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.

Thalamic neurochemical abnormalities in individuals with prodromal symptoms of schizophrenia - relationship to auditory event-related potentials.

Thalamic neurochemical abnormalities may underlie psychotic symptoms and auditory event-related potential (ERP) abnormalities in schizophrenia. We investigated this hypothesis in subjects at risk of psychosis using magnetic resonance spectroscopy and electroencephalography (EEG). Reduced thalamic glutamate plus glutamine and N-acetyl aspartate levels were associated with abnormal frontal ERPs, supporting a thalamic basis for filtering impairments.

Biological stress response in women at risk of postpartum psychosis: The role of life events and inflammation.

BACKGROUND: Postpartum psychosis (PP) is the most severe psychiatric disorder associated with childbirth, and the risk is particularly high in women with a history of bipolar disorder, schizoaffective disorder or in those who have suffered previous episodes of PP. While studies in patients with psychosis not related to the puerperium have demonstrated that abnormalities in stress response are important risk factors for psychosis, it remains unknown whether this is also the case for PP. METHODS: This study includes 30 postpartum women, assessed, on average, at postpartum week 14.8 ± 10.1 either with a current episode of PP (n = 14), or at-risk of PP because of a history of bipolar/schizoaffective disorder but who were well (n = 16), and a group of healthy women (n = 26). Details about recent stressful life events were obtained using the List of Threatening Experiences questionnaire, while perceived stress was evaluated using the Perceived Stress Scale. We estimated hypothalamic-pituitary adrenal (HPA) activity by measuring salivary cortisol at awakening; at 15, 30, and 60 min after awakening; at noon; and at 8 pm. An Area Under the Curve analysis was performed to assess the awakening response (AUCi) and cortisol levels during the day (AUCg). Immune markers, including high sensitivity C-Reactive Protein (hs-CRP) and Interleukin (IL)-1a, IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, Tumor Necrosis Factor (TNFa), Vascular Endothelial Growth Factor (VEGF), Interferon gamma (INFγ), Monocyte Chemoattractant Protein 1 (MCP-1), and Epidermal Growth Factor (EGF) were evaluated from peripheral blood samples. RESULTS: Women with current PP reported more frequent recent stressful life events, and higher perceived stress than healthy women. They also showed an activation of the stress and immune response, with higher levels of cortisol AUCg and hs-CRP (but not of other inflammatory markers) than healthy controls. Women at-risk of PP who remained well had values on these measures that were intermediate between those of women with a current episode of PP and those of healthy women. Stress measures and markers of stress and immune response explained 78 % of the variance of in group status between PP and healthy women, and 46 % of variance of in group status between women at-risk and healthy women. CONCLUSION: These findings suggest that an immune-HPA axis dysregulation, together with current stress may represent an important underlying pathophysiological mechanism in the onset of psychosis after childbirth in vulnerable women.

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.

Methylphenidate effects on prefrontal functioning during attentional-capture and response inhibition.

BACKGROUND: Methylphenidate improves motor response inhibition, typically assessed with the stop-signal task. The exact underlying mechanism for this, however, remains unknown. In addition, recent studies highlight that stop signals can have a confounding attentional-capture effect because of their low frequency in the task. In the current study, we assessed the effects of methylphenidate on neural networks of inhibitory control and attentional-capture within the context of two inhibitory control tasks. METHODS: The effects of methylphenidate (40 mg) were assessed using functional magnetic resonance imaging in 16 healthy volunteers in a within-subject, double-blind, placebo-controlled design. RESULTS: Methylphenidate significantly reduced activation of different regions within the right inferior frontal gyrus/insula to infrequent stimuli associated with successful inhibition, failed inhibition, and attentional capture. These inferior frontal gyrus regions showed different interregional connections with inhibitory and attention networks. For failed inhibitions, methylphenidate increased activation within performance-monitoring regions, including the superior frontal, anterior cingulate, and parietal-occipital cortices, but only after controlling for attentional capture. CONCLUSIONS: Our findings suggest that the improvement of response inhibition seen following methylphenidate administration is due to its influence on underlying attentional mechanisms linked to response control requirements.