A new interactive computer simulation system for violence risk assessment of mentally disordered violent offenders.

BACKGROUND: Assessment of risk of future violence has developed from reliance on static indicators towards a more dynamic approach. In the latter context, however, the offender is seldom confronted with real life situations. AIMS: The aim of this study is to evaluate a computer-based system--Reactions on Display, which presents human interactions based on real-life situations--for its effectiveness in distinguishing between potentially violent offenders with mental disorder and a healthy comparison group. METHODS: Male offenders with autism spectrum disorders or psychosis were recruited from specialist forensic psychiatric units in Sweden and healthy participants from the local communities. Each consenting participant was presented with film clips of a man in neutral and violent situations, which at critical moments stopped the story to ask him to predict the thoughts, feelings and actions of the actor. RESULTS: Offender patients, irrespective of diagnosis, detected fewer emotional reactions in the actor in the non-violent sequence compared with controls. When asked to choose one of four violent actions, the offender patients chose more violent actions than did the controls. They also reported fewer physical reactions in the actors when actors were being violent. There were also some examples of incongruent or deviant responses by some individual patients. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The use of interactive computer simulation techniques is not only generally acceptable to offender patients, but it also helps to differentiate their current response style to particular circumstances from that of healthy controls in a way that does not rely on their verbal abilities and may tap more effectively into their emotional reactions than standard verbal questions and answer approaches. This may pave the way for Reactions on Display providing a useful complement to traditional risk assessment, and a training route with respect to learning more empathic responding, thus having a role in aiding risk management.

Consequences of early career nurse burnout: A prospective long-term follow-up on cognitive functions, depressive symptoms, and insomnia.

BACKGROUND: Burnout is common among nurses and midwives. We examined whether an early career episode of burnout has long-term consequences on; a) cognitive functions, b) symptoms of depression, and/or c) insomnia for nurses a decade after graduation. METHODS: Symptoms of burnout were investigated in an observational longitudinal study of three national cohorts of registered nurses (RNs). Nursing students were recruited from all 26 of Sweden's nursing programs. Burnout was subsequently measured through annual assessment over the first three years post graduation, with one long-term follow-up 11-15 years after graduation. A total of 2474 nurses (62%) consented to participate at follow-up. Burnout was measured using items from the Oldenburg Burnout Inventory, cognitive function by a study specific instrument, depressive symptoms by the Major Depression Inventory, and sleep problems using items from the Karolinska Sleep Questionnaire. We used logistic regression to identify factors associated with consequences of early career burnout, adjusting for concurrent levels at follow up. FINDINGS: The prevalence of nurses reporting high levels of burnout symptoms at least one of the first three years of working life was 299 (12·3%). High levels of burnout symptoms in early working life were significantly related to more frequent symptoms of cognitive dysfunction, depression, and impaired sleep a decade later when taking current burnout levels into account. After controlling for both current symptoms of burnout and the other outcome variables, nurses with early career burnout still reported more frequent problems with cognitive functions and sleep but not depression. INTERPRETATION: The results of this study show that the detrimental processes caused by overwhelming or chronic stress start early on in nurses' careers and thus preventive efforts should preferably be introduced early on (e.g. as part of nursing education and onboarding programs). FUNDING: AFA Insurance Grant [number 150284].

Arthritis-induced increase in cholecystokinin release in the rat anterior cingulate cortex is reversed by diclofenac.

Given a hypothesised role for CCK in the anterior cingulate cortex (ACC) for the sensation of pain, the aim of the present study was to investigate whether the increased CCK release could be affected by two different analgesic drugs, morphine and the non-selective cyclooxygenase inhibitor diclofenac. Since opioids stimulate CCK release in other CNS regions we have also studied the effect of morphine by itself on the CCK-LI release in the ACC of non-arthritic rats. Three to seven hours after intraarticular carrageenan injection, at the time when the animals are known to show pain-related behaviour, in vivo microdialysis in awake rats revealed increased CCK-LI release in the ACC. The CCK-LI release was significantly attenuated by diclofenac (25 mg/kg i.m.), but not by morphine (10 mg/kg s.c.). Neither diclofenac (25 mg/kg i.m.) nor morphine (5 or 10 mg/kg s.c.) affected the CCK-LI release in the ACC in non-arthritic rats. The results obtained with diclofenac indicate that prostaglandins contribute to the increased CCK-LI release in the ACC during monoarthritis. However, the lack of effect of morphine suggests that the CCK release in the ACC is not directly related to the sensation of pain. Further on, the failure of morphine to affect the extracellular level of CCK-LI in the ACC in control animals as well as in animals with carrageenan-induced monoarthritis is in contrast to previous studies on the frontal cortex or the dorsal horn of the spinal cord, in which similar doses of morphine stimulate CCK release. Thus, compared to these regions, CCK release may be differently regulated in the ACC.

Spontaneous nociceptive behaviour in female mice with Freund's complete adjuvant- and carrageenan-induced monoarthritis.

The development of transgenic techniques has accentuated the need for valid disease models in mice. In the present study, we have in female mice characterized adjuvant-induced monoarthritis, an inflammatory model which is commonly used in rats. Freund's complete adjuvant (FCA), 20 microl, was injected into the left knee joint. Pain was inferred from impairment of gait and stance. Two commonly used mouse strains were compared. Outbred NMRI mice showed significant levels of pain behaviour lasting for at least 7 days after injection of FCA while inbred BALB/c mice showed altered behaviour at 3, but not at 5 days. The effects of three commercially available preparations of FCA were compared in NMRI mice. All adjuvants caused highly reproducible spontaneous pain behaviour at 1-3 days with a reduction at 5 days and no significant pain-related behaviour at 10 days. Intraarticular injection of 2% carrageenan performed for comparison, caused pain-related behaviour for less than 24 h. The adjuvant-induced pain behaviour was dose-dependently reduced by 3-30 micromol/kg morphine and 3-30 micromol/kg diclofenac. In conclusion, adjuvant-induced monoarthritis in mice provides a robust model for pharmacological studies of inflammatory pain, but the choice of mouse strain is important for the outcome.

Twice daily long maternal separations in Wistar rats decreases anxiety-like behaviour in females but does not affect males.

Prolonged daily separations of rat pups from their mother have been reported to increase anxiety-like behaviour in adult offspring. However, there are an increasing number of studies not showing this. It has been proposed that the effect of long maternal separation (LMS) is partly due to the disruption of maternal care caused by the separations. The aim of the present study was to investigate whether increasing the number of daily separations would produce more robust effects in the adult offspring on anxiety-like behaviour in the defensive withdrawal test, and on spontaneous motor activity. Since previous studies of LMS have revealed sex differences in behaviour, we included both males and females. In our separation paradigm we subjected rat pups to either two daily 3h maternal separations during the first 2 weeks postpartum (LMS), two daily 15 min maternal separations (brief maternal separations, BMS) during the same time period to control for the effects of handling, or to normal husbandry conditions. As adults we found no effects of this LMS paradigm in male rats, although BMS males showed a tendency toward decreased anxiety-like behaviour. In contrast, LMS females showed a decrease in anxiety-like behaviour. We also found significant sex differences that were most prominent in the LMS group, indicating that females are more sensitive to our maternal separation paradigm. The present study suggests that increasing the number of maternal separations does not increase anxiety-like behaviour in neither male nor female Wistar rats.

Increased responsiveness of presumed 5-HT cells to citalopram in adult rats subjected to prolonged maternal separation relative to brief separation.

RATIONALE: Certain adverse events in childhood, such as loss of a parent or sexual abuse, are associated with an increased vulnerability to develop depression later in life. Prolonged, daily maternal separation of rat pups induces several behavioral, endocrine and neurochemical changes similar to those observed in human depression. OBJECTIVES: Because dysfunction of brain serotonergic systems has been implicated in the pathophysiology of depression, the effects of neonatal maternal separation on these systems was studied in adult rats. METHODS: Male rat pups were subjected to daily maternal separation for 180 min (HMS180) from postnatal day 2 to day 14. Neonatal handled rats, i.e., pups undergoing daily 15-min separations during the same time period (HMS15), were chosen as a control group, since the 180-min separations involved handling of the pups, i.e., the pups were removed from the home cage during the separations. As adults, the effect of citalopram (0.05-0.80 mg/kg, intravenous) on the firing rate of 5-HT neurons in the dorsal raphe nucleus (DRN) was studied. RESULTS: The inhibitory effect of citalopram on serotonergic cell firing was significantly enhanced at doses of 0.1 mg/kg and 0.4 mg/kg in the HMS180 compared with that in the HMS15 rats. However, the number of binding sites and mRNA expression of the 5-HT transporter and 5-HT(1A) receptors in the DRN did not differ between the two rearing groups. CONCLUSION: These findings suggest that early life stress gives rise to persistent changes in the function, but not the density or mRNA expression of central 5-HT(1A) receptors and/or 5-HT transporters.

Increased cholecystokinin release in the rat anterior cingulate cortex during carrageenan-induced arthritis.

Several human and animal studies indicate that the anterior cingulate cortex (ACC) plays an important role in the affective component of pain. The neuropeptide cholecystokinin (CCK) is especially abundant in the ACC. CCK has been suggested to be involved in the mediation of anxiety and in the modulation of opioid effects in the spinal cord and medulla oblongata. However, its possible role in pain transmission or modulation in the brain is far less clear. In this study, a model of subchronic inflammatory pain in rats, carrageenan-induced monoarthritis, was used to study the effect of pain on the release of CCK-like immunoreactivity (CCK-LI) in the ACC. Pain-related behaviour quantified by weight bearing and stance scoring, as well as inflammation measured by ankle oedema, was increased for at least 24 h after carrageenan injection with a maximum at 5 h. Using microdialysis in freely moving rats, extracellular concentrations of CCK-LI was measured in the ACC during a time period when the animals showed significant pain behaviour. In animals with carrageenan-induced arthritis, both basal and potassium-evoked release of CCK-LI were significantly increased compared to controls. HPLC analysis of dialysates from the ACC during potassium stimulation showed that the main part of the immunoreactive material was sulphated CCK-8. Because CCK has been implicated in anxiety, we suggest that an altered CCK-ergic activity in the ACC may be of importance for the affective component of pain, but an involvement in the modulation of nociception is also possible.

Ethanol-induced effects on the dopamine and serotonin systems in adult Wistar rats are dependent on early-life experiences.

Some individuals control their ethanol consumption throughout life, but others escalate their intake to levels that increase the risk for addiction. The early environment influences the individual response to ethanol and affects the underlying physiological processes that lead to a transition from a voluntary to a compulsive use of ethanol. However, the neurobiological substrates for these processes are not understood. The present study aimed to test the hypothesis that early environmental experiences affect the neurobiological effects that are induced by voluntary ethanol consumption. Rat pups were subjected to three different rearing environments: conventional animal facility rearing or separation from dam and littermates for either 15 or 360min. In adulthood, the rats were exposed to a two-bottle free choice between ethanol and water for seven weeks. Tissue levels of dopamine, 5-hydroxytryptamine (5-HT) and their metabolites were measured in brain areas that have been implicated in reward and addiction processes. Differences in ethanol-induced effects were noted in 5-HT-related measurements in the nucleus accumbens and ventral tegmental area and in dopamine-related measurements in the dorsal raphe nucleus (DRN). These results provided evidence of an early environmental impact on interactive neuronal circuits between the DRN and reward pathways. The amygdala, a key area in addiction processes, was particularly sensitive to early-life conditions. The animals that experienced the longest separation differed from the others; they had low basal 5-HT levels and responded with an increase in 5-HT after ethanol. These altered responses to initial ethanol consumption as a result of early environmental factors may affect the transition from habitual to compulsive drinking and contribute to individual vulnerability or resilience to addiction.

Male but not female Wistar rats show increased anxiety-like behaviour in response to bright light in the defensive withdrawal test.

The defensive withdrawal test (DWT) is used to model anxiety-like behaviour in rats. The aim of this study was to investigate whether an aversive stimulus, bright light, affects the behaviour in this test. Additionally, the effect of habituation to the apparatus was studied. Both male and female Wistar rats were used to study whether sex differences exist in the DWT, as reported for other tests of anxiety. On day 1 half of the rats were tested under low light and half under bright light. Two to seven days after trial one the same rats were repeatedly tested under the same light condition for five consecutive days. The male rats showed a higher degree of anxiety-like behaviour when tested under bright light than under low light. In contrast, the behaviour of the female rats was not affected by changes in illumination. Male rats also exhibited elevated anxiety-like behaviour compared to female rats under bright light, whereas under low light conditions no sex difference was seen. Males in low light habituated much faster than males tested under bright light, whereas in females there was little difference in habituation between low and bright light. In summary, we found that bright light is aversive for male but not female Wistar rats in the DWT. Whether this is due to sex differences in light sensitivity or if females respond with a different behavioural strategy in response to bright light, which could not be detected in the DWT, remains to be elucidated.

Differential effects of repeated long and brief maternal separation on behaviour and neuroendocrine parameters in Wistar dams.

Repeated, prolonged maternal separation has been suggested to model the development of a depression-like syndrome in rats. The long separations from the pups have been proposed to be stressful for the dams, which in turn could mediate the changes seen in adult offspring. In the present study we investigated whether prolonged maternal separation really is stressful for rat dams by studying parameters known to be affected by long-term stress such as spontaneous motor activity, anxiety-like behaviour, adrenal gland weight and plasma corticosterone levels. Dams were separated from their litter for either 4 h (MS240) or 15 min (MS15) on eight random days during postnatal day 1-14, or left undisturbed (animal facility reared, AFR). After weaning MS240 dams showed decreased peripheral activity and habituated slower in horizontal activity. On the contrary, MS15 dams showed more peripheral activity and less rearing activity compared to both AFR and MS240 dams when habituated to the testing apparatus, suggesting that MS15 dams are more anxious. The adrenal glands from MS15 dams weighed significantly less and plasma corticosterone levels were significantly higher compared to AFR and MS240 dams. These results suggest that repeated brief maternal separations from pups could be stressful for rat mothers, whereas prolonged separations are not. Since these results are in contrast to the current notion that the short separation procedure may be considered as a safe milieu, whereas the prolonged separations have been suggested to be stressful for both dams and pups, further studies in this field are warranted.

Two repeated maternal separation procedures differentially affect brain 5-hydroxytryptamine transporter and receptors in young and adult male and female rats.

Early environment is a known determinant for individual differences in vulnerability for adult psychopathology, e.g., ethanol addiction. One underlying mechanism could be dysfunction in serotonergic neurotransmission. This study focused on the methodological considerations regarding an animal model for studying effects of early environment, maternal separation (MS), using two different paradigms. Age- and sex-specific effects on brain stem 5-hydroxytryptamine (5-HT) transporter and receptors were examined. Male and female rat pups were assigned to either litter-wise MS for 15 or 360 min (MS15l or MS360l) or individual MS for 15 or 360 min (MS15i or MS360i) daily during postnatal days 1-21. Normal animal facility reared rats were used as controls. Analyses were performed in young and adult rats. As compared to the other males, MS15l males had lower 5-HT(1A) and 5-HT(2C) receptor mRNA expression at both ages, lower 5-HT(2A) receptor mRNA when young and lower 5-HTT mRNA expression when adult. In contrast, adult MS15l females had higher 5-HT(2C) receptor mRNA expression than other female rats. The strong impact of MS15l on 5-HT-related genes was either transient or persistent depending on sex and fewer effects on gene expression were observed in females than in males. This study shows the importance of tactile contact for the consequences of short but not prolonged MS, as evidenced by major differences between MS15l and MS15i. The results suggest that MS15i is less suitable than MS15l to simulate a protective environment in studies of, for instance, ethanol addiction processes.

A putative role for cytokines in the impaired appetite in depression.

Impaired appetite and weight changes are commonly seen in patients with depression, but the pathophysiology behind this imbalance between energy intake and energy expenditure remains largely unknown. The aim of this paper is to review the literature regarding a possible role for cytokines in the regulation of appetite and body weight, with special emphasis on depression. There now exists a substantial amount of evidence that depressed patients show signs of immune activation including increased levels of proinflammatory cytokines. Cytokines, which by themselves have anorectic properties, stimulate the release of the cytokine-like anorexogenic peptide leptin. In addition to their anorectic properties, both proinflammatory cytokines and leptin interact with the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic nervous system (SNS) and the immune system. In turn, these systems regulate energy balance as well as they are dysfunctional in depression. Furthermore, both proinflammatory cytokines and leptin can induce anhedonia, one of the cardinal symptoms of depression. In view of the different effects on appetite and/or body weight observed in melancholic versus atypical depression, we suggest that cytokines are differentially altered in these subtypes of depression, and that this may explain some of the inconsistency in the reported findings of cytokine as well as leptin levels in depressed patients. Finally, we propose that the immune system uses the interoceptive pathway projecting to the insular cortex, a brain region where cytokine-induced changes in appetite could be partly mediated, and that this pathway is activated in depression.