Functional Recovery After Postpartum Psychosis: A Prospective Longitudinal Study.

OBJECTIVE: Postpartum psychosis is an acute and severe mood disorder. Although the prognosis is generally good, postpartum psychosis is a highly stressful life-event presumed to have a major impact on functioning and well-being beyond the acute stage of the illness. We studied functional recovery, including psychosocial functioning and the presence of psychological distress, in patients with a recent diagnosis of postpartum psychosis. METHODS: Seventy-eight patients with postpartum psychosis consecutively admitted for inpatient hospitalization between 2005 and 2011 were assessed 9 months postpartum. Included were patients with DSM-IV-TR diagnoses of psychotic disorder not otherwise specified, brief psychotic disorder, or mood disorder with psychotic features, each requiring the additional specifier "with postpartum onset." Functioning was assessed in 4 domains by the Longitudinal Interval Follow-up Evaluation-Range of Impaired Functioning Tool (LIFE-RIFT). Symptomatology was measured by the Brief Symptom Inventory and compared to a matched population-based cohort. RESULTS: Nine months postpartum, 74% (58/78) of women with postpartum psychosis reported good functioning on the domains of work, interpersonal relations, recreation, and global satisfaction. Moreover, 88% (69/78) of patients with postpartum psychosis had resumed their premorbid employment and household responsibilities. Compared to the general population, patients with postpartum psychosis reported a higher burden of depression and anxiety (effect sizes r ≤ 0.14). Patients who had a relapse episode (18%) experienced considerable functional impairments across several domains. CONCLUSIONS: Nine months postpartum, the majority of patients with postpartum psychosis reported good functional recovery. Our relatively improved functional outcomes compared to nonpostpartum onset could be attributed to the postpartum onset and/or more favorable risk factor profile.

Tryptophan pathway alterations in the postpartum period and in acute postpartum psychosis and depression.

OBJECTIVES: Women are at very high risk for the first onset of acute and severe mood disorders the first weeks after delivery. Tryptophan breakdown is increased as a physiological phenomenon of the postpartum period and might lead to vulnerability for affective psychosis (PP) and severe depression (PD). The aim of the current study was to investigate alterations in tryptophan breakdown in the physiological postpartum period compared to patients with severe postpartum mood disorders. METHODS: We included 52 patients (29 with PP, 23 with PD), 52 matched healthy postpartum women and 29 healthy non-postpartum women. Analyzes of serum tryptophan metabolites were performed using LC-MS/MS system for tryptophan, kynurenine, 3-hydroxykynurenine, kynurenic acid and 5-hydroxyindoleacetic acid. RESULTS: The first two months of the physiological postpartum period were characterized by low tryptophan levels, increased breakdown towards kynurenine and a downstream shift toward the 3-OH-kynurenine arm, away from the kynurenic acid arm. Kynurenine was significantly lower in patients with PP and PD as compared to healthy postpartum women (p=0.011 and p=0.001); the remaining tryptophan metabolites demonstrated few differences between patients and healthy postpartum women. LIMITATION: Low prevalence of the investigated disorders and strict exclusion criteria to obtain homogenous groups, resulted in relatively small sample sizes. CONCLUSION: The high kynurenine levels and increased tryptophan breakdown as a phenomenon of the physiological postpartum period was not present in patients with severe postpartum mood disorders. No differences were observed in the levels of the 'neurotoxic' 3-OH-kynurenine and the 'neuroprotective' kynurenic acid arms between patients and healthy postpartum women.

Treatment of psychosis and mania in the postpartum period.

Postpartum psychosis is a severe disorder that warrants acute clinical intervention. Little is known, however, about what interventions are most effective. The authors present treatment response and remission outcomes at 9 months postpartum using a four-step algorithm in patients with first-onset psychosis or mania in the postpartum period. Treatment involved the structured sequential administration of benzodiazepines, antipsychotics, lithium, and ECT. The outcome of clinical remission was examined in 64 women consecutively admitted for postpartum psychosis. Remission was defined as the absence of psychotic, manic, and severe depressive symptoms for at least 1 week. Women who remitted on antipsychotic monotherapy were advised to continue this treatment as maintenance therapy, and women who required both antipsychotics and lithium to achieve remission were maintained on lithium monotherapy. Relapse was defined as the occurrence of any mood or psychotic episode fulfilling DSM-IV-TR criteria. Using this treatment algorithm, the authors observed that nearly all patients (98.4%) achieved complete remission within the first three steps. None of the patients required ECT. At 9 months postpartum, sustained remission was observed in 79.7%. Patients treated with lithium had a significantly lower rate of relapse compared with those treated with antipsychotic monotherapy. Multiparity and nonaffective psychosis were identified as risk factors for relapse. The authors conclude that a structured treatment algorithm with the sequential addition of benzodiazepines, antipsychotics, and lithium may result in high rates of remission in patients with first-onset postpartum psychosis and that lithium maintenance may be most beneficial for relapse prevention.

Down-regulation of inflammation-protective microRNAs 146a and 212 in monocytes of patients with postpartum psychosis.

BACKGROUND: Postpartum psychosis (PP) is thought to belong to the bipolar spectrum. Recently we described an immune activation signature in monocytes of patients with PP using gene expression profiling. Immune activation genes are regulated by microRNAs (miRNAs). We therefore profiled miRNA expression in monocytes of PP patients to identify differentially expressed miRNAs between PP and the healthy state. METHODS: In a profiling study we carried out miRNA profiling using TaqMan array human microRNA A cards v2.0 and monocytes of 8 PP patients. Data were analyzed against monocytes of healthy postpartum women (CP). Nine miRNAs were selected and tested using individual Q-PCR in a larger validation study on monocytes of 20 PP patients, 20 CP and 20 healthy non-postpartum women (HC). RESULTS: In the validation study miR-146a expression was significantly down-regulated in the monocytes of first onset PP patients as compared to CP and HC; miR-212 expression was significantly down-regulated in PP patients with prior bipolar disorder. In silico miR-146a targeted 4 genes of the previously described monocyte activation signature in bipolar disorder; miR-212 targeted 2 of such genes. In a correlation study decreased expression of miR-146a in monocytes was related to decreased natural T regulator cells in PP patients; decreased miR-212 was correlated to increased Adrenomedulin and decreased IL-6 expression in monocytes and to higher Th2 cell levels. CONCLUSIONS: This study identified changes in miR-146a and -212 expression in PP. Since these miRNAs are linked to inflammation, the study strengthens the view that PP is an inflammation-like condition.

Immune system dysregulation in first-onset postpartum psychosis.

BACKGROUND: Accumulating evidence suggests that dysregulation of the immune system represents an important vulnerability factor for mood disorders. Postpartum psychosis (PP) is a severe mood disorder occurring within 4 weeks after delivery, a period of heightened immune responsiveness and an altered endocrine set point. Therefore, the aim of this study was to examine immune activation in patients with first-onset PP at the level of monocytes, T cells, and serum cytokines/chemokines. METHODS: We included 63 women admitted with first-onset PP. Control groups included healthy postpartum (n = 56) and nonpostpartum (n = 136) women. A quantitative-polymerase chain reaction monocyte gene expression analysis was performed with 43 genes previously identified as abnormally regulated in nonpostpartum mood disorder patients including the isoforms of the glucocorticoid receptor. Peripheral blood mononuclear cells percentages were measured by fluorescence-activated cell sorter analysis, whereas serum cytokines/chemokines were determined with a cytometric bead array. RESULTS: In healthy women, postpartum T cell levels were significantly elevated compared with nonpostpartum. Patients with PP failed to show the normal postpartum T cell elevation. In contrast, these patients showed a significant elevation of monocyte levels and a significant upregulation of several immune-related monocyte genes compared with control subjects postpartum and nonpostpartum. Furthermore, the glucocorticoid receptor α/ß gene expression ratio was decreased in monocytes of PP patients, strongly correlating with their immune activation. CONCLUSIONS: This study demonstrates a robust dysregulation of the immuno-neuro-endocrine set point in PP, with a notable over-activation of the monocyte/macrophage arm of the immune system.