Robert Göder

Reduced olfactory performance in patients with major depression

The aim of the present study is to investigate olfactory sensitivity and odor evaluations in a homogeneous sample of unipolar depressive patients using pure olfactory odors. Twenty-four in-patients with major depressive disorder (MDD) were investigated during their acute depressive phase. Eighteen of them participated a second time after successful treatment. A group of healthy subjects, matched by age, sex, and smoking behavior, served as a control. Olfactory sensitivity, as measured by threshold tests, was strongly reduced in patients with severe depression. Additional correlative analyses revealed that the lowered sensitivity could partly be predicted by high depression scores. After successful medical treatment, these sensitivity differences were reduced and did not reach the significance level. The subjective odor evaluations (valence and intensity ratings) were not markedly changed in general. The results reveal that olfactory performance in MDD patients is reduced at an early perceptional level of stimulus processing. It is discussed whether this effect can be attributed to the close functional connection between the main olfactory bulb and the amygdala.

Sleep in children enhances preferentially emotional declarative but not procedural memories.

Although the consolidation of several memory systems is enhanced by sleep in adults, recent studies suggest that sleep supports declarative memory but not procedural memory in children. In the current study, the influence of sleep on emotional declarative memory (recognition task) and procedural memory (mirror tracing task) in 20 healthy children (10-13 years of age) was examined. After sleep, children showed an improvement in declarative memory. Separate analysis with respect to the emotional stimulus content revealed that sleep enhances the recognition of emotional stimuli (p>.001) rather than neutral stimuli (p=.084). In the procedural task, however, no sleep-enhanced memory improvement was observed. The results indicate that sleep in children, comparable to adults, enhances predominantly emotional declarative memory; however, in contrast to adults, it has no effect on the consolidation of procedural memory.

Morning headaches in patients with sleep disorders: a systematic polysomnographic study

OBJECTIVES Patients with sleep disorders suffer more often from headache after awakening than healthy subjects. However, it still is a matter of controversy whether this applies only to patients with sleep apnea syndrome (SAS) or also to patients with other diagnoses of sleep disorders. METHODS We asked all patients in our sleep laboratory about the frequency of past headaches and also ascertained the occurrence of morning headaches after awakening in the sleep laboratory. Polysomnographic recordings from nights before morning headache were compared with nights without following headache. Four hundred and thirty-two patients with sleep disorders (age range 18-86 years, 37% women) and 30 healthy subjects (age range 24-55 years, 27% women) participated in this prospective study. RESULTS The reported frequency of past headaches and the frequency of morning headache in the sleep laboratory were significantly increased in patients with SAS and other sleep disorders compared with healthy subjects. The occurrence of morning headache in the sleep laboratory was associated polysomnographically with a decrease in total sleep time, sleep efficiency and amount of rapid eye movement sleep and with an increase in the wake-time during the preceding night. CONCLUSIONS We conclude that morning headaches in patients with sleep disorders might be associated with particular disturbances of the preceding nights sleep. We speculate that dysregulation in anatomically identical central regions modulating sleep and nociception might be relevant to morning headache, rather than one particular sleep disorder such as SAS.

Effects of intranasal hypocretin-1 (orexin A) on sleep in narcolepsy with cataplexy

BACKGROUND The neuropeptides hypocretin-1 and -2 (hcrt-1 and -2, also known as orexin A and B) are crucially involved in the regulation of sleep/wake states. On the one hand, the sleep-wake disorder narcolepsy can be caused by an hcrt-1 deficiency. On the other, intracerebral administration of hcrt-1 produces an increase in wakefulness at the expense of REM sleep in normal and narcoleptic animals. In humans intranasal administration has been shown to effectively deliver neuropeptides directly to the central nervous system. We hypothesised that the intranasal application of hcrt-1 increases wakefulness and reduces REM sleep in the natural human hcrt-1 deficiency narcolepsy with cataplexy. METHODS In this double-blind, random-order crossover, placebo-controlled, within-subject design study we administered human recombinant hcrt-1 (435 nmol) intranasally to eight subjects with narcolepsy with cataplexy before night sleep, followed by standard polysomnography. RESULTS Although intranasal administration of hcrt-1 had no statistically significant effect on nocturnal wakefulness, we found that it reduced REM sleep quantity, particularly during the second half of the recording. Furthermore, intranasal hcrt-1 had a clear REM sleep stabilising effect and led to significantly reduced direct wake to REM transitions. CONCLUSION In this pilot study we found, first, evidence that the intranasal administration of hcrt-1 has functional effects on sleep in narcolepsy with cataplexy. Our results may encourage the use of the intranasal approach in further studies on hypocretinergic sleep regulation and might also contribute to the future development of a causal treatment for narcolepsy with cataplexy.

Effects of daytime naps on procedural and declarative memory in patients with schizophrenia.

Sleep has been identified as a state that optimizes the consolidation of newly acquired information in memory. Straight memory deficits and sleep disturbances are well-known in patients with schizophrenia. This study tested the hypothesis that patients with schizophrenia have a deficit in procedural and declarative memory consolidation after a short midday nap when compared to healthy controls and patients with remitted to moderate major depression. Following a normal nights sleep, 22 healthy subjects, 20 patients with major depression and 21 patients with schizophrenia were studied in a napping and wake condition in a random-order cross-over design, early in the afternoon. To test declarative memory, the Rey-Osterrieth Complex Figure Test respectively the Taylor Complex Figure Test and, for procedural learning, a mirror tracing task were performed. The present study is the first to demonstrate significant differences between individuals with schizophrenia, depression and healthy matched controls with regard to measures of sleep and memory performance after a short period of daytime sleep (napping). In particular we found that a daytime nap of only about 40min led to improvement of declarative memory performance in all investigated groups, whereas no beneficial effect was seen on procedural performance in the group of medicated patients with schizophrenia in contrast to healthy controls and patients with remitted to moderate major depression.

Transcranial Oscillatory Direct Current Stimulation During Sleep Improves Declarative Memory Consolidation in Children With Attention-deficit/hyperactivity Disorder to a Level Comparable to Healthy Controls

BACKGROUND Slow oscillations (<1 Hz) during slow wave sleep (SWS) promote the consolidation of declarative memory. Children with attention-deficit/hyperactivity disorder (ADHD) have been shown to display deficits in sleep-dependent consolidation of declarative memory supposedly due to dysfunctional slow brain rhythms during SWS. OBJECTIVE Using transcranial oscillating direct current stimulation (toDCS) at 0.75 Hz, we investigated whether an externally triggered increase in slow oscillations during early SWS elevates memory performance in children with ADHD. METHODS 12 children with ADHD underwent a toDCS and a sham condition in a double-blind crossover study design conducted in a sleep laboratory. Memory was tested using a 2D object-location task. In addition, 12 healthy children performed the same memory task in their home environment. RESULTS Stimulation enhanced slow oscillation power in children with ADHD and boosted memory performance to the same level as in healthy children. CONCLUSION These data indicate that increasing slow oscillation power during sleep by toDCS can alleviate declarative memory deficits in children with ADHD.

The effect of intranasal orexin-A (hypocretin-1) on sleep, wakefulness and attention in narcolepsy with cataplexy

Narcolepsy with cataplexy is a sleep dysregulation disorder with alterations of REM sleep, i.e., sleep onset REM periods and REM sleep instability. Deficient orexin-A (hypocretin-1) signaling is assumed to be a major cause of narcolepsy with cataplexy. In this study we investigated fourteen subjects with narcolepsy with cataplexy in a within-subject, random-order crossover, placebo-controlled design. Patients received double-blinded intranasal orexin-A (435 nmol) or sterile water (placebo) in the morning. Administration was preceded by an adaptation night and followed by a modified maintenance of wakefulness test, attention testing and a second full night of polysomnographic recording. We found comparable sleep behavior during the adaptation nights between both conditions. After orexin-A administration patients had less wake-REM sleep transitions and a decreased REM sleep duration. In the subsequent night, patients showed an increased N2 duration. In the test of divided attention, patients had fewer false reactions after orexin-A administration. Our results support orexin-A to be a REM sleep stabilizing factor and provide functional signs for effects of orexin-A on sleep alterations and attention in narcolepsy with cataplexy.

Reduced sleep-associated consolidation of declarative memory in attention-deficit/hyperactivity disorder

OBJECTIVE Sleep supports the consolidation of declarative memory. Patients with attention-deficit/hyperactivity disorder (ADHD) are not only characterized by sleep problems but also by declarative memory deficits. Given that the consolidation of declarative memory during sleep is supported by slow oscillations, which are predominantly generated by the prefrontal cortex, and that ADHD patients display low prefrontal brain activity, we assumed that ADHD patients show reduced sleep-associated consolidation of declarative memory. METHODS The impact of sleep on the consolidation of declarative memory was examined with a picture recognition task. Twelve ADHD patients (10-16 years) and 12 healthy controls participated in two experimental conditions: in the sleep condition, learning was performed in the evening and picture recognition was tested after nocturnal sleep; in the wake condition, learning was conducted in the morning while retrieval took place after a day of wakefulness. RESULTS Analyses of recognition accuracy revealed reduced sleep-associated enhancement of recognition accuracy in ADHD. While sleep-associated enhancement of recognition accuracy was correlated with slow oscillation power during non-REM sleep in healthy controls, no such correlations were observed in ADHD. CONCLUSIONS These data indicate a deficit in sleep-associated consolidation of declarative memory in ADHD. Moreover, our results suggest reduced functionality of slow oscillations in sleep-associated consolidation of declarative memory in ADHD.

Changes in CREB Phosphorylation and BDNF Plasma Levels during Psychotherapy of Depression

Background: The cyclic adenosine monophosphate response element-binding proteins (CREB) and their interaction with brain-derived neurotrophic factor (BDNF) are essential elements in signal transduction pathways important for cellular resilience and neuroplasticity. They play a decisive role in the concept of altered neuroplasticity in major depression. We have previously demonstrated that the increase in phosphorylated CREB (pCREB) in T lymphocytes is significantly associated with clinical improvement in patients treated with antidepressants. In the present study, we focused on patients treated only with psychotherapy to exclude direct pharmacological actions. In addition to pCREB, we also measured the BDNF plasma levels. Methods: pCREB in T lymphocytes was determined by Western blot; the BDNF plasma levels with solid-phase ELISA. Psychopathology was evaluated with the Hamilton Rating Scale for Depression (HAMD). Thirty patients meeting DSM-IV criteria for major depressive episodes (MDE) were recruited into this 6-week study. They received interpersonal psychotherapy (IPT) twice weekly. Results: After 6 weeks of IPT, 17 patients responded (reduction of ≥50% of baseline HAMD); after 1 week of treatment pCREB increased significantly compared to the nonresponder group. Measurement of the BDNF plasma levels revealed no differences between the responder and nonresponder groups. Furthermore, the correlations between BDNF plasma levels and pCREB were not significant. Conclusions: The early increase in pCREB is related to treatment response and does not depend on pharmacological interventions or BDNF plasma levels. For the first time, cellular biological markers could be associated with response to psychotherapy.

Impairment of sleep-related memory consolidation in schizophrenia: relevance of sleep spindles?

OBJECTIVES Deficits in declarative memory performance are among the most severe neuropsychological impairments in schizophrenia and contribute to poor clinical outcomes. The importance of sleep for brain plasticity and memory consolidation is widely accepted, and sleep spindles seem to play an important role in these processes. The aim of this study was to test the associations of sleep spindles and picture memory consolidation in patients with schizophrenia and healthy controls. METHODS We studied 16 patients with schizophrenia on stable antipsychotic medication (mean age ± standard deviation, 29.4 ± 6.4 years) and 16 healthy controls matched for age and educational level. Sleep was recorded and scored according to American Academy of Sleep Medicine (AASM) standard criteria. We performed a picture recognition paradigm and compared recognition performance for neutral and emotional pictures in sleep and wake conditions. RESULTS Recognition accuracy was better in healthy controls than in patients with schizophrenia in the sleep and wake conditions. However, the memory-promoting effect of sleep was significantly lower in schizophrenia patients than in controls. Sleep spindle activity was reduced in patients, and sleep spindle density was correlated with sleep-associated facilitation of recognition accuracy for neutral pictures. CONCLUSION Reduced sleep spindles seem to play an important role as a possible mechanism or biomarker for impaired sleep-related memory consolidation in patients with schizophrenia, and are a new target for treatment to improve memory functions and clinical outcomes in these patients.