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International Journal of Bipolar... Jun 2024Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide...
BACKGROUND
Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II.
RESULTS
We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism.
CONCLUSIONS
Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.
PubMed: 38865039
DOI: 10.1186/s40345-024-00341-y -
Open Biology Jun 2024Frontotemporal lobe abnormalities are linked to neuropsychiatric disorders and cognition, but the role of cellular heterogeneity between temporal lobe (TL) and frontal...
Frontotemporal lobe abnormalities are linked to neuropsychiatric disorders and cognition, but the role of cellular heterogeneity between temporal lobe (TL) and frontal lobe (FL) in the vulnerability to genetic risk factors remains to be elucidated. We integrated single-nucleus transcriptome analysis in 'fresh' human FL and TL with genetic susceptibility, gene dysregulation in neuropsychiatric disease and psychoactive drug response data. We show how intrinsic differences between TL and FL contribute to the vulnerability of specific cell types to both genetic risk factors and psychoactive drugs. Neuronal populations, specifically PVALB neurons, were most highly vulnerable to genetic risk factors for psychiatric disease. These psychiatric disease-associated genes were mostly upregulated in the TL, and dysregulated in the brain of patients with obsessive-compulsive disorder, bipolar disorder and schizophrenia. Among these genes, GRIN2A and SLC12A5, implicated in schizophrenia and bipolar disorder, were significantly upregulated in TL PVALB neurons and in psychiatric disease patients' brain. PVALB neurons from the TL were twofold more vulnerable to psychoactive drugs than to genetic risk factors, showing the influence and specificity of frontotemporal lobe differences on cell vulnerabilities. These studies provide a cell type resolved map of the impact of brain regional differences on cell type vulnerabilities in neuropsychiatric disorders.
Topics: Humans; Psychotropic Drugs; Frontal Lobe; Temporal Lobe; Mental Disorders; Neurons; Receptors, N-Methyl-D-Aspartate; Genetic Predisposition to Disease; Gene Expression Profiling; Transcriptome; Gene Expression Regulation; Schizophrenia; Bipolar Disorder
PubMed: 38864245
DOI: 10.1098/rsob.240063 -
BMC Psychiatry Jun 2024Cognitive impairment is a recognized fundamental deficit in individuals diagnosed with schizophrenia (SZ), bipolar II disorder (BD II), and major depressive disorder... (Comparative Study)
Comparative Study
BACKGROUND
Cognitive impairment is a recognized fundamental deficit in individuals diagnosed with schizophrenia (SZ), bipolar II disorder (BD II), and major depressive disorder (MDD), among other psychiatric disorders. However, limited research has compared cognitive function among first-episode drug-naïve individuals with SZ, BD II, or MDD.
METHODS
This study aimed to address this gap by assessing the cognitive performance of 235 participants (40 healthy controls, 58 SZ patients, 72 BD II patients, and 65 MDD patients) using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) before and after 12 weeks of treatment in SZ, BD II, and MDD patients. To clarify, the healthy controls only underwent RBANS testing at baseline, whereas the patient groups were assessed before and after treatment. The severity of symptoms in SZ patients was measured using the Positive and Negative Syndrome Scale (PANSS), and depression in BD II and MDD patients was assessed using the Hamilton Depression Scale-24 items (HAMD-24 items).
RESULTS
Two hundred participants completed the 12-week treatment period, with 35 participants dropping out due to various reasons. This group included 49 SZ patients, 58 BD II patients, and 53 MDD patients. Among SZ patients, significant improvements in immediate and delayed memory were observed after 12 weeks of treatment compared to their initial scores. Similarly, BD II patients showed significant improvement in immediate and delayed memory following treatment. However, there were no significant differences in RBANS scores for MDD patients after 12 weeks of treatment.
CONCLUSIONS
In conclusion, the findings of this study suggest that individuals with BD II and SZ may share similar deficits in cognitive domains. It is important to note that standardized clinical treatment may have varying degrees of effectiveness in improving cognitive function in patients with BD II and SZ, which could potentially alleviate cognitive dysfunction.
Topics: Humans; Depressive Disorder, Major; Male; Female; Bipolar Disorder; Adult; Schizophrenia; Cognitive Dysfunction; Young Adult; Neuropsychological Tests; Antipsychotic Agents; Psychiatric Status Rating Scales; Middle Aged
PubMed: 38862969
DOI: 10.1186/s12888-024-05897-8 -
Scientific Reports Jun 2024The recovery process in bipolar disorder is a subjective and multidimensional experience that seeks to develop new meanings and purposes for living a satisfying life...
The recovery process in bipolar disorder is a subjective and multidimensional experience that seeks to develop new meanings and purposes for living a satisfying life despite the limitations imposed by the disorder. Thus, this qualitative study aimed to explore the perceptions of recovery and the meanings attributed by individuals undergoing treatment for bipolar disorder to the elements considered relevant in this process. Semi-structured interviews with open-ended questions were conducted to explore the experiences and perspectives of recovery in individuals undergoing treatment for bipolar disorder. Grounded Theory was used as the method for qualitative analysis. The study included 26 participants aged between 18 and 65 years. Based on the analysis of participant reports, we identified two main themes: living with the illness and what it means to be in recovery. The perception of recovery is an individual process and can differ from the medical model. Participants suggest that accepting the diagnosis of bipolar disorder and finding meaning in life are essential to their recovery. They also describe how mental health professionals can facilitate or hinder this process. Understanding patients' perceptions can facilitate access to healthcare services and treatment adherence.
Topics: Humans; Bipolar Disorder; Adult; Female; Male; Middle Aged; Grounded Theory; Adolescent; Aged; Young Adult; Qualitative Research
PubMed: 38862539
DOI: 10.1038/s41598-024-61923-5 -
Frontiers in Psychiatry 2024
PubMed: 38859881
DOI: 10.3389/fpsyt.2024.1430990 -
Human Genomics Jun 2024Epidemiological studies have revealed a significant association between impaired kidney function and certain mental disorders, particularly bipolar disorder (BIP) and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Epidemiological studies have revealed a significant association between impaired kidney function and certain mental disorders, particularly bipolar disorder (BIP) and major depressive disorder (MDD). However, the evidence regarding shared genetics and causality is limited due to residual confounding and reverse causation.
METHODS
In this study, we conducted a large-scale genome-wide cross-trait association study to investigate the genetic overlap between 5 kidney function biomarkers (eGFRcrea, eGFRcys, blood urea nitrogen (BUN), serum urate, and UACR) and 2 mental disorders (MDD, BIP). Summary-level data of European ancestry were extracted from UK Biobank, Chronic Kidney Disease Genetics Consortium, and Psychiatric Genomics Consortium.
RESULTS
Using LD score regression, we found moderate but significant genetic correlations between kidney function biomarker traits on BIP and MDD. Cross-trait meta-analysis identified 1 to 19 independent significant loci that were found shared among 10 pairs of 5 kidney function biomarkers traits and 2 mental disorders. Among them, 3 novel genes: SUFU, IBSP, and PTPRJ, were also identified in transcriptome-wide association study analysis (TWAS), most of which were observed in the nervous and digestive systems (FDR < 0.05). Pathway analysis showed the immune system could play a role between kidney function biomarkers and mental disorders. Bidirectional mendelian randomization analysis suggested a potential causal relationship of kidney function biomarkers on BIP and MDD.
CONCLUSIONS
In conclusion, the study demonstrated that both BIP and MDD shared genetic architecture with kidney function biomarkers, providing new insights into their genetic architectures and suggesting that larger GWASs are warranted.
Topics: Humans; Depressive Disorder, Major; Bipolar Disorder; Genome-Wide Association Study; Polymorphism, Single Nucleotide; Kidney; Genetic Predisposition to Disease; Biomarkers; Glomerular Filtration Rate; Quantitative Trait Loci; Uric Acid
PubMed: 38858783
DOI: 10.1186/s40246-024-00627-3 -
BMC Psychiatry Jun 2024Objective and quantifiable markers are crucial for developing novel therapeutics for mental disorders by 1) stratifying clinically similar patients with different...
BACKGROUND
Objective and quantifiable markers are crucial for developing novel therapeutics for mental disorders by 1) stratifying clinically similar patients with different underlying neurobiological deficits and 2) objectively tracking disease trajectory and treatment response. Schizophrenia is often confounded with other psychiatric disorders, especially bipolar disorder, if based on cross-sectional symptoms. Awake and sleep EEG have shown promise in identifying neurophysiological differences as biomarkers for schizophrenia. However, most previous studies, while useful, were conducted in European and American populations, had small sample sizes, and utilized varying analytic methods, limiting comprehensive analyses or generalizability to diverse human populations. Furthermore, the extent to which wake and sleep neurophysiology metrics correlate with each other and with symptom severity or cognitive impairment remains unresolved. Moreover, how these neurophysiological markers compare across psychiatric conditions is not well characterized. The utility of biomarkers in clinical trials and practice would be significantly advanced by well-powered transdiagnostic studies. The Global Research Initiative on the Neurophysiology of Schizophrenia (GRINS) project aims to address these questions through a large, multi-center cohort study involving East Asian populations. To promote transparency and reproducibility, we describe the protocol for the GRINS project.
METHODS
The research procedure consists of an initial screening interview followed by three subsequent sessions: an introductory interview, an evaluation visit, and an overnight neurophysiological recording session. Data from multiple domains, including demographic and clinical characteristics, behavioral performance (cognitive tasks, motor sequence tasks), and neurophysiological metrics (both awake and sleep electroencephalography), are collected by research groups specialized in each domain.
CONCLUSION
Pilot results from the GRINS project demonstrate the feasibility of this study protocol and highlight the importance of such research, as well as its potential to study a broader range of patients with psychiatric conditions. Through GRINS, we are generating a valuable dataset across multiple domains to identify neurophysiological markers of schizophrenia individually and in combination. By applying this protocol to related mental disorders often confounded with each other, we can gather information that offers insight into the neurophysiological characteristics and underlying mechanisms of these severe conditions, informing objective diagnosis, stratification for clinical research, and ultimately, the development of better-targeted treatment matching in the clinic.
Topics: Humans; Schizophrenia; Electroencephalography; Sleep; Research Design; Neurophysiology; Adult; Male; Female; Biomarkers; Cohort Studies
PubMed: 38858652
DOI: 10.1186/s12888-024-05882-1 -
The incidence risk of gynecological cancer by antipsychotic use: a meta-analysis of 50,402 patients.BMC Cancer Jun 2024Female gynecological cancers represent a serious public health problem, with 1,398,601 new diagnoses and 671,875 deaths per year worldwide. Antipsychotics are often used... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Female gynecological cancers represent a serious public health problem, with 1,398,601 new diagnoses and 671,875 deaths per year worldwide. Antipsychotics are often used in psychiatric disorders, including schizophrenia, bipolar disorder, and major depression. It is estimated that the prescription of these drugs is linked to 1,800 deaths a year in the United States, but their association with cancer remains controversial.
METHODS
We searched PubMed, Scopus, and Web of Science databases for studies reporting the correlation in the incidence risk of gynecological cancer by antipsychotic use. We used DerSimonian and Laird random-effect models to compute logit transformed odds ratio (OR) for the primary binary endpoint with 95% confidence interval (CI). Heterogeneity was assessed through effect size width along with I-squared and Tau-squared statistics. Review Manager 5.4.1. was used for statistical analyses. A p-value of < 0.05 denoted statistically significant.
RESULTS
50,402 patients were included, of whom 778 (1,54%) took antipsychotic medication for at least 1 year. 1,086 (2,15%) with ovarian cancer and 49,316 (97,85%) with endometrial cancer. Antipsychotic use (OR 1.50; 1.06 to 2.13 95% CI; p-value 0.02), hypertension (OR 1.50; 95% CI 1.06 to 2.13; p-value < 0.01), nulliparity (OR 1.98; 95% CI 1.53 to 2.57; p-value < 0.01) and multiparity (OR 0.53; 95% CI 0.41 to 0.69; p-value < 0.01) showed significantly different distributions between groups of cancer and cancer-free patients. The primary endpoint of incidence risk of gynecological cancer by antipsychotic therapy showed a statistically significant difference (OR 1.67; 95% CI 1.02 to 2.73; p-value < 0.05) against the use of antipsychotic drugs.
CONCLUSIONS
Our meta-analysis showed that the use of antipsychotic drugs increases the risk of gynecological cancers, particularly endometrial cancer. This result should be weighed against the potential effects of treatment for a balanced prescribing decision.
Topics: Humans; Female; Incidence; Antipsychotic Agents; Genital Neoplasms, Female; Risk Factors; Endometrial Neoplasms; Odds Ratio; Ovarian Neoplasms
PubMed: 38858638
DOI: 10.1186/s12885-024-12481-6 -
Neuropsychiatric Disease and Treatment 2024Despite the high prevalence of anxiety disorders in BD and its known impact on cognitive performance, the presence and severity of anxious symptoms is not systematically...
PURPOSE
Despite the high prevalence of anxiety disorders in BD and its known impact on cognitive performance, the presence and severity of anxious symptoms is not systematically evaluated in studies on cognition in BD. Our aim was to determine if attention and/or inhibition of cognitive interference in euthymic patients with type I Bipolar Disorder (BD-I) is affected by symptoms of anxiety.
PATIENTS AND METHODS
Eighty-seven euthymic BD-I patients were included. Patients with comorbidities other than Generalized Anxiety Disorder (GAD) or Panic Disorder (PD) were excluded. State anxiety was measured with the Brief Inventory of Anxious Responses and Situations (ISRA-B). Subjective cognitive performance was evaluated with the COBRA scale, attention with the Digit-Span Forward task and inhibition of cognitive interference was assessed with the StroopTest interference score. Multiple linear regression models were used to test if anxious symptoms were associated with attention or inhibition of cognitive interference, considering other known contributors for cognitive impairment.
RESULTS
Attention was unaffected by anxiety symptoms, but the overall regression for inhibition of cognitive interference was significant: years of schooling (β=1.12, p = 0.001), cognitive complaints (β=0.44, p = 0.008), and anxiety (β=-0.21, p = 0.017) explained 15% of the interference score of the Stroop test (R2 = 0.15).
CONCLUSION
Beyond residual affective symptoms, anxious symptoms seem to affect inhibition of cognitive interference. We recommend routine testing of anxiety when considering cognitive evaluations, especially when screening for cognitive deficits.
PubMed: 38855382
DOI: 10.2147/NDT.S457186 -
Industrial Psychiatry Journal 2024Gender confusion in the context of mania is very less frequently described in the literature. The actuality of a primary psychiatric condition in gender identity...
Gender confusion in the context of mania is very less frequently described in the literature. The actuality of a primary psychiatric condition in gender identity complaint has significant bearing on the applicable operation and prognostic. This case series describes cases of bipolar affective complaint presenting in a manic occasion whose mania was marked by hypersexuality and the desire to be of opposite gender. Both of these symptoms resolved with treatment of the manic occasion. Case 1 describes a 17-year-old male presenting with an episodic illness, with current manic episode. He is currently interested in boys and has started enjoying feminine activities. Upon treatment, his symptoms showed improvement. Case 2 describes a 22-year-old gay male, with a total duration of 7 years, current episode mania. Now, he is considering himself a lesbian and feels he is mentally a modern female. After 4 months of treatment, there was significant improvement in his complaints and he stopped cross-dressing as a female. Case 3 shows a 21-year-old female, with manic episode. After 1 month, the patient began acting and speaking more like a boy. The patient has shown improvement while taking lithium 900 mg, divalproex sodium 1000 mg, risperidone 6 mg, and chlorpromazine 150 mg. Gender dysphoria occurring along with a psychotic episode and resolving with management of the primary psychiatric disorder are rarely recorded. The central issue in similar cases is a proper workup and diagnosis. Psychiatrists should be aware of this scenario so that proper treatment strategies for gender incongruence can be planned and not be brushed aside as "just another symptom."
PubMed: 38853792
DOI: 10.4103/ipj.ipj_156_23