Carmen Schröder

Depression and Obstructive Sleep Apnea (OSA)

For over two decades clinical studies have been conducted which suggest the existence of a relationship between depression and Obstructive Sleep Apnea (OSA). Recently, Ohayon underscored the evidence for a link between these two disorders in the general population, showing that 800 out of 100,000 individuals had both, a breathing-related sleep disorder and a major depressive disorder, with up to 20% of the subjects presenting with one of these disorders also having the other. In some populations, depending on age, gender and other demographic and health characteristics, the prevalence of both disorders may be even higher: OSA may affect more than 50% of individuals over the age of 65, and significant depressive symptoms may be present in as many as 26% of a community-dwelling population of older adults.In clinical practice, the presence of depressive symptomatology is often considered in patients with OSA, and may be accounted for and followed-up when considering treatment approaches and response to treatment. On the other hand, sleep problems and specifically OSA are rarely assessed on a regular basis in patients with a depressive disorder. However, OSA might not only be associated with a depressive syndrome, but its presence may also be responsible for failure to respond to appropriate pharmacological treatment. Furthermore, an undiagnosed OSA might be exacerbated by adjunct treatments to antidepressant medications, such as benzodiazepines.Increased awareness of the relationship between depression and OSA might significantly improve diagnostic accuracy as well as treatment outcome for both disorders. In this review, we will summarize important findings in the current literature regarding the association between depression and OSA, and the possible mechanisms by which both disorders interact. Implications for clinical practice will be discussed.

Serotonin Transporter Polymorphism, Memory, and Hippocampal Volume in the Elderly: Association and Interaction with Cortisol

The s allele variant of the serotonin transporter gene (5-HTT) has recently been observed to moderate the relationship of stress to depression and anxiety. To date no study has considered interactive effects of 5-HTT genotype, stress and hypothalamic–pituitary–adrenal (HPA) function on cognition in healthy, older adults, which may reflect developmental, functional or neurodegenerative effects of the serotonin transporter polymorphism. We investigated whether 5-HTT genotype interacts with cumulative life stress and HPA-axis measures of waking and diurnal cortisol slope to impact cognition in 154 non-depressed, older adults. Structural images of hippocampal volume were acquired on a subsample of 56 participants. The 5-HTT s allele was associated with both significantly lower delayed recall and higher waking cortisol levels. Presence of the s allele interacted with higher waking cortisol to negatively impact memory. We also observed a significant interaction of higher waking cortisol and the s allele on lower hippocampal volume. Smaller hippocampi and higher cortisol were associated with lower delayed recall only in s allele carriers. No impact or interactions of cumulative life stress with 5-HTT or cortisol were observed. This is the first investigation to identify an association of the 5-HTT s allele with poorer memory function in older adults. The interactive effects of the s allele and waking cortisol levels on reduced hippocampal volume and lower memory suggest that the negative effect of the serotonin polymorphism on memory is mediated by the HPA axis. Further, given the significant association of the s allele with higher waking cortisol in our investigation, future studies may be needed to evaluate the impact of the serotonin transporter polymorphism on any neuropsychiatric or behavioral outcome which is influenced by HPA axis function in older adults.

Nocturnal sleep apnea/hypopnea is associated with lower memory performance in APOE ε4 carriers

The authors investigated the relationship between obstructive sleep apnea/hypopnea (OSAH) and cognition in 36 older adults, 18 APOE ε4 carriers, and 18 non-carriers. Greater numbers of respiratory events negatively impacted memory function in ε4 carriers only. This is the first study to provide preliminary evidence for a negative interaction of APOE ε4 and OSAH on memory in older adults, which may have important implications for treating cognitive decline and delaying dementia onset.

The frontal predominance in human EEG delta activity after sleep loss decreases with age.

Sleep loss has marked and selective effects on brain wave activity during subsequent recovery sleep. The electroencephalogram (EEG) responds to sleep deprivation with a relative increase in power density in the delta and theta range during non‐rapid eye movement sleep. We investigated age‐related changes of the EEG response to sleep deprivation along the antero‐posterior axis (Fz, Cz, Pz, Oz) under constant routine conditions. Both healthy young (20–31 years) and older (57–74 years) participants manifested a significant relative increase in EEG power density in the delta and theta range after 40 h of sleep deprivation, indicating a sustained capacity of the sleep homeostat to respond to sleep loss in ageing. However, the increase in relative EEG delta activity (1.25–3.75 Hz) following sleep deprivation was significantly more pronounced in frontal than parietal brain regions in the young, whereas such a frontal predominance was diminished in the older volunteers. This age‐related decrease of frontal delta predominance was most distinct at the beginning of the recovery sleep episode. Furthermore, the dissipation of homeostatic sleep pressure during the recovery night, as indexed by EEG delta activity, exhibited a significantly shallower decline in the older group. Activation of sleep regulatory processes in frontal brain areas by an extension of wakefulness from 16 to 40 h appears to be age‐dependent. These findings provide quantitative evidence for the hypothesis that frontal brain regions are particularly vulnerable to the effects of elevated sleep pressure (‘prefrontal tiredness’) and ageing (‘frontal ageing’).

Chronobiology, excessive daytime sleepiness and depression: Is there a link?

The complaint of excessive daytime sleepiness (EDS), commonly encountered in clinical practice, may arise from a variety of psychiatric disorders, most importantly depression. Even though EDS frequently leads depressed patients to seek medical assistance, it is commonly under-evaluated and under-diagnosed. Therefore, a comprehensive understanding and management of EDS is essential in the clinical assessment of depression. Within a theoretical framework, a chronobiological approach may shed new light on the complex interaction of EDS and depression. In this review, studies on EDS and depression are summarized and discussed within the context of circadian and sleep regulatory mechanisms. Furthermore, potential chronobiological therapeutic strategies are proposed to address some of the unmet needs in the treatment of EDS and depression.

Hormone replacement therapy and longitudinal cognitive performance in postmenopausal women

OBJECTIVE The authors examined the impact of hormone replacement therapy (HRT) on longitudinal cognitive performance (controlling for mood state) in 69 community-dwelling, postmenopausal women. METHODS The authors conducted a 5-year follow-up of cognitive performance in 37 postmenopausal HRT users and 32 non-users. The groups did not differ with respect to age, years of education, or inter-test interval. RESULTS No main effect of HRT was observed on any of the cognitive measures, and depressive symptomatology did not affect the relationship between HRT and cognition. CONCLUSION Overall, our findings do not suggest that HRT affects longitudinal cognitive performance in postmenopausal, community-dwelling older women.

Serotonin transporter polymorphism is associated with increased apnea-hypopnea index in older adults.

A functional polymorphism of the serotonin transporter gene (5‐HTTLPR) has previously been related to upper airway pathology, but its contribution to obstructive sleep apnea (OSA), a highly prevalent sleep disorder in older adults, remains unclear.

The Circadian Rest-Activity Cycle in Korsakoff Psychosis

OBJECTIVES Alzheimer disease (AD) has been associated with diminished function of the biological clock in the suprachiasmatic nuclei (SCN) and pronounced circadian sleep-wake cycle disturbances. Few studies have investigated other dementia etiologies. Because alcohol acts on the SCN and modifies circadian rhythms in animal studies, Korsakoff psychosis (KP) may also be associated with circadian rhythm abnormalities. This pilot study investigated the rest-activity cycle of KP to see whether there were sleep-wake cycle disturbances similar to those that the authors had observed in patients with AD. DESIGN AND SETTING Cross-sectional observational study in a single academic medical center. PARTICIPANTS, MEASUREMENTS: The authors investigated the circadian rest-activity cycle of six moderately demented patients with KP who wore an activity/lux monitor for 10-26 days and compared these patterns with those of six home-living healthy individuals of the same age group. In addition, rest-activity cycle data from previous studies of patients with AD were examined. INTERVENTIONS None. RESULTS The rest-activity cycle of KP was remarkably well entrained, without the marked circadian and sleep disturbances found in patients with AD on the same ward. KP had a >2 hour earlier bedtime and rest onset than healthy subjects and a 30-minute earlier wake-up time, resulting in longer nocturnal rest duration. The major difference was a greatly diminished daytime activity level and extremely low light exposure. CONCLUSION A stably entrained, although low-amplitude and phase-advanced rest-activity cycle may reflect the different neuropathology of demented patients with KP compared with patients with AD.