Mother-infant interaction and infant development in women at risk of postpartum psychosis with and without a postpartum relapse.

BACKGROUND: This study aimed to investigate mother-infant interaction and infant development in women at-risk of postpartum psychosis (PP), with and without a postpartum relapse. METHODS: 103 women (and their offspring) were included, 43 at-risk-of-PP because of a diagnosis of bipolar disorder, schizoaffective disorder or previous PP, and 60 with no current/previous mental illness or family history of PP. Of the at-risk women, 18 developed a psychiatric relapse within 4 weeks after delivery (AR-unwell), while 25 remained symptom-free (AR-well). Mother-infant interaction was assessed using the CARE-Index at 8 weeks' and 12 months' postpartum and infant development using the Bayley-III at 12 months' postpartum. RESULTS: Women at-risk-of-PP as a group, regardless of whether they developed a psychiatric relapse within 4 weeks after delivery, had less synchronous mother-infant interactions and had infants with less optimal cognitive, language, motor and socio-emotional development than healthy controls. In particular, boys of at-risk women had the lowest scores in cognitive, language and motor development and in mother-infant interaction, while girls of the at-risk women had the lowest scores in socio-emotional development. The synchrony in the dyad predicted infant cognitive and language development. There was no evidence for a difference in mother-infant interaction nor in infant development between the AR-unwell and AR-well groups. CONCLUSIONS: These results suggest that, while there is a lack of evidence that an early postpartum relapse in women at-risk-of-PP could represent a risk for the infant per se, maternal risk for PP may be associated with less optimal mother-infant interaction and infant development.

Maternal perceived bonding towards the infant and parenting stress in women at risk of postpartum psychosis with and without a postpartum relapse.

BACKGROUND: Postpartum psychosis (PP) is the most severe psychiatric disorder associated with childbirth. However, there is little research on maternal bonding towards the infant and parenting stress in this clinical population. METHODS: We investigated maternal bonding during pregnancy and post-partum in 75 women: 46 at risk of PP (AR), because of a DSM-IV diagnosis of bipolar disorder, schizoaffective disorder or previous PP, and 29 healthy controls. Of the AR women, 19 developed a psychiatric relapse within 4 weeks' post-partum (AR-unwell), while 27 remained symptom-free (AR-well). We investigated childhood maltreatment, parenting stress and psychiatric symptoms as potential predictors of maternal bonding. RESULTS: In pregnancy, AR-unwell women reported a more negative affective experience towards their infants than AR-well women (d = 0.87, p = .001), while postnatally there was no significant difference in bonding. In contrast, AR women as a group reported a more negative affective experience than HC postnatally (d = 0.69, p = .002; d = 0.70, p = .010), but not antenatally. Parenting stress and psychiatric symptoms significantly predicted less optimal postnatal bonding (b = -0.10, t = -4.29, p < .001; b = -0.37, t = -4.85, p < .001) but only psychiatric symptoms explained the difference in bonding between AR and HC (b = -1.18, 95% BCa CI [-2.70,-0.04]). LIMITATIONS: A relatively small sample size precluded a more in-depth investigation of underlying pathways. CONCLUSION: This study provides new information on maternal bonding in women at risk of PP, and particularly in those that do and do not develop a postpartum relapse. The results suggest that improving maternal symptoms and parenting stress in the perinatal period in women at risk of PP could also have positive effects on bonding.

Altered dynamics of the prefrontal networks are associated with the risk for postpartum psychosis: a functional magnetic resonance imaging study.

Postpartum psychosis (PP) is a severe mental disorder that affects women in the first few weeks after delivery. To date there are no biomarkers that distinguish which women at risk (AR) develop a significant psychiatric relapse postpartum. While altered brain connectivity may contribute to the risk for psychoses unrelated to the puerperium, this remains unexplored in PP. We followed up 32 AR and 27 healthy (HC) women from pregnancy to 8-week postpartum. At this point, we classified women as AR-unwell (n = 15) if they had developed a psychiatric relapse meeting DSM-IV diagnostic criteria, or impacting on daily functioning and requiring treatment, or AR-well (n = 17) if they remained asymptomatic. Women also underwent an fMRI scan at rest and during an emotional-processing task, to study within- and between-networks functional connectivity. Women AR, and specifically those in the AR-well group, showed increased resting connectivity within an executive network compared to HC. During the execution of the emotional task, women AR also showed decreased connectivity in the executive network, and altered emotional load-dependent connectivity between executive, salience, and default-mode networks. AR-unwell women particularly showed increased salience network-dependent modulation of the default-mode and executive network relative to AR-well, who showed greater executive network-dependent modulation of the salience network. Our finding that the executive network and its interplay with other brain networks implicated in goal-directed behavior are intrinsically altered suggest that they could be considered neural phenotypes for postpartum psychosis and help advance our understanding of the pathophysiology of this disorder.

Impact of the COVID-19 pandemic on the mental health and well-being of UK healthcare workers.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a significant psychological impact on healthcare workers (HCWs). AIMS: There is an urgent need to understand the risk and protective factors associated with poor mental well-being of UK HCWs working during the COVID-19 pandemic. METHOD: Shortly after the April 2020 UK COVID-19 peak 2773 HCWs completed a survey containing measures of anxiety, depression, post-traumatic stress disorder and stress, as well as questions around potential predictors such as roles, COVID-19 risk perception and workplace-related factors. Respondents were classified as high or low symptomatic on each scale and logistic regression revealed factors associated with severe psychiatric symptoms. Change in well-being from pre- to during COVID-19 was also quantified. RESULTS: Nearlya third of HCWs reported moderate to severe levels of anxiety and depression, and the number reporting very high symptoms was more than quadruple that pre-COVID-19. Several controllable factors were associated with the most severe level of psychiatric symptoms: insufficient personal protective equipment availability, workplace preparation, training and communication, and higher workload. Being female, 'front line', previous psychiatric diagnoses, traumatic events, and being an allied HCW or manager were also significantly associated with severe psychiatric symptoms. Sharing stress, resilience and ethical support for treatment decisions were significantly associated with low psychiatric symptoms. Front-line workers showed greater worsening of mental health compared with non-front-line HCWs. CONCLUSIONS: Poor mental well-being was prevalent during the COVID-19 response, however, controllable factors associated with severe psychiatric symptoms are available to be targeted to reduce the detrimental impact of COVID-19 and other pandemics on HCW mental health.

Risk factors for postpartum relapse in women at risk of postpartum psychosis: The role of psychosocial stress and the biological stress system.

BACKGROUND: Postpartum psychosis is the most severe psychiatric disorder associated with childbirth, and the risk is particularly high for women with a history of bipolar disorder, schizoaffective disorder or those who have suffered a previous episode of postpartum psychosis. Whilst there is a lot of evidence linking stress to psychosis unrelated to childbirth, the role of stress in the onset of postpartum psychosis has not been fully investigated. METHODS: A prospective longitudinal study of 112 pregnant women, 51 at risk of postpartum psychosis because of a DSM-IV diagnosis of bipolar disorder (n = 41), schizoaffective disorder (n = 6) or a previous postpartum psychosis (n = 4) and 61 healthy women with no past or current DSM-IV diagnosis and no family history of postpartum psychosis. Women were followed up from the third trimester of pregnancy to 4 weeks' post partum. Women at risk who had a psychiatric relapse in the first 4 weeks' post partum (AR-unwell) (n = 22), were compared with those at risk who remained well (AR-well) (n = 29) on measures of psychosocial stress (severe childhood maltreatment and stressful life events) and biological stress (cortisol and inflammatory biomarkers). RESULTS: Logistic regression analyses revealed that severe childhood maltreatment (OR = 4.9, 95% CI 0.5-49.2) and higher daily cortisol in the third trimester of pregnancy (OR=3.7, 95% CI 1.2-11.6) predicted psychiatric relapse in the first 4 weeks' post partum in women at risk of postpartum psychosis after adjusting for clinical and sociodemographic covariates. CONCLUSION: The current study provides evidence for the role of psychosocial stress and the biological stress system in the risk of postpartum relapse in women at risk of postpartum psychosis.

Neurocognitive correlates of working memory and emotional processing in postpartum psychosis: an fMRI study.

BACKGROUND: Postpartum psychosis (PP) is a severe postpartum disorder. While working memory and emotional processing-related brain function are consistently impaired in psychoses unrelated to the puerperium, no studies have investigated them in PP. METHODS: Twenty-four women at risk of developing PP (11 developed an episode - PE; 13 remained well - NPE) and 20 healthy postpartum women completed two functional magnetic resonance imaging tasks within a year of delivery: working memory (n-back) and emotional face recognition (fearful faces). We compared women at-risk of PP to controls, as well as NPE, PE, and controls to test for potential effects of a PP episode occurrence. RESULTS: Women at-risk of PP and PE showed hyperactivation of lateral visual areas, precuneus, and posterior cingulate during the n-back task. The at-risk group as a whole, as well as the PE and NPE groups, showed hyperconnectivity of the right dorsolateral prefrontal cortex (DLPFC) with various parieto-occipito-temporo-cerebellar regions compared to controls during several n-back conditions. Increases in connectivity between the right DLPFC and ipsilateral middle temporal gyrus were observed in the PE group compared to NPE during 2-back. During the fearful faces task, at-risk women as a group showed hyperactivation of fronto-cingulo-subcortical regions, and hypoconnectivity between the left amygdala and ipsilateral occipito-parietal regions compared to controls. No significant performance differences were observed. CONCLUSIONS: These results present preliminary evidence of a differential nature of functional brain abnormalities in PP compared to the typically observed reduced connectivity with the DLPFC in psychoses unrelated to puerperium, such as bipolar disorder.

Do Defective Immune System-Mediated Myelination Processes Increase Postpartum Psychosis Risk?

Postpartum (or puerperal) psychosis (PP) is a rare, severe psychiatric disorder that affects women shortly after childbirth; risk is particularly high in individuals with a history of bipolar disorder or PP, but the underlying pathophysiology remains poorly understood. Emerging evidence suggests that immune system (dys)function plays an important role in disorder onset. On the basis of new findings from clinical and animal model studies, we hypothesise that the abundance and/or activity of regulatory T cells, and the efficacy of consequent (re)myelination processes in the brain mediated by CCN proteins, is perturbed in PP; this pathway may be modulated by risk and protective/treatment factors for the disorder, and identifying abnormalities within it could signpost novel predictive biomarkers and therapeutic targets.

Brain structure in women at risk of postpartum psychosis: an MRI study.

Postpartum psychosis (PP) is the most severe psychiatric disorder associated with childbirth. The risk of PP is very high in women with a history of bipolar affective disorder or schizoaffective disorder. However, the neurobiological basis of PP remains poorly understood and no study has evaluated brain structure in women at risk of, or with, PP. We performed a cross-sectional study of 256 women at risk of PP and 21 healthy controls (HC) in the same postpartum period. Among women at risk, 11 who developed a recent episode of PP (PPE) (n = 2 with lifetime bipolar disorder; n = 9 psychotic disorder not otherwise specified) and 15 at risk women who did not develop an episode of PP (NPPE) (n = 10 with lifetime bipolar disorder; n = 1 with schizoaffective disorder; n = 1 with a history of PP in first-degree family member; n = 3 with previous PP). We obtained T1-weighted MRI scans at 3T and examined regional gray matter volumes with voxel-based morphometry and cortical thickness and surface area with Freesurfer. Women with PPE showed smaller anterior cingulate gyrus, superior temporal gyrus and parahippocampal gyrus compared to NPPE women. These regions also showed decreased surface area. Moreover, the NPPE group showed a larger superior and inferior frontal gyrus volume than the HC. These results should be interpreted with caution, as there were between-group differences in terms of duration of illness and interval between delivery and MRI acquisition. Nevertheless, these are the first findings to suggest that MRI can provide information on brain morphology that characterize those women at risk of PP more likely to develop an episode after childbirth.

Specificity proteins 1 and 4, hippocampal volume and first-episode psychosis.

We assessed specificity protein 1 (SP1) and 4 (SP4) transcription factor levels in peripheral blood mononuclear cells and conducted a voxel-based morphometry analysis on brain structural magnetic resonance images from 11 patients with first-episode psychosis and 14 healthy controls. We found lower SP1 and SP4 levels in patients, which correlated positively with right hippocampal volume. These results extend previous evidence showing that such transcription factors may constitute a molecular pathway to the development of psychosis.

Phosphorylation of transcription factor specificity protein 4 is increased in peripheral blood mononuclear cells of first-episode psychosis.

BACKGROUND: Altered expression of transcription factor specificity protein 4 (SP4) has been found in the postmortem brain of patients with psychiatric disorders including schizophrenia and bipolar disorder. Reduced levels of SP4 protein have recently been reported in peripheral blood mononuclear cells in first-episode psychosis. Also, SP4 levels are modulated by lithium treatment in cultured neurons. Phosphorylation of SP4 at S770 is increased in the cerebellum of bipolar disorder subjects and upon inhibition of NMDA receptor signaling in cultured neurons. The aim of this study was to investigate whether SP4 S770 phosphorylation is increased in lymphocytes of first-episode psychosis patients and the effect of lithium treatment on this phosphorylation. METHODS: A cross-sectional study of S770 phosphorylation relative to total SP4 immunoreactivity using specific antibodies in peripheral blood mononuclear cells in first-episode psychosis patients (n = 14, treated with lithium or not) and matched healthy controls (n = 14) by immunoblot was designed. We also determined the effects of the prescribed drugs lithium, olanzapine or valproic acid on SP4 phosphorylation in rat primary cultured cerebellar granule neurons. RESULTS: We found that SP4 S770 phosphorylation was significantly increased in lymphocytes in first-episode psychosis compared to controls and decreased in patients treated with lithium compared to patients who did not receive lithium. Moreover, incubation with lithium but not olanzapine or valproic acid reduced SP4 phosphorylation in rat cultured cerebellar granule neurons. CONCLUSIONS: The findings presented here indicate that SP4 S770 phosphorylation is increased in lymphocytes in first-episode psychosis which may be reduced by lithium treatment in patients. Moreover, our study shows lithium treatment prevents this phosphorylation in vitro in neurons. This pilot study suggests that S770 SP4 phosphorylation could be a peripheral biomarker of psychosis, and may be regulated by lithium treatment in first-episode psychosis.

The 4th Schizophrenia International Research Society Conference, 5-9 April 2014, Florence, Italy: a summary of topics and trends.

The 4th Schizophrenia International Research Society Conference was held in Florence, Italy, April 5-9, 2014 and this year had as its emphasis, "Fostering Collaboration in Schizophrenia Research". Student travel awardees served as rapporteurs for each oral session, summarized the important contributions of each session and then each report was integrated into a final summary of data discussed at the entire conference by topic. It is hoped that by combining data from different presentations, patterns of interest will emerge and thus lead to new progress for the future. In addition, the following report provides an overview of the conference for those who were present, but could not participate in all sessions, and those who did not have the opportunity to attend, but who would be interested in an update on current investigations ongoing in the field of schizophrenia research.

Reduced expression of SP1 and SP4 transcription factors in peripheral blood mononuclear cells in first-episode psychosis.

Alterations of transcription factor specificity protein 4 (SP4) and 1 (SP1) have been linked to different neuropsychiatric diseases. Reduced SP4 and SP1 protein levels in the prefrontal cortex have been associated with bipolar disorder and schizophrenia, respectively, suggesting that both factors could be involved in the pathogenesis of disorders with psychotic features. The aim of this study was to investigate whether the reduction of SP1, SP4 and SP3 protein and mRNA expression in peripheral blood mononuclear cells in the early stages of psychosis may act as a potential biomarker of these disorders. A cross-sectional study of first-episode psychosis patients (n = 14) compared to gender- and age-matched healthy controls (n = 14) was designed. Patients were recruited through the adult mental health services of Parc Sanitari Sant Joan de Déu. Protein and gene expression levels of SP1, SP4 and SP3 were assessed in peripheral blood mononuclear cells of patients with first-episode psychosis and healthy control subjects. We report that protein levels of SP1 and SP4, but not SP3, are significantly reduced in patients compared to controls. In contrast, we did not observe any differences in expression levels for SP1, SP4 or SP3 genes between patient and control groups. In patients, SP4 protein levels were significantly associated with SP1 protein levels. No association was found, however, between protein and gene expression levels for each factor. Our study shows reduced SP1 and SP4 protein levels in first-episode psychosis in lymphocytes, suggesting that these transcription factors are potential peripheral biomarkers of psychotic spectrum disorders in the early stages.

Functional similarity of facial emotion processing between people with a first episode of psychosis and healthy subjects.

BACKGROUND: Neurofunctional and behavioral abnormalities in facial emotion processing (FEmoP) have been consistently found in schizophrenia patients, but studies assessing brain functioning in early phases are scarce and the variety of experimental paradigms in current literature make comparisons difficult. The present work focuses on assessing FEmoP in people experiencing a psychotic episode for the first time with different experimental paradigm approaches. METHODS: Twenty-two patients with a first psychotic episode (FPe) (13 males) took part in a functional magnetic resonance imaging study (1.5T) examining neural responses to explicit and implicit processing of fearful and happy facial expressions presented at two different intensities: 50% and 100%. Their brain activation was compared to that of 31 healthy subjects (15 males). RESULTS: Control subjects show differential patterns of brain activation regarding the task demands (implicit or explicit processing), the emotional content (happy or fear) and the intensities of the emotion (50% or 100%); such differences are not found in participants with a first psychotic episode (FPe). No interaction or group effects are seen between control and FPe participants with any of the emotional tasks assessed, although FPe subjects show worse behavioral performance. CONCLUSIONS: No brain areas recruited for FEmoP emerge as significantly different between people with a FPe and healthy subjects, independently on the demands of the task, the emotion processed, or the intensity of the emotion; but FPe participants show a limited recruitment of differential brain regions that could be associated with poor emotional processing in the short term. Our results outline the need of investigating the underlying processes that lead FPe participants to worse FEmoP performance.