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

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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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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Cytomegalovirus and the Brain

PEDIATRICS ◽

10.1542/peds.79.5.841 ◽

1987 ◽

Vol 79 (5) ◽

pp. 841-841

Author(s):

THOMAS J. CONBOY ◽

ROBERT F. PASS ◽

THOMAS J. BOLL

Keyword(s):

Hearing Loss ◽

Sample Size ◽

Small Sample Size ◽

Normal Hearing ◽

Small Sample ◽

Intellectual Impairment ◽

Intellectual Performance ◽

Asymptomatic Children ◽

The Brain

In Reply.— We agree with Ades et al that our study1 was not definitive in ruling out the possibility of intellectual impairment in children born with asymptomatic cytomegalovirus and said as much in our discussion, mentioning the relatively small sample size as one of several caveats. It is important to note that our study included only asymptomatic children with normal hearing in order not to confound the effects of hearing loss on intellectual performance with possible effects of the virus.

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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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Role of MicroRNAs in Parkinson’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms20225649 ◽

2019 ◽

Vol 20 (22) ◽

pp. 5649 ◽

Cited By ~ 20

Author(s):

Suh Yee Goh ◽

Yin Xia Chao ◽

Shaikali Thameem Dheen ◽

Eng-King Tan ◽

Samuel Sam-Wah Tay

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Small Sample Size ◽

Small Sample ◽

Biological Molecules ◽

Incomplete Penetrance ◽

Cellular Functions ◽

Druggable Targets ◽

The Brain

Parkinson’s disease (PD) is a disabling neurodegenerative disease that manifests with resting tremor, bradykinesia, rigidity and postural instability. Since the discovery of microRNAs (miRNAs) in 1993, miRNAs have been shown to be important biological molecules involved in diverse processes to maintain normal cellular functions. Over the past decade, many studies have reported dysregulation of miRNA expressions in PD. Here, we identified 15 miRNAs from 34 reported screening studies that demonstrated dysregulation in the brain and/or neuronal models, cerebrospinal fluid (CSF) and blood. Specific miRNAs-of-interest that have been implicated in PD pathogenesis include miR-30, miR-29, let-7, miR-485 and miR-26. However, there are several challenges and limitations in drawing definitive conclusions due to the small sample size in clinical studies, varied laboratory techniques and methodologies and their incomplete penetrance of the blood–brain barrier. Developing an optimal delivery system and unravelling druggable targets of miRNAs in both experimental and human models and clinical validation of the results may pave way for novel therapeutics in PD.

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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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Epidemiology of psoriatic arthritis

10.1093/med/9780198737582.003.0003 ◽

2018 ◽

Author(s):

Elaine Husni ◽

Madonna Michael

Keyword(s):

Psoriatic Arthritis ◽

Primary Care Physicians ◽

Small Sample Size ◽

Epidemiological Studies ◽

Case Definition ◽

Small Sample ◽

Contributing Factors ◽

Wide Range ◽

And Gender ◽

High Level

The epidemiological studies of psoriatic arthritis (PsA) is quite challenging as our understanding of the disease is evolving. A wide range of incidence and prevalence is reported among different countries suggesting genetic and environmental factors influencing the epidemiology of PsA. Other contributing factors accounting for the wide range and variation of PsA epidemiology include age and gender variations, ethnicity, lack of precise case definition, and small sample size. A high level of suspicion in patients with pre-existing psoriasis, and collaborative efforts shared between primary care physicians (PCP), dermatologist, and rheumatologist, will enhance early detection and management of PsA, subsequently improving overall patient outcomes, and quality of life.

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Digital biomarkers from geolocation data in bipolar disorder and schizophrenia: a systematic review

Journal of the American Medical Informatics Association ◽

10.1093/jamia/ocz043 ◽

2019 ◽

Vol 26 (11) ◽

pp. 1412-1420 ◽

Cited By ~ 5

Author(s):

Paolo Fraccaro ◽

Anna Beukenhorst ◽

Matthew Sperrin ◽

Simon Harper ◽

Jasper Palmier-Claus ◽

...

Keyword(s):

Bipolar Disorder ◽

Mobile Communications ◽

Continuous Monitoring ◽

Data Extraction ◽

Small Sample ◽

Clinical Aspects ◽

Accelerometer Data ◽

Other Information ◽

Digital Biomarkers

Abstract Objective The study sought to explore to what extent geolocation data has been used to study serious mental illness (SMI). SMIs such as bipolar disorder and schizophrenia are characterized by fluctuating symptoms and sudden relapse. Currently, monitoring of people with an SMI is largely done through face-to-face visits. Smartphone-based geolocation sensors create opportunities for continuous monitoring and early intervention. Materials and Methods We searched MEDLINE, PsycINFO, and Scopus by combining terms related to geolocation and smartphones with SMI concepts. Study selection and data extraction were done in duplicate. Results Eighteen publications describing 16 studies were included in our review. Eleven studies focused on bipolar disorder. Common geolocation-derived digital biomarkers were number of locations visited (n = 8), distance traveled (n = 8), time spent at prespecified locations (n = 7), and number of changes in GSM (Global System for Mobile communications) cell (n = 4). Twelve of 14 publications evaluating clinical aspects found an association between geolocation-derived digital biomarker and SMI concepts, especially mood. Geolocation-derived digital biomarkers were more strongly associated with SMI concepts than other information (eg, accelerometer data, smartphone activity, self-reported symptoms). However, small sample sizes and short follow-up warrant cautious interpretation of these findings: of all included studies, 7 had a sample of fewer than 10 patients and 11 had a duration shorter than 12 weeks. Conclusions The growing body of evidence for the association between SMI concepts and geolocation-derived digital biomarkers shows potential for this instrument to be used for continuous monitoring of patients in their everyday lives, but there is a need for larger studies with longer follow-up times.

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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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Network-level functional topological changes after mindfulness-based cognitive therapy in mood dysregulated adolescents at familial risk for bipolar disorder: a pilot study

BMC Psychiatry ◽

10.1186/s12888-021-03211-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Kun Qin ◽

Du Lei ◽

Jing Yang ◽

Wenbin Li ◽

Maxwell J. Tallman ◽

...

Keyword(s):

Bipolar Disorder ◽

Emotion Regulation ◽

Cognitive Therapy ◽

Path Length ◽

Small Sample Size ◽

Functional Integration ◽

Familial Risk ◽

Small Sample ◽

Adverse Outcomes ◽

Characteristic Path Length

Abstract Background Given that psychopharmacological approaches routinely used to treat mood-related problems may result in adverse outcomes in mood dysregulated adolescents at familial risk for bipolar disorder (BD), Mindfulness-Based Cognitive Therapy for Children (MBCT-C) provides an alternative effective and safe option. However, little is known about the brain mechanisms of beneficial outcomes from this intervention. Herein, we aimed to investigate the network-level neurofunctional effects of MBCT-C in mood dysregulated adolescents. Methods Ten mood dysregulated adolescents at familial risk for BD underwent a 12-week MBCT-C intervention. Resting-state functional magnetic resonance imaging (fMRI) was performed prior to and following MBCT-C. Topological metrics of three intrinsic functional networks (default mode network (DMN), fronto-parietal network (FPN) and cingulo-opercular network (CON)) were investigated respectively using graph theory analysis. Results Following MBCT-C, mood dysregulated adolescents showed increased global efficiency and decreased characteristic path length within both CON and FPN. Enhanced functional connectivity strength of frontal and limbic areas were identified within the DMN and CON. Moreover, change in characteristic path length within the CON was suggested to be significantly related to change in the Emotion Regulation Checklist score. Conclusions 12-week MBCT-C treatment in mood dysregulated adolescents at familial risk for BD yield network-level neurofunctional effects within the FPN and CON, suggesting enhanced functional integration of the dual-network. Decreased characteristic path length of the CON may be associated with the improvement of emotion regulation following mindfulness training. However, current findings derived from small sample size should be interpreted with caution. Future randomized controlled trials including larger samples are critical to validate our findings.

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Do children with mental disorders have higher prevalence of hypovitaminosis D?

F1000Research ◽

10.12688/f1000research.2-159.v1 ◽

2013 ◽

Vol 2 ◽

pp. 159 ◽

Cited By ~ 4

Author(s):

Mini Zhang ◽

Keith Cheng ◽

Robert Rope ◽

Elizabeth Martin ◽

Ajit Jetmalani

Keyword(s):

Vitamin D ◽

Mental Disorders ◽

Sample Size ◽

Psychiatric Disorders ◽

Psychiatric Symptoms ◽

Small Sample Size ◽

Hypovitaminosis D ◽

Small Sample ◽

Diagnostic Categories ◽

Significant Difference

Inadequate vitamin D level is associated with various adverse medical outcomes. There is a growing concern that insufficient vitamin D may play a role in the development of psychiatric symptoms. This study aims to answer the question: do children with mental disorders have a higher prevalence of hypovitaminosis D? A retrospective chart review examined 25 hydroxyvitamin D (25(OH)D) levels in youth ages 7 to 17 (n=67) at two Oregon psychiatric residential facilities. Vitamin D deficiency is defined as <20 ng/ml and insufficiency as <30 ng/ml. Diagnoses were organized into six categories. 25(OH)D levels were compared across genders and diagnostic groups using a two-sample t-test and ANOVA, respectively. Statistical differences in prevalence across diagnostic categories were calculated using a Pearson chi-square test. Using the data from Saintonge’s NHANES III study on healthy US children for comparison, 21% of our cohorts were found to be vitamin D deficient and 64% insufficient, in contrast to 14% and 48%, respectively. While our results are not statistically significant, mainly because of small sample size, the overall mean 25(OH)D level in our cohort was insufficient (27.59 ± 9.35 ng/ml), compared to a sufficient mean value of 32.1 ng/ml in the general population. No statistical significant difference was found in the prevalence across diagnostic categories. This study found that children with psychiatric disorders might have a higher prevalence of hypovitaminosis D than the general pediatric population. Although a causal relationship between hypovitaminosis D and psychiatric disorders cannot be derived based on the study design, our study provides initial descriptive data on the prevalence of hypovitaminosis D in children with psychiatric disorders, which has not been previously reported to our knowledge. Prospective studies with a larger sample size and controlled variables would allow more precise analysis of the relationship between hypovitaminosis D and childhood mental disorders.

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