Inhibitory control as possible risk and/or resilience factor for the development of trauma related symptoms-a study of the Utøya terror attack survivors.

PTSD symptomatology is known to be associated with executive dysfunction. Inhibitory control is a core component of executive functioning, and inhibitory skills are essential both for adequate functioning in everyday life and important in situations following trauma. The aim of the present study was to examine the relationship between trauma exposure, inhibitory control and PTSD symptomatology in adolescent survivors of the terror attack at Utøya, Norway on the 22nd of July, 2011. In this cross-sectional case-control study, 20 trauma exposed adolescents and 20 healthy controls matched in age and gender were compared on a neuropsychological test of cognitive inhibition (Color-Word Interference Test) and a self-report measure of inhibition ability (BRIEF-A). Our analyses revealed that the trauma exposed group differed significantly on the self-reported measure of inhibitory control compared to the control group, but there were no differences between groups on the objective measures of cognitive inhibition. Follow-up analyses with subgroups in the trauma exposed group based on PTSD symptomatology (PTSD + and PTSD-) and the control group revealed that the PTSD- group showed significantly better results than both the PTSD + and the control group on the measures of inhibitory control. Moreover, the follow-up analyses showed that the PTSD + group showed significantly poorer results from the other two groups on the measures of inhibitory control and self-reported inhibition. We conclude that impaired inhibitory control, measured both objectively and by self-reported questionnaire, is related to PTSD symptomatology. Findings suggest that inhibitory dysfunctions may be a vulnerability factor for the development of PTSD symptomatology in trauma exposed adolescents, and thus it seems that the ability to exhibit inhibitory control could be a possible resilience factor to prevent the development of PTSD symptoms.

Does a single exposure to social defeat render rats more vulnerable to chemically induced colitis than brief inescapable foot-shocks?

All mammals are to different degrees exposed to stressors being physical or social, which may affect health and well-being. Stressful and traumatic situations have direct effects on immune responses that may alter susceptibility to developing somatic illnesses. In animal research, different types of stressors have been investigated in studying the effect on bowel disorders, some stressors being more or less of environmental origin. We aimed, therefore, to explore whether a more natural stressor would differ from a stressor of more unnatural characteristics on dextran sulphate sodium (DSS) induced colitis in adult rats. Specifically, whether social stress within a single social defeat (SD) paradigm would be a more potent stressor than brief inescapable foot-shocks (IFS) in causing elevated faecal granulocyte marker protein (GMP), and crypt- and inflammation scores in colonic tissue. Three groups of male Wistar rats were used; socially defeated rats; inescapable foot-shock rats; and comparison rats. Main findings showed no difference between the groups on GMP levels. However, there was a significant difference on inflammation and crypt scores for the distal part of colon, detected through histology, where socially defeated rats were more susceptible. A single SD seems to be more adverse than inescapable foot-shock on DSS induced colitis, but further studies are recommended to validate a broader range of different outcomes comparing two such different rodent stress models.

The Relationship Between Perceived Social Support and PTSD Symptoms After Exposure to Physical Assault: An 8 Years Longitudinal Study.

Consequences of nondomestic violence are known to be multifaceted with high rates of emotional and psychological problems in addition to physical injuries, and victims report many trauma related symptoms. This study explore if perceived social support (PSS) (Social Provisions Scale [SPS]) and post-traumatic stress disorder (PTSD) symptoms (Impact of Event Scale [IES-22]) are interrelated among adult victims at four assessment points up until eight years after the exposure to physical assault; soon after the event (T1), three months after T1 (T2), one year after T1 (T3), and eight years after T1 (T4). One hundred and forty-three subjects participated at T1, 94 at T2, 73 at T3, and 47 accepted a follow-up at T4. At T1, 138 of 143 completed the questionnaires within 16 weeks after the incident. PTSD symptoms were highly correlated across time (p < .001); PSS were significantly correlated only between T1 and T2 (p < .001), T1 and T3 (p < .05), and between T2 and T3 (p < .05). Cross-lagged analyses showed an inverse relationship between prior PSS and later PTSD symptoms across all time points (ps < .05); not proved between prior PTSD symptoms and later PSS (ps > .1). PSS at T1 was an independent predictor of PSS one year and eight years after the incident. We conclude that higher perception of social support protects against the development of PTSD symptoms; diminished perception of social support increases the risk of developing PTSD symptoms. These findings suggest that PSS after experiencing a violent assault should be considered as an important factor in natural recovery in the long run, as well as essential alongside psychiatric treatment. Establishing psychosocial interventions for victims of physical violence in the acute phase may prevent prolonged trauma reactions.

Predictors and correlates of lifetime and persistent non-suicidal self-injury and suicide attempts among adult survivors of childhood sexual abuse.

Background: Childhood sexual abuse (CSA) is a well-established risk factor for non-suicidal self-injury (NSSI) and suicide attempts (SA); still few studies have examined predictors of individual differences in NSSI/SA amongst CSA survivors. Objective: To examine predictors of NSSI and SA among adult CSA-survivors. Methods: In a sample of 516, primarily female adult CSA-survivors recruited from support centres for sexual abuse survivors in Norway, we examined the role of abuse/perpetrator characteristics, and the degree/severity of exposure to other types of childhood maltreatment (cumulative childhood maltreatment; CCM), as predictors of lifetime NSSI and SA. In a subsample of 138 individuals responding to follow-up waves two- and four years later, these same distal factors, as well as previous NSSI and proximal factors in the form of symptoms of mental health disorders (posttraumatic stress, anxiety, depression, sleep disturbances, and eating disorders), relational problems, and perceived social support, were examined as predictors of persistent NSSI. Finally, those attempting new SA during the follow-up period were compared to those who did not on these variables. Results: Higher CCM scores and having had an unknown perpetrator positively predicted lifetime NSSI scores. Higher CCM scores, violent abuse, and having had an unknown perpetrator predicted lifetime SA. Higher CCM scores, previous NSSI, having had a known perpetrator, as well as higher depression-, anxiety- and eating disorder scores, positively predicted persistent NSSI during the four-year follow-up period. Compared to those with no new SA, those reporting new SA during the follow-up period had higher CCM, lifetime NSSI, mental health symptoms and relational problem scores, lower perceived social support scores, and were more likely to have done a past SA and to have experienced abuse involving physical violence. Conclusions: A broad range of both distal and proximal factors should be assessed as potential predictors of NSSI and SA among adult CSA-survivors.

Antecedentes: El abuso sexual infantil (CSA por sus siglas en inglés) es un factor de riesgo bien establecido para las autolesiones no suicidas (NSSI por sus siglas en inglés) y los intentos suicidas (SA por sus siglas en inglés); aun así, pocos estudios han examinado los predictores de las diferencias individuales en NSSI/SA en los sobrevivientes de CSA. Objetivo: Examinar los predictores de NSSI y SA entre adultos sobrevivientes de CSA.Métodos: En una muestra de 516, primariamente mujeres adultas sobrevivientes de CSA reclutadas de centros de apoyo para sobrevivientes de abuso sexual en Noruega, examinamos el rol de las características del abuso/perpetrador y el grado/severidad de la exposición a otros tipos de maltrato infantil (maltrato acumulativo infantil; CCM por sus siglas en ingles), como predictores de NSSI y SA en la vida. En una submuestra de 138 individuos que respondieron a las etapas de seguimiento dos y cuatro años después, se examinaron como predictores de NSSI persistente, estos mismos factores distales, así como NSSI previos y factores proximales en la forma de síntomas de trastornos de salud mental (estrés postraumático, ansiedad, depresión, trastornos del sueño y trastornos de la conducta alimentaria), problemas relacionales, y apoyo social percibido. Finalmente, se compararon en estas variables los que intentaron un nuevo SA durante el periodo de seguimiento con los que no lo hicieron.Resultados: Puntajes más altos de CCM y haber tenido un perpetrador desconocido, predijeron positivamente puntajes de NSSI en la vida. Puntajes de CCM más altos, abuso violento y haber tenido un perpetrador desconocido predijeron el SA en la vida. Los puntajes más altos de CCM, NSSI previos, haber tenido un perpetrador conocido, así como puntajes más altos de depresión, ansiedad y trastornos alimentarios, predijeron positivamente NSSI persistente durante el periodo de seguimiento de 4 años. Comparado con los individuos sin nuevos SA, los que reportaron SA nuevos durante el periodo de seguimiento tenían puntajes más altos de CCM, NSSI en la vida, síntomas de salud mental y problemas relacionales, puntajes más bajos de apoyo social percibido y tenían más probabilidades de haber realizado SA en el pasado y haber experimentado abuso que involucraba violencia física.Conclusiones: Se debe evaluar una amplia gama de factores distales y proximales como posibles predictores de NSSI y SA entre adultos sobrevivientes de CSA.

The association of PTSD symptom severity with amygdala nuclei volumes in traumatized youths.

The amygdala is a core component in neurobiological models of stress and stress-related pathologies, including post-traumatic stress disorder (PTSD). While numerous studies have reported increased amygdala activity following traumatic stress exposure and in PTSD, the findings regarding amygdala volume have been mixed. One reason for these mixed findings may be that the amygdala has been considered as a homogenous entity, while it in fact consists of several nuclei with unique cellular and connectivity profiles. Here, we investigated amygdala nuclei volumes of the basolateral and the centrocorticomedial complex in relation to PTSD symptom severity in 47 young survivors from the 2011 Norwegian terror attack 24-36 months post-trauma. PTSD symptoms were assessed 4-5, 14-15 and 24-36 months following the trauma. We found that increased PTSD symptom severity 24-36 months post-trauma was associated with volumetric reductions of all basolateral as well as the central and the medial nuclei. However, only the lateral nucleus was associated with longitudinal symptom development, and mediated the association between 4-5 months and 24-36 months post-trauma symptoms. The results suggest that the amygdala nuclei may be differentially associated with cross-sectional and longitudinal measures of PTSD symptom severity. As such, investigations of amygdala total volume may not provide an adequate index of the association between amygdala and stress-related mental illness.

Longitudinal Relationships between Perceived Social Support and Symptom Outcomes: Findings from a sample of Adult Survivors of Childhood Sexual Abuse.

INTRODUCTION: Cross-sectional studies have consistently reported an inverse association between perceived social support and the severity of mental health symptoms among adult survivors of childhood sexual abuse (CSA). However, there is a lack of longitudinal studies investigating the bidirectional association between social support and the severity of symptoms among adult CSA-survivors, as well as the role of relational problems in predicting perceived social support and symptom levels over time. The present study addressed these questions in a sample of primarily female CSA-survivors. METHODS: In a three-wave, four-year longitudinal study of 506 CSA-survivors (94.9% women, 5.1% men) recruited from support centers for sexual abuse survivors in Norway, we used cross-lagged panel structural equation modeling to examine the directionality of the longitudinal associations between perceived social support and symptoms of posttraumatic stress, anxiety, depression and insomnia. RESULTS: Cross-lagged panel analyses revealed significant weak reciprocal associations between perceived social support and depression, posttraumatic stress symptoms and anxiety symptoms, but not with insomnia symptoms. The observed effects were partly overlapping and partly inconsistent across the different symptom domains. Relational problems predicted social support cross-sectionally and longitudinally, whereas only cross-sectional associations were found between the relational problems variable and mental health symptoms. Theoretical and clinical implications of the findings are discussed, alongside methodological limitations of the study.

Plunging Into a Dark Sea of Emotions: Professionals' Emotional Experiences Addressing Child Abuse in Interviews With Children.

Comprehending professionals' emotional challenges when addressing child abuse can help to improve identification, protection, and care for exposed children. This study presents an interpretive description analysis of qualitative interviews with ten child protective services workers and nine child mental health services psychologists in Norway. The participants described intense negative reactions due to addressing child abuse during assessments and investigations. We identified five main themes: (a) facing children's suffering caused by adults, (b) feeling mean, (c) doubting one's ability and skills, (d) feeling that one is betraying children, and (e) being obstructed by heavy workload and dysfunctional structure. To improve professionals' capacity to help exposed children, it is necessary to change the organizational structure and culture. In addition, professionals would benefit from systematic training in handling complexity and in efficient emotion regulation. Finally, we strongly suggest that institutions responsible for investigating child abuse facilitate and prioritize deliberate practice for their staff.

Entering an emotional minefield: professionals' experiences with facilitators to address abuse in child interviews.

BACKGROUND: Extensive research documents that child abuse is widespread and that it has detrimental effects on victims' physical, psychological and social well-being. Efforts to help abused children by removing stressors and administering restorative care can reverse these negative effects, but the evidence suggests that professionals often fail to expose child abuse. This study aims to generate insight into professionals' experiences with facilitators in handling the challenges of addressing abuse in child interviews. We expect that this knowledge can improve interventions that qualify professionals in the identification, protection and care of abused children. METHODS: Within the qualitative approach and an Interpretive Description framework, we performed in-depth interviews with nineteen participants from southern Norway, specifically ten social workers from child protective services and nine psychologists from child mental health services. Then, Interpretive Description analysis was performed by using constant comparison, reflexive and critical examinations, and contextualized theoretical interpretations. RESULTS: The participants' accounts revealed that various facilitators relative to the stages of the skill development and intrinsic motivation of the practitioner enhance the explorative work of the professional. We identified the following five main themes: (a) alleviating personal choice; (b) collective accountability; (c) sharing vulnerability; (d) finding your own way; and (e) doing it for the right reasons. CONCLUSIONS: To facilitate explorative work, our findings suggest that competence development should apply goal-directed reflective practice combined with positive feedback on performance. Furthermore, our results indicate that developing personal competence is contingent on supporting individual choice and volition while decreasing demands towards following rules and guidelines. To promote the relatedness and the emotion regulation of professionals, we suggest endorsing shared vulnerability with colleagues and promoting an organizational culture that supports openness and allows professionals to discuss their emotions when addressing difficult and complex issues. It is also advisable to promote autonomy by helping professionals to find meaning in their work that is compatible with their personal values.

Insomnia symptom trajectories among adult survivors of childhood sexual abuse: A longitudinal study.

BACKGROUND: Childhood sexual abuse (CSA) is associated with sleep disturbances in adulthood. However, longitudinal studies have yet to identify among CSA-survivors subgroups distinguished by the trajectory of their insomnia severity, or predictors of subgroup membership. OBJECTIVE: The objective of this study was to examine longitudinal insomnia symptom trajectories, as well as predictors and correlates of the identified trajectories, over a 4 year study period in a sample of adult, mainly female CSA-survivors. PARTICIPANTS AND SETTING: The sample comprised 533 adult survivors of CSA (94.9% women, mean age 39.2 years, mean age of abuse onset 6.5 years), recruited from support centers for sexual abuse survivors in Norway. METHODS: Latent class growth analyses were used to identify insomnia symptom trajectories. RESULTS: Three distinct trajectories of insomnia symptoms were identified; one characterized by high insomnia symptom scores minimally decreasing over the study period ('high and decreasing', 30.6%), one characterized by stable intermediate insomnia symptom scores ('intermediate and stable', 41.5%), and one characterized by stable low insomnia symptom scores ('low and stable', 27.9%). Predictors of belonging to the high and decreasing trajectory (using the low and stable trajectory as a reference), was lower age of abuse onset (expotentiated coefficient (EC): 0.93, p = 0.026), abuse involving penetration (EC: 2.36, p = 0.005), threats (EC: 3.06, p < 0.001) or physical violence (EC: 3.29 p < 0.001), a higher score on a composite variable comprising multiple other abuse and perpetrator aspects (EC: 2.55, p < 0.001), as well as scoring above a clinical cut-off on a measure of posttraumatic stress symptoms (EC: 12.17, p < 0.001). Those belonging to the high and decreasing trajectory also reported lower levels of perceived social support and higher levels of subjectively experienced relational difficulties compared to those belonging to the two other trajectories. CONCLUSIONS: We conclude that different longitudinal insomnia trajectories exist among adult CSA survivors. The overall results, as well as the significant predictors, are discussed alongside their potential clinical implications.

Prefrontal glutamate levels predict altered amygdala-prefrontal connectivity in traumatized youths.

BACKGROUND: Neurobiological models of stress and stress-related mental illness, including post-traumatic stress disorder, converge on the amygdala and the prefrontal cortex (PFC). While a surge of research has reported altered structural and functional connectivity between amygdala and the medial PFC following severe stress, few have addressed the underlying neurochemistry. METHODS: We combined resting-state functional magnetic resonance imaging measures of amygdala connectivity with in vivo MR-spectroscopy (1H-MRS) measurements of glutamate in 26 survivors from the 2011 Norwegian terror attack and 34 control subjects. RESULTS: Traumatized youths showed altered amygdala-anterior midcingulate cortex (aMCC) and amygdala-ventromedial prefrontal cortex (vmPFC) connectivity. Moreover, the trauma survivors exhibited reduced levels of glutamate in the vmPFC which fits with the previous findings of reduced levels of Glx (glutamate + glutamine) in the aMCC (Ousdal et al., 2017) and together suggest long-term impact of a traumatic experience on glutamatergic pathways. Importantly, local glutamatergic metabolite levels predicted the individual amygdala-aMCC and amygdala-vmPFC functional connectivity, and also mediated the observed group difference in amygdala-aMCC connectivity. CONCLUSIONS: Our findings suggest that traumatic stress may influence amygdala-prefrontal neuronal connectivity through an effect on prefrontal glutamate and its compounds. Understanding the neurochemical underpinning of altered amygdala connectivity after trauma may ultimately lead to the discovery of new pharmacological agents which can prevent or treat stress-related mental illness.

Life Threat and Sleep Disturbances in Adolescents: A Two-Year Follow-Up of Survivors From the 2011 Utøya, Norway, Terror Attack.

A significant number of adolescents have been exposed to traumatic life events. However, knowledge about the specific sleep disturbance that occurs in individuals after trauma exposure is predominantly based on studies of adults. This study reports specific sleep disturbance in 42 survivors of the 2011 mass shooting at a youth summer camp on the Norwegian island Utøya, mean age = 20.91 years, SD = 2.32, 62.5% females. When compared with matched controls, significantly more survivors reported having sleep disturbances, 52.4% versus 13.6%, d = 0.93, of which onset began at the time of the shooting, χ2 = 14.9, p < .001. The prevalence of insomnia, 56.3% versus 11.0%, d = 0.73; excessive daytime sleepiness, 34.4% versus 13.6%, d = 0.61; symptoms of obstructive sleep apnea, 18.8% versus 0%, d = 0.70; and frequent nightmares, 37.5% versus 2.3%, d = 0.90, were all higher in the survivors than in the controls. In a subgroup of survivors (n = 20) with psychiatric diagnoses, sleep disturbances were more prevalent than in survivors without psychiatric diagnosis. Actigraphy data revealed delayed bedtime, sleep onset, and rise time in survivors compared with controls, ts > 1.7, ps = .044 to .028. These results corroborate the effects of a life threat on the range and extent of sleep disturbances, and emphasize the need to better assess and treat sleep disorders in adolescents exposed to trauma.

Posttraumatic symptom profiles among adult survivors of childhood sexual abuse: A longitudinal study.

In the present study, our aim was to examine longitudinal posttraumatic stress symptom (PTSS) trajectories in a Norwegian sample of adults who had experienced sexual abuse during childhood, and to identify predictors of PTSS-trajectory belongingness. The sample consisted of 138 adult survivors of childhood sexual abuse (96.4% women, mean age=42.9years, mean age at the first abuse=5.9 years), recruited from support centers for sexual abuse survivors. The majority (78.3%) reported penetrative abuse, and a large proportion of the sample reported that the perpetrator was a biological parent (38.4%) or someone they trusted (76.1%), reflecting a high severity level of the abusive experiences. Latent Profile Analyses revealed the best overall fit for a two PTSS-trajectories model; one trajectory characterized by sub-clinical and decreasing level of PTSS (54.9%), and the other by high and slightly decreasing level of PTSS (45.1%). Increased odds for belonging to the trajectory with clinical level symptoms was found among those who reported higher levels of exposure to other types of childhood maltreatment (OR=3.69, p=0.002), sexual abuse enforced by physical violence (OR=3.04, p=0.003) or threats (OR=2.56, p=0.014), very painful sexual abuse (OR=2.73, p=0.007), or who had experienced intense anxiety, helplessness or fear during the abuse (OR=2.97, p=0.044). Those in the trajectory with clinical level PTSS reported lower levels of perceived social support and more relational difficulties compared to those in the sub-clinical PTSS trajectory. In conclusion, different longitudinal PTSS trajectories can be found among adult survivors of childhood sexual abuse. Significant predictors of PTSS-trajectory belongingness are discussed alongside their potential implications for preventive efforts and clinical interventions.

Cumulative childhood maltreatment and its dose-response relation with adult symptomatology: Findings in a sample of adult survivors of sexual abuse.

In the present study, we examined the role of cumulative childhood maltreatment experiences for several health related outcomes in adulthood, including symptoms of psychological distress as well as perceived social support and hardiness. The sample comprised adult survivors of sexual abuse (N=278, 95.3% women, mean age at first abusive incident=6.4 years). One-way ANOVAs revealed a statistically significant dose-response relation between cumulative childhood maltreatment scores and self-reported symptoms of posttraumatic stress (PTSS), anxiety, depression, eating disorders, dissociation, insomnia, nightmare related distress, physical pain, emotional pain, relational problems, self-harm behaviors as well as on a measure of symptom complexity. Cumulative childhood maltreatment was also associated with lower levels of work functioning. An inverse dose-response relation was found for perceived social support and hardiness. Using a Bonferroni corrected alpha level, cumulative childhood maltreatment remained significantly associated with all outcome measures with the exception of eating disorder symptoms after controlling for abuse-related independent variables in hierarchical regression analyses. Results add to previous literature by showing that dose-response relation between cumulative childhood adversities and adult symptom outcomes could also be identified in a sample characterized by high exposure to adversities, and lends support to the notion put forth by previous authors that cumulative childhood adversities seem to be related to the severity of adult health outcomes in a rule-governed way.

Mild daily stressors in adulthood may counteract behavioural effects after constant presence of mother during early life.

This study investigated adult rat behaviour in three early life conditions, and how behaviour was affected after exposure to chronic mild stressors in later life. During postnatal days 2-14, male Wistar rats were exposed daily to either long or brief maternal separation, or were left undisturbed with their mothers (non-handled). As adults, non-handled and long maternally separated offspring demonstrated less object exploration than brief maternally separated offspring. Non-handled offspring also showed lower pre-pulse inhibition compared to both long and brief maternally separated offspring. Sucrose preference and open field behaviour as adults did not differ between the early life conditions. Exposure to four weeks of chronic mild stress in adulthood (mimicking daily hassles in humans) increased object exploration, increased pre-pulse inhibition and induced habituation of acoustic startle in non-handled offspring, similar to brief maternally separated offspring. Long maternally separated offspring exposed to chronic mild stress failed to show an increase in object exploration and enhanced pre-pulse inhibition, and did not show habituation of acoustic startle. In conclusion, different early life conditions have a different long-term impact on behaviour. Offspring from all three conditions differed from each other in terms of adult behaviour. Mild daily stressors in the adulthood counteracted the effects observed in the non-handled condition.

Effects of social defeat on sleep and behaviour: importance of the confrontational behaviour.

We studied the short- and long-term effects of a double social defeat (SD) on sleep parameters, EEG power, behaviour in the open field emergence test, corticosterone responsiveness, and acoustic startle responses. Pre-stress levels of corticosterone were assessed before all rats were surgically implanted with telemetric transmitters for sleep recording, and allowed 3weeks of recovery. Rats in the SD group (n=10) were exposed to 1hour SD on two consecutive days, while control rats (n=10) were left undisturbed. Telemetric sleep recordings were performed before SD (day -1), day 1 post SD, and once weekly for 3weeks thereafter. The open field emergence test was performed on day 9 and weekly for 2weeks thereafter. Blood samples for measures of corticosterone responsiveness were drawn after the last emergence test (day 23). Acoustic startle responses were tested on day 24 post SD. Overall, SD rats as a group were not affected by the social conflict. Effects of SD seemed, however, to vary according to the behaviours that the intruder displayed during the social confrontation with the resident. Compared to those SD rats showing quick submission (SDS, n=5), SD rats fighting the resident during one or both SD confrontations before defeat (SDF, n=5) showed more fragmented slow wave sleep, both in SWS1 and SWS2. They also showed longer latency to leave the start box and spent less time in the open field arena compared to SDS rats. In the startle test, SDF rats failed to show response decrement at the lowest sound level. Our results indicate that how animals behave during a social confrontation is more important than exposure to the SD procedure itself, and that rapid submission during a social confrontation might be more adaptive than fighting back.

Hypothermia after chronic mild stress exposure in rats with a history of postnatal maternal separations.

The circadian system develops and changes in a gradual and programmed process over the lifespan. Early in life, maternal care represents an important zeitgeber and thus contributes to the development of circadian rhythmicity. Exposure to early life stress may affect circadian processes and induce a latent circadian disturbance evident after exposure to later life stress. Disturbance of the normal regulation of circadian rhythmicity is surmised to be an etiological factor in depression. We used postnatal maternal separation in rats to investigate how the early life environment might modify the circadian response to later life unpredictable and chronic stress. During postnatal days 2-14, male Wistar rats (n = 8 per group) were daily separated from their mothers for a period of either 180 min (long maternal separation; LMS) or 10 min (brief maternal separation; BMS). In adulthood, rats were exposed to chronic mild stress (CMS) for 4 weeks. Body temperature, locomotor activity and heart rate were measured and compared before and after CMS exposure. LMS offspring showed a delayed body temperature acrophase compared to BMS offspring. Otherwise, adult LMS and BMS offspring demonstrated similar diurnal rhythms of body temperature, locomotor activity and heart rate. Exposure to CMS provoked a stronger and longer lasting hypothermia in LMS rats than in BMS rats. The thermoregulatory response appears to be moderated by maternal care following reunion, an observation made in the LMS group only. The results show that early life stress (LMS) in an early developmental stage induced a thermoregulatory disturbance evident upon exposure to unpredictable adult life stressors.

Early and later life stress alter brain activity and sleep in rats.

Exposure to early life stress may profoundly influence the developing brain in lasting ways. Neuropsychiatric disorders associated with early life adversity may involve neural changes reflected in EEG power as a measure of brain activity and disturbed sleep. The main aim of the present study was for the first time to characterize possible changes in adult EEG power after postnatal maternal separation in rats. Furthermore, in the same animals, we investigated how EEG power and sleep architecture were affected after exposure to a chronic mild stress protocol. During postnatal day 2-14 male rats were exposed to either long maternal separation (180 min) or brief maternal separation (10 min). Long maternally separated offspring showed a sleep-wake nonspecific reduction in adult EEG power at the frontal EEG derivation compared to the brief maternally separated group. The quality of slow wave sleep differed as the long maternally separated group showed lower delta power in the frontal-frontal EEG and a slower reduction of the sleep pressure. Exposure to chronic mild stress led to a lower EEG power in both groups. Chronic exposure to mild stressors affected sleep differently in the two groups of maternal separation. Long maternally separated offspring showed more total sleep time, more episodes of rapid eye movement sleep and higher percentage of non-rapid eye movement episodes ending in rapid eye movement sleep compared to brief maternal separation. Chronic stress affected similarly other sleep parameters and flattened the sleep homeostasis curves in all offspring. The results confirm that early environmental conditions modulate the brain functioning in a long-lasting way.

Increased wall thickness using ultrasonography is associated with inflammation in an animal model of experimental colitis.

Experimentally induced colitis is used in animals to investigate pathophysiological mechanisms in inflammatory bowel disease. When following disease course and treatment effects, it should be possible to perform repeated measurements without harming the animals. This pilot study was performed to investigate whether transabdominal ultrasound using a clinical scanner could be used on rats to demonstrate bowel inflammation in an experimental colitis model. Colitis was induced by either 5% dextran sodium sulfate (DSS) in drinking water for 7 days or a single dose of intracolonic trinitrobenzene sulfonic acid (TNBS). Using ultrasonography, wall thickness of distal colon, cecum, and small bowel was recorded prior to and after DSS, and prior to, 2, and 7 days after TNBS. Blood (tumor necrosis factor [TNF]-alpha) and fecal samples (HemoFEC occult blood) were taken from each group on the same days as sonography. Thereafter, rats were killed and specimens for histology were taken. Wall thickness of distal colon, not of cecum or small bowel, increased significantly after 7 days of DSS, and wall thickness of both distal colon and small bowel increased on day 2 and 7 after TNBS. TNF-alpha increased after 7 days in the latter group only. There was a significant correlation between ultrasonographic measurements and combined histology score of distal colon in the DSS group. HemoFEC was also positive in accordance with sonographic and histological features. Increased intestinal wall thickness in response to both DSS- and TNBS-induced colitis was able to be visualized by transabdominal sonography. Moreover, ultrasound findings, occult blood sampling, and histological findings supported each other, indicating that ultrasonography can be used to assess inflammation in a rat experimental model.

Post-transcriptional effects and interactions between chronic mild stress and acute sleep deprivation: regulation of translation factor and cytoplasmic polyadenylation element-binding protein phosphorylation.

Stress and restricted or disrupted sleep trigger adaptive responses in the brain at the level of gene transcription. We investigated the possible impact of chronic mild stress (CMS), acute sleep deprivation, and a combination of these in male rats on post-transcriptional mechanisms important for cognitive function and synaptic plasticity. Relationships between sleep architecture and translational regulators were also assessed. After four weeks of CMS, phosphorylation of two key translation factors, eukaryotic initiation factor 4E (eIF4E) and elongation factor 2 (eEF2), was enhanced in the prefrontal cortex, but unchanged in the hippocampus and dentate gyrus. Sleep deprivation decreased phosphorylated eIF4E in the dentate gyrus. In contrast, eEF2 phosphorylation was elevated in all brain regions after sleep deprivation. Thus, CMS and sleep deprivation, when given alone, have distinct region-specific effects. Furthermore, the combined treatment revealed striking interactions with eEF2 phosphorylation in which sleep deprivation counteracts the effect of CMS cortically and CMS modulates the effects of sleep deprivation in the hippocampus proper. Although CMS exposure alone had no effect in the hippocampus, it inhibited the sleep deprivation-induced eIF4E phosphorylation, while inducing phosphorylation of a major regulatory RNA-binding protein, cytoplasmic polyadenylation element-binding protein (CPEB) in the combined treatment. CMS had no effect on plasma corticosterone, but led to disruption of sleep. Sleep quality and sleep quantity in non-stressed animals showed predictive changes in eIF4E and eEF2 phosphorylation cortically. Prior exposure to CMS abolishes this relationship. We conclude that CMS and acute sleep deprivation have interactive and brain region-specific effects on translational regulators of relevance to mechanisms of stress responsiveness and sleep homeostasis.

A salmon based diet protects mice from behavioural changes in the cuprizone model for demyelination.

BACKGROUND & AIMS: Although many patients with multiple sclerosis (MS) use special diets, the data available at present are insufficient to assess any potential benefit of diet modification. Cuprizone induced demyelination is a commonly used animal model for demyelination in the central nervous system. METHODS: The present study was designed to analyse behaviour and activity due to demyelination in mice fed with 0.2% cuprizone on three different diets. The diets consisted of (1) salmon fillets rich in marine n-3 polyunsaturated fatty acids (PUFAs), (2) cod liver oil rich in marine n-3 PUFAs, or (3) a control diet containing soybean oil rich in n-6 PUFAs. After 5 weeks of continuous cuprizone treatment, animal activity was assessed with the elevated plus maze (EPM) test. After 6 weeks the brains were fixated in paraformaldehyde and stained with luxol fast blue (LFB). RESULTS: There was significantly less demyelination in the salmon-cuprizone group than in the two other cuprizone-treatment groups (P<0.0005). The salmon-cuprizone mice had less weight loss (P<0.001) and showed more visits in both open and closed arms of the elevated plus maze than the other cuprizone-treated groups (P<0.0001). In addition they had more entries in the open arms than both the cod liver oil-cuprizone (P<0.02) and the soybean oil-cuprizone-treated mice (P<0.0001). CONCLUSIONS: A diet containing salmon seems to protect against behavioural changes induced by demyelination in the cuprizone model, indicating that a fish diet could have a protective effect in demyelinating diseases.