Multiple lines of evidence suggest that psychopathological symptoms of bipolar disorder arise in part from a malfunction of the circadian system, linking the disease with an abnormal internal timing. ...Alterations in circadian rhythms and sleep are core elements in the disorders, characterizing both mania and depression and having recently been shown during euthymia. Several human genetic studies have implicated specific genes that make up the genesis of circadian rhythms in the manifestation of mood disorders with polymorphisms in molecular clock genes not only showing an association with the disorder but having also been linked to its phenotypic particularities. Many medications used to treat the disorder, such as antidepressant and mood stabilizers, affect the circadian clock. Finally, circadian rhythms and sleep researches have been the starting point of the developing of chronobiological therapies. These interventions are safe, rapid and effective and they should be considered first-line strategies for bipolar depression.
Chronobiological Therapy for Mood Disorders Dallaspezia, Sara; Suzuki, Masahiro; Benedetti, Francesco
Current psychiatry reports,
12/2015, Letnik:
17, Številka:
12
Journal Article
Recenzirano
Chronobiological therapies for mood disorders include manipulations of the sleep–wake cycle such as sleep deprivation and sleep phase advance and the controlled exposure to light and darkness. Their ...antidepressant efficacy can overcome drug resistance and targets the core depressive symptoms including suicide, thus making them treatment options to be tried either alone or as adjunctive treatments combined with common psychopharmacological interventions. The specific pattern of mood change observed with chronobiological therapies is characterized by rapid and sustained effects, when used among themselves or combined with drugs. Effects sizes are the same reported for the most effective psychiatric treatments, but side effects are usually marginal or absent. New treatment protocols are developed to adapt them in different clinical settings. This review deals with the general principles of clinical chronobiology and the latest findings in this rapidly developing field.
One third of patients with bipolar disorder attempt suicide. Depression in bipolar disorder is associated with drug resistance. The efficacy of antidepressants on suicidality has been questioned. ...Total sleep deprivation and light therapy prompt a rapid and stable antidepressant response in bipolar disorder.
We studied 143 consecutively admitted inpatients (December 2006-August 2012) with a major depressive episode in the course of bipolar disorder (DSM-IV criteria). Among the 141 study completers, 23% had a positive history of attempted suicide and 83% had a positive history of drug resistance. During 1 week, patients were administered 3 consecutive total sleep deprivation cycles (each composed of a period of 36 hours awake followed by recovery sleep) combined with bright light therapy in the morning for 2 weeks. At admission, patients who had been taking lithium continued it, and those who had not been taking lithium started it. Severity of depression was rated according to the Hamilton Depression Rating Scale (HDRS) (primary outcome measure) and Beck Depression Inventory (BDI).
Two patients switched polarity. Among the 141 who completed the treatment, 70% achieved a 50% reduction in HDRS score in 1 week, which persisted 1 month after in 55%. The amelioration involved an immediate and persistent decrease in suicide scores soon after the first total sleep deprivation cycle (F3,411 = 42.78, P < .00001). A positive history of suicide attempts was associated with worse early life stress and with worse suicide scores at baseline, but it did not influence response. Patients with current suicidal thinking or planning responded equally well (F3,42 = 20.70, P < .000001). Remarkably, however, nonresponders achieved a benefit, with significantly decreased final scores also including suicidality ratings (F3,120 = 6.55, P = .0004). Self-ratings showed the same pattern of change. Previous history of drug resistance did not hamper response. During the following month, 78 of 99 responders continued to stay well and were discharged from the hospital on lithium therapy alone.
The combination of total sleep deprivation, light therapy, and lithium is able to rapidly decrease depressive suicidality and prompt antidepressant response in drug-resistant major depression in the course of bipolar disorder.
Alteration of the sleep-wake cycle and of the sleep structure are core symptoms of a major depressive episode, and occur both in course of bipolar disorder and of major depressive disorder. Many ...other circadian rhythms, such as the daily profiles of body temperature, cortisol, thyrotropin, prolactin, growth hormone, melatonin and excretion of various metabolites in the urine, are disrupted in depressed patients, both unipolar and bipolar individuals. These disrupted rhythms seem to return to normality with patient recovery. Research on circadian rhythms and sleep have led to the definition of nonpharmacological therapies of mood disorder that can be used in everyday practice. These strategies, named chronotherapeutics, are based on controlled exposures to environmental stimuli that act on biological rhythms, and demonstrate good efficacy in the treatment of illness episodes. They include manipulations of the sleep-wake rhythm (such as partial and total sleep deprivation, and sleep phase advance) and of the exposure to the light-dark cycle (light therapy and dark therapy). In recent years, an increasing literature about the safety and efficacy of chronobiological treatments in everyday psychiatric settings has supported the inclusion of these techniques among the first-line antidepressant strategies for patients affected by mood disorders.
Sleep disturbances and dysregulation of circadian rhythms are core elements of bipolar disorder that might be involved in its pathogenesis. It has been proposed that patients with bipolar disorder ...have an abnormally shifted or arrhythmic circadian system and that the disturbance of circadian rhythms may be caused by an alteration in the circadian clock machinery. Chronotherapeutic strategies based on controlled exposures to environmental stimuli that act on biological rhythms have shown good efficacy in the treatment of illness episodes, thus confirming
ex juvantibus
the clinical relevance of internal timing in this illness.
Aim
Studies have demonstrated neuropsychological deficits across a variety of cognitive domains in depression. These deficits are observable both in major depressive disorder (MDD) and in bipolar ...disorder (BD) and are present in each phase of the illness, including euthymia. Adverse childhood experiences (ACE) have been associated with an increased risk of developing psychiatric disorders and cognitive deficits. The aim of this study was to assess neuropsychological performances in a sample of MDD and BD patients during a depressive episode compared to healthy controls (HC) and, to investigate if ACE affect the cognitive profiles in the three groups.
Methods
Seventy‐six BD patients, 57 MDD patients, and 57 HC underwent neuropsychological assessment for cognitive performances through the Brief Assessment of Cognition in Schizophrenia and Wisconsin Card Sorting Test.
Results
Both BD and MDD patients obtained significantly lower domain scores across the entire battery compared to HC. Splitting the sample according to exposure to ACE (high and low), the differences observed in the whole sample persisted only in the subsample of those patients exposed to high ACE.
Conclusion
This study confirms that cognitive impairment is present both in MDD and BD, albeit in different degrees of severity, and highlights the importance of early stress as a moderator factor when investigating cognitive functions in mood disorders.
Background Diffusion tensor imaging allows the study of integrity of white matter (WM) tracts. Literature suggests that WM integrity could be altered in bipolar disorder. Heterogeneity of brain ...imaging methods, the studied samples, and drug treatments make localization, nature, and severity of the WM abnormalities unclear. Methods We applied tract-based spatial statistics of diffusion tensor imaging measures to compare fractional anisotropy (FA), mean, and radial diffusivity of the WM skeleton in a group of 40 consecutively admitted inpatients affected by a major depressive episode without psychotic features with a diagnosis of bipolar disorder type I and 21 unrelated healthy volunteers from the general population. Results Compared with control subjects, patients showed lower FA in the genu of the corpus callosum and in anterior and right superior-posterior corona radiata and higher values of radial diffusivity in WM tracts of splenium, genu and body of corpus callosum, right mid-dorsal part of the cingulum bundle, left anterior and bilateral superior and posterior corona radiata, bilateral superior longitudinal fasciculus, and right posterior thalamic radiation. Patients had no brain areas with higher FA or lower diffusivity values than control subjects. Conclusions Reduced FA with increased mean and radial diffusivity suggests significant demyelination and/or dysmyelination without axonal loss. Comparing our findings with other observations in homogeneous samples of euthymic and manic patients, it can be hypothesized that changes in measures of WM integrity might parallel illness phases of bipolar illness.
Seasonal rhythms affect the immune system. Evidence supports the involvement of immuno-inflammatory mechanisms in bipolar disorder (BD), with the neutrophil to lymphocyte ratio (NLR), and the ...systemic immune-inflammatory index (SII; platelets × neutrophils/lymphocytes) consistently reported to be higher in patients with BD than in HC, but seasonal rhythms of innate and adaptive immunity have never been studied. We retrospectively studied NLR and SII in 824 participants divided into three groups: 321 consecutively admitted inpatients affected by a major depressive episode in course of BD, and 255 consecutively admitted inpatients affected by obsessive-compulsive disorder (OCD; positive psychiatric control), and 248 healthy controls (HC). Patients with BD showed markedly higher markers of systemic inflammation in autumn and winter, but not in spring and summer, in respect to both HC and patients with OCD, thus suggesting a specific effect of season on inflammatory markers in BD, independent of a shared hospital setting and drug treatment. Given that systemic inflammation is emerging as a new marker and as target for treatment in depressive disorders, we suggest that seasonal rhythms should be considered for tailoring antidepressant immuno-modulatory treatments in a precision medicine approach.
Background: Patients with mood disorders show a high dependence of behavior on the molecular characteristics of the biological clock. CLOCK rs1801260 gene polymorphism influences circadian behavior ...in bipolar disorder (BD), with *C carriers showing a delayed sleep onset and worse insomnia. Sleep phase delay and insomnia associate with suicide in the general population. Methods: We investigated the effects of rs1801260, and of exposure to stressful life events, on current suicidal ideation and history of suicide attempts in 87 depressed patients with BD. Results: rs1801260*C carriers currently showed worse Hamilton Depression Rating Scale scores for suicide and worse ratings for depressive cognitive distortions. Previous history of attempted suicide associated with exposure to higher stressful events in the early life, with rs1801260*C carriers showing a higher dependency of the modeled probability of attempting suicide on the severity of exposure to early stress. Discussion: CLOCK rs1801260 modulated the relationship between early stress, adult history of attempted suicide and current suicide ideation. Factors affecting the biological clock can influence "non-clock" core psychopathological features of mood disorders.
Abstract Background Combined Total sleep deprivation (TSD) and light therapy (LT) cause a rapid improvement in bipolar depression which has been hypothesized to be paralleled by changes in sleep ...homeostasis. Recent studies showed that bipolar patients had lower changes of EEG theta power after sleep and responders to antidepressant TSD+LT slept less and showed a lower increase of EEG theta power then non-responders. A polymorphism in PER3 gene has been associated with diurnal preference, sleep structure and homeostatic response to sleep deprivation in healthy subjects. We hypothesized that the individual variability in the homeostatic response to TSD could be a correlate of antidepressant response and be influenced by genetic factors. Methods We administered three TSD+LT cycles to bipolar depressed patients. Severity of depression was rated on Hamilton Depression Rating Scale. Actigraphic recordings were performed in a group of patients. Results PER3 polymorphism influenced changes in total sleep time ( F =2.24; p =0.024): while PER34/4 and PER34/5 patients showed a reduction in it after treatment, PER35/5 subjects showed an increase of about 40 min, suggesting a higher homeostatic pressure. The same polymorphism influenced the change of depressive symptomatology during treatment ( F =3.72; p =0.028). Limitations Sleep information was recorded till the day after the end of treatment: a longer period of observation could give more information about the possible maintenance of allostatic adaptation. Conclusions A higher sleep homeostatic pressure reduced the antidepressant response to TSD+LT, while an allostatic adaptation to sleep loss was associated with better response. This process seems to be under genetic control.
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