Posttraumatic stress disorder (PTSD) has been shown to be associated with pro-inflammatory markers, including elevated plasma levels of interleukin-1β (IL-1β). However, the precise role of neuroinflammation and central immune signaling on the development of this debilitating psychological disorder is not known. Here, we used stress-enhanced fear learning (SEFL), an animal model of the disorder, to examine the role of central IL-1β in PTSD. The results show that the severe stressor in SEFL induces a time-dependent increase in IL-1β immunoreactivity and mRNA expression within the dentate gyrus of the dorsal hippocampus (DH). There was no increase in IL-1β in the basolateral amygdala or the perirhinal cortex. Moreover, blocking the action of IL-1β following the severe stressor with IL-1 receptor antagonist (10 μg, intracerebroventricular (i.c.v.), 24 and 48 h after the stressor) prevented the development of SEFL. To provide further support for the role of IL-1β in the development of SEFL, we show that systemic morphine, a treatment which is known to reduce both PTSD and SEFL, also reduces IL-1β expression in the DH induced by the severe stressor. These studies provide the first evidence that IL-1 is involved SEFL and suggest that IL-1 signaling in the brain may have a critical role in the development of PTSD.

The Types of Intuition Scale (TIntS) measures three types of intuition identified in a literature review by Pretz and Totz (2007): holistic, inferential, and affective. Holistic intuitions integrate diverse sources of information in a Gestalt‐like, non‐analytical manner; inferential intuitions are based on previously analytical processes that have become automatic; and affective intuitions are based on feelings. Current intuition measures inadequately assess these distinct types. We report four validity studies: Study 1 reports the reliability and factor structure of the TIntS and correlations with extant intuition and personality measures. Study 2 presents a confirmatory factor analysis. Studies 3 and 4 examine the predictive validity of the TIntS with respect to clinical decision making in occupational therapy and musical performance. Scales were internally consistent and stable over time, and factor analyses supported the predicted distinctions among them. Correlations with existing measures of intuition, personality, and behavior showed that the TIntS is unique in its assessment of all three types of intuition in one measure. Copyright © 2014 John Wiley & Sons, Ltd.

BackgroundOlanzapine use has been reported during pregnancy and breastfeeding, but there are no controlled clinical trials assessing the safety of olanzapine exposure to infants and fetuses. The purpose of this report was to review and analyze prospective post-marketing cases of pregnancy and breastfeeding with olanzapine, in order to guide clinicians and women on the use of olanzapine therapy during pregnancy and/or breastfeeding.MethodsA worldwide safety database maintained by Eli Lilly and Company was searched for all spontaneous-reported data regarding olanzapine use during pregnancy and/or breastfeeding. Cases reported prior to pregnancy outcome were considered to be prospective, and follow-up was pursued after the delivery date to assess outcome.ResultsOutcome data were available for 610 prospectively identified pregnancies during which olanzapine was used. The majority of women had normal births (66%), although premature births were reported in 9.8% and perinatal conditions in 8% of the pregnancies. A total of 102 pregnancies reported olanzapine treatment during breastfeeding. In these infants, the most commonly reported adverse events were somnolence (3.9%), irritability (2%), tremor (2%), and insomnia (2%), although the majority of pregnancies reported no adverse events (82.3%).ConclusionsThe frequency of fetal outcomes in these prospectively identified pregnancies exposed to olanzapine did not differ from rates of outcomes reported in the general population. These data may be useful to help guide clinicians and women decide to continue, or discontinue, olanzapine therapy during pregnancy and/or breastfeeding, but should be considered within the limitations associated with spontaneously reported data. Women should notify their clinicians if they become pregnant or intend to become pregnant while being treated with olanzapine. Because of limited experience in humans, olanzapine should be used in pregnancy only when potential benefit justifies potential risk to the fetus. Olanzapine should only be considered during breastfeeding when the potential benefit justifies the potential risk to the infant.

Post-traumatic stress disorder (PTSD) is associated with immune dysregulation. We have previously shown that severe stress exposure in a preclinical animal model of the disorder, stress-enhanced fear learning (SEFL), is associated with an increase in hippocampal interleukin-1β (IL-1β) and that blocking central IL-1 after the severe stress prevents the development of SEFL. Here, we tested whether blocking hippocampal IL-1 signaling is sufficient to prevent enhanced fear learning and identified the cellular source of stress-induced IL-1β in this region. Experiment 1 tested whether intra-dorsal hippocampal (DH) infusions of interleukin-1 receptor antagonist (IL-1RA, 1.25µg per hemisphere) 24 and 48h after stress exposure prevents the development of enhanced fear learning. Experiment 2 used triple fluorescence immunohistochemistry to examine hippocampal alterations in IL-1β, glial fibrillary acidic protein (GFAP), an astrocyte-specific marker, and ionized calcium binding adaptor molecule -1 (Iba-1), a microglial-specific marker, 48h after exposure to the severe stressor of the SEFL paradigm. Intra-DH IL-1RA prevented SEFL and stress-induced IL-1β was primarily colocalized with astrocytes in the hippocampus. Further, hippocampal GFAP immunoreactivity was not altered, whereas hippocampal Iba-1 immunoreactivity was significantly attenuated following severe stress. These data suggest that hippocampal IL-1 signaling is critical to the development of SEFL and that astrocytes are a predominant source of stress-induced IL-1β.

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Objective. Antipsychotics have been associated with increased cardiac events including mortality. This study assessed cardiac events including mortality among antipsychotic users relative to nonusers. Methods. The General Practice Research Database (GPRD) was used to identify antipsychotic users, matched general population controls, and psychiatric diseased nonusers. Outcomes included cardiac mortality, sudden cardiac death (SCD), all-cause mortality (excluding suicide), coronary heart disease (CHD), and ventricular arrhythmias (VA). Sensitivity analyses were conducted for age, dose, duration, antipsychotic type, and psychiatric disease. Results. 183,392 antipsychotic users (115,491 typical and 67,901 atypical), 544,726 general population controls, and 193,920 psychiatric nonusers were identified. Nonusers with schizophrenia, dementia, or bipolar disorder had increased risks of all-cause mortality compared to general population controls, while nonusers with major depression had comparable risks. Relative to psychiatric nonusers, the adjusted relative ratios (aRR) of all-cause mortality in antipsychotic users was 1.75 (95% CI: 1.64–1.87); cardiac mortality 1.72 (95% CI: 1.42–2.07); SCD primary definition 5.76 (95% CI: 2.90–11.45); SCD secondary definition 2.15 (95% CI: 1.64–2.81); CHD 1.16 (95% CI: 0.94–1.44); and VA 1.16 (95% CI: 1.02–1.31). aRRs of the various outcomes were lower for atypical versus typical antipsychotics (all-cause mortality 0.83 (95% CI: 0.80–0.85); cardiac mortality 0.89 (95% CI: 0.82–0.97); and SCD secondary definition 0.76 (95% CI: 0.55–1.04). Conclusions. Antipsychotic users had an increased risk of cardiac mortality, all-cause mortality, and SCD compared to a psychiatric nonuser cohort.

These results do not support an increased risk of CV events with atomoxetine compared with the stimulant ADHD medication. Users of ADHD medications may be at an increased risk of TIA compared with the general population.

Objective. Assess risk of cardiac events and mortality among users of olanzapine and other antipsychotics relative to nonusers. Methods. The General Practice Research Database was used to identify cohorts of antipsychotic users and nonusers with psychiatric illness. Outcomes included cardiac mortality, sudden cardiac death (SCD), all-cause mortality (excluding suicide), coronary heart disease (CHD), and ventricular arrhythmias (VA). Results. 183,392 antipsychotic users (including 20,954 olanzapine users) and 193,920 psychiatric nonusers were identified. There was a significantly higher rate of cardiac mortality (adjusted RR [aRR]: 1.53, CI, 1.12–2.09) in olanzapine users relative to psychiatric nonusers, consistent with findings for both atypical and typical antipsychotics. Relative to psychiatric nonusers, no increased risk of all-cause mortality was observed among olanzapine users (aRR: 1.04, CI, 0.93–1.17), but elevated all-cause mortality risk was observed when compared to all antipsychotic users (aRR: 1.75, CI, 1.64–1.87). There was no increased risk of CHD or VA among olanzapine users relative to psychiatric nonusers, consistent with findings for atypical but not typical antipsychotics. SCD cases were uncommon. Conclusions. Use of antipsychotic agents was associated with increased risk of all-cause and cardiac mortality. Patients treated with olanzapine were found to be at increased risk of cardiac mortality versus psychiatric nonusers.