Bipolar Disorder Cases Research Articles

Bipolar disorder and early childhood trauma

Case Background There is a reported 48.8 million case of bipolar disorder (BD) world- wide. It can also be one of the most challenging disorders to manage clinically as patients often have poor medical compliance and numerous relapses throughout their lifetime. The etiology of this illness is still poorly understood, but it is recognized to compromise both genetic and environmental factors. Regarding the latter, abuse and instability in childhood and adolescence was reported as an important area of consideration in regard to the development and prognosis of bipolar disorder. We report here the case of a female who exemplifies the significance of early childhood experience in this disorder. Case Presentation Isabelle is a 21 year old, female, with a background history of bipolar disorder. She presented to the Cork University Hospital accident and emergency 2 weeks after discharge after a 4 week admission for a depressive episode. Isabelle was referred from the home-based team with an acute episode of mania and was detained involuntarily under the Mental Health Act. Her history is significant for childhood neglect, physical, emotional and sexual abuse, along with multiple foster care placements. She was managed as an inpatient with antipsychotics and a mood stabilizer before being discharged after a lengthy, arduous, admission. Conclusion Childhood trauma is an important consideration in BD. Therefore, practitioner awareness of the role of such trauma with regard to its etiology and prognosis is of great importance. It is also essential to the practice of preventive medicine. Patient Consent Obtained: Yes

The number of episodes of major psychiatric and substance use disorders as an index of genetic risk and genetic heterogeneity.

We investigate whether number of episodes (NoEs) meaningfully reflect genetic risk and genetic heterogeneity for five primary disorders-Drug Use Disorder (DUD), Alcohol Use Disorder (AUD), Major Depression (MD), Bipolar Disorder (BD), and Schizophrenia (SZ) ascertained from Swedish population registries. We utilize Genetic Risk Ratios (GRR)-defined as the ratio of the genetic risk for secondary disorders to the genetic risk for the primary disorder-derived from Family Genetic Risk Scores (FGRS). For all five primary disorders, genetic risk rose robustly with increasing NoEs. For both AUD and DUD, the GRR for all six secondary disorders-selected to have a likely genetic relationship with the particular primary disorder-declined with increasing NoEs so that cases of AUD and DUD with high versus low NoEs had both a higher genetic risk and a purer genetic signal. With MD, genetic risk maximized at an intermediate NoEs. While the GRRs for AUD and DUD in MD cases dropped sharply with increasing NoEs, GRR for BD increased. For BD, genetic risk rose sharply with increasing NoEs while for all secondary disorders the GRRs showed a mixture of modest increases and decreases. Like AUD and DUD, but even more markedly, selecting BD cases with high rates of recurrence would produce a sample with a high overall genetic risk and a relatively homogeneous genetic signal. For SZ, genetic risk rose moderately with increases in NoEs. GRRs for other non-affective psychoses (ONAP) and autism spectrum disorder (ASD) fell quite slowly with increasing NoEs, and more rapidly for other secondary disorders. Cases of SZ with high recurrence rates had a high genetic risk and a relatively pure signal, albeit with contributions from ONAP and ASD. In summary, NOEs are a robust index of genetic risk and genetic heterogeneity across our primary disorders with important inter-disorder differences.

The Prediction of Diagnostic Change From Bipolar Disorder to Schizophrenia and Schizophrenia to Bipolar Disorder in a Population-Based, Longitudinal, National Swedish Sample.

To clarify, in a large, representative, longitudinal sample, the rate and predictors of diagnostic conversion from Bipolar Disorder (BD) to Schizophrenia (SZ) and from SZ→BD. From individuals born in Sweden 1950-1995 and living there in 1970 or later, we identified at least one initial diagnoses of SZ (n = 8449) and BD (n = 8438) followed for a minimum of 10 and a mean of 24 years. Diagnostic conversion required, respectively, at least two final diagnoses of BD and SZ 30 days apart with no intervening diagnosis of SZ or BD. At follow-up, rates of BD→SZ and SZ→BD conversion were 10.1 and 4.5%, respectively. Conversions occurred slowly, with around 50% completed in the first decade. Using a diverse range of variables available at first onset including family genetic risk scores, BD→SZ conversion was predicted with greater accuracy (AUC = 0.78) than SZ→BD conversion (AUC = 0.65). The strongest predictors of BD→SZ conversion were earlier years of birth, younger age at BD onset, low BD genetic risk, and being unmarried at BD onset. SZ→BD conversion was most strongly predicted by high BD genetic risk, being married at SZ onset, female sex, early age at SZ onset, and an MD episode prior to SZ onset. Cases of BD and SZ in the highest decile for conversion risk had HRs for a diagnostic change of, respectively, 12.5 and 3.4. Diagnostic conversion of BD→SZ and SZ→BD are not rare, are moderately predictable, and should likely be accounted for in many research designs.

Druggable genome-wide Mendelian randomization for identifying the role of integrated stress response in therapeutic targets of bipolar disorder

For bipolar disorder (BD), the inconsistency of treatment guidelines and the long phases of pharmacological adjustment remain major challenges. BD is known to be comorbid with many medical and psychiatric conditions and they may share inflammatory and stress-related aetiologies, which could give rise to this association. The integrated stress response (ISR) responds to various stress conditions that lead to alterations in cellular homeostasis. However, as a causative mechanism underlying cognitive deficits and neurodegeneration in a broad range of brain disorders, the impact of ISR on BD is understudied. Mendelian randomization has been widely used to repurpose licensed drugs and discover novel therapeutic targets. Thus, we aimed to identify novel therapeutic targets for BD and analyze their pathophysiological mechanisms, using the summary data-based Mendelian Randomization (SMR) and Bayesian colocalization (COLOC) methods to integrate the summary-level data of the GWAS on BD and the expression quantitative trait locus (eQTL) study in blood. We utilized the GWAS data including 41,917 BD cases and 371,549 controls from the Psychiatric Genomics Consortium and the eQTL data from 31,684 participants of predominantly European ancestry from the eQTLGen consortium. The SMR analysis identified the EIF2B5 gene that was associated with BD due to no linkage but pleiotropy or causality. The COLOC analysis strongly suggested that EIF2B5 and the trait of BD were affected by shared causal variants, and thus were colocalized. Utilizing data in EpiGraphDB we find other putative causal BD genes (EIF2AK4 and GSK3B) to prioritize potential alternative drug targets.

Antidepressant-associated diagnostic change from major depressive to bipolar disorder.

Anticipating diagnostic change from major depressive (MDD) to bipolar disorder (BD) can support better prognosis and treatment, especially of depression but is challenging and reported research results are inconsistent. We therefore assessed clinical characteristics associated with diagnostic change from MDD to BD with antidepressant treatments. We compared characteristics of 3212 initially MDD patients who became (hypo)manic during antidepressant treatment to those with stable MDD diagnoses as well as with cases of stable, spontaneous BD, using standard bivariate and multivariate statistics. Among MDD patients, 6.69% [CI: 5.85-7.61] changed to BD, mostly type II (BD2, 76.7%). BD-converters had higher rates of familial mood disorders (74.1% vs. 57.1%) or BD (33.7% vs. 21.0%) and 2.8-years younger onset than stable MDD patients. They also had more prior depressive recurrences/year, years-of-illness, mood-stabilizer treatment, divorces, fewer children, more suicide attempts and drug-abuse, and higher intake cyclothymia, YMRS and MDQ scores. Predictors independently associated with diagnostic conversion were: more familial BD, depressions/year, unemployment, cyclothymic temperament, suicidal ideation or acts, and fewer children. BD-converters vs. spontaneous BD cases had significantly more suicide attempts, BD2 diagnoses, and affected relatives. Converting to vs. spontaneous BD1 was associated with more ADHD, more suicidal ideation or behavior, MDI course, and younger onset; converting to vs. spontaneous BD2 had more episodes/year, unemployment, ADHD, substance abuse, suicidal ideation or attempts, and more relatives with BD. Few (6.69%) initially MDD subjects converted to BD, most (76.7%) to BD2. Independent predictive associations with diagnostic change included: familial BD, more depressions/year, unemployment, cyclothymic temperament, suicidal behavior and fewer children. Notably, several characteristics were stronger among those changing to BD during antidepressant treatment vs. others with spontaneous BD.

Impact of traumatic brain injury on risk for schizophrenia and bipolar disorder

The impact of traumatic brain injury (TBI) on subsequent risk of schizophrenia (SCZ) or bipolar disorder (BD) remains contested. Possible genetic and environmental confounding effects have also been understudied. Therefore, we aim to investigate the impact of TBI on the risk of SCZ and BD and whether the effect varies by injury severity, age at injury, and sex. We identified 4,184 SCZ and 18,681 BD cases born between 1973 and 1998 in the Swedish National Registers. Case-control samples matched (1:5) on birth year, sex, and birthplace were created along with a family design study, with cases matched to non-case full siblings. TBI was associated with higher risk of SCZ and BD (IRR=1.33 for SCZ, IRR=1.78 for BD). The association remained significant in the sibling comparison study. Moderate or severe TBI was associated with higher risk for both SCZ and BD compared to mild TBI. Older age at injury was associated with higher risk of SCZ and BD, and the effect of TBI was stronger in women than men. Findings indicate that TBI is a risk factor for both SCZ and BD with differential impact by age, severity and sex and that this association cannot be explained by familial confounding alone.

Maintenance electroconvulsive therapy: An effective yet underused treatment modality in psychiatry: A case series

Maintenance Electroconvulsive Therapy (M-ECT) refers to ECTs administered beyond 6 months after the remission of illness. Maintenance electroconvulsive therapy (M-ECT) can be used to reduce the risk for relapse and recurrence of illness in patients who fare poorly with standard medication regimens. There is improvement in the relapse rate of major psychiatric disorders when continuation or maintenance (C or M-ECT) are used with psychotropics. These are single-center, retrospective case studies of patients diagnosed with major psychiatric disorders (as per International Classification of Diseases, 11th edition) who are receiving M-ECT in Department of Psychiatry, B.J. Government Medical College and Sassoon Hospital, Pune. We included 12 patients- 8 males and 4 females in this study. 4 cases were of patients suffering from schizophrenia, 3 cases were of patients suffering from depression, 1 case of bipolar affective disorder and 4 cases of patients of intellectual disability with psychosis. There was a reduction in hospitalization rate for acute exacerbation and significant improvement in the patients’ overall functioning on standardized rating scales without any significant adverse effects. Maintenance ECT is an underused treatment option that can substantially reduce risks of relapse in patients with major depressive disorder, bipolar disorder and schizophrenia as well. Despite the potential value of these ECT schedules, these are relatively neglected in clinical practice. This article aims to explore the clinical utility of maintenance ECTs and emphasizes the use of maintenance ECTs in routine psychiatric care.

Comparison of Val66met Polymorphism of BDNF gene in patients of bipolar disorder and healthy controls.

IntroductionThe study aims to explore the utility of BDNF Val66Met polymorphism as a potential biomarker in Indian bipolar disorder patients and its correlation with clinical characteristics.ObjectivesGenotyping Val66Met in BDNF geneExploring its association with bipolar disorder (BD).Methods150 consenting BD patients and matched controls were recruited using a case-control study design. BD severity was assessed using Young’s mania rating scale and the Clinical Global Impression - Severity (CGI-S) scale. BDNF Val66Met polymorphism was identified through real-time PCR after DNA extraction. Data was tested for normal distribution. Genotype frequencies between two groups were compared and the Hardy-Weinberg equilibrium assumptions were tested using Chi-Square tests. Clinical-genotypic associations were explored using the Kruskal-Wallis test and confirmed using hierarchical regression.ResultsOur sample had more males (60%) than females (40%) with mean age of 35.05 years. Most patients had established bipolar disorder and were severely ill (CGI: 38.75, YMRS). Val66Met SNP genotype frequency differed significantly between cases and controls. Val66Val genotype and Val allele were higher in cases. Results consistent with Hardy-Weinberg equilibrium.Table 1.Genotype frequencies of BDNF (rs6265) in cases and controlsGENOTYPECCCTTTCASES94(62.6%)47(31.3%)9(6%)CONTROL71(47.3%)69(46%)10(6.6%)CHI-SQUARE- 7.431DF(Degree of freedom) - 2p-value- 0.024Table 2.Dominant genotype frequencies in cases and controlsDOMINANT GENOTYPECCCT+TTCASES94(62.6%)56(37.3%)CONTROLS71(47.3%)79(52.6)CHI-SQUARE-7.125DF(Degree of freedom)-1p-value-0.007Table 3.Allelic frequencies of BDNF (rs6265) in BD cases and healthy controlsALLELIC VARIATIONCTCASES235(78.3%)65(21.6%)CONTROLS211(70.3%)89(29.6%)CHI-SQUARE-5.032DF(Degree of freedom)-1p-value- 0.024ConclusionsOur study found that Val66Val genotype and Val allele were higher in cases and could be a potential biomarker for bipolar disorder (BD), which is consistent with previous research conducted on the European population. However, further investigations are required to gain a more comprehensive understanding of its impact on BD, including its association with serum BDNF levels, treatment outcomes, and a more diverse study population.Disclosure of InterestNone Declared

Bipolar disorder, Deafness and Culturality in Psychiatric Home Hospitalization: A Clinical Case

IntroductionMental health in the deaf community is a complex issue. Challenges in diagnosis and treatment arise from a lack of experienced interpreters and difficulties in translating Sign Language to spoken language. Deaf individuals, due to auditory limitations, are more vulnerable to abuse, increasing their risk of mental health disorders, including bipolar affective disorder (BPAD). BPAD is a prevalent, debilitating condition with varied prevalence estimates. Managing it is tough due to its lifelong, unpredictable nature. A new approach called Psychiatric Home Hospitalization Unit aims to provide acute mental health care at home as an alternative to hospitalization.ObjectivesTo show the management of severe bipolar disorder with comorbidity from a Psychiatric Home Hospitalization UnitMethodsA clinical case of bipolar disorder with deafness attended at the Psychiatric Home Hospitalization Unit of our hospital is presented.ResultsA 24-year-old deaf woman borned in Pakistan and later moving to Catalonia, she faced educational challenges but ultimately completed her studies with sign language support. Afterward, she struggled to find suitable employment, and her family had a history of bipolar disorder.She exhibited a sudden change in behavior, characterized by irritability, paranoia, and distrust. Communication was challenging due to her speech difficulties, but assessments using sign language and observation were conducted. Her physical examination was normal, but her speech was disorganized and pressured, suggesting possible auditory hallucinations and thought disturbances. She was hospitalized and diagnosed with bipolar disorder with psychotic features.During her initial hospitalization, she received lithium, olanzapine, clotiapine and benzodiacepines. After discharge, she continued treatment through a home hospitalization service during almost 4 month. During follow-up she presented a course with high affective instability, rapid cycling alternating brief periods of stability with other presenting manic and mixed features with high disorganization.Due to the rapid cycling pattern Valproic acid was considered. Valproic acid was introduced up to 700 mg/d (97.1 mcg/mL). Treatment with lithium carbonate 800 mg/d (0.91 mEq/L) was maintained. Previous antipsychotic regimen was changed to quetiapine 400mg/d, olanzapine 5mg/d. Her condition improved significantly with the adjusted treatment regimen. She was discharged to an outpatient service.ConclusionsDiagnosing and treating bipolar affective disorder (BPAD) in a deaf and mute patient posed unique challenges. The rapid mood cycling pattern and complexity of her case made treatment challenging. Family information and interpreter support were vital. Cultural factors were considered, and home hospitalization was crucial in managing symptoms that lasted over four months.Disclosure of InterestNone Declared

Late Onset Bipolar Disorder (LOBD): a case report

Introduction Bipolar disorder (BD) in the elderly patient may present as the evolution of illness initiated earlier in life or as a new-onset entity. Therefore, two groups of patients are distinguished: “late onset” (LOBD) when the first mania occurs in old age and “early onset” in elderly patients with long-standing history. BD in elderly patients (≥60 years) constitutes 25% of all BD cases. Specific aspects of older age bipolar disorder (OABD) are somatic and psychiatric comorbidity, impaired cognition and age-related psychosocial functioning. The management of BD in the elderly is complex given the high sensitivity of these patients to pharmacological side effects, particularly of psychotropic drugs.ObjectivesThe case of a patient with LOBD is presented, followed by a theoretical review of the subject.MethodsA case is presented with a bibliographic review.Results A 76-year-old woman who had no prior history of mental health issues until March 2023 when she was initially admitted to a geriatric hospitalization unit for manifesting manic symptoms. She was readmitted in July 2023 due to worsening depressive symptoms that included a declining mood, passive thoughts of death, deterioration in self-care, weight loss, insomnia, constipation, and dry mouth despite recent changes in her medications. She was on treatment with escitalopram (which was gradually discontinued and replaced with mirtazapine), quetiapine, lormetazepam, and lorazepam. Imaging tests showed chronic ischemic lesions in her brain and a small meningioma, the rest of the test were normal.The initial diagnostic hypothesis was a bipolar depressive episode, and her treatment was adjusted accordingly. She was started on lithium, and her quetiapine dosage was increased, along with the anxiolytic lorazepam. Due to the persistence of depressive symptoms, including low mood, anhedonia, apathy, and negative thoughts, she was also prescribed antidepressant medication (venlafaxine and mirtazapine). Her condition gradually improved, with better eating and sleep patterns, increased participation in activities, and reduced somatic complaints and anxiety.As she continued to experience somnolence and decreased morning energy, her antipsychotic medication was switched from quetiapine to lurasidone. The dose of lithium was decreased due to tremors in her extremities, although they remained within the therapeutic range. Despite these adjustments, her mood significantly improved, and she showed no signs of worsening or psychotic symptoms, leading to her discharge.ConclusionsSummarizing different studies, LOBD who develop mania for the first time at an advanced age (≥ 50 years) constitute 5-10% of all BD. It is important to perform a thorough differential diagnosis, as an organic substrate and diverse etiologies may be present. Current guidelines recommend that first-line treatment of OABD should be similar to that of BD in young patients, with careful use of psychotropic drugs.Disclosure of InterestNone Declared

Adaption and validation of the Rwandese version of the Mood Disorder Questionnaire for the screening of bipolar disorder

BackgroundBipolar disorder is challenging to diagnose. In Rwanda, a sub-Saharan country with a limited number of psychiatrists, the number of people with an undetected diagnosis of bipolar disorder could be high. Still, no screening tool for the disorder is available in the country. This study aimed to adapt and validate the Mood Disorder Questionnaire in the Rwandan population. MethodsThe Mood Disorder Questionnaire was translated into Kinyarwanda. The process involved back-translation, cross-cultural adaptation, field testing of the pre-final version, and final adjustments. A total of 331 patients with either bipolar disorder or unipolar major depression from two psychiatric outpatient hospitals were included. The statistical analysis included reliability and validity analyses and receiver operating characteristic curve (ROC) analysis. The optimal cut-off was chosen by maximizing Younden's index. ResultsThe Rwandese version of The Mood Disorder Questionnaire had adequate internal consistency (Cronbach's alpha =0.91). The optimal threshold value was at least six positive items, which yielded excellent sensitivity (94.7%), and specificity (97.3%). The ROC area under the curve (AUC) was 0.99. ConclusionThe adapted tool showed good psychometric properties in terms of reliability and validity for the screening of bipolar disorder, with a recommended cutoff value of six items on the symptom checklist for a positive score and an exclusion of items 14 and 15. The tool has the potential to be a crucial instrument to identify otherwise undetected cases of bipolar disorder in Rwanda, improving access to mental health treatment, thus enhancing the living conditions of people with bipolar disorder.

Environmental risk factors for schizophrenia and bipolar disorder from childhood to diagnosis: a Swedish nested case-control study.

Shared genetic risk between schizophrenia (SCZ) and bipolar disorder (BD) is well-established, yet the extent to which they share environmental risk factors remains unclear. We compare the associations between environmental exposures during childhood/prior to disorder onset with the risk of developing SCZ and BD. We conducted a Swedish register-based nested case-control study using 4184 SCZ cases and 18 681 BD cases diagnosed 1988-2013. Cases were matched to five controls by birth year, birth region, and sex. Conditional logistic regression was used to estimate incidence rate ratios (IRR) for SCZ and BD for each exposure (severe childhood infections, adverse childhood experiences (ACEs), substance use disorders (SUDs), urban birth/longest residence). All SUD types were associated with very high risk (IRR 4.9-25.5), and all forms of ACEs with higher risk (IRR 1.5-4.3) for both disorders. In the mutually adjusted models, ACEs demonstrated slightly higher risk for BD (SCZ IRR 1.30, 1.19-1.42; BD IRR 1.49, 1.44-1.55), while for SUD, risk was higher for SCZ (SCZ IRR 9.43, 8.15-10.92; BD IRR 5.50, 5.15-5.88). Infections were associated with increased risk of BD (IRR 1.21, 1.17-1.26) but not SCZ. Urban birth and urban longest residence were associated with higher risk of SCZ (IRR 1.19, 1.03-1.37), while only the combination of urban birth and rural longest residence showed higher risk for BD (IRR 1.24, 1.13-1.35). There were both shared and unique environmental risk factors: SUDs and ACEs were risk factors for both disorders, while infections were more strongly associated with BD and urbanicity with SCZ.

Development and multi-site external validation of a generalizable risk prediction model for bipolar disorder

Bipolar disorder is a leading contributor to disability, premature mortality, and suicide. Early identification of risk for bipolar disorder using generalizable predictive models trained on diverse cohorts around the United States could improve targeted assessment of high risk individuals, reduce misdiagnosis, and improve the allocation of limited mental health resources. This observational case-control study intended to develop and validate generalizable predictive models of bipolar disorder as part of the multisite, multinational PsycheMERGE Network across diverse and large biobanks with linked electronic health records (EHRs) from three academic medical centers: in the Northeast (Massachusetts General Brigham), the Mid-Atlantic (Geisinger) and the Mid-South (Vanderbilt University Medical Center). Predictive models were developed and valid with multiple algorithms at each study site: random forests, gradient boosting machines, penalized regression, including stacked ensemble learning algorithms combining them. Predictors were limited to widely available EHR-based features agnostic to a common data model including demographics, diagnostic codes, and medications. The main study outcome was bipolar disorder diagnosis as defined by the International Cohort Collection for Bipolar Disorder, 2015. In total, the study included records for 3,529,569 patients including 12,533 cases (0.3%) of bipolar disorder. After internal and external validation, algorithms demonstrated optimal performance in their respective development sites. The stacked ensemble achieved the best combination of overall discrimination (AUC = 0.82–0.87) and calibration performance with positive predictive values above 5% in the highest risk quantiles at all three study sites. In conclusion, generalizable predictive models of risk for bipolar disorder can be feasibly developed across diverse sites to enable precision medicine. Comparison of a range of machine learning methods indicated that an ensemble approach provides the best performance overall but required local retraining. These models will be disseminated via the PsycheMERGE Network website.

Genetic proxies for antihypertensive drugs and mental disorders: Mendelian randomization study in European and East Asian populations.

Mental disorders are among the top causes of disease burden worldwide. Existing evidence regarding the repurposing of antihypertensives for mental disorders treatment is conflicting and cannot establish causation. We used Mendelian randomization to assess the effects of angiotensin-converting-enzyme inhibitors (ACEIs), beta blockers (BBs), and calcium channel blockers (CCBs) on risk of bipolar disorder (BD), major depression disorder (MDD), and schizophrenia (SCZ). We used published genetic variants which are in antihypertensive drugs target genes and correspond to systolic blood pressure (SBP) in Europeans and East Asians, and applied them to summary statistics of BD (cases = 41,917; controls = 371,549 in Europeans), MDD (cases = 170,756; controls = 329,443 in Europeans and cases = 15,771; controls = 178,777 in East Asians), and SCZ (cases = 53,386; controls = 77,258 in Europeans and cases = 22,778; controls = 35,362 in East Asians) from the Psychiatric Genomics Consortium. We used inverse variance weighting with MR-Egger, weighted median, weighted mode, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier. We performed gene-specific analysis and utilized various methods to address potential pleiotropy. After multipletesting correction, genetically proxied ACEIs were associated with an increased risk of SCZ in Europeans (odds ratio (OR) per 5mmHg lower in SBP 2.10, 95% CI 1.54 to 2.87) and East Asians (OR per 5mmHg lower in SBP 2.51, 95% CI 1.38 to 4.58). Genetically proxied BBs were not associated with any mental disorders in both populations. Genetically proxied CCBs showed no benefits on mental disorders. Antihypertensive drugs have no protection for mental disorders but potential harm. Their long-term use among hypertensive patients with, or with high susceptibility to, psychiatric illness needs careful evaluation.

A clinical case of the new-onset bipolar affective disorder in the postcovid period

A large number of people who have had COVID-19 have developed mental symptoms and mood disorders. Anxiety and depression prevail among affective pathology. Evidence is accumulating that the Sars-CoV-2 virus can induce mania or hypomania in people with no personal psychopathological history. Some clinical, anamnestic and paraclinical patterns of new-onset mania and hypomania have been found. In cases of severe manic symptoms, it is possible to quickly assume the occurrence of bipolar affective disorder. The predominance of depressive and anxiety syndromes in the long-term disease and the presence of vivid vegetative symptoms can mask brief and syndromally incomplete episodes of hypomania, which distorts the understanding of the disease as a bipolar disorder. This article presents such a clinical case of the occurrence of bipolar affective disorder in a patient who had COVID-19 with an asymptomatic course. Approaches to rational diagnosis and treatment are discussed.

Association of fatty acid desaturase 2 gene polymorphism (rs28456) with susceptibility to bipolar disorder in the Turkish population: A case-control study

The FADS2 gene encodes a key, rate-limiting enzyme involved in polyunsaturated fatty acid (PUFA) metabolism. Recent studies suggest that changes in plasma PUFA levels can lead to disruptions in the neurotransmission system and increase the risk of mood disorders. FADS2 variations may contribute to the individual risk of developing bipolar disorder (BD). We investigated the association of regulatory FADS2 rs28456 with BD in the Turkish population. We performed TaqMan genotyping on 100 patients with BD and 91 healthy controls. Our results did not show significantly different genotype or allele frequencies of rs28456 in the BD cases compared to controls. However, we stratified the cases based on family history, which revealed that minor rs28456-G was observed more frequently (P=0.056) in cases without a family history of psychiatric illness compared to those with a family history of psychiatric illness. A marginally significant difference in the distribution of the ?G? allele (P=0.053) between male patients and healthy males without a family history was observed. Our findings did not provide strong evidence supporting the reported association between rs28456 and BD, yet they point to its potential gender-specific effect, which requires further investigation. Future studies are necessary to explore the impact of FADS2 variations on BD risk in larger study groups, considering their potential interaction with non-inherited risk factors.

Using the Bayesian variational spike and slab model in a genome-wide association study for finding associated loci with bipolar disorder.

The genome-wide association studies (GWAS) analysis, the most successful technique for discovering disease-related genetic variation, has some statistical concerns, including multiple testing, the correlation among variants (single-nucleotide polymorphisms) based on linkage disequilibrium and omitting the important variants when fitting the model with just one variant. To eliminate these problems in a small sample-size study, we used a sparse Bayesian learning model for finding bipolar disorder (BD) genetic variants. This study used the Wellcome Trust Case Control Consortium data set, including 1998 BD cases and 1500 control samples, and after quality control, 380,628 variants were analysed. In this GWAS, a Bayesian logistic model with hierarchical shrinkage spike and slab priors was used, with all variants considered simultaneously in one model. In order to decrease the computational burden, an alternative inferential method, Bayesian variational inference, has been used. Thirteen variants were selected as associated with BD. The three of them (rs7572953, rs1378850 and rs4148944) were reported in previous GWAS. Eight of which were related to hemogram parameters, such as lymphocyte percentage, plateletcrit and haemoglobin concentration. Among selected related genes, GABPA, ELF3 and JAM2 were enriched in the platelet-derived growth factor pathway. These three genes, along with APP, ARL8A, CDH23 and GPR37L1, could be differential diagnostic variants for BD. By reducing the statistical restrictions of GWAS analysis, the application of the Bayesian variational spike and slab models can offer insight into the genetic link with BD even with a small sample size. To uncover related variations with other traits, this model needs to be further examined.

The relationship between familial-genetic risk and pharmacological treatment in a Swedish national sample of patients with major depression, bipolar disorder, and schizophrenia.

Using Swedish registers, we examine whether the prescription of and the response to antidepressants (AD), mood stabilizers (MS), and antipsychotics (AP) in the treatment of, respectively, major depression (MD), bipolar disorder (BD), and schizophrenia (SZ), are influenced by familial-genetic risk. We examined individuals born in Sweden 1960-1995 with a first diagnosis of MD (n = 257,177), BD (n = 23,032), and SZ (n = 4248) from 2006 to 2018. Drug classes and Defined Daily Dose (DDD) were obtained from the Pharmacy register using the Anatomical Therapeutic Chemical system. We utilized the Familial Genetic Risk Scores (FGRS) calculated from morbidity risks in first- through fifth degree relatives. Treatment with antidepressants (AD) in MD, mood-stabilizers (MS) in BD, and antipsychotics (AP) in SZ were associated with significantly higher disorder-specific familial-genetic risks. Using dosage trajectory analysis of AD, MS, and AP treatment for MD, BD, and SZ, respectively, familial-genetic risk was positively associated with higher and/or increasing drug dosages over time. For MD and BD, examining cases started on the most common pharmacologic treatment class (SSRIs for MD and "other anti-epileptics" for BD), familial-genetic risks were significantly lower in those who did not versus did later receive treatment from other AD and MS classes, respectively. Higher familial-genetic risk for BD predicted switching AD medication in cases of MD. Among pharmacologically treated cases of BD, familial-genetic risk was significantly higher for those treated with lithium. In a large population-based patient cohort, we found evidence of a wide-spread association between higher familial-genetic risk and i) increased likelihood of receiving pharmacologic treatment but 2) responding more poorly to it-as indicated by a switching of medications -- and/or requiring higher doses. Further investigations into the clinical utility of genetic risk scores in the clinical managements of MD, BD, and SZ are warranted.

Dissecting the impact of complement component 4A in bipolar disorder

The genetic overlap between schizophrenia (SZ) and bipolar disorder (BD) is substantial. Polygenic risk scores have been shown to dissect different symptom dimensions within and across these two disorders. Here, we focused on the most strongly associated SZ risk locus located in the extended MHC region, which is largely explained by copy numbers of the gene coding for complement component 4A (C4A). First, we utilized existing brain tissue collections (N = 1,202 samples) and observed no altered C4A expression in BD samples. The generated C4A seeded co-expression networks displayed no genetic enrichment for BD. To study if genetically predicted C4A expression discriminates between subphenotypes of BD, we applied C4A expression scores to symptom dimensions in a total of 4,739 BD cases with deep phenotypic data. We identified a significant association between C4A expression and psychotic mood episodes in BD type 1 (BDI). No significant association was observed between C4A expression and the occurrence of non-affective psychotic episodes in BDI, the psychosis dimensions in the total BD sample, or any other subphenotype of BD. Overall, these results points to a distinct role of C4A in BD that is restricted to vulnerability for developing psychotic symptoms during mood episodes in BDI.

Education on sharia drug use in bipolar disorder patients during fasting month at Prof. dr. Soerojo Mental Hospital Magelang

Bipolar disorder is an emotional state or mood that ranges from manic (high) to depressive. The role of the Qur'an in dealing with mental disorders can be as a therapist in changing the mind, personality of the patient gradually, and as a healer for patients suffering from mental disorders. The purpose of this study was to determine the impact of sharia drug use education on bipolar patients at Prof. Dr. Soerojo Magelang Mental Hospital during the fasting month. Methods: This research is a descriptive qualitative research. Data collection for this study was conducted in February-March 2023. This study used a questionnaire as a tool to collect data and information media delivered through brochures. The results showed that bipolar disorder cases mostly had female gender characteristics (52%), and most had high school education (80%) as the last recorded education. With the results of the percentage value of understanding sharia drug use education in bipolar disorder patients, there is an increase in the influence on the success of patient therapy in peace of mind, quality of life and compliance in taking medication.