Increased Hypocretin (Orexin) Plasma Level in Depression, Bipolar Disorder Patients

As hypocretin can markedly affect neurophysiological and behavioural processes in mood disorders. However, few studies have measured changes in hypocretin levels in patients with mood disorders. We estimated the hypocretin-1 plasma levels in mood disorder patients and controls (CON) using an enzyme-linked immunosorbent assay. Results: (i) The hypocretin-1 plasma level was significantly higher in major depressive disorder (MDD) patients [59.04 (35.78–80.12) pg/ml, P < 0.001] and bipolar disorder (BD) patients [65.50 (58.46–74.57) pg/ml, P < 0.001] patients than in CON [49.25 (28.51–80.40) pg/ml]. Moreover, the plasma hypocretin-1 levels in the BD group were significantly higher than those in the MDD group (P < 0.001). (ii). In the MDD group, patients with higher suicidal ideation had higher hypocretin-1 levels [62.09 (38.23–80.12) pg/ml] than those with lower suicidal ideation [59.63 (35.79–77.37) pg/ml), P = 0.032]. (iii). Plasma hypocretin-1 levels were increased in both female and male mood disorder patients compared to CON [male: MDD 60.51 (35.79–80.12) pg/ml; BD 65.40 (58.76–74.14) pg/ml; CON 45.63 (28.51–62.05) pg/ml; all P < 0.016; female: MDD 57.37 (34.59–80.40) pg/ml; BD 65.61 (58.46–74.57) pg/ml; CON 52.92 (38.23–78.89) pg/ml; all P < 0.015]. (iv). In CON, we found a significant negative correlation between plasma hypocretin-1 levels and age (rho = −0.251, P = 0.032), while this negative correlation was absent in the MDD and BD groups. Limitations may partly arise from the relatively small sample size and the medication history of patients participating in our research. We concluded that the clear changes found in plasma hypocretin-1 levels might be applied in the diagnosis of depression and the differential diagnosis of MDD and BD. The clear suicidal-ideation-related change found in hypocretin-1 levels in depression might be taken into account in the prevention of suicidal behaviour and further study of hypocretin-targeted therapies.

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Thought overactivation as a marker of bipolar disorder

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.547 ◽

2016 ◽

Vol 33 (S1) ◽

pp. s222-s223 ◽

Cited By ~ 2

Author(s):

M. Ferrari ◽

P. Ossola ◽

V. Lucarini ◽

V. Accardi ◽

C. De Panfilis ◽

...

Keyword(s):

Bipolar Disorder ◽

Mood Disorders ◽

Subjective Experience ◽

Small Sample Size ◽

Mental States ◽

Small Sample ◽

Bipolar Spectrum ◽

Global Functioning ◽

Competing Interest ◽

Bipolar Patients

IntroductionRecent studies have underlined the importance of considering the form of thoughts, beyond their content, in order to achieve a better phenomenological comprehension of mental states in mood disorders. The subjective experience of thought overactivation is an important feature of mood disorders that could help in identifying, among patients with a depressive episode, those who belong to the bipolar spectrum.ObjectivesPatients with a diagnosis of bipolar disorder (BD) were compared with matched healthy controls (HC) on a scale that evaluates thought overactivation.AimsValidate the Italian version of a scale for thought overactivation (i.e. STOQ) in a sample of bipolar patients.MethodsThirty euthymic BD and 30 HC completed the Subjective Thought Overactivation Questionnaire (STOQ), the Ruminative Responses Scale (RRS), the Beck Depression Inventory-II (BDI-II) and global functioning (VGF).ResultsThe 9-items version of the STOQ has been back translated and its internal consistency in this sample was satisfactory (alpha = .91). Both the brooding subscore of RRS (b-RRS) (r = .706; P < .001) and STOQ (r = .664; P < .001) correlate significantly with depressive symptoms whereas only the first correlate with VGF (r = –.801; P < .001). The two groups did not differed in the b-RRS (HC = 8.41 vs BD = 9.72; P = .21), whereas BD where significantly higher in the STOQ total score (HC = 6.62 vs. BD = 14.9; P = .007).ConclusionOur results, although limited by the small sample size, confirm the validity of the STOQ and suggest that this scale could grasp a feature characteristic of BD, independently from their tendency to ruminate. The latter seems to impact more on global functioning.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Investigating the Dynamics of Suicidal Ideation

Crisis ◽

10.1027/0227-5910/a000464 ◽

2018 ◽

Vol 39 (1) ◽

pp. 65-69 ◽

Cited By ~ 22

Author(s):

Nina Hallensleben ◽

Lena Spangenberg ◽

Thomas Forkmann ◽

Dajana Rath ◽

Ulrich Hegerl ◽

...

Keyword(s):

Suicidal Ideation ◽

Small Sample Size ◽

Unipolar Depression ◽

Small Sample ◽

History Of ◽

Severity Of Depression ◽

Ecological Momentary ◽

Depressive Episodes ◽

Ema Method ◽

Shed Light

Abstract. Background: Although the fluctuating nature of suicidal ideation (SI) has been described previously, longitudinal studies investigating the dynamics of SI are scarce. Aim: To demonstrate the fluctuation of SI across 6 days and up to 60 measurement points using smartphone-based ecological momentary assessments (EMA). Method: Twenty inpatients with unipolar depression and current and/or lifetime suicidal ideation rated their momentary SI 10 times per day over a 6-day period. Mean squared successive difference (MSSD) was calculated as a measure of variability. Correlations of MSSD with severity of depression, number of previous depressive episodes, and history of suicidal behavior were examined. Results: Individual trajectories of SI are shown to illustrate fluctuation. MSSD values ranged from 0.2 to 21.7. No significant correlations of MSSD with several clinical parameters were found, but there are hints of associations between fluctuation of SI and severity of depression and suicidality. Limitations: Main limitation of this study is the small sample size leading to low power and probably missing potential effects. Further research with larger samples is necessary to shed light on the dynamics of SI. Conclusion: The results illustrate the dynamic nature and the diversity of trajectories of SI across 6 days in psychiatric inpatients with unipolar depression. Prediction of the fluctuation of SI might be of high clinical relevance. Further research using EMA and sophisticated analyses with larger samples is necessary to shed light on the dynamics of SI.

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Longitudinal assessment of S100B serum levels and clinical factors in youth patients with mood disorders

Scientific Reports ◽

10.1038/s41598-021-91577-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Aleksandra Rajewska-Rager ◽

Monika Dmitrzak-Weglarz ◽

Pawel Kapelski ◽

Natalia Lepczynska ◽

Joanna Pawlak ◽

...

Keyword(s):

Mood Disorders ◽

Calcium Binding ◽

Clinical Symptoms ◽

Small Sample Size ◽

Serum Levels ◽

Small Sample ◽

Drop Out ◽

Control Group ◽

Longitudinal Assessment ◽

Depressed Group

AbstractMood disorders have been discussed as being in relation to glial pathology. S100B is a calcium-binding protein, and a marker of glial dysfunctions. Although alterations in the S100B expression may play a role in various central nervous system diseases, there are no studies on the potential role of S100B in mood disorders in adolescents and young adults . In a prospective two-year follow-up study, peripheral levels of S100B were investigated in 79 adolescent/young adult patients (aged 14–24 years), diagnosed with mood disorders and compared with 31 healthy control subjects. A comprehensive clinical interview was conducted which focused on clinical symptoms and diagnosis change. The diagnosis was established and verified at each control visit. Serum S100B concentrations were determined. We detected: lower S100B levels in medicated patients, compared with those who were drug-free, and healthy controls; higher S100B levels in a depressed group with a family history of affective disorder; correlations between age and medication status; sex-dependent differences in S100B levels; and lack a of correlation between the severity of depressive or hypo/manic symptoms. The results of our study indicate that S100B might be a trait-dependent rather than a state-dependent marker. Due to the lack of such studies in the youth population, further research should be performed. A relatively small sample size, a lack of exact age-matched control group, a high drop-out rate.

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Dengue Fever and Severe Dengue in Barbados, 2008–2016

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed5020068 ◽

2020 ◽

Vol 5 (2) ◽

pp. 68

Author(s):

Kirk Osmond Douglas ◽

Sudip Kumar Dutta ◽

Byron Martina ◽

Fatih Anfasa ◽

T. Alafia Samuels ◽

...

Keyword(s):

Dengue Virus ◽

Dengue Fever ◽

Small Sample Size ◽

Health Planning ◽

Case Fatality ◽

Small Sample ◽

Severe Dengue ◽

Medical Attention ◽

Enzyme Linked Immunosorbent Assay ◽

Virus Serotype

Analysis of the temporal, seasonal and demographic distribution of dengue virus (DENV) infections in Barbados was conducted using national surveillance data from a total of 3994 confirmed dengue cases. Diagnosis was confirmed either by DENV–specific real time reverse transcriptase polymerase chain reaction (rRT–PCR), or non–structural protein 1 (NS1) antigen or enzyme linked immunosorbent assay (ELISA) tests; a case fatality rate of 0.4% (10/3994) was observed. The dengue fever (DF) prevalence varied from 27.5 to 453.9 cases per 100,000 population among febrile patients who sought medical attention annually. DF cases occurred throughout the year with low level of transmission observed during the dry season (December to June), then increased transmission during rainy season (July to November) peaking in October. Three major dengue epidemics occurred in Barbados during 2010, 2013 and possibly 2016 with an emerging three–year interval. DF prevalence among febrile patients who sought medical attention overall was highest among the 10–19 years old age group. The highest DF hospitalisation prevalence was observed in 2013. Multiple serotypes circulated during the study period and Dengue virus serotype 2 (DENV–2) was the most prevalent serotype during 2010, whilst DENV–1 was the most prevalent serotype in 2013. Two DENV–1 strains from the 2013 DENV epidemic were genetically more closely related to South East Asian strains, than Caribbean or South American strains, and represent the first ever sequencing of DENV strains in Barbados. However, the small sample size (n = 2) limits any meaningful conclusions. DF prevalence was not significantly different between females and males. Public health planning should consider DENV inter–epidemic periodicity, the current COVID–19 pandemic and similar clinical symptomology between DF and COVID–19. The implementation of routine sequencing of DENV strains to obtain critical data can aid in battling DENV epidemics in Barbados.

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Pharmacogenetic Tests in Reducing Accesses to Emergency Services and Days of Hospitalization in Bipolar Disorder: A 2-Year Mirror Analysis

Journal of Personalized Medicine ◽

10.3390/jpm9020022 ◽

2019 ◽

Vol 9 (2) ◽

pp. 22 ◽

Cited By ~ 2

Author(s):

Camilla Callegari ◽

Celeste Isella ◽

Ivano Caselli ◽

Nicola Poloni ◽

Marta Ielmini

Keyword(s):

Bipolar Disorder ◽

Cost Saving ◽

Emergency Services ◽

Small Sample Size ◽

Economic Value ◽

Small Sample ◽

Control Group ◽

First Year ◽

Potential Cost ◽

Related Group

Despite the enormous costs associated to mood disorders’, few studies evaluate potential cost saving from the use of pharmacogenetic tests (PGT). This study compares 12 months before the execution of the PGT versus 12 months after, in terms of number and days of hospitalization and accesses to emergency services, in a sample of 30 patients affected by bipolar disorder. Secondarily, the study gives an economic value to the data based on the diagnosis-related group (DRG). Patients included in the study were required to be aged ≥18 years, sign an informed consent, have a score of Clinical Global Impression item Severity (CGIs) ≥3, and have a discordant therapy compared to the PGT in the 12 months preceding it and a therapy consistent with it for the following 12 months. Cost saving has been evaluated by paired t-tests in a mirror analysis. Statistically significant differences in all the comparisons (p < 0.0001) emerged. Important cost saving emerged after the use of PGT (€148,920 the first year versus €39,048 the following year). Despite the small sample size and lack of a control group in this study, the potential role of PGT in cost saving for the treatment of bipolar disorder treatment emerged. To confirm this result, larger and clinical trials are needed.

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Bipolar Disorder and Comorbid Use of Illicit Substances

Medicina ◽

10.3390/medicina57111256 ◽

2021 ◽

Vol 57 (11) ◽

pp. 1256

Author(s):

Ulrich W. Preuss ◽

Martin Schaefer ◽

Christoph Born ◽

Heinz Grunze

Keyword(s):

Bipolar Disorder ◽

Substance Use ◽

Best Practices ◽

Multidisciplinary Approach ◽

Small Sample Size ◽

Basic Research ◽

Small Sample ◽

Epigenetic Alterations ◽

Open Label ◽

Addictive Disorders

Substance use disorders (SUD) are highly prevalent in bipolar disorder (BD) and significantly affect clinical outcomes. Incidence and management of illicit drug use differ from alcohol use disorders, nicotine use of behavioral addictions. It is not yet clear why people with bipolar disorder are at higher risk of addictive disorders, but recent data suggest common neurobiological and genetic underpinnings and epigenetic alterations. In the absence of specific diagnostic instruments, the clinical interview is conducive for the diagnosis. Treating SUD in bipolar disorder requires a comprehensive and multidisciplinary approach. Most treatment trials focus on single drugs, such as cannabis alone or in combination with alcohol, cocaine, or amphetamines. Synopsis of data provides limited evidence that lithium and valproate are effective for the treatment of mood symptoms in cannabis users and may reduce substance use. Furthermore, the neuroprotective agent citicoline may reduce cocaine consumption in BD subjects. However, many of the available studies had an open-label design and were of modest to small sample size. The very few available psychotherapeutic trials indicate no significant differences in outcomes between BD with or without SUD. Although SUD is one of the most important comorbidities in BD with a significant influence on clinical outcome, there is still a lack both of basic research and clinical trials, allowing for evidence-based and specific best practices.

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Use of paliperidone in bipolar disorder

European Psychiatry ◽

10.1016/s0924-9338(11)72867-x ◽

2011 ◽

Vol 26 (S2) ◽

pp. 1162-1162

Author(s):

M.C. Campos Mangas ◽

M.A. Ruiz Feliu

Keyword(s):

Bipolar Disorder ◽

Partial Response ◽

Mental Health Center ◽

Small Sample Size ◽

Combined Treatment ◽

Small Sample ◽

New Drugs ◽

Response To Treatment ◽

Positive Contribution ◽

Prevention Of Relapse

IntroductionIn recent years have seen significant advances in the treatment of bipolar disorder with the appearance of new drugs such as atypical antipsychotics. However, there is still a therapeutic challenge to effectively cover the prevention of relapse.The appearance of new drugs such as paliperidone with demonstrated successful experience in the field of schizophrenia can expect the use of this drug in usual clinical setting like positive contributionObjectivesThe aim of this study is to evaluate the efficacy and safety results after 6 months of combined treatment with paliperidone in patients diagnosed with bipolar disorderMethodsThis study is an observational retrospective of the effectiveness of paliperidone as adjunctive therapy in a sample of 11 patients with bipolar disorder I treated as outpatients in a mental health center.Paliperidone addiction was caused by lack of efficacy or partial response to treatment. Scundary effects were collected during the study periodResultsIn all cases except two, was added paliperidone because of partial response to the treatment. After six months of treatment only one patient discontinued treatment due to problems of tolerability and another for lack of efficacy. The mean dose of paliperidone used was 5.7 mg / day. The addition of paliperidone significantly improved affective symptomatology.ConclusionsPharmacological treatment combined with paliperidone is effective and quite well tolerated in patients with bipolar disorder. The limitations of our study (small sample size, open study) do need more research and the realization of controlled clinical trials to confirm these findings.

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Ultra-Brief Crisis IPT-A Based Intervention for Suicidal Children and Adolescents (IPT-A-SCI) Pilot Study Results

Frontiers in Psychiatry ◽

10.3389/fpsyt.2020.553422 ◽

2020 ◽

Vol 11 ◽

Author(s):

Liat Haruvi Catalan ◽

Mira Levis Frenk ◽

Ella Adini Spigelman ◽

Yair Engelberg ◽

Shira Barzilay ◽

...

Keyword(s):

Pilot Study ◽

Suicidal Ideation ◽

Children And Adolescents ◽

Crisis Intervention ◽

Mental Health Treatment ◽

Small Sample Size ◽

Age Groups ◽

Small Sample ◽

Preliminary Results ◽

Study Results

In recent years, suicidal behaviors have shown substantial increase worldwide. This trend is also prominent in Israel and has led to a dramatic increase in mental health treatment demand resulting in long wait times and low treatment acceptance rate. To address the critical need in crisis intervention for children and adolescents at suicidal risk we developed an ultra-brief acute crisis intervention, based on Interpersonal Psychotherapy (IPT). IPT is an evidence-based intervention for various psychopathologies among different age groups. The current adaptation of IPT-A is comprised of five weekly sessions, followed by monthly follow-up caring email contacts to the patients and their parents, over a period of 3 months. This paper aims to review the theoretical foundation of this intervention, describe the research design, and present preliminary results of a pilot study. Preliminary Results from our samples of 26 adolescents indicate meaningful trends for both the suicidal ideation (SIQ) and depression (MFQ) outcome measures. Significant interaction was found concerning suicidal ideation but not for depression. Main limitations include small sample size and stratified controls. The treatment appears to be safe, feasible and acceptable and initial results show promising trends to support further study of the approach.

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Epidemiological and clinical aspects will guide the neuroimaging research in bipolar disorder

Epidemiology and Psychiatric Sciences ◽

10.1017/s2045796014000766 ◽

2015 ◽

Vol 24 (2) ◽

pp. 117-120 ◽

Cited By ~ 6

Author(s):

J. Houenou ◽

C. Perlini ◽

P. Brambilla

Keyword(s):

Bipolar Disorder ◽

Emotional Processing ◽

Small Sample Size ◽

Epidemiological Studies ◽

Small Sample ◽

Clinical Aspects ◽

Diagnostic Categories ◽

Parahippocampal Cortex ◽

Magnetic Resonance Imaging Mri ◽

The Brain

Although neurobiological mechanisms of bipolar disorder (BD) are still unclear, neural models of the disease have recently been conceptualised thanks to neuroimaging. Indeed, magnetic resonance imaging (MRI) studies investigating structural and functional connectivity between different areas of the brain suggest an altered prefrontal–limbic coupling leading to disrupted emotional processing in BD, including uncinate fasciculus, amygdala, parahippocampal cortex, cingulate cortex as well corpus callosum. Specifically, these models assume an altered prefrontal control over a hyperactivity of the subcortical limbic structures implicated in automatic emotional processing. This impaired mechanism may finally trigger emotional hyper-reactivity and mood episodes. In this review, we first summarised some key neuroimaging studies on BD. In the second part of the work, we focused on the heterogeneity of the available studies. This variability is partly due to methodological factors (i.e., small sample size) and differences among studies (i.e., MRI acquisition and post-processing analyses) and partly to the clinical heterogeneity of BD. We finally outlined how epidemiological studies should indicate which risk factors and clinical dimensions of BD are relevant to be studied with neuroimaging in order to reduce heterogeneity and go beyond diagnostic categories.

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Temperament as a basic element of bipolar spectrum and subthreshold manifestations

European Psychiatry ◽

10.1016/s0924-9338(11)71925-3 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 215-215

Author(s):

D. Harnic ◽

A. Koukopoulos ◽

M. Mazza ◽

P. Bria

Keyword(s):

Bipolar Disorder ◽

Clinical Practice ◽

Mood Disorder ◽

Mood Disorders ◽

Affective Disorders ◽

Basic Element ◽

Bipolar Spectrum ◽

Everyday Clinical Practice ◽

History Of ◽

Xix Century

ObjectivesTemperament represents one of the basic elements of bipolar spectrum.MethodsA systematic search was undertaken in MEDLINE (from 1977 to 2007) to obtain articles published in English regarding the association of temperament and bipolar disorder. Keywords used were “temperament”, “bipolar disorder”, “assessment”, “bipolar spectrum”, “subthreshold”.ResultsIn opposition to the dichotomic conception which up to the end of XIX century considered mania and depression as two distinct and separate categories, Kraepelin has postulated a psychopathological “continuum” between temperament and affective disorders called “bipolar spectrum”. This concept has been reintroduced in contemporary psychiatry by Akiskal's works. By rebuilding the history of patients affected by bipolar disorder, temperamental traits can be already observed in the pre-morbid period and can also persist during disorder-free intervals.ConclusionsBy interpreting and diagnosing multiple expressions of bipolar spectrum, psychiatrists today are facing one of the most important challenges in everyday clinical practice. The temperamental “dysregulation” is the pathological basis of mood disorders and some temperamental traits in individuals can reflect a predisposition to develop a mood disorder.

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