Tianeptine modulates synaptic vesicle dynamics and favors synaptic mitochondria processes in socially isolated rats.

Deregulation of synaptic function and neurotransmission has been linked with the development of major depression disorder (MDD). Tianeptine (Tian) has been used as antidepressant with anxiolytic properties and recently as a nootropic to improve cognitive performance, but its mechanism of action is unknown. We conducted a proteomic study on the hippocampal synaptosomal fractions of adult male Wistar rats exposed to chronic social isolation (CSIS, 6 weeks), an animal model of depression and after chronic Tian treatment in controls (nootropic effect) and CSIS-exposed rats (lasting 3 weeks of 6-week CSIS) (therapeutic effect). Increased expression of Syn1 and Camk2-related neurotransmission, vesicle transport and energy processes in Tian-treated controls were found. CSIS led to upregulation of proteins associated with actin cytoskeleton, signaling transduction and glucose metabolism. In CSIS rats, Tian up-regulated proteins involved in mitochondrial energy production, mitochondrial transport and dynamics, antioxidative defense and glutamate clearance, while attenuating the CSIS-increased glycolytic pathway and cytoskeleton organization proteins expression and decreased the expression of proteins involved in V-ATPase and vesicle endocytosis. Our overall findings revealed that synaptic vesicle dynamics, specifically exocytosis, and mitochondria-related energy processes might be key biological pathways modulated by the effective nootropic and antidepressant treatment with Tian and be a potential target for therapeutic efficacy of the stress-related mood disorders.

Emerging Benefits: Pathophysiological Functions and Target Drugs of the Sigma-1 Receptor in Neurodegenerative Diseases.

The sigma-1 receptor (Sig-1R) is encoded by the SIGMAR1 gene and is a nonopioid transmembrane receptor located in the mitochondrial-associated endoplasmic reticulum membrane (MAM). It helps to locate endoplasmic reticulum calcium channels, regulates calcium homeostasis, and acts as a molecular chaperone to control cell fate and participate in signal transduction. It plays an important role in protecting neurons through a variety of signaling pathways and participates in the regulation of cognition and motor behavior closely related to neurodegenerative diseases. Based on its neuroprotective effects, Sig-1R has now become a breakthrough target for alleviating Alzheimer's disease and other neurodegenerative diseases. This article reviews the most cutting-edge research on the function of Sig-1R under normal or pathologic conditions and target drugs of the sigma-1 receptor in neurodegenerative diseases.

The Current Evidence Levels for Biofeedback and Neurofeedback Interventions in Treating Depression: A Narrative Review.

This article is aimed at showing the current level of evidence for the usage of biofeedback and neurofeedback to treat depression along with a detailed review of the studies in the field and a discussion of rationale for utilizing each protocol. La Vaque et al. criteria endorsed by the Association for Applied Psychophysiology and Biofeedback and International Society for Neuroregulation & Research were accepted as a means of study evaluation. Heart rate variability (HRV) biofeedback was found to be moderately supportable as a treatment of MDD while outcome measure was a subjective questionnaire like Beck Depression Inventory (level 3/5, "probably efficacious"). Electroencephalographic (EEG) neurofeedback protocols, namely, alpha-theta, alpha, and sensorimotor rhythm upregulation, all qualify for level 2/5, "possibly efficacious." Frontal alpha asymmetry protocol also received limited evidence of effect in depression (level 2/5, "possibly efficacious"). Finally, the two most influential real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback protocols targeting the amygdala and the frontal cortices both demonstrate some effectiveness, though lack replications (level 2/5, "possibly efficacious"). Thus, neurofeedback specifically targeting depression is moderately supported by existing studies (all fit level 2/5, "possibly efficacious"). The greatest complication preventing certain protocols from reaching higher evidence levels is a relatively high number of uncontrolled studies and an absence of accurate replications arising from the heterogeneity in protocol details, course lengths, measures of improvement, control conditions, and sample characteristics.

Light-sensitive circuits related to emotional processing underlie the antidepressant neural targets of light therapy.

Since Aaron Beck proposed his cognitive model of depression, biased attention, biased processing, and biased rumination (different phases of biased cognition) have been considered as the key elements consistently linked with depression. Increasing evidence suggests that the functional failures in the "emotional processing system (EPS)" underlie the neurological foundation of the biased cognition of depression. Light therapy, a non-intrusive approach, exerts powerful effects on emotion and cognition and affects the activity, functional connectivity, and plasticity of multiple brain structures. Although numerous studies have reported its effectiveness in treating depression, the findings have not been integrated with Beck's cognitive model and EPS, and the neurobiological mechanisms of antidepressant light therapy remain largely unknown. In this review, integrated with the classical theories of Beck's cognitive model of depression and EPS, we identified the key neural circuits and abnormalities involved in the cognitive bias of depression and, accordingly, identified and depicted several light-sensitive circuits (LSCs, neural circuits in the EPS that are responsive to light stimulation) that may underlie the antidepressant neural targets of light therapy, as listed below: In summary, the LSCs above narrow down the research scope of identifying the neural targets of antidepressant light therapy and help elucidate the neuropsychological mechanism of antidepressant light therapy.

Applications of Acupuncture Therapy in Modulating the Plasticity of Neurodegenerative Disease and Depression: Do MicroRNA and Neurotrophin BDNF Shed Light on the Underlying Mechanism?

As the global population ages, the incidence of neurodegenerative diseases has risen. Furthermore, it has been suggested that depression, especially in elderly people, may also be an indication of latent neurodegeneration. Stroke, Alzheimer's disease (AD), and Parkinson's disease (PD) are usually accompanied by depression. The urgent challenge is further enforced by psychiatric comorbid conditions, particularly the feeling of despair in these patients. Fortunately, as our understanding of the neurobiological substrates of maladies affecting the central nervous system (CNS) has increased, more therapeutic options and novel potential biological mechanisms have been presented: (1) Neurodegenerative diseases share some similarities in their pathological characteristics, including changes in neuron structure or function and neuronal plasticity. (2) MicroRNAs (miRNAs) are small noncoding RNAs that contribute to the pathogenesis of diverse neurological disease. (3) One ubiquitous neurotrophin, brain-derived neurotrophic factor (BDNF), is crucial for the development of the nervous system. Accumulating data have indicated that miRNAs not only are related to BDNF regulation but also can directly bind with the 3'-UTR of BDNF to regulate BDNF and participate in neuroplasticity. In this short review, we present evidence of shared biological substrates among stroke, AD, PD, and depression and summarize the possible influencing mechanisms of acupuncture on the neuroplasticity of these diseases. We discuss neuroplasticity underscored by the roles of miRNAs and BDNF, which might further reveal the potential biological mechanism of neurodegenerative diseases and depression by acupuncture.

Role of Yoga and Meditation as Complimentary Therapeutic Regime for Stress-Related Neuropsychiatric Disorders: Utilization of Brain Waves Activity as Novel Tool.

During recent decades, stress-related neuropsychiatric disorders such as anxiety, depression, chronic tension headache, and migraine have established their stronghold in the lives of a vast number of people worldwide. In order to address this global phenomenon, intensive studies have been carried out leading to the advancement of drugs like anti-depressants, anxiolytics, and analgesics which although help in combating the symptoms of such disorders but also create long-term side effects. Thus, as an alternative to such clinical practices, various complementary therapies such as yoga and meditation have been proved to be effective in alleviating the causes and symptoms of different neuropsychiatric disorders. The role of altered brain waves in this context has been recognized and needs to be pursued at the highest level. Thus, the current study provides a review focused on describing the effects of yoga and meditation on anxiety and depression as well as exploring brain waves as a tool for assessing the potential of these complementary therapies for such disorders.

[The effect of multichannel electrostimulation of neck nervous structures on the brain connectivity of patients with depressive disorders]. / Vliianie mnogokanal'noi élektrostimuliatsii nervnykh struktur shei na konnektivnost' golovnogo mozga u patsientov s depressivnym rasstroistvom.

AIM: To study neurophysiological processes during multichannel electrostimulation in patients with depressive disorder. MATERIAL AND METHODS: The study involved 6 patients with depressive disorder (F33). The technology noninvasive multichannel stimulation of neck neural struct SYMPATHOKOR-01 device. Clinical and psychometric methods, functional neuroimaging (fMRTP) and multichannel electroencephalography (EEG) were used to assess treatment effect. RESULTS: In all patients, fMRTP and EEG results show the disturbances of brain connectivity, which are correlated with the clinical state of the disease, before treatment. After five stimulation procedures, there is an increase in functional connection of the medial prefrontal cortex (according to rs-fMRI results) and an increase in the synchronization of various parts of the cortex (EEG results). CONCLUSION: The results demonstrate the possibilities of multichannel electrical stimulation of the neck nervous structures to restore the intracerebral connections disturbed during depression due to the activation of neuroplasticity.

Common and specific dimensions of internalizing disorders are characterized by unique patterns of brain activity on a task of emotional cognitive control.

Alterations in neural systems underlying cognitive control are well-documented across individuals with various internalizing disorders. The current study examined how individual differences in underlying traits related to internalizing disorders influence brain activation, as assessed by fMRI, when cognitive control must be exerted to make a decision about the emotional valence (positive, negative) of a task-relevant word displayed concurrently with a task-irrelevant emotional face. Taking a bi-factor model approach, fifty-five middle-aged female participants were characterized on symptom level on a common internalizing latent factor representing shared symptoms across anxiety and depression, as well as on specific factors remaining after taking the common internalizing factor into account: low positive affect, anxious arousal, and anxious apprehension. Contrasting activation on trials requiring higher vs. lower control revealed that higher levels of the Common Internalizing factor are associated with less deactivation of regions of the default mode network. Higher levels of the Low Positive Affect-specific factor are associated with less differentiation in engagement of portions of the fronto-parietal control network, while higher levels of the Anxious Arousal-specific factor are associated with less of a differentiation in activation of the thalamus. No effects were observed for level of the Anxious Apprehension-specific factor. These results suggest that prior findings of alterations in default mode activity associated with depression may not be specific to depressive symptoms per se but may characterize internalizing symptoms more generally. In addition, they suggest that reduced engagement of cognitive control regions may be more associated with low positive affect than depressive symptoms more generally.

Exploring Differences Among Video Gamers With and Without Depression: Contrasting Emotion Regulation and Mindfulness.

Video games are a leisure activity with mass appeal for individuals of all ages. However, for some individuals, playing video games may become problematic and addictive, resulting in negative consequences affecting their physical, social, and psychological well-being. Internet gaming disorder (IGD) has estimated prevalence rates of around 3 percent and has been strongly associated with several psychopathologies, including depression. Given that emotion regulation (ER) and mindfulness are fluid constructs that can be enhanced, the potential for intervention and prevention is considerable. Thus, this study sought to, as a first step in determining clinical relevance, explore the differences in ER, mindfulness, and impulsivity among emerging adult gamers who met criteria for IGD, depression, or both IGD and depression (Dep + IGD). A sample of 1,536 gamers (45 percent male, Mage = 20.45 years old) completed an online survey, including an assessment for IGD, depression, difficulties with ER, impulsivity, and mindfulness. Relative to individuals below IGD and depression cutoffs (control), the clinical groups (IGD, depression, and Dep + IGD) reported greater ER difficulties, higher impulsivity, and lower mindfulness. Finally, relative to the IGD + depression group, the other two clinical groups had fewer difficulties with cognitive impulsivity, whereas the depression group reported more difficulties with strategy use. These results suggest that gamers should be considered a heterogeneous group and that comorbid disorders are important considerations when developing targeted treatments for individuals with IGD.

Garlic (Allium sativum) improves anxiety- and depressive-related behaviors and brain oxidative stress in diabetic rats.

This study investigated the effects of garlic on anxiety- and depression-related behaviors and brain oxidative markers in streptozotocin (STZ)-induced diabetes in rats. Fifty-six male Wistar rats were randomly divided into seven experimental groups (n = 8/group): control, diabetic + saline, diabetic + garlic, diabetic + imipramine, and diabetic + diazepam groups. Animals received garlic homogenate (0.1, 0.25, and 0.5 g/kg) for 10 days. At the end of the treatments, anxiety- and depressive-related behaviors were evaluated by elevated plus maze (EPM) and forced swimming test (FST), respectively. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and malondialdehyde (MDA) levels were measured in the brain. Diabetic + garlic (0.5 g/kg) group showed lower anxiety- and- depressive-like behaviors as compared to the diabetic rats. Furthermore, garlic treatment (0.5 g/kg) attenuated MDA levels and enhanced SOD and GPx activities in the brain. Our findings indicate that garlic alleviates anxiety- and depression-related behaviors in the diabetic rats possibly by attenuation of brain oxidative stress.

Defining Success in Measurement-Based Care for Depression: A Comparison of Common Metrics.

OBJECTIVE: The National Committee for Quality Assurance recommends response and remission as indicators of successful depression treatment for the Healthcare Effectiveness and Data Information Set. Effect size and severity-adjusted effect size (SAES) offer alternative metrics. This study compared measures and examined the relationship between baseline symptom severity and treatment success. METHODS: Electronic records from two large integrated health systems (Kaiser Permanente Colorado and Washington) were used to identify 5,554 new psychotherapy episodes with a baseline Patient Health Questionnaire (PHQ-9) score of ≥10 and a PHQ-9 follow-up score from 14-180 days after treatment initiation. Treatment success was defined for four measures: response (≥50% reduction in PHQ-9 score), remission (PHQ-9 score <5), effect size ≥0.8, and SAES ≥0.8. Descriptive analyses examined agreement of measures. Logistic regression estimated the association between baseline severity and success on each measure. Sensitivity analyses evaluated the impact of various outcome definitions and loss to follow-up. RESULTS: Effect size ≥0.8 was most frequently attained (72% across sites), followed by SAES ≥0.8 (66%), response (46%), and remission (22%). Response was the only measure not associated with baseline PHQ-9 score. Effect size ≥0.8 favored episodes with a higher baseline PHQ-9 score (odds ratio [OR]=2.3, p<0.001, for 10-point difference in baseline PHQ-9 score), whereas SAES ≥0.8 (OR=0.61, p<0.001) and remission (OR=0.43, p<0.001) favored episodes with lower baseline scores. CONCLUSIONS: Response is preferable for comparing treatment outcomes, because it does not favor more or less baseline symptom severity, indicates clinically meaningful improvement, and is transparent and easy to calculate.

Reduction of PTSD in South African University Students Using Transcendental Meditation Practice.

A study was conducted on South African college students using the Transcendental Meditation technique to reduce posttraumatic stress disorder. Students meeting the criteria for possible posttraumatic stress disorder were included. Thirty-four students at the experimental university in South Africa clinically diagnosed with posttraumatic stress disorder were instructed in and practiced the Transcendental Meditation technique twice daily compared to 34 diagnosed posttraumatic stress disorder comparison students at the comparison university. The multivariate effect was significant for both the posttraumatic stress disorder symptomatology and depression. Results were significantly associated with regularity of practice. The study replicates recent findings and offers an alternative educational treatment for higher education.

White Ginseng Ameliorates Depressive Behavior and Increases Hippocampal 5-HT Level in the Stressed Ovariectomized Rats.

Postmenopausal depression is closely associated with depletion of estrogen which modulates transmission of 5-HT, a key neurotransmitter that regulates stress-managing circuits in the brain. In this study, antidepressive efficacy of white ginseng (Panax gingseng Meyer, WG) was evaluated in stressed ovariectomized rats. Female Sprague Dawley rats were ovariectomized and repeatedly restraint stressed for 2 weeks (2h/day). Thirty minutes before restraint stress, rats were administered saline (control), WG 200 mg/kg (p.o.), WG 400 mg/kg (p.o.), or fluoxetine (PC, 10 mg/kg, i.p.). Tail suspension test (TST) and forced swimming test (FST) were performed to assess antidepressant effect of WG. After behavioral tests, levels of serum corticosterone (CORT) and hippocampal 5-HT were measured. Significant decrease of immobility time in TST and FST was shown in rats administered with PC or WG 400 compared to the control. WG200-treated rats showed remarkable reduction in immobility time of TST. PC, WG 200, or WG 400-administred group exhibited significant reduction of CORT compared to the control. PC or WG-treated rats exhibited remarkable increase in hippocampal 5-HT concentration compared to the control. Hippocampal 5-HT levels in WG groups were higher than those in the PC group. The present study demonstrated that WG had antidepressant efficacy in an animal model of menopausal depression. Treatment with WG enhanced hippocampal 5-HT level while suppressing depressive symptom and serum CORT level. These results provide evidence that WG plays an important role in activating serotonergic neurons in stressful situation, suggesting that WG might be a reliable natural alternative of antidepressant drugs to treat menopausal depression.

Efficacy of a standardised saffron extract (affron®) as an add-on to antidepressant medication for the treatment of persistent depressive symptoms in adults: A randomised, double-blind, placebo-controlled study.

BACKGROUND: As a stand-alone intervention, saffron has efficacy for the treatment of mild-to-moderate depression. However, research as an adjunct agent is limited. AIMS: The effects of saffron as an adjunct to pharmaceutical antidepressants in adults with persistent depression was investigated. METHODS: In this eight-week, randomised, double-blind, placebo-controlled study, adults with persistent depression, currently taking a pharmaceutical antidepressant were given a placebo or a saffron extract (affron®, 14 mg b.i.d.). Primary outcome measures included the clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS) and self-rated MADRS (MADRS-S). Secondary outcome measures included the Antidepressant Side-Effect Checklist (ASEC) and Short Form-36 Health Survey (SF-36). RESULTS: Of the 160 participants enrolled, 139 provided usable data. Based on the MADRS, depressive symptoms decreased more in participants taking saffron compared with a placebo, with reductions of 41 and 21%, respectively (p = 0.001). However, scores on the MADRS-S decreased 27 and 26% in the saffron and placebo conditions, respectively (p = 0.831). Saffron was associated with a greater reduction in adverse effects of antidepressants (p = 0.019), although this was non-significant after covarying for baseline values (p = 0.449). Quality of life improved in both groups with no significant between-group differences (p = 0.638). CONCLUSION: Adjunctive administration of a standardised saffron extract (affron®) for eight weeks was associated with a greater improvement in depressive symptoms as measured by the clinician-rated MADRS but not the self-report MADRS-S. Given the conflicting results, further research is needed to clarify the clinical benefits of saffron as an adjunctive treatment for adults with persistent depressive symptoms despite antidepressant drug treatment.

Frequency of Utilization of Beta Blockers in Patients With Heart Failure and Depression and Their Effect on Mortality.

Beta blockers reduce mortality and morbidity in patients with heart failure. Early reports linking ß-blockers with depression may have limited their use in heart failure patients with co-morbid depression. Although more recent studies have challenged the association between ß-blocker therapy and depression, patient and physicians remain concerned. The goal of this study is to evaluate the utilization and outcomes of ß-blocker therapy in heart failure patients with depression. This is a retrospective cohort study of patients at a multicenter integrated healthcare system with a diagnosis of heart failure from 2008 to 2014. Among 6,915 patients with heart failure with left ventricular ejection fraction of <50%, 1,252 (18.1%) had a diagnosis of depression. Patients with depression were more likely to be women and had a higher prevalence of cardiovascular risk factors. Depression was associated with decreased odds of ß-blocker treatment (adjusted odds ratio [OR], 0.77; 95% confidence interval [CI], 0.62 to 0.95; p = 0.016). During a mean follow-up of 2.6 years, 439 (35.1%) patients with depression died compared with 1,549 (27.4%) patients without depression. Depressed patients not treated with ß-blocker had higher mortality compared with nondepressed patients (adjusted hazard ratio [HR], 1.4, 95% CI 1.09 to 1.7, p = 0.005). When treated with ß-blockers, their risk of mortality was attenuated (HR 1.1, 95% CI 0.97 to 1.2, p = 0.14). In conclusion, ß-blocker therapy remains underutilized in heart failure patients with depression, and its underutilization contributes to the reduced survival rate observed in this cohort.

Sleep, circadian rhythm, and physical activity patterns in depressive and anxiety disorders: A 2-week ambulatory assessment study.

BACKGROUND: Actigraphy may provide a more valid assessment of sleep, circadian rhythm (CR), and physical activity (PA) than self-reported questionnaires, but has not been used widely to study the association with depression/anxiety and their clinical characteristics. METHODS: Fourteen-day actigraphy data of 359 participants with current (n = 93), remitted (n = 176), or no (n = 90) composite international diagnostic interview depression/anxiety diagnoses were obtained from the Netherlands Study of Depression and Anxiety. Objective estimates included sleep duration (SD), sleep efficiency, relative amplitude (RA) between day-time and night-time activity, mid sleep on free days (MSF), gross motor activity (GMA), and moderate-to-vigorous PA (MVPA). Self-reported measures included insomnia rating scale, SD, MSF, metabolic equivalent total, and MVPA. RESULTS: Compared to controls, individuals with current depression/anxiety had a significantly different objective, but not self-reported, PA and CR: lower GMA (23.83 vs. 27.4 milli-gravity/day, p = .022), lower MVPA (35.32 vs. 47.64 min/day, p = .023), lower RA (0.82 vs. 0.83, p = .033). In contrast, self-reported, but not objective, sleep differed between people with current depression/anxiety compared to those without current disorders; people with current depression/anxiety reported both shorter and longer SD and more insomnia. More depressive/anxiety symptoms and number of depressive/anxiety diagnoses were associated with larger disturbances of the actigraphy measures. CONCLUSION: Actigraphy provides ecologically valid information on sleep, CR, and PA that enhances data from self-reported questionnaires. As those with more severe or comorbid forms showed the lowest PA and most CR disruptions, the potential for adjunctive behavioral and chronotherapy interventions should be explored, as well as the potential of actigraphy to monitor treatment response to such interventions.

Anhedonia in depression symptomatology: Appetite dysregulation and defective brain reward processing.

Anhedonia is an elusive symptom in depression symptomatology. The present review frames the notion of anhedonia as reduced ability to experience pleasure and diminished sensitivity to rewarding stimuli such as palatable food or social interaction within the context of appetite dysregulation in depression, addressing the main neural networks involved in the alteration of brain reward processing. This circuit-based framework focuses on selected brain regions such as lateral hypothalamus, ventral pallidum, lateral habenula and mesocorticolimbic target areas such as nucleus accumbens and ventral tegmental area. The examination in particular of the role of dopamine, orexin and GABAergic neurotransmission is complemented by the exploration of the endocannabinoid signaling as homeostatic, anti-stress system and its relevance in depression pathophysiology and anhedonia symptoms.

HCN channel antagonist ZD7288 ameliorates neuropathic pain and associated depression.

Chronic neuropathic pain has demonstrated that coexisting psychiatric disorders are associated with disability and poorer treatment outcomes. Hyperpolarization-activated cyclic nucleotide-gated (HCN, Ih) channels play a major role in pain via hyperexcitability and facilitation of ectopic firing in neurons. Neuronal hyperexcitability contributes to pain maintenance and anxiety/depression. GABA-mediated inhibitory postsynaptic neurotransmission in the brain is impaired in the pathophysiology of chronic neuropathic pain with comorbidity mood disorders. Currently, interaction of HCN channels and GABAergic synaptic transmission inhibition in neuropathic pain and the associated comorbidity anxiety/depression mechanism remains relatively unknown. To address this, the HCN channel inhibitor, ZD7288, was administrated to Wistar Kyoto (WKY) rats after spared nerve injury (SNI). Our findings show that intracerebroventricular injection of ZD7288 concurrently attenuates co-existing nociceptive and depression-like behaviors, and increases glutamicacid decarboxylase (GAD67/65) expression and GABA levels in the hippocampus and thalamus with High-performance liquid chromatography technique. It suggests that inhibition of HCN channels is likely to decrease the hyperexcitability of neurons in rat SNI and improve the level of GABA. Further, HCN channel may offer a new strategy to alleviate both neuropathic pain and comorbidity for depression.

Increased brain entropy of resting-state fMRI mediates the relationship between depression severity and mental health-related quality of life in late-life depressed elderly.

BACKGROUND: Entropy analysis is a computational method used to quantify the complexity in a system, and loss of brain complexity is hypothesized to be related to mental disorders. Here, we applied entropy analysis to the resting-state functional magnetic resonance imaging (rs-fMRI) signal in subjects with late-life depression (LLD), an illness combined with emotion dysregulation and aging effect. METHODS: A total of 35 unremitted depressed elderly and 22 control subjects were recruited. Multiscale entropy (MSE) analysis was performed in the entire brain, 90 automated anatomical labeling-parcellated ROIs, and five resting networks in each study participant. LIMITATIONS: Due to ethical concerns, all the participants were under medication during the study. RESULTS: Regionally, subjects with LLD showed decreased entropy only in the right posterior cingulate gyrus but had universally increased entropy in affective processing (putamen and thalamus), sensory, motor, and temporal nodes across different time scales. We also found higher entropy in the left frontoparietal network (FPN), which partially mediated the negative correlation between depression severity and mental components of the quality of life, reflecting the possible neural compensation during depression treatment. CONCLUSION: MSE provides a novel and complementary approach in rs-fMRI analysis. The temporal-spatial complexity in the resting brain may provide the adaptive variability beneficial for the elderly with depression.

Treating Circadian Rhythm Disruption in Bipolar Disorder.

PURPOSE OF REVIEW: Disruptions in circadian rhythms are believed to underlie the illness course of bipolar disorder (BD). This review evaluates recent studies on the treatment of circadian dysfunction in BD. RECENT FINDINGS: Targeted social rhythm therapy may be useful for bipolar depression though some studies suggest that a non-targeted psychosocial or pharmacological intervention may be just as efficacious. Lithium holds potential for addressing circadian dysfunction in BD. Blue-blocking therapy may be useful for mania and midday bright light therapy may relieve depression. CONCLUSIONS: Psychosocial, pharmacological, and light-based approaches are promising avenues for treating circadian dysfunction in BD.