Psychology

Abstract: Consistent daily rhythms are important to healthy aging according to studies linking disrupted circadian rhythms with negative health impacts. We studied the effects of age and exercise on baseline circadian rhythms and on the circadian system�¢??s ability to respond to the perturbation induced by an 8h advance of the light:dark (LD) cycle, as a test of the system�¢??s robustness. Mice (male, mPer2luc/C57Bl6) were studied at one of 2 ages: 3.5 mos (n=39), and >18 mos (n=72). We examined activity records of these mice under entrained and shifted conditions, as well as mPER2::LUC measures ex vivo to assess circadian function in the SCN and important target organs. Age was associated with reduced running-wheel use, fragmentation of activity, and slowed resetting in both behavioral and molecular measures. Furthermore, we observed that for aged mice the presence of a running wheel altered the amplitude of the spontaneous firing rate rhythm in the SCN in vitro. Following a shift of the LD cycle both young and aged mice showed a change in rhythmicity properties of the mPER2::LUC oscillation of the SCN in vitro, and aged mice exhibited longer lasting internal desynchrony. Access to a running wheel alleviated some age-related changes in the circadian system. In an additional experiment we replicated the effect of the running wheel, comparing behavioral and in vitro results from aged mice housed with or without a running wheel (>21 mos, n=8 per group, all examined 4 days after the shift). The impact of voluntary exercise on circadian rhythm properties in an aged animal is a novel finding and has implications for the health of older people living with environmentally induced circadian disruption.

Abstract: The present study examined psychophysiological reactivity to emotional stimuli related and non-related to sleep in people with primary insomnia (PPI) and in good sleepers (CS). Twenty-one PPI and 18 CS were presented with five blocks of neutral, negative, positive, sleep-related negative and sleep-related positive pictures. During the presentation of the pictures, facial electromyography (EMG) of the corrugator and the zygomatic muscles, heart rate (HR) and cardiac vagal tone (CVT) were recorded. Subjective ratings of the stimuli were also collected. We found that only PEA exhibited greater inhibition of the corrugator activity in response to sleep-related positive stimuli compared to the other blocks of stimuli. Furthermore, PPI rated the sleep-related negative stimuli as more unpleasant and arousing and showed higher CVT in response to all stimuli as compared to GS. Results were interpreted as indicating that PPI exhibit craving for sleep-related positive stimuli, and also hyper-arousability in response to sleep-related negative stimuli, as compared to GS. Our results suggest that psychological treatment of insomnia could benefit by the inclusion of strategies dealing with emotional processes linked with sleep processes.

Abstract: The most widely recognised consequence of normal age-related changes in biological timing is the sleep disruption that appears in old age and diminishes the quality of life. These sleep disorders are part of the normal ageing process and consist primarily of increased amounts of wakefulness and reduced amounts of deep sleep. Changes in the amplitude and timing of the sleep-wake cycle appear to represent, at least in part, a loss of effective circadian regulation of sleep. Understanding alterations in the characteristics of stimuli that help to consolidate internal rhythms will lead to recommendations to improve synchronisation in old age. Converging evidence from both human and animal studies indicate that senescence is associated with alterations in the neural structure thought to be primarily responsible for the generation of the circadian oscillation, the suprachiasmatic nuclei (SCN). Work has shown that there are changes in the anatomy, physiology and ability of the clock to reset in response to stimuli with age. Therefore it is possible that at least some of the observed age-related changes in sleep and circadian timing could be mediated at the level of the SCN. The SCN contain a circadian clock whose activity can be recorded in vitro for several days. We have tested the response of the circadian clock to a number of neurochemicals that reset the clock in a manner similar to light, including glutamate, N-methyl-D-aspartate (NMDA), gastrin-releasing peptide (GRP) and histamine (HA). In addition, we have also tested agents which phase shift in a pattern similar to behavioural 'non-photic' signals, including neuropeptide Y (NPY), serotonin (5HT) and gamma-aminobutyric acid (GABA). These were tested on the circadian clock in young and older mice (approximately 4 and 15 months old). We found deficits in the response to specific neurochemicals but not to others in our older mice. These results indicate that some changes seen in the responsiveness of the circadian clock to light with age may be mediated at the level of the SCN. Further, the responsiveness of the circadian clock with age is attenuated to some, but not all stimuli. This suggests that not all clock stimuli loose their effectiveness with age, and that it may be possible to compensate for deficits in clock performance by enhancing the strength of those stimulus pathways which are intact.

Abstract: Espie and colleagues [(2006). The attention&#8211;intention&#8211;effort pathway in the development of psychophysiological insomnia: a theoretical review. Sleep Medicine Reviews, 10, 215&#8211;245] propose a route into psychophysiological insomnia along the attention&#8211;intention&#8211;effort pathway which focuses on the inhibition of sleep-wake automaticity. A contributing factor to this is selective attention to sleep (alongside explicit intention to sleep and effort in the sleep engagement process). Following on from previous work on selective attention to sleep [Marchetti, L. M., Biello, S. M., Broomfield, N. M., Mac- Mahon, K. M. A., & Espie, C. A. (2006). Who is pre-occupied with sleep?. A comparison of attention bias in people with psychphysiological insomnia, delayed sleep phase syndrome and good sleepers using the induced change blindness paradigm. Journal of Sleep Research, 15, 212&#8211;221; MacMahon, K., Broomfield, N., Macphee, L., & Espie, C. A. (2006). Attention bias for sleep related stimuli in primary insomnia and delayed sleep phase syndrome using the dot-probe task. Sleep, 29, 11] and considering the importance of monitoring both internal and external cues in the maintenance of insomnia, as highlighted in the cognitive model of insomnia [Harvey, A. G. (2002). A cognitive model of insomnia. Behaviour Research and Therapy, 40, 869&#8211;893], a cognitive probe task was employed to investigate further the role of the clock as a focus of selective attention in those with primary insomnia. A 2 2 between participants design comparing reaction time of individuals with primary insomnia (n &frac14; 22) and normal sleepers (n &frac14; 22) on a modified Posner paradigm. Responses obtained from a computer task presenting times which fall within a normal sleep period were analysed. Individuals with primary insomnia demonstrated delayed disengagement to the clock (F(1,84) &frac14; 6.9, p < 0.05) which is taken as further support for previous research demonstrating that individuals with primary insomnia exhibit an attentional bias to sleep related stimuli. These results lend support to the attention&#8211;intention&#8211;effort model (Espie et al., 2006) and the cognitive model (Harvey, 2002) both of which recognise the importance of selective attention towards salient stimuli in the maintenance of insomnia. Possible clinical implications of attentional bias to sleep as a marker of psychopathology progression and treatment efficacy are discussed.

Abstract: 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-HT1A/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.

Abstract: Cognitive models of insomnia suggest that selective attention may be involved in maintaining the disorder. However, direct assessment of selective attention is limited. Using the inducing change blindness (ICB) paradigm we aimed to determine whether there is attentional preference for sleep-related stimuli in psychophysiological insomnia (PI) relative to delayed sleep phase syndrome (DSPS) and good sleepers (GS). In the ICB task, a visual scene, comprising both sleep-related and neutral stimuli, flickers back and forth with one element (sleep or neutral) of the scene changing between presentations. Therefore, a 2 &#8226; 3 totally between-participants design was employed. The dependent variable was the number of flickers it took for the participant to identify the change. Ninety individuals (30 per group) were classified using ICSD-R criteria, self-report diaries and wrist actigraphy. As predicted, PI detected a sleep-related change significantly quicker than DSPS and GS, and significantly quicker than a sleep-neutral change. Unexpectedly, DSPS detected a sleep-related change significantly quicker than GS. No other differences were observed between the two controls. These results support the notion that there is an attention bias to sleep stimuli in PI, suggesting that selective attention tasks such as the ICB may be a useful objective index of cognitive arousal in insomnia. The results also suggest that there may be an element of sleep preoccupation associated with DSPS. Results are discussed with reference to other experiments on attentional processing in insomnia.

Abstract: The affinity of several antidepressant and antipsychotic drugs for the 5-HT7 receptor and its CNS distribution suggest potential in the treatment of psychiatric diseases. However, there is little direct evidence of receptor function in vivo to support this. We therefore evaluated 5-HT7 receptors as a potential drug target by generating and assessing a 5-HT7 receptor knockout mouse. No difference in assays sensitive to potential psychotic or anxiety states was observed between the 5-HT7 receptor knockout mice and wild type controls. However, in the Porsolt swim test, 5-HT7 receptor knockout mice showed a significant decrease in immobility compared to controls, a phenotype similar to antidepressant treated mice. Intriguingly, treatment of wild types with SB-258719, a selective 5-HT7 receptor antagonist, did not produce a significant decrease in immobility unless animals were tested in the dark (or active) cycle, rather than the light, adding to the body of evidence suggesting a circadian influence on receptor function. Extracellular recordings from hypothalamic slices showed that circadian rhythm phase shifts to 8-OH-DPAT are attenuated in the 5-HT7 receptor KO mice also indicating a role for the receptor in the regulation of circadian rhythms. These pharmacological and genetic knockout studies provide the first direct evidence that 5-HT7 receptor antagonists should be investigated for efficacy in the treatment of depression.