Challenging behaviour and sleep cycle disorder following brain injury: a preliminary response to agomelatine treatment.

BACKGROUND: Sleep disturbances are common after acquired brain injury. Sedatives can exacerbate behavioural disorders. OBJECTIVES: This study reports the case of a severely brain damaged man (TM) who developed a non-24 hour sleep cycle disorder that was effectively managed by the administration of a melatonin receptor agonist, agomelatine. METHOD: TM suffered significant brain damage as a result of a large subarachnoid haemorrhage of his right anterior cerebral artery complicated by midline shift and subsequent infarction of his left middle cerebral artery. In addition to challenging behaviour and cognitive impairment, TM presented with a recurrent disturbed sleep-wake pattern that significantly worsened his quality-of-life. He was diagnosed as suffering of non-24 hour sleep-wake disorder. Challenge was recorded using the Overt Aggression Scale Modified for Neuro-Rehabilitation (OASMNR). RESULTS: Typical hypnotics had no or ill effects. Agomelatine prescription (25 mg) led to significant OASMNR and sleep efficiency change with effects apparent at 1.5 years later. CONCLUSIONS: Administration of the melatonin receptor (MT1 and MT2) agonist agomelatine each night resulted in an immediate and sustained improvement on sleep and on indices of challenging behaviour.

The effects of photic and nonphotic stimuli in the 5-HT7 receptor knockout mouse.

5-HT and agonists of the 5-HT receptor can modify the response of the mammalian pacemaker, which is located in the hypothalamic suprachiasmatic nuclei (SCN), to photic and nonphotic stimulation. Previous studies suggest that the 5-HT7 receptor is involved in the regulation of photic input, and the modulation of nonphotic circadian resetting of the circadian clock. The present study investigated the role of the 5-HT7 receptor by evaluating a wide variety of circadian parameters in mice lacking a functional allele for this receptor (5-HT7 knockout (KO)) compared with wild type (WT) animals that were bred on the same genetic background, including rate of entrainment, photic responsiveness and nonphotic response to a serotonergic agonist. No significant differences were detected in the average number of days 5-HT7 KO mice needed to reach entrainment to an advance of 6 h in the LD cycle compared with WT animals. Further, we investigated the acute responsiveness of both groups of mice to acute light stimulation at various times (circadian time (CT) 0, 6, 9, 12, 14, 16, 18, 20 and 22). A significant difference in the phase resetting response to light between the groups was revealed at CT22. Finally, as the 5-HT7 receptor has been associated with the modulation of nonphotic resetting in vitro, we examined the response of the 5-HT7 KO mice to systemic administration of a 5-HT(1A/7) agonist. The current study is the first to demonstrate the elimination of a nonphotic response to (+) 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in mice lacking the 5-HT7 receptor compared with WT animals in vivo. Taken together, the present findings provide additional evidence that reform the established view on the role of the 5-HT7 in the photic regulation of retinohypothalamic (RHT) input, and support further the involvement of the 5-HT7 receptor in the modulation of nonphotic resetting in circadian clock.

Head injury in asylum seekers and refugees referred with psychological trauma.

OBJECTIVE: Individuals who seek asylum are frequently fleeing violent persecution and may experience head injury (HI). However, little is known about the prevalence of HI in asylum seekers and refugees (ASR) despite the potential for HI to significantly affect cognitive and emotional functioning and to compromise asylum outcomes. This preliminary study investigates the prevalence of HI in ASR referred to a complex psychological trauma service. METHOD: Participants were 115 adult ASR referred to a community psychological trauma service with moderate to severe mental health problems associated with psychological trauma. They were screened for a history of HI using a questionnaire developed for the study. Interpreters were used when required. RESULTS: The overall prevalence of HI was 51%. At least 38% of those with HI had a moderate-severe HI that could cause persisting disability. In 53% of those with HI, the cause was torture, human trafficking or domestic violence. Repeat HI can have cumulative effects on function; it was common, and was reported in 68% of those with HI. An injury to the head was not known to mental health clinicians prior to screening in 64% of cases. CONCLUSION: The emotional and cognitive consequences of HI in ASR may increase the vulnerability of this disadvantaged group, and can be associated with neurobehavioural problems affecting daily life and may compromise asylum outcomes. Routine screening for HI in ASR is needed, as are links to neuropsychology and brain injury services for advice, assessment and intervention.

MDMA alters the response of the mammalian circadian clock in hamsters: effects on re-entrainment and triazolam-induced phase shifts.

Serotonin (5-hydroxytryptamine or 5-HT) is a neurotransmitter that is involved in a wide range of behavioural and physiological processes. Previous work has indicated that serotonin is important in the regulation of the circadian clock, which is located in the suprachiasmatic nuclei (SCN) of the hypothalamus. 3,4-methylenedioxymethamphetamine (MDMA or 'Ecstasy'), which is widely used as a recreational drug of abuse, is a serotonin neurotoxin in animals and non-human primates. Previous work has shown that MDMA exposure can alter circadian clock function both in vitro and in vivo. Evidence shows that 5-HT may have a modulatory role in the regulation of the circadian clock by non-photic stimuli, such as the benzodiazepine triazolam (TRZ). Triazolam is a short-acting benzodiazepine that results in phase advances of the wheel running activity in hamsters when administered during the mid-subjective day. In the present study, male Syrian hamsters treated with TRZ (5 mg/kg) at ZT6 significantly phase advanced their clock. Treatment with MDMA significantly diminished the TRZ induced phase shift in hamsters. Previous evidence shows the involvement of 5-HT in the re-synchronisation of the endogenous clock to a new shifted light-dark cycle. Untreated animals were successfully entrained to a new, 6 h advanced light-dark cycle within an average of 4.5 +/- 0.1 days. Following treatment with MDMA, these animals took an average of 8.3 +/- 0.1 days to re-entrain to a shifted environmental cycle. Immunohistochemical analysis revealed that animals treated with MDMA showed reduced serotonin staining, as evidenced by a decrease in innervation density in the SCN. No significant differences were found in cell counts within the raphe nuclei. These results demonstrate the importance of the serotonergic system in the modulation of photic and non-photic responses of the circadian pacemaker.