Immunization stress-related responses presenting as psychogenic non-epileptic seizures following HPV vaccination in Rio Branco, Brazil.

IMPORTANCE: The absence of a positive diagnosis of psychogenic non-epileptic seizures (PNES) in immunization stress-related response (ISRR) clusters may have not only a direct impact on affected patients' health but may also reduce compliance to national vaccination programs. It is therefore crucial to develop efficient diagnostic tools and a feasible proposal for proper communication and treatment of ISRR. PURPOSE: To explore the psychogenic nature of patients' convulsive seizures in a suspected outbreak of an ISRR cluster following human papillomavirus vaccination in Rio Branco, Brazil. METHODS: Twelve patients with convulsive seizures were submitted to prolonged intensive video-electroencephalography monitoring, brain magnetic resonance imaging, cerebrospinal fluid diagnostic testing, laboratory subsidiary examinations, and complete neurological and psychiatric evaluations. RESULTS: Ten patients received the positive diagnosis of PNES, and two patients received the diagnosis of idiopathic generalized epilepsy. No biological association was found between the HPV vaccine and the clinical problems presented by the patients. CONCLUSIONS: Prolonged VEEG monitoring can contribute significantly to the positive diagnosis of PNES in ISRR clusters and to avoid hesitancy to vaccinate.

Diazepam Reduces Escape and Increases Closed-Arms Exploration in Gerbils After 5 min in the Elevated Plus-Maze.

Despite the wide implementation of the elevated plus-maze (EPM) test to assess anxiety-related behaviors in rodents, the interpretation of these measures in gerbils has received limited attention. Here, male gerbils were treated with vehicle or diazepam, followed by a 20-min EPM session. EPM data were subjected to minute-by-minute, 5-min bins and factor analyses. During the first 5-min, gerbils avoided the closed arms in favor of the open arms and diazepam increased open-arms entries; furthermore, a single factor (escape behavior) explained all the analyzed measures. Only after 5-min, gerbils reduced open-arms exploration and three independent factors emerged for each subsequent 5-min bin. These findings suggest that EPM data from gerbils should be analyzed in at least two 5-min bins. Measures from the standard 5-min session seem to be related to an escape response from the EPM through the open arms. Once habituated, measures from the second 5-min bin seem to be related to a conflictive situation: keep trying to escape unsuccessfully (due to open-arms height) or seek protection in the closed arms (unsafe places). Diazepam seems to reduce this conflict by mitigating the escape response (Factor 1 - Anxiety) and increasing closed-arms approach (Factor 2) and risk assessment (Factor 3). Unlike mice and rats, a decrease in open-arms exploration and an increase in risk assessment could be interpreted as an anxiolytic-like effect in gerbils.

Early protein malnutrition negatively impacts physical growth and neurological reflexes and evokes anxiety and depressive-like behaviors.

Malnutrition is a worldwide problem affecting millions of unborn and young children during the most vulnerable stages of their development. In humans, poor maternal nutrition is a major cause of intrauterine growth restriction which is associated with an increased risk of perinatal mortality and long-term morbidity. In addition, intrauterine growth restriction correlates with neurodevelopmental delays and alterations of brain structure and neurochemistry. While there is no doubt that maternal malnutrition is a principal cause of perturbed development of the fetal brain and that all nutrients have certain influence on brain maturation, proteins appear to be the most critical for the development of neurological functions. In the present study we assessed male and female mouse offspring, born to dams protein restricted during pregnancy and lactation, in physical growth and neurobehavioral development and also in social interaction, motivation, anxiety and depressive behaviors. Moreover, we evaluate the impact of the low protein diet on dams in relation to their maternal care and anxiety-related behavior given that these clearly affect pups development. We observed that maternal protein restriction during pregnancy and lactation delayed the physical growth and neurodevelopment of the offspring in a sex-independent manner. In addition, maternal undernutrition negatively affected offspring's juvenile social play, motivation, exploratory activity and risk assessment behaviors. These findings show that protein restriction during critical periods of development detrimentally program progeny behavior.

Effect of nutritional rehabilitation on gastric motility and somatization in adolescents with anorexia.

OBJECTIVE: To examine gastric function, as well as the presence of somatic complaints, anxiety symptoms, and functional gastrointestinal disorders (FGIDs), in adolescents with anorexia nervosa (AN) before and after nutritional rehabilitation. STUDY DESIGN: Sixteen females with AN and 22 healthy controls with similar demographic profiles were included. Gastric emptying (measured as residual gastric volume) and gastric accommodation (measured as postprandial antral diameter) were assessed with abdominal ultrasonography. Participants completed the Children's Somatization Inventory (CSI), the Screen for Child Anxiety-Related Emotional Disorders, and the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III version. All testing was repeated 3-4 months later. RESULTS: Body mass index in the AN group improved over time (P = .012). Fasting gastric parameters were similar in the 2 groups. Maximum postprandial antral diameter was significantly greater in controls compared with the AN group (P = .008). Only adolescents with AN demonstrated a significant increase in maximum postprandial diameter at repeat testing (P = .009). There was no difference in residual gastric volume between the 2 groups. Initial CSI scores were higher in adolescents with AN (P < .0001), including higher scores for nausea and abdominal pain. CSI scores were significantly lower in adolescents with AN (P = .035). Initial scores on the Screen for Child Anxiety-Related Emotional Disorders were significantly higher in adolescents with AN (P = .0005), but did not change over time. Adolescents with AN met significantly more criteria for FGIDs (P = .003). CONCLUSION: Adolescents with AN have impaired gastric accommodation that improves after nutritional rehabilitation, have significantly more somatic complaints, and meet more criteria for anxiety disorders and FGIDs. After nutritional rehabilitation, somatization improves and FGIDs become less common, but symptoms of anxiety persist.

Hippocampal SPARC regulates depression-related behavior.

SPARC (secreted protein acidic and rich in cysteine) is a matricellular protein highly expressed during development, reorganization and tissue repair. In the central nervous system, glial cells express SPARC during development and in neurogenic regions of the adult brain. Astrocytes control the glutamate receptor levels in the developing hippocampus through SPARC secretion. To further characterize the role of SPARC in the brain, we analyzed the hippocampal-dependent adult behavior of SPARC KO mice. We found that SPARC KO mice show increased levels of anxiety-related behaviors and reduced levels of depression-related behaviors. The antidepressant-like phenotype could be rescued by adenoviral vector-mediated expression of SPARC in the adult hippocampus, but anxiety-related behavior persisted in these mice. To identify the cellular mechanisms underlying these behavioral alterations, we analyzed neuronal activity and neurogenesis in the dentate gyrus (DG). SPARC KO mice have increased levels of neuronal activity, evidenced as more neurons that express c-Fos after a footshock. SPARC also affects cell proliferation in the subgranular zone of the DG, although it does not affect maturation and survival of new neurons. SPARC expression in the adult DG does not revert the proliferation phenotype in KO mice, but our results suggest a role of SPARC in limiting the survival of new neurons in the DG. This work suggests that SPARC could affect anxiety-related behavior by modulating neuronal activity, and that depression-related behavior is dependent upon the adult expression of SPARC, which affects adult brain function by mechanisms that need to be elucidated.

REM Sleep Rebound as an Adaptive Response to Stressful Situations.

Stress and sleep are related to each other in a bidirectional way. If on one hand poor or inadequate sleep exacerbates emotional, behavioral, and stress-related responses, on the other hand acute stress induces sleep rebound, most likely as a way to cope with the adverse stimuli. Chronic, as opposed to acute, stress impairs sleep and has been claimed to be one of the triggering factors of emotional-related sleep disorders, such as insomnia, depressive- and anxiety-disorders. These outcomes are dependent on individual psychobiological characteristics, conferring even more complexity to the stress-sleep relationship. Its neurobiology has only recently begun to be explored, through animal models, which are also valuable for the development of potential therapeutic agents and preventive actions. This review seeks to present data on the effects of stress on sleep and the different approaches used to study this relationship as well as possible neurobiological underpinnings and mechanisms involved. The results of numerous studies in humans and animals indicate that increased sleep, especially the rapid eye movement phase, following a stressful situation is an important adaptive behavior for recovery. However, this endogenous advantage appears to be impaired in human beings and rodent strains that exhibit high levels of anxiety and anxiety-like behavior.