Lukas Frase

The reorganisation of memory during sleep

Sleep after learning promotes the quantitative strengthening of new memories. Less is known about the impact of sleep on the qualitative reorganisation of memory, which is the focus of this review. Studies have shown that, in the declarative system, sleep facilitates the abstraction of rules (schema formation), the integration of knowledge into existing schemas (schema integration) and creativity that requires the disbandment of existing patterns (schema disintegration). Schema formation and integration might primarily benefit from slow wave sleep, whereas the disintegration of a schema might be facilitated by rapid eye movement sleep. In the procedural system, sleep fosters the reorganisation of motor memory. The neural mechanisms of these processes remain to be determined. Notably, emotions have been shown to modulate the sleep-related reorganisation of memories. In the final section of this review, we propose that the sleep-related reorganisation of memories might be particularly relevant for mental disorders. Thus, sleep disruptions might contribute to disturbed memory reorganisation and to the development of mental disorders. Therefore, sleep-related interventions might modulate the reorganisation of memories and provide new inroads into treatment.

REM sleep and memory reorganization: Potential relevance for psychiatry and psychotherapy

Sleep can foster the reorganization of memory, i.e. the emergence of new memory content that has not directly been encoded. Current neurophysiological and behavioral evidence can be integrated into a model positing that REM sleep particularly promotes the disintegration of existing schemas and their recombination in the form of associative thinking, creativity and the shaping of emotional memory. Particularly, REM sleep related dreaming might represent a mentation correlate for the reconfiguration of memory. In a final section, the potential relevance for psychiatry and psychotherapy is discussed.

Hypnotika – Stand der Forschung

ZusammenfassungDie vorliegende Arbeit fasst den gegenwärtigen Kenntnisstand zur medikamentösen Behandlung von gestörtem Nachtschlaf zusammen. Eine medikamentöse Behandlung sollte erst nach unzureichender Wirkung nichtmedikamentöser Verfahren in Erwägung gezogen werden. Benzodiazepine und Benzodiazepinrezeptoragonisten sind für eine Kurzzeitanwendung bei schwerer Schlafstörung geeignet. Aufgrund der Gefahr einer Toleranz- und Abhängigkeitsentwicklung hat sich für eine längere Anwendung die Gabe sedierender Antihistaminika und Antidepressiva etabliert. Andere Präparate, wie Phytopharmaka oder Melatonin, zeigen zwar eine gute Verträglichkeit, sind jedoch bei schwerer Schlafstörung oft nicht ausreichend wirksam. Insgesamt liegen aktuell keine hinreichenden Daten für eine Langzeitbehandlung mit Hypnotika vor. Bei unzureichender Besserung von Einschlafstörungen, Durchschlafstörungen oder nichterholsamem Schlaf sollte eine erneute und umfassende differenzialdiagnostische Abklärung und ggf. eine Behandlung der assoziierten Erkrankungen erfolgen.SummaryThis article provides an overview of the indications and effects of sleep-inducing drugs. Pharmacological treatment should only be considered in cases of insufficient response to non-pharmacological interventions. Benzodiazepines and benzodiazepine receptor agonists are indicated for the short-term treatment of acute insomnia. Due to the risk of tolerance and dependency, sedative antihistamines and antidepressants are widely used as long-term hypnotics. Other substances, including herbal compounds and melatonin have few side effects; however, the therapeutic efficacy is very limited. Currently, long-term data on the efficacy and tolerability of sleep-inducing substances are lacking. Specifically in cases of non-response to first line treatment, extended psychiatric and somatic evaluation and treatment of associated disorders are recommended.This article provides an overview of the indications and effects of sleep-inducing drugs. Pharmacological treatment should only be considered in cases of insufficient response to non-pharmacological interventions. Benzodiazepines and benzodiazepine receptor agonists are indicated for the short-term treatment of acute insomnia. Due to the risk of tolerance and dependency, sedative antihistamines and antidepressants are widely used as long-term hypnotics. Other substances, including herbal compounds and melatonin have few side effects; however, the therapeutic efficacy is very limited. Currently, long-term data on the efficacy and tolerability of sleep-inducing substances are lacking. Specifically in cases of non-response to first line treatment, extended psychiatric and somatic evaluation and treatment of associated disorders are recommended.

Interpersonal psychotherapy (IPT) in major depressive disorder.

In this article, we will introduce interpersonal psychotherapy as an effective short-term treatment strategy in major depression. In IPT, a reciprocal relationship between interpersonal problems and depressive symptoms is regarded as important in the onset and as a maintaining factor of depressive disorders. Therefore, interpersonal problems are the main therapeutic targets of this approach. Four interpersonal problem areas are defined, which include interpersonal role disputes, role transitions, complicated bereavement, and interpersonal deficits. Patients are helped to break the interactions between depressive symptoms and their individual interpersonal difficulties. The goals are to achieve a reduction in depressive symptoms and an improvement in interpersonal functioning through improved communication, expression of affect, and proactive engagement with the current interpersonal network. The efficacy of this focused and structured psychotherapy in the treatment of acute unipolar major depressive disorder is summarized. This article outlines the background of interpersonal psychotherapy, the process of therapy, efficacy, and the expansion of the evidence base to different subgroups of depressed patients.

Modulation of Total Sleep Time by Transcranial Direct Current Stimulation (tDCS)

Arousal and sleep are fundamental physiological processes, and their modulation is of high clinical significance. This study tested the hypothesis that total sleep time (TST) in humans can be modulated by the non-invasive brain stimulation technique transcranial direct current stimulation (tDCS) targeting a ‘top-down’ cortico-thalamic pathway of sleep-wake regulation. Nineteen healthy participants underwent a within-subject, repeated-measures protocol across five nights in the sleep laboratory with polysomnographic monitoring (adaptation, baseline, three experimental nights). tDCS was delivered via bi-frontal target electrodes and bi-parietal return electrodes before sleep (anodal ‘activation’, cathodal ‘deactivation’, and sham stimulation). Bi-frontal anodal stimulation significantly decreased TST, compared with cathodal and sham stimulation. This effect was location specific. Bi-frontal cathodal stimulation did not significantly increase TST, potentially due to ceiling effects in good sleepers. Exploratory resting-state EEG analyses before and after the tDCS protocols were consistent with the notion of increased cortical arousal after anodal stimulation and decreased cortical arousal after cathodal stimulation. The study provides proof-of-concept that TST can be decreased by non-invasive bi-frontal anodal tDCS in healthy humans. Further elucidating the ‘top-down’ pathway of sleep-wake regulation is expected to increase knowledge on the fundamentals of sleep-wake regulation and to contribute to the development of novel treatments for clinical conditions of disturbed arousal and sleep.

Sodium oxybate–induced central sleep apneas

Sodium oxybate (γ-hydroxybutyric acid, GHB) is a neurotransmitter in the human brain which exerts sedative effects and is used therapeutically in the treatment of narcolepsy. Current safety recommendations have been formulated for the use of GHB in patients with preexisting breathing disorders. We report the case of a 39-year-old female with narcolepsy and cataplexy revealing the de novo emergence of central sleep apneas in a Cheyne-Stokes pattern under constant treatment with GHB. After discontinuation of GHB, polysomnographic re-evaluation demonstrated the disappearance of central sleep apneas. To our knowledge, this is the first report of de novo central sleep apneas induced by GHB in a patient without pre-existing sleep-disordered breathing, suggesting that there is a need for further investigation and potentially an extension of the safety guidelines to patients without a pre-existing breathing disorder.

The effect of sleep-specific brain activity versus reduced stimulus interference on declarative memory consolidation.

Studies suggest that the consolidation of newly acquired memories and underlying long‐term synaptic plasticity might represent a major function of sleep. In a combined repeated‐measures and parallel‐group sleep laboratory study (active waking versus sleep, passive waking versus sleep), we provide evidence that brief periods of daytime sleep (42.1 ± 8.9 min of non‐rapid eye movement sleep) in healthy adolescents (16 years old, all female), compared with equal periods of waking, promote the consolidation of declarative memory (word‐pairs) in participants with high power in the electroencephalographic sleep spindle (sigma) frequency range. This observation supports the notion that sleep‐specific brain activity when reaching a critical dose, beyond a mere reduction of interference, promotes synaptic plasticity in a hippocampal‐neocortical network that underlies the consolidation of declarative memory.

Steroid-responsive depression

A 48-year-old man presented with long-standing symptoms of major depression in the absence of markedly abnormal neurological findings or structural brain alterations. Antidepressive treatment, including medication and psychotherapy, had not led to significant improvement. The EEG, cerebrospinal fluid (CSF) analysis, fluorodeoxyglucose-positron emission tomography and neuropsychological testing showed pathological findings. An epileptic state provided further evidence for an organic encephalopathy. Extensively elevated thyroid-antibodies in the serum and CSF, as well as the rapid and sustained recovery after intravenous treatment with prednisolone, pointed to the diagnosis of a primarily psychiatric manifestation of a steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT).

Neuroenhancement strategies for psychiatric disorders: rationale, status quo and perspectives

With the growing mechanistic understanding of higher brain functions like learning and memory, vigilance and social cognition, new pharmacological approaches for the treatment of psychiatric disorders arise. Substances used as neuroenhancers for the improvement of cognitive or emotional functions in healthy subjects might provide novel pharmacological opportunities in psychiatry. Intriguingly, drugs like modafinil, d-cycloserine or oxytocin have shown significant improvements in key symptoms in several psychiatric disorders. When used as augmentation strategies, they could either directly interfere with psychopathological impairments or improve response to other treatment modalities like psychotherapy or psychopharmacological drugs. While initial studies yielded promising results, further research on beneficial or adverse effects is required.

[Hypnotics--state of the science].

ZusammenfassungDie vorliegende Arbeit fasst den gegenwärtigen Kenntnisstand zur medikamentösen Behandlung von gestörtem Nachtschlaf zusammen. Eine medikamentöse Behandlung sollte erst nach unzureichender Wirkung nichtmedikamentöser Verfahren in Erwägung gezogen werden. Benzodiazepine und Benzodiazepinrezeptoragonisten sind für eine Kurzzeitanwendung bei schwerer Schlafstörung geeignet. Aufgrund der Gefahr einer Toleranz- und Abhängigkeitsentwicklung hat sich für eine längere Anwendung die Gabe sedierender Antihistaminika und Antidepressiva etabliert. Andere Präparate, wie Phytopharmaka oder Melatonin, zeigen zwar eine gute Verträglichkeit, sind jedoch bei schwerer Schlafstörung oft nicht ausreichend wirksam. Insgesamt liegen aktuell keine hinreichenden Daten für eine Langzeitbehandlung mit Hypnotika vor. Bei unzureichender Besserung von Einschlafstörungen, Durchschlafstörungen oder nichterholsamem Schlaf sollte eine erneute und umfassende differenzialdiagnostische Abklärung und ggf. eine Behandlung der assoziierten Erkrankungen erfolgen.SummaryThis article provides an overview of the indications and effects of sleep-inducing drugs. Pharmacological treatment should only be considered in cases of insufficient response to non-pharmacological interventions. Benzodiazepines and benzodiazepine receptor agonists are indicated for the short-term treatment of acute insomnia. Due to the risk of tolerance and dependency, sedative antihistamines and antidepressants are widely used as long-term hypnotics. Other substances, including herbal compounds and melatonin have few side effects; however, the therapeutic efficacy is very limited. Currently, long-term data on the efficacy and tolerability of sleep-inducing substances are lacking. Specifically in cases of non-response to first line treatment, extended psychiatric and somatic evaluation and treatment of associated disorders are recommended.This article provides an overview of the indications and effects of sleep-inducing drugs. Pharmacological treatment should only be considered in cases of insufficient response to non-pharmacological interventions. Benzodiazepines and benzodiazepine receptor agonists are indicated for the short-term treatment of acute insomnia. Due to the risk of tolerance and dependency, sedative antihistamines and antidepressants are widely used as long-term hypnotics. Other substances, including herbal compounds and melatonin have few side effects; however, the therapeutic efficacy is very limited. Currently, long-term data on the efficacy and tolerability of sleep-inducing substances are lacking. Specifically in cases of non-response to first line treatment, extended psychiatric and somatic evaluation and treatment of associated disorders are recommended.