A description of adaptive and maladaptive behaviour in children and adolescents with Cri-du-chat syndrome

Background Psychological tests can be useful to record adaptive and maladaptive behaviours of children with intellectual disability. The objective of this study was to describe the adaptive and maladaptive behaviour of children and adolescents with Cri-du-chat syndrome. Methods The sample consisted of 10 children and adolescents with Cri-du-chat syndrome (mean chronological age = 11.3 years, mean mental age = 18 months). The developmental quotient was calculated through the Psychoeducational Profile - Revised. An observational protocol was used to record adaptive and maladaptive behaviours. Results The number of maladaptive behaviours observed was different among participants. However, all of them had high rates of adaptive behaviours, such as rule-following. Conclusions These results, though preliminary, justify that we continue to think about the need for psychoeducational interventions aimed at stimulating the repertoire of adaptive behaviours, in people with Cri-du-chat syndrome.

Childhood adversities as risk factors for onset and persistence of suicidal behaviour

Background Suicide is a leading cause of death worldwide, but the precise effect of childhood adversities as risk factors for the onset and persistence of suicidal behaviour (suicide ideation, plans and attempts) are not well understood. Aims To examine the associations between childhood adversities as risk factors for the onset and persistence of suicidal behaviour across 21 countries worldwide. Method Respondents from nationally representative samples (n = 55 299) were interviewed regarding childhood adversities that occurred before the age of 18 years and lifetime suicidal behaviour. Results Childhood adversities were associated with an increased risk of suicide attempt and ideation in both bivariate and multivariate models (odds ratio range 1.2-5.7). The risk increased with the number of adversities experienced, but at a decreasing rate. Sexual and physical abuse were consistently the strongest risk factors for both the onset and persistence of suicidal behaviour, especially during adolescence. Associations remained similar after additional adjustment for respondents` lifetime mental disorder status. Conclusions Childhood adversities (especially intrusive or aggressive adversities) are powerful predictors of the onset and persistence of suicidal behaviours.

Post-craniotomy headache: characteristics, behaviour and effect on quality of life in patients operated for treatment of supratentorial intracranial aneurysms

We prospectively studied headache characteristics during 6 months after craniotomy performed for treatment of cerebral aneurysms in 79 patients. Semistructured interviews, headache diaries, the Hospital Anxiety and Depression Scale and the Epworth Sleepiness Scales, the Short Form-36 Health Survey (SF-36) and McGill Pain Questionnaire were used. Seventy-two patients had headaches, half before the fifth day after surgery. Changes were observed in headache diagnosis, side and site in the postoperative period. Headache frequency increased immediately after surgery and then decreased over time. Headache frequency was associated with depressive and anxiety symptoms. Pain intensity was higher in women and in patients with more anxiety symptoms. An incidence of post-craniotomy headache of 40% was observed according to International Headache Society classification criteria, 10.7% of the acute and 29.3% of the chronic type. The bodily pain domain of the SF-36 was worse in patients with more anxiety symptoms. Greater frequencies of headache were associated with lower scores on bodily pain and social functioning.

Modulation of anxiety-like behaviour by Transient Receptor Potential Vanilloid Type 1 (TRPV1) channels located in the dorsolateral periaqueductal gray

The endocannabinoid anandamide is a possible agonist at the Transient Receptor Potential Vanilloid Type 1 (TRPV1) channel, in addition to its agonist activity at cannabinoid type 1 (CB1) receptor. In the midbrain dorsolateral periaqueductal gray (dlPAC) our previous data showed that CB1 activation induces anxiolytic-like effects. However, the rote of TRPV1 has remained unclear. Thus, in the present study we tested the hypothesis that this channel would contribute to the modulation of anxiety-like behaviour in the dlPAG. Mate Wistar rats received local injections of the TRPV1 antagonist capsazepine (10-60 nmol) and were submitted to the elevated plus-maze (EPM) and to the Vogel test. In addition, animals received local injections of capsaicin (0.01-1nmol), a TRPV1 agonist, and were tested in the same models. In accordance with our hypothesis, capsazepine produced anxiolytic-like effects both in the EPM and in the Vogel test. Capsaicin mimicked these results, which might be attributed to its ability to quickly desensitize the channel. Altogether, our data suggest that, while CB1 receptors seem to inhibit aversive responses in the dlPAG, TRPV1 could facilitate them. Thus, CB1 and TRPV1 may have opposite functions in modulating anxiety-like behaviour in this region. (C) 2008 Elsevier B.V. and ECNP. All rights reserved.

Cellular prion protein modulates defensive attention and innate fear-induced behaviour evoked in transgenic mice submitted to an agonistic encounter with the tropical coral snake Oxyrhopus guibei

The cellular prion protein (PrPC) is a neuronal anchored glycoprotein that has been associated with distinct functions in the CNS, such as cellular adhesion and differentiation, synaptic plasticity and cognition. Here we investigated the putative involvement of the PrPC in the innate fear-induced behavioural reactions in wild-type (WT), PrPC knockout (Prnp(0/0)) and the PrPC overexpressing Tg-20 mice evoked in a prey versus predator paradigm. The behavioural performance of these mouse strains in olfactory discrimination tasks was also investigated. When confronted with coral snakes, mice from both Prnp(0/0) and Tg-20 strains presented a significant decrease in frequency and duration of defensive attention and risk assessment, compared to WT mice. Tg-20 mice presented decreased frequency of escape responses, increased exploratory behaviour, and enhancement of interaction with the snake, suggesting a robust fearlessness caused by PrPC overexpression. Interestingly, there was also a discrete decrease in the attentional defensive response (decreased frequency of defensive alertness) in Prnp(0/0) mice in the presence of coral snakes. Moreover, Tg-20 mice presented an increased exploration of novel environment and odors. The present findings indicate that the PrPC overexpression causes hyperactivity, fearlessness, and increased preference for visual, tactile and olfactory stimuli-associated novelty, and that the PrPC deficiency might lead to attention deficits. These results suggest that PrPC exerts an important role in the modulation of innate fear and novelty-induced exploration. (C) 2008 Published by Elsevier B.V.

alpha(1)-Adrenoceptors in the lateral septal area modulate food intake behaviour in rats

Background and purpose: Control of food intake is a complex behaviour which involves many interconnected brain structures. The present work assessed if the noradrenergic system in the lateral septum (LS) was involved in the feeding behaviour of rats. Experimental approach: In the first protocol, the food intake of rats was measured. Then non-food-deprived animals received either 100 nL of 21 nmol of noradrenaline or vehicle unilaterally in the LS 10 min after local 10 nmol of WB4101, an alpha(1)-adrenoceptor antagonist, or vehicle. In the second protocol, different doses of WB4101 (1, 10 or 20 nmol in 100 nL) were microinjected bilaterally into the LS of rats, deprived of food for 18 h and food intake was compared to that of satiated animals. Key results: One-sided microinjection of noradrenaline into the LS of normal-fed rats evoked food intake, compared with vehicle-injected control animals, which was significantly reduced by alpha(1)-adrenoceptor antagonism. In a further investigation, food intake was significantly higher in food-deprived animals, compared to satiated controls. Pretreatment of the LS with WB4101 reduced food intake in only food-deprived animals in a dose-related manner, suggesting that the LS noradrenergic system was involved in the control of food intake. Conclusion and implications: Activation by local microinjection of noradrenaline of alpha(1)-adrenoceptors in the LS evoked food intake behaviour in rats. In addition, blockade of the LS alpha(1)-adrenoceptors inhibited food intake in food-deprived animals, suggesting that the LS noradrenergic system modulated food intake behaviour and satiation.

Role of IL-18 in overt pain-like behaviour in mice

There are evidences that targeting IL-18 might be beneficial to inhibit inflammatory symptoms, including hypernociception (decrease in nociceptive threshold). The mechanism of IL-18 mechanical hypernociception depends on endothelin in rats and mice. However, the role of IL-18 in overt pain-like behaviour remains undetermined. Therefore, we addressed the role of IL-18 in writhing response induced by intraperitoneal (i.p.) injection of phenyl-p-benzoquinone (PBQ) and acetic acid in mice. Firstly, it was detected that PBQ and acetic acid i.p. injection induced a dose-dependent number of writhes in Balb/c mice. Subsequently, it was observed that the PBQ- but not the acetic acid-induced writhes were diminished in IL-18 deficient ((-/-)) mice. Therefore, considering that IFN-gamma, endothelin and prostanoids mediate IL-18-induced mechanical hypernociception, we also investigated the role of these mediators in the same model of writhing response in which IL-18 participates. It was noticed that PBQ-induced writhes were diminished in IFN-gamma(-/-) mice and by the treatment with bosentan (mixed enclothelin ETA/ETB receptor antagonist), BQ 123 (cyclo[DTrp-DAsp-Pro-DVal-Leu], selective enclothelin ETA receptor antagonist), BQ 788 (N-cys-2,6-dimethylpiperidinocarbonyl-L-methylleucyl-D-1 -methoxycarboyl-D-norleucine, selective endothelin ETB receptor antagonist) or indomethacin (cycloxigenase inhibitor). Thus, IL-18, IFN-gamma, endothelin acting on endothelin ETA and ETB receptors, and prostanoids mediate PBQ-induced writhing response in mice. To conclude, these results further advance the understanding of the physiopathology of overt pain-like behaviour, and suggest for the first time a role for IL-18 in writhing response in mice. (C) 2008 Elsevier B.V. All rights reserved.

Cannabidiol inhibitory effect on marble-burying behaviour: involvement of CB1 receptors

Cannabidiol (CBD) is a major nonpsychotomimetic component of Cannabis sativa that has been shown to have an anxiolytic effect in human and animal models. Earlier studies suggest that these effects involve facilitation of serotonin, a neurotransmitter that has also been related to obsessive-compulsive disorder. On the basis of this evidence, this study investigated the effects of CBD in C57BL/6J mice submitted to the marble-burying test (MBT), an animal model proposed to reflect compulsive behaviour. CBD (15, 30 and 60 mg/kg) induced a significant decrease in the number of buried marbles compared with controls (34, 41 and 48%, respectively). A similar, although larger, decrease was also found after the serotonin selective reuptake inhibitor paroxetine (10 mg/kg, 77% decrease) and the benzodiazepine diazepam (2.5 mg/kg, 84% decrease). The effect of CBD (30 mg/kg) was still significant after 7 days of daily repeated administration, whereas the effect of diazepam disappeared. Pretreatment with WAY100635 (3 mg/kg), a 5HT1A receptor antagonist, prevented the effects of paroxetine but failed to alter those of CBD. These latter effects, however, were prevented by pretreatment with the CB1 receptor antagonist AM251 (1 mg/kg). These results indicated that CBD and paroxetine decrease the number of buried marbles in the MBT through distinct pharmacological mechanisms. They also suggest a potential role of drugs acting on the cannabinoid system in modulating compulsive behaviour. Behavioural Pharmacology 21: 353-358 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

GABA(A) receptor blockade in dorsomedial and ventromedial nuclei of the hypothalamus evokes panic-like elaborated defensive behaviour followed by innate fear-induced antinociception

Dysfunction in the hypothalamic GABAergic system has been implicated in panic syndrome in humans. Furthermore, several studies have implicated the hypothalamus in the elaboration of pain modulation. Panic-prone states are able to be experimentally induced in laboratory animals to study this phenomenon. The aim of the present work was to investigate the involvement of medial hypothalamic nuclei in the organization of panic-like behaviour and the innate fear-induced oscillations of nociceptive thresholds. The blockade of GABA(A) receptors in the neuronal substrates of the ventromedial. or dorsomedial hypothalamus was followed by elaborated defensive panic-like reactions. Moreover, innate fear-induced antinociception was consistently elicited after the escape behaviour. The escape responses organized by the dorsomedial and ventromedial hypothalamic nuclei were characteristically more elaborated, and a remarkable exploratory behaviour was recorded during GABA(A) receptor blockade in the medial hypothalamus. The motor characteristic of the elaborated defensive escape behaviour and the patterns of defensive alertness and defensive immobility induced by microinjection of the bicuculline either into the dorsomedial. or into the ventromedial hypothalamus were very similar. This was followed by the same pattern of innate fear-induced antinociceptive response that lasted approximately 40 min after the elaborated defensive escape reaction in both cases. These findings suggest that dysfunction of the GABA-mediated neuronal system in the medial hypothalamus causes panic-like responses in laboratory animals, and that the elaborated escape behaviour organized in both dorsomedial and ventromedial hypothalamic nuclei are followed by significant innate-fear-induced antinociception. Our findings indicate that the GABA(A) receptor of dorsomedial and ventromedial hypothalamic nuclei are critically involved in the modulation of panic-like behaviour. (C) 2009 Elsevier B.V. All rights reserved.