that cycloid psychoses, in particular motility psychoses, account for the majority of postpartum psychoses, and do not support the hypothesis of a nosological independence of postpartum psychoses. They provide further evidence of a favourable prognosis of severe postpartum psychiatric disorder despite a relatively high rate of non-puerperal and especially puerperal relapses.     

Prophylactic lithium in postpartum affective psychosis

Women with a history of bipolar affective disorder or postpartum affective psychosis have a greatly increased risk for recurrence of psychosis following subsequent pregnancies. The use of lithium carbonate for prophylaxis of postpartum psychosis in such women remains controversial. Four women are described with a history of puerperal affective psychosis, who were given lithium prophylactically following delivery and had no recurrence of postpartum psychosis. The rationale for the timing, dosage, and monitoring of lithium administration in this situation is discussed. Given the apparent safety of lithium prophylaxis relative to the dangers of postpartum affective psychosis, more effort should be directed to definitive research to resolve whether lithium prophylaxis is indicated for this population, as contemporary knowledge and these four cases would suggest.     

Orbitofrontal dysfunction in a monozygotic twin discordant for postpartum affective psychosis: a functional magnetic resonance imaging study

BACKGROUND: Incomplete concordance for psychosis in monozygotic (MZ) twins has been interpreted as indicative of non-genetic cofactors in transmission of the illness. In this case study, we consider childbirth a landmark in the onset of psychotic symptoms, leading to the diagnosis of puerperal psychosis and then to bipolar/schizoaffective disorder. At the end of the third trimester, there is a sudden drop in estrogen, which exerts prominent effects on the serotonergic system in the orbitofrontal cortex (OFC). OBJECTIVES: The purpose of the present study was to investigate OFC activation during emotional processing in MZ twins discordant for affective psychosis. METHODS: Blood-oxygen-level-dependent activation using functional magnetic resonance imaging was measured during the passive viewing of emotional film excerpts. RESULTS: Consistent with our hypothesis, a significant locus of activation was found in the left OFC in the normal MZ twin, but not in the psychosis MZ twin. CONCLUSIONS: The personality changes noted in the psychosis MZ twin (postpartum psychosis) may be related to dysfunctional OFC. Ms J's childbirth may have triggered the onset of psychotic symptoms, leading to the diagnosis of bipolar or schizoaffective disorder.     

Long-term course and outcome of severe postpartum psychiatric disorders.

Thirty-nine women who had suffered from a severe first-episode postpartum psychiatric illness were re-examined after a period of 6-26 years (averaging 12.5 years). Diagnoses were established according to ICD-10 and Leonhard's classification, revealing a marked predominance of cycloid psychoses (54%) according to Leonhard. There was no evidence of the nosological independence of postpartum psychosis. Only 4 patients (10%) had never recovered fully since the onset of the illness. In contrast, 6 patients had undergone a monophasic course without any further psychopathology. In 20 cases (51%) the illness had run a multiphasic course. The average number of episodes per patient was 2.5 (range 2-6). The course was not determinable in 4 patients (10%). Nineteen women (49%) had 22 further deliveries after the first manifestation of the illness. The frequency of a relapse in connection with further pregnancy or delivery was 50%. Applying the Strauss-Carpenter Outcome Scale, we found a favourable outcome for the total sample with a mean value of 14.1 (SD = 2.6). The vast majority of patients (75%) showed no persistent alterations. Our findings provide further evidence of a favourable prognosis of severe postpartum psychiatric disorder despite the remarkably high rate of puerperal relapses.     

Psychiatric symptoms after therapy with new antiepileptic drugs: psychopathological and seizure related variables.

The purpose of this paper is to understand the association between antiepileptic drugs (AEDs), patient characteristics, changes in seizure pattern and emergent psychiatric disorder, i.e. psychosis or affective disorder. To this end we carried out a retrospective casenote study on 89 patients who developed psychiatric symptoms during treatment with topiramate, vigabatrin or tiagabine. The psychiatric problem was either an affective or a psychotic disorder (not including affective psychoses). It was discovered that 99% of the patients suffered from complex partial seizures with or without secondary generalization. More than half were on polytherapy with two or more other AEDs. Nearly two-thirds had a previous psychiatric history. There was a strong association between the type of previous psychiatric illness and the type of emerging psychiatric problem, both for psychoses and for affective disorders. Patients on vigabatrin had an earlier onset of epilepsy and more neurological abnormalities than those on topiramate. Those patients on lower doses had a shorter interval between the start of the AED therapy and the onset of the psychiatric problem. A seizure-free period was observed in more than half of the patients before they developed the psychiatric symptoms, and of these more were likely to develop a psychosis rather than an affective disorder. There seemed to be an association of suppression of right-sided seizures and the onset of the psychiatric problem. The conclusions drawn were that patients with a previous history of psychosis or affective disorder tended to develop the same psychiatric problem with new AEDs. Those with a seizure-free period before the onset of the psychiatric problem were more likely to develop a psychosis than an affective disorder.     

Autoimmune diseases,bipolar disorder,and non‐affective psychosis

Eaton WW, Pedersen MG, Nielsen PR, Mortensen PB. Autoimmune diseases, bipolar disorder, and non‐affective psychosis. Bipolar Disord 2010: 12: 638–646. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objective: Clinic‐based studies of immune function, as well as comorbidity of autoimmune diseases, bipolar disorder, and schizophrenia, suggest a possible autoimmune etiology. Studies of non‐affective psychosis and schizophrenia suggest common etiologies. The objective was to determine the degree to which 30 different autoimmune diseases are antecedent risk factors for bipolar disorder, schizophrenia, and non‐affective psychosis. Methods: A cohort of 3.57 million births in Denmark was linked to the Psychiatric Case Register and the National Hospital Register. There were 20,317 cases of schizophrenia, 39,076 cases of non‐affective psychosis, and 9,920 cases of bipolar disorder. Results: As in prior studies, there was a range of autoimmune diseases which predicted raised risk of schizophrenia in individuals who had a history of autoimmune diseases, and also raised risk in persons whose first‐degree relatives had an onset of autoimmune disease prior to onset of schizophrenia in the case. These relationships also existed for the broader category of non‐affective psychosis. Only pernicious anemia in the family was associated with raised risk for bipolar disorder (relative risk: 1.7), suggesting a small role for genetic linkage. A history of Guillain‐Barré syndrome, Crohn’s disease, and autoimmune hepatitis in the individual was associated with raised risk of bipolar disorder. Conclusions: The familial relationship of schizophrenia to a range of autoimmune diseases extends to non‐affective psychosis, but not to bipolar disorder. The data suggest that autoimmune processes precede onset of schizophrenia, but also non‐affective psychosis and bipolar disorder.     

First admission with puerperal psychosis: 7–14 years of follow-up

The aim of this study was to investigate women who had first-episode psychosis within 1 year after parturition. The Danish Psychiatric Central Register and the Danish Medical Birth Register were linked to identify all women admitted for the first time to a psychiatric department in Århus County with a psychotic episode. Fifty cases were found, giving a frequency of first-episode psychosis within 1 year after delivery of 1 per 1000. First-episode psychotic disease within the first month postpartum occurred in 1 case per 2000 deliveries. The age distribution corresponded to that of the background population, but the cases were primiparous more often than expected. The socioeconomic status was equal to that of a matched control group of obstetric patients. Birth complications did not occur more frequently than expected, but the probands had a higher risk of preterm delivery than the controls. The clinical picture of the index episode was that of manic-depressive psychosis in nearly half of the cases, but no cases of schizophrenia were found. Sixty percent of the patients had a picture of severe depression, and 20% suffered from manic disorder. The follow-up, 7 to 14 years later, was carried out by interviewing the general practitioners. Forty percent of the women had not preserved full working capacity due to mental disorder. Moreover, the follow-up pointed to schizophreniform symptoms at the index episode as a predictor of incapacity to work. Recurrences were very common (60%), especially of the nonpuerperal type, and half of the recurrences belonged to the manic-depressive disorders. Schizophrenia was diagnosed in one case at the follow-up. Cases with exclusively puerperal episodes were rare (4%).     

Women with nonorganic psychosis: psychiatric and demographic characteristics of cases with versus without postpartum psychotic episodes

Within a sample of 88 reproducing women with nonorganic psychosis, psychiatric and demographic characteristics were compared for women having only postpartum psychotic episodes (PPPs), women never having PPPs, and women having both PPPs and other psychotic episodes. Cases with only PPPs or both PPPs/other episodes most frequently had affective disorders. Cases with no PPPs most frequently had schizophrenia. Even with diagnosis controlled, cases with only PPPs were comparatively high in social class and in age at initial illness onset and were less severely ill than others. Cases with both PPPs/other episodes had the opposite characteristics. Cases never having PPPs had an intermediary position between the other two groups. PPPs in patients having only PPPs bore a special relationship to parity, not seen in other patients. PPPs appear to be associated with two different types of clinical/demographic patterns, depending upon whether the PPPs occur in isolation or as part of another illness pattern.     

Bipolar affective puerperal psychosis: genome-wide significant evidence for linkage to chromosome 16

OBJECTIVE: Vulnerability to the triggering of bipolar episodes by childbirth aggregates in families and may define a genetically relevant subtype of bipolar disorder. The authors conducted a search by systematic whole genome linkage scan for loci influencing vulnerability to bipolar affective puerperal psychosis. METHOD: The authors selected families with bipolar disorder from their previous bipolar disorder genome scan, in which there was at least one family member with a manic or psychotic episode with an onset within 6 weeks of delivery. Individuals were coded as affected if they had been diagnosed with bipolar I disorder; bipolar II disorder; or schizoaffective disorder, bipolar type, according to DSM-IV. A total of 36 pedigrees contributed 54 affected sibling pairs to the cohort. A genome scan with 494 microsatellite markers was analyzed using GENEHUNTER and MAPMAKER/SIBS. RESULTS: A genome-wide significant linkage signal was observed on chromosome 16p13, and a genome-wide suggestive linkage was observed on chromosome 8q24. No significant or suggestive linkage was observed in these regions in our original bipolar scan. CONCLUSIONS: This study identifies chromosomal regions that are likely to harbor genes that predispose individuals to bipolar affective puerperal psychosis. The identification of susceptibility genes would enhance understanding of pathogenesis and offer the possibility of improvements in treatment and risk prediction.     

Neuregulin 1 and age of onset in the major psychoses

Genetic vulnerability to psychiatric illness extends across major psychiatric illness. Neuregulin 1 (NRG1) is a large gene on chromosome 8p, that has been identified as a susceptibility factor in bipolar disorder and schizophrenia. In particular, a core at risk haplotype has received considerable attention for a putative role in the pathophysiology of the major psychoses (schizophrenia and bipolar disorder). This core haplotype can be represented by three markers 478B14-848, 420M9-1395, and SNP8NRG221533. We genotyped 312 families with bipolar probands, and 120 families with schizophrenia probands. Association of the core haplotype was tested for with age-at-onset and with three phenotypes: major psychosis, schizophrenia, and bipolar disorder. Neither age of onset (P = 0.893) nor the major psychosis phenotype (P = 0.374) was associated with the core haplotype in the overall sample. Ours was the first study to investigate the NRG1 core haplotype with age of onset of major psychoses, and despite our preliminary negative findings, this area deserves further investigation.