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Human Genomics Mar 2024Hemorrhoids and psychiatric disorders exhibit high prevalence rates and a tendency for relapse in epidemiological studies. Despite this, limited research has explored...
BACKGROUND
Hemorrhoids and psychiatric disorders exhibit high prevalence rates and a tendency for relapse in epidemiological studies. Despite this, limited research has explored their correlation, and these studies are often subject to reverse causality and residual confounding. We conducted a Mendelian randomization (MR) analysis to comprehensively investigate the association between several mental illnesses and hemorrhoidal disease.
METHODS
Genetic associations for four psychiatric disorders and hemorrhoidal disease were obtained from large consortia, the FinnGen study, and the UK Biobank. Genetic variants associated with depression, bipolar disorder, anxiety disorders, schizophrenia, and hemorrhoidal disease at the genome-wide significance level were selected as instrumental variables. Screening for potential confounders in genetic instrumental variables using PhenoScanner V2. Bidirectional MR estimates were employed to assess the effects of four psychiatric disorders on hemorrhoidal disease.
RESULTS
Our analysis revealed a significant association between genetically predicted depression and the risk of hemorrhoidal disease (IVW, OR=1.20,95% CI=1.09 to 1.33, P <0.001). We found no evidence of associations between bipolar disorder, anxiety disorders, schizophrenia, and hemorrhoidal disease. Inverse MR analysis provided evidence for a significant association between genetically predicted hemorrhoidal disease and depression (IVW, OR=1.07,95% CI=1.04 to 1.11, P <0.001).
CONCLUSIONS
This study offers MR evidence supporting a bidirectional causal relationship between depression and hemorrhoidal disease.
Topics: Humans; Bipolar Disorder; Schizophrenia; Hemorrhoids; Mendelian Randomization Analysis; Anxiety Disorders; Genome-Wide Association Study
PubMed: 38509615
DOI: 10.1186/s40246-024-00588-7 -
Molecular Psychiatry Dec 2023Differential diagnosis is sometimes difficult in practical psychiatric settings, in terms of using the current diagnostic system based on presenting symptoms and signs....
Differential diagnosis is sometimes difficult in practical psychiatric settings, in terms of using the current diagnostic system based on presenting symptoms and signs. The creation of a novel diagnostic system using objective biomarkers is expected to take place. Neuroimaging studies and others reported that subcortical brain structures are the hubs for various psycho-behavioral functions, while there are so far no neuroimaging data-driven clinical criteria overcoming limitations of the current diagnostic system, which would reflect cognitive/social functioning. Prior to the main analysis, we conducted a large-scale multisite study of subcortical volumetric and lateralization alterations in schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder using T1-weighted images of 5604 subjects (3078 controls and 2526 patients). We demonstrated larger lateral ventricles volume in schizophrenia, bipolar disorder, and major depressive disorder, smaller hippocampus volume in schizophrenia and bipolar disorder, and schizophrenia-specific smaller amygdala, thalamus, and accumbens volumes and larger caudate, putamen, and pallidum volumes. In addition, we observed a leftward alteration of lateralization for pallidum volume specifically in schizophrenia. Moreover, as our main objective, we clustered the 5,604 subjects based on subcortical volumes, and explored whether data-driven clustering results can explain cognitive/social functioning in the subcohorts. We showed a four-biotype classification, namely extremely (Brain Biotype [BB] 1) and moderately smaller limbic regions (BB2), larger basal ganglia (BB3), and normal volumes (BB4), being associated with cognitive/social functioning. Specifically, BB1 and BB2-3 were associated with severe and mild cognitive/social impairment, respectively, while BB4 was characterized by normal cognitive/social functioning. Our results may lead to the future creation of novel biological data-driven psychiatric diagnostic criteria, which may be expected to be useful for prediction or therapeutic selection.
Topics: Humans; Schizophrenia; Depressive Disorder, Major; Bipolar Disorder; Female; Male; Magnetic Resonance Imaging; Adult; Neuroimaging; Brain; Autism Spectrum Disorder; Middle Aged; Mental Disorders; Organ Size
PubMed: 37537281
DOI: 10.1038/s41380-023-02141-9 -
European Review For Medical and... Oct 2023Bipolar disorder (manic episode) is an essential psychiatric disorder with unknown etiology, in which inflammation is considered to play a role. Klotho and FGF-23 are...
OBJECTIVE
Bipolar disorder (manic episode) is an essential psychiatric disorder with unknown etiology, in which inflammation is considered to play a role. Klotho and FGF-23 are known to be associated with inflammation. Therefore, this study aimed to determine the link between Klotho and FGF-23 levels and bipolar disorder.
PATIENTS AND METHODS
In this study, 42 men with BD and 41 healthy controls were enrolled, followed up, and/or treated at the High-Security Forensic Psychiatry Clinic. Sociodemographic data form, Young Mania Rating Scale, and Hamilton Depression Rating Scale were applied to all participants.
RESULTS
Klotho and FGF-23 levels were significantly increased in patients with BD manic episodes. There was no correlation between Klotho and FGF-23 levels and clinical parameters. For Klotho and FGF-23, cutoff values of 69 and 1,646 yielded 67.4% sensitivity and 72.1% specificity and 81.4% sensitivity and 51.2% specificity, respectively.
CONCLUSIONS
Klotho and FGF-23 may play critical roles in the etiopathology of manic episodes and are potential candidate biomarkers for bipolar disorder. This relationship might contribute to the etiopathogenesis of the disease and determine its treatment. Anti-Klotho and anti-FGF-23 administration may be a future treatment for controlling the course of the disease.
Topics: Male; Humans; Bipolar Disorder; Mania; Inflammation
PubMed: 37869955
DOI: 10.26355/eurrev_202310_34078 -
Journal of Affective Disorders Oct 2023Antipsychotic medications are increasingly used for difficult-to-treat depression in young people. However, the evidence-base for this is unclear. Our aim was to assess... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antipsychotic medications are increasingly used for difficult-to-treat depression in young people. However, the evidence-base for this is unclear. Our aim was to assess the evidence for the efficacy of atypical antipsychotics in treating unipolar and bipolar depression in adolescents and young adults.
METHOD
We conducted a comprehensive systematic review and meta-analysis of randomized-control-trial studies (RCTs) of antipsychotic medications for 10- to 25-year-olds with unipolar and bipolar depression. The primary outcome of interest was change in depressive symptoms from baseline to trial endpoint.
RESULTS
No studies were identified that evaluated the use of antipsychotics in the treatment of unipolar depression. However, we identified four studies, of quetiapine, lurasidone and olanzapine/fluoxetine combination, comprising a total of 866 randomized patients, that evaluated treatment of bipolar depression. All studies used the Children's Depression Rating Scale-Revised (CDRS-R). Our meta-analysis revealed the weighted mean difference (WMD) was -4.58 (95 % CI, -6.59 to -2.57) between antipsychotic and placebo-treated groups. Response and remission rates were also significantly in favor of antipsychotic treatment.
LIMITATIONS
There were few studies, several did not address risk-of-bias domains and there was a lack of non-industry sponsored studies.
CONCLUSION
There is an absence of evidence for the use of antipsychotic medications in treatment of youth unipolar depression, and no recommendations can be made. There is some evidence for the efficacy of antipsychotics, specifically lurasidone and olanzapine/fluoxetine combination, in the treatment of young people with bipolar depression. However, this evidence is limited and more studies investigating the use of these medications in young people are needed.
Topics: Child; Adolescent; Young Adult; Humans; Antipsychotic Agents; Bipolar Disorder; Fluoxetine; Olanzapine; Lurasidone Hydrochloride
PubMed: 37467794
DOI: 10.1016/j.jad.2023.07.082 -
European Neuropsychopharmacology : the... Jul 2023The treatment of bipolar depression is one of the most challenging needs in contemporary psychiatry. Currently, only quetiapine, olanzapine-fluoxetine combination,... (Review)
Review
The treatment of bipolar depression is one of the most challenging needs in contemporary psychiatry. Currently, only quetiapine, olanzapine-fluoxetine combination, lurasidone, cariprazine, and recently lumateperone have been FDA-approved to treat this condition. The neurobiology of bipolar depression and the possible targets of bipolar antidepressant therapy remain elusive. The current study investigated whether the pharmacodynamic properties of cariprazine fit into a previously developed model which was the first to be derived based on the strict combination of clinical and preclinical data. The authors performed a systematic review of the literature to identify the pharmacodynamic properties of cariprazine. The original model suggests that a constellation of effects on different receptors is necessary and that serotonin reuptake inhibition does not appear to play a significant role in acute bipolar depression. On the contrary, norepinephrine activity seems to be necessary. Probably the early antidepressant effect can be achieved through an agonistic activity at 5HT-1A and antagonism at alpha1 noradrenergic and 5-HT2A receptors, but the presence of a norepinephrine reuptake inhibition appears essential to sustain it. Overall, the properties of cariprazine fit well the proposed model and add to its validity. A point that needs further clarification is norepinephrine reuptake inhibition which is not yet fully studied for cariprazine.
Topics: Humans; Bipolar Disorder; Antidepressive Agents; Lurasidone Hydrochloride; Norepinephrine; Antipsychotic Agents
PubMed: 37060629
DOI: 10.1016/j.euroneuro.2023.03.009 -
The Primary Care Companion For CNS... Jan 2024The prompt effective treatment of acute agitation among patients with schizophrenia or bipolar disorder can alleviate distressing symptoms for the patient and decrease... (Review)
Review
The prompt effective treatment of acute agitation among patients with schizophrenia or bipolar disorder can alleviate distressing symptoms for the patient and decrease the risk of escalation to aggression and the potential for serious harm to the patient, health care providers, and others. A commonly used approach for the management of acute agitation has been the intramuscular administration of antipsychotic medications and/or benzodiazepines. However, US Food and Drug Administration-approved treatments with alternative routes of delivery now include inhaled loxapine powder and, more recently, dexmedetomidine sublingual film. Two formulations of intranasal olanzapine for acute agitation are in development. Intranasal formulations offer the potential for favorable pharmacokinetics and onset of action combined with ease of delivery obviating the need for injections and are thus consistent with patient-centered factors such as preference and self-administration. In this review, alternative methods of medication delivery are discussed, with an emphasis on the potential for intranasal administration to treat acute agitation in adult patients with schizophrenia or bipolar disorder. .
Topics: Adult; Humans; Schizophrenia; Antipsychotic Agents; Bipolar Disorder; Psychomotor Agitation; Loxapine
PubMed: 38301034
DOI: 10.4088/PCC.23nr03596 -
Psychological Medicine Dec 2023People with bipolar disorder (BD) often present emotion dysregulation (ED), a pattern of emotional expression interfering with goal-directed behavior. ED is a... (Meta-Analysis)
Meta-Analysis Review
People with bipolar disorder (BD) often present emotion dysregulation (ED), a pattern of emotional expression interfering with goal-directed behavior. ED is a transdiagnostic construct, and it is unclear whether it manifests itself similarly in other conditions, such as major depressive disorder (MDD) or borderline personality disorder (BPD), or has specific features in BD. The present systematic review and meta-analysis explored ED and adopted emotion regulation (ER) strategies in BD compared with other psychiatric conditions. PubMed/MEDLINE, EMBASE, Scopus, and PsycINFO databases were systematically searched from inception to April 28th, 2022. Studies implementing validated instruments assessing ED or ER strategies in BD and other psychiatric disorders were reviewed, and meta-analyses were conducted. Twenty-nine studies yielding multiple comparisons were included. BD was compared to MDD in 20 studies ( = 2451), to BPD in six studies ( = 1001), to attention deficit hyperactivity disorder in three studies ( = 232), to anxiety disorders in two studies ( = 320), to schizophrenia in one study ( = 223), and to post-traumatic stress disorder in one study ( = 31). BD patients did not differ from MDD patients in adopting most adaptive and maladaptive ER strategies. However, small-to-moderate differences in positive rumination and risk-taking behaviors were observed. In contrast, patients with BPD presented an overall higher degree of ED and more maladaptive ER strategies. There were insufficient data for a meta-analytic comparison with other psychiatric disorders. The present report further supports the idea that ED is a transdiagnostic construct spanning a continuum across different psychiatric disorders, outlining specific clinical features that could represent potential therapeutic targets.
Topics: Humans; Bipolar Disorder; Depressive Disorder, Major; Emotional Regulation; Attention Deficit Disorder with Hyperactivity; Borderline Personality Disorder; Emotions
PubMed: 37842774
DOI: 10.1017/S003329172300243X -
International Journal of Molecular... Jan 2024Bipolar disorder (BD) is a severe and common chronic mental illness characterized by recurrent mood swings between depression and mania. The biological basis of the...
Bipolar disorder (BD) is a severe and common chronic mental illness characterized by recurrent mood swings between depression and mania. The biological basis of the disease is poorly understood, and its treatment is unsatisfactory. Na, K-ATPase is a major plasma membrane transporter and signal transducer. The catalytic α subunit of this enzyme is the binding site for cardiac steroids. Three α isoforms of the Na, K-ATPase are present in the brain. Previous studies have supported the involvement of the Na, K-ATPase and endogenous cardiac steroids (ECS) in the etiology of BD. Decreased brain ECS has been found to elicit anti-manic and anti-depressive-like behaviors in mice and rats. However, the identity of the specific α isoform involved in these behavioral effects is unknown. Here, we demonstrated that decreasing ECS through intracerebroventricular (i.c.v.) administration of anti-ouabain antibodies (anti-Ou-Ab) decreased the activity of α1 mice in forced swimming tests but did not change the activity in wild type (wt) mice. This treatment also affected exploratory and anxiety behaviors in α1 but not wt mice, as measured in open field tests. The i.c.v. administration of anti-Ou-Ab decreased brain ECS and increased brain Na, K-ATPase activity in wt and α1 mice. The serum ECS was lower in α1 than wt mice. In addition, a study in human participants demonstrated that serum ECS significantly decreased after treatment. These results suggest that the Na, K-ATPase α1 isoform is involved in depressive- and manic-like behaviors and support that the Na, K-ATPase/ECS system participates in the etiology of BD.
Topics: Animals; Humans; Mice; Rats; Depression; Ouabain; Protein Isoforms; Sodium-Potassium-Exchanging ATPase; Steroids
PubMed: 38338921
DOI: 10.3390/ijms25031644 -
Journal of Affective Disorders Aug 2023Affective temperaments represent the stable, biologically determined substrates of mood disorders. The relationship between affective temperaments and bipolar disorder... (Observational Study)
Observational Study
BACKGROUND
Affective temperaments represent the stable, biologically determined substrates of mood disorders. The relationship between affective temperaments and bipolar disorder (BD) or major depressive disorder (MDD) has been described. However, the strength of such relationship should be tested while considering other factors influencing the diagnosis of BD/MDD. Literature also lacks a comprehensive description of the interplay between affective temperament and characteristics of mood disorders. The aim of the present study is to address these issues.
METHODS
This is a multicentric observational study including 7 Italian university sites. Five-hundred-fifty-five euthymic subjects with BD/MDD were enrolled and further divided in those with hyperthymic (Hyper, N = 143), cyclothymic (Cyclo, N = 133), irritable (Irr, N = 49), dysthymic (Dysth, N = 155), and anxious (Anx N = 76) temperaments. Linear, binary, ordinal and logistic regressions were performed to assess the association between affective temperaments and i) diagnosis of BD/MDD; ii) characteristics of illness severity and course.
RESULTS
Hyper, Cyclo and Irr were more likely to be associated with BD, together with earlier age of onset and presence of a first-degree relative with BD. Anx and Dysth were more associated with MDD. Differences in association between affective temperaments and characteristics of BD/MDD were observed for hospital admissions, phase-related psychotic symptoms, length and type of depression, comorbidity and pharmacological intake.
LIMITATIONS
Small sample size, cross-sectional design, recall biases.
CONCLUSION
Specific affective temperaments were associated to certain characteristics of illness severity and course of BD or MDD. Evaluation of affective temperaments might help a deeper understanding of mood disorders.
Topics: Humans; Bipolar Disorder; Depressive Disorder, Major; Temperament; Cross-Sectional Studies; Cyclothymic Disorder
PubMed: 37156280
DOI: 10.1016/j.jad.2023.04.130 -
Journal of Nephrology Jul 2023People who have severe mental illness experience higher rates of long-term conditions and die on average 15-20 years earlier than people who do not have severe mental... (Review)
Review
BACKGROUND
People who have severe mental illness experience higher rates of long-term conditions and die on average 15-20 years earlier than people who do not have severe mental illness, a phenomenon known as the mortality gap. Long-term conditions, such as diabetes, impact health outcomes for people who have severe mental illness, however there is limited recognition of the relationship between chronic kidney disease and severe mental illness. Therefore, the aim of this scoping review was to explore the available evidence on the relationship between chronic kidney disease and severe mental illness.
METHODS
Electronic databases, including MEDLINE, Embase, CINAHL, and PsycINFO were searched. The database searches were limited to articles published between January 2000-January 2022, due to significant progress that has been made in the detection, diagnosis and treatment of both SMI and CKD. Articles were eligible for inclusion if they explored the relationship between SMI and CKD (Stages 1-5) in terms of prevalence, risk factors, clinical outcomes, and access to treatment and services. Severe mental illness was defined as conditions that can present with psychosis, including schizophrenia, schizoaffective disorder, bipolar disorder, and other psychotic disorders. Thirty articles were included in the review.
RESULTS
The included studies illustrated that there is an increased risk of chronic kidney disease amongst people who have severe mental illness, compared to those who do not. However, people who have severe mental illness and chronic kidney disease are less likely to receive specialist nephrology care, are less likely to be evaluated for a transplant, and have higher rates of mortality.
CONCLUSION
In conclusion, there is a dearth of literature in this area, but the available literature suggests there are significant health inequalities in kidney care amongst people who have severe mental illness. Further research is needed to understand the factors that contribute to this relationship, and to develop strategies to improve both clinical outcomes and access to kidney care.
Topics: Humans; Mental Disorders; Psychotic Disorders; Schizophrenia; Bipolar Disorder; Renal Insufficiency, Chronic
PubMed: 37029882
DOI: 10.1007/s40620-023-01599-8