RESUMO
Mental illnesses are one of the biggest contributors to the global disease burden. Despite the increased recognition, diagnosis and ongoing research of mental health disorders, the etiology and underlying molecular mechanisms of these disorders are yet to be fully elucidated. Moreover, despite many treatment options available, a large subset of the psychiatric patient population is nonresponsive to standard medications and therapies. There has not been a comprehensive study to date examining the burden and impact of treatable genetic disorders (TGDs) that can present with neuropsychiatric features in psychiatric patient populations. In this study, we test the hypothesis that TGDs that present with psychiatric symptoms are more prevalent within psychiatric patient populations compared to the general population by performing targeted next-generation sequencing of 129 genes associated with 108 TGDs in a cohort of 2301 psychiatric patients. In total, 48 putative affected and 180 putative carriers for TGDs were identified, with known or likely pathogenic variants in 79 genes. Despite screening for only 108 genetic disorders, this study showed a two-fold (2.09%) enrichment for genetic disorders within the psychiatric population relative to the estimated 1% cumulative prevalence of all single gene disorders globally. This strongly suggests that the prevalence of these, and most likely all, genetic diseases is greatly underestimated in psychiatric populations. Increasing awareness and ensuring accurate diagnosis of TGDs will open new avenues to targeted treatment for a subset of psychiatric patients.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Transtornos Mentais , Humanos , Transtornos Mentais/genética , Transtornos Mentais/epidemiologia , Transtornos Mentais/terapia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Predisposição Genética para Doença , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/epidemiologia , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/terapia , Prevalência , Testes GenéticosRESUMO
People living with severe mental illness, such as schizophrenia and bipolar affective disorder, frequently experience poorer physical health compared to those without mental illness. This issue has hitherto been approached through the disease-centred construct of comorbidity, where subsequent conditions are viewed as secondary to an 'index condition'. In contrast, this Viewpoint sets out to explain why multimorbidity, a patient-centred concept that instead refers to the coexistence of multiple chronic illnesses, is a more versatile and robust framework for tackling the issue of poor physical health in people with severe mental illness. In establishing this argument, this Viewpoint has sought to address three key areas. First, this article will discuss the epidemiology of both physical and psychiatric multimorbidity, with respect to how they manifest at greater frequency and at younger ages in people with severe mental illness. Second, the profound consequences of this multimorbidity burden will be explored, with respect to the 'three D's' of death (premature mortality), disability (functional impacts) and deficit (health-economic impacts). Finally, the utility of multimorbidity as a framework will be illustrated through a proposal for a three-dimensional multimorbidity construct composed of (1) quantity, (2) severity and (3) duration of an individual's chronic illnesses. Consequently, this Viewpoint aims to capture why it is necessary for modern psychiatry to grasp the concept of multimorbidity to facilitate holistic healthcare for people living with severe mental illness.
Assuntos
Transtorno Bipolar , Transtornos Mentais , Esquizofrenia , Humanos , Multimorbidade , Transtornos Mentais/epidemiologia , Esquizofrenia/epidemiologia , Transtorno Bipolar/epidemiologia , Comorbidade , Doença CrônicaRESUMO
Bipolar affective disorder refers to a category of mood disorders characterized clinically by the presence of both manic or hypomanic episodes and depressive episodes. Lithium stands out as the primary pharmacological intervention for managing bipolar affective disorder. However, its therapeutic dosage closely approaches toxic levels. Toxic symptoms appear when the blood lithium concentration surpasses 1.4 mmol/L, typically giving rise to gastrointestinal and central nervous system reactions. Cardiac toxicity is rare but serious in cases of lithium poisoning. The study reports a case of a patient with bipolar affective disorder who reached a blood lithium concentration of 6.08 mmol/L after the patient took lithium carbonate sustained-release tablets beyond the prescribed dosage daily and concurrently using other mood stabilizers. This resulted in symptoms such as arrhythmia, shock, impaired consciousness, and coarse tremors. Following symptomatic supportive treatment, including blood dialysis, the patient's physical symptoms gradually improved. It is necessary for clinicians to strengthen the prevention and recognition of lithium poisoning.
Assuntos
Hemodinâmica , Lítio , Humanos , Anticonvulsivantes , Arritmias Cardíacas/induzido quimicamente , Sistema Nervoso CentralRESUMO
BACKGROUND: Bipolar affective disorder (BAD) is a common severe mental health condition with a relapsing course that may include periods of hospital re-admissions. With recurrent relapses and admissions, the course, prognosis, and patient's overall quality of life can be affected negatively. This study aims to explore the rates and clinical factors associated with re-admission among individuals with BAD. METHOD: This study used data from a retrospective chart review of all records of patients with BAD admitted in 2018 and followed up their hospital records for four years till 2021 at a large psychiatric unit in Uganda. Cox regression analysis was used to determine the clinical characteristics associated with readmission among patients diagnosed with BAD. RESULTS: A total of 206 patients living with BAD were admitted in 2018 and followed up for four years. The average number of months to readmission was 9.4 (standard deviation = 8.6). The incidence of readmission was 23.8% (n = 49/206). Of those readmitted during the study period, 46.9% (n = 23/49) and 28.6% (n = 14/49) individuals were readmitted twice and three times or more, respectively. The readmission rate in the first 12 months following discharge was 69.4% (n = 34/49) at first readmission, 78.3% (n = 18/23) at second readmission, and 87.5% (n = 12/14) at third or more times. For the next 12 months, the readmission rate was 22.5% (n = 11/49) for the first, 21.7% (n = 5/23) for the second, and 7.1% (n = 1/14) for more than two readmissions. Between 25 and 36 months, the readmission rate was 4.1% (n = 2/49) for the first readmission and 7.1% (n = 1/14) for the third or more times. Between 37 and 48 months, the readmission rate was 4.1% (n = 2/49) for those readmitted the first time. Patients who presented with poor appetite and undressed in public before admission were at increased risk of being readmitted with time. However, the following symptoms/clinical presentations, were protective against having a readmission with time, increased number of days with symptoms before admission, mood lability, and high energy levels. CONCLUSION: The incidence of readmission among individuals living with BAD is high, and readmission was associated with patients' symptoms presentation on previous admission. Future studies looking at BAD using a prospective design, standardized scales, and robust explanatory model are warranted to understand causal factors for hospital re-admission and inform management strategies.
Assuntos
Transtorno Bipolar , Psiquiatria , Humanos , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/terapia , Readmissão do Paciente , Uganda/epidemiologia , Qualidade de Vida , Estudos Retrospectivos , Transtornos do HumorRESUMO
BACKGROUND: Hospitalization is often necessary for individuals with Bipolar affective Disorder (BAD) during severe manic or depressive episodes, as well as for stabilizing treatment regimens. However, a significant proportion of patients admitted for treatment of BAD abscond or leave the hospital without permission during their stay. In addition, patients managed for BAD may have unique characteristics that might force them into absconding. For example, the high prevalence of co-morbid substance use disorder - craving to use substances, suicidal behaviors - attempts to die by suicide, and cluster B personality disorders - characterized by impulsive acts. It is, therefore, essential to understand the factors contributing to absconding among patients with BAD, to facilitate designing strategies for preventing and managing this behavior. METHOD: This study was based on a retrospective chart review of the inpatients diagnosed with BAD at a tertiary psychiatry facility in Uganda from January 2018 to December 2021. RESULTS: Approximately 7.8% of those with BAD absconded from the hospital. The likelihood of absconding among those with BAD increased with the use of cannabis [adjusted odds ratio (aOR) = 4.00, 95% confidence interval (CI) = 1.22-13.09, p-value = 0.022] and having mood lability [aOR = 2.15, 95% CI = 1.10-4.21, p-value = 0.025]. However, receiving psychotherapy during the admission (aOR = 0.44, 95 CI = 0.26-0.74, p-value = 0.002) and treatment with haloperidol (aOR = 0.39, 95% CI = 0.18-0.83, p-value = 0.014) reduced the likelihood of absconding. CONCLUSION: Absconding among patients with BAD is common in Uganda. Those with symptoms of affective lability and those with comorbid cannabis use tend to abscond more, while those who receive haloperidol and psychotherapy are less likely to abscond.
Assuntos
Transtorno Bipolar , Humanos , Transtorno Bipolar/complicações , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/epidemiologia , Estudos Retrospectivos , Haloperidol , Uganda/epidemiologia , Pacientes Desistentes do Tratamento/psicologia , Hospitalização , Transtornos do Humor/complicações , Transtornos do Humor/diagnóstico , Transtornos do Humor/epidemiologiaRESUMO
BACKGROUND: In Schizophrenia (SCZ) and Bipolar Affective Disorder (BAD) patients using the Framingham Heart Risk Scoring (FHRS), we aimed to investigate the possible cardiac arrhythmia risk by calculating electrocardiogram (ECG) parameters (QT, QTc, Tpe, and TPE/QTc ratios), which are ventricular repolarization markers. SUBJECTS AND METHODS: A total of 140 BAD and 253 SCZ patients were included in the study. Age, blood test results (fasting blood glucose, LDL-HDL-TC levels, hemogram values), blood pressure and heart rate, smoking status, antihypertensive drug use, and FHRS were calculated from the patient files, and sociodemographic information was recorded. In addition, ECG calculations were performed, and QT, QTc, TPe, TPe/QTc ratios and heart rate were measured. RESULTS: When we evaluated the cardiac risk indexes of SCZ and BAD patients, we detected that FHRS was higher in smokers, female patients, and those with other medical diseases such as diabetes mellitus (DM) (p<0.05). In addition, we found that QTc rates, markers of ventricular repolarization, were associated with FHRS, the number of antipsychotics used, patient age, disease duration, and the number of hospitalizations. TPe and QT rates were found to increase in parallel with FHRS. In addition, a positive correlation was found between QTc rates in females, patients with DM, and those using additional medical drugs. (p<0.05) CONCLUSIONS: In BAD and SCZ patients, diabetes diagnosis, other medical drug use, a high Framingham heart score, the number of antipsychotics, the disease duration, the patient's age, and an increased number of hospitalizations may increase the risk of cardiac arrhythmia. Therefore, possible cardiac risk should be considered in patients with chronic drug use, such as BAD and SCZ. Regulating the treatment and follow-up of this group of patients against possible cardiac risks will reduce cardiac mortality and morbidity
Assuntos
Antipsicóticos , Transtorno Bipolar , Doenças Cardiovasculares , Esquizofrenia , Humanos , Feminino , Doenças Cardiovasculares/epidemiologia , Antipsicóticos/efeitos adversos , Transtorno Bipolar/epidemiologia , Esquizofrenia/epidemiologia , CoraçãoRESUMO
In this study we describe the management of postnatal women with a bipolar disorder diagnosis who were prescribed either lithium or sodium valproate. There was a 38.2% (13 out of 34) relapse rate in patients discharged on lithium, compared to 46.7% (14 out of 30) relapse in patients discharged with valproate. Only 20 women (29.9%) continued to breastfeed at discharge. There were 32 (47.8%) who ceased breastfeeding during their MBU admission and 23 (34.3%) of whom ceased due to initiation of lithium therapy.
Assuntos
Antimaníacos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Aleitamento Materno/estatística & dados numéricos , Compostos de Lítio/uso terapêutico , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Assistência Perinatal , Complicações na Gravidez/tratamento farmacológico , Ácido Valproico/uso terapêutico , Adulto , Feminino , Seguimentos , Humanos , Alta do Paciente/estatística & dados numéricos , Período Pós-Parto , Gravidez , Recidiva , Adulto JovemRESUMO
BACKGROUND: German S3 guidelines are subject to the highest methodological standards. This includes that they are only valid for a certain time period. Following the first edition in 2012 the first update of the S3 guidelines on bipolar disorder has now been published (2019). OBJECTIVE: What has changed in the field of pharmacological recommendations comparing the first edition with the update in 2019? MATERIAL AND METHODS: Comparison of the 1st edition from 2012 with the update from 2019 of the S3 guidelines for the diagnostics and treatment of bipolar disorders. RESULTS: The three principle treatment targets of acute treatment of bipolar depression, acute treatment of mania and phase prophylaxis (maintenance treatment) can be distinguished. For acute treatment of bipolar depression, for the first time a medication has received a level A recommendation: quetiapine. For the acute treatment of mania, several drugs are still recommended with the same level of recommendation (B). Asenapine has been added as the tenth substance. Lithium is still the only drug with a level A recommendation for maintenance and prophylactic treatment and is also the only drug approved for this indication without restrictions. A new recommendation is that in the absence of contraindications, phase prophylaxis with a serum level of at least 0.6â¯mmol/l should be carried out. With a B recommendation, quetiapine has been added to the drugs for phase prophylactic treatment. CONCLUSION: The S3 guidelines make recommendations at the highest scientific level. In view of these findings, lithium is clearly underutilized for maintenance therapy. In the absence of clear contraindications (advanced renal insufficiency), every patient with bipolar disease should be given the chance of lithium prophylaxis for an adequately long period.
Assuntos
Antipsicóticos , Transtorno Bipolar , Guias como Assunto , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Tratamento Farmacológico/tendências , Alemanha , Humanos , Fumarato de Quetiapina/uso terapêuticoRESUMO
Tremor is a well-known side effect from many psychiatric medications, including lithium and dopamine antagonists. In patients whose psychiatric symptoms are stabilized and only respond to certain medications, deep brain stimulation may offer relief of the consequent motor complications. We report the case of an elderly male with disabling tremor related to lithium therapy for bipolar affective disorder, who was subsequently treated with deep brain stimulation. In this patient, we obtained recordings from the substantia nigra pars reticulata and performed a high-frequency stimulation protocol that robustly elicits long-term potentiation (LTP)-like changes in patients with Parkinson's disease. We hypothesized that in this patient, who did not have Parkinson's disease, the levels of inhibitory plasticity would be much greater. However, we found an unanticipated lack of plasticity in the patient with lithium-induced tremor, compared with two de novo control patients with Parkinson's disease. This patient was successfully treated with deep brain stimulation in the vicinity of the ventral oral posterior nucleus, an area of the thalamus that receives inputs from the basal ganglia. We postulate that the lithium-induced blockade of LTP may bring about motor complications such as tremor while simultaneously contributing to the therapeutic mechanism for treating the symptoms of psychiatric disorders such as bipolar affective disorder.NEW & NOTEWORTHY Use of a dual-microelectrode technique enabled us to compare long-term potentiation (LTP)-like changes in a patient with lithium-induced tremor to that of patients with Parkinson's disease. This study corroborated the findings in rodent brain slices that chronic lithium treatment may block LTP. Whereas a deficit in LTP may underlie the therapeutic mechanism for treating psychiatric disorders such as bipolar affective disorder, it may simultaneously contribute to consequent appearance of tremor.
Assuntos
Transtorno Bipolar/fisiopatologia , Lítio/efeitos adversos , Potenciação de Longa Duração/efeitos dos fármacos , Neurônios/fisiologia , Parte Reticular da Substância Negra/fisiopatologia , Tremor/induzido quimicamente , Tremor/fisiopatologia , Idoso , Transtorno Bipolar/complicações , Transtorno Bipolar/tratamento farmacológico , Estimulação Encefálica Profunda , Humanos , MasculinoRESUMO
INTRODUCTION: Continuation electroconvulsive therapy (c-ECT) is highly effective for the prevention of depressive symptom relapse. There is a lack of understanding, about how c-ECT works in humans, particularly with regard to its effects on brain derived neurotrophic factor (BDNF) concentrations. Here, we aimed to close a gap in the literature by evaluating BDNF levels in patients receiving c-ECT. METHODS: We included 13 patients with either unipolar or bipolar depression (mean age ± SD: 55.5 ± 17.1; f/m: 10/3; unipolar/bipolar: 10/3) who received between one and four c-ECT (average per patient: 2.8). Serum BDNF (sBDNF) levels were assessed before and after each c-ECT sessions. Clinical assessments were also administered both before and after treatment. RESULTS: Our analysis revealed a significant increase in sBDNF after each treatment (c-ECT 1-3: P < 0.001, c-ECT 4: P = 0.018). The application of multiple c-ECT treatments was not, however, associated with further sBDNF enhancements. Psychometric scores were not significantly altered following c-ECT. DISCUSSION: An increase in sBDNF concentrations subsequent to c-ECT parallel data from the animal literature, which has linked regularly applied electrical stimulation to neuroplastic processes. This finding suggests a relationship between ECT-induced sBDNF concentrations and (sustained) remission status, considering a stable clinical condition across c-ECT.
Assuntos
Transtorno Bipolar/sangue , Transtorno Bipolar/terapia , Fator Neurotrófico Derivado do Encéfalo/sangue , Transtorno Depressivo/sangue , Transtorno Depressivo/terapia , Eletroconvulsoterapia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevenção Secundária , Adulto JovemRESUMO
BACKGROUND: Rebound cholinergic syndrome is a rare, but well known unwanted phenomenon occurring after abrupt clozapine discontinuation. There have been previous reported cases of cholinergic rebound in the literature; however, these reports described cholinergic rebound following cessation of high doses of clozapine in patients diagnosed with schizophrenia. Here, we report a case of rebound cholinergic syndrome and catatonia in a male patient three days after abrupt discontinuation of 50 mg of clozapine prescribed for type I bipolar affective disorder. CASE PRESENTATION: A 66-year old male of Spanish origin, treated for type I bipolar affective disorder for 15 years and for Crohn disease, was brought to the emergency department because of a sudden onset of mutism, dysphagia and trismus. He was described catatonic and presented hypertension, tachycardia and tachypnea. His body temperature was normal and the laboratory tests were unremarkable at presentation. A head CT and an EEG were in the normal range. While reviewing his history, it appeared the he was on clozapine 50 mg a day, first introduced 2 months ago, during a previous hospitalization for a manic episode resistant to other mood stabilizers. For an unknown reason, the patient's psychiatrist stopped clozapine three days before the admission and replaced it by risperidone 5 mg and quetiapine 200 mg daily. A cholinergic rebound syndrome was then evoked. The patient's ability to speak recovered dramatically and fast after the intravenous administration of 2.5 mg of biperiden supporting the diagnosis. Risperidone and quetiapine were also stopped. The patient fully recovered in 20 days after the reintroduction of 50 mg of clozapine and 2.5 mg of biperiden daily. CONCLUSIONS: This case report underscores that cholinergic rebound syndrome may occur in patients suffering from bipolar affective disorders, being on clozapine as a mood stabilizer. The low dose clozapine does not preclude severe manifestations of the phenomenon. Progressive tapering should therefore be adopted in any case.
Assuntos
Catatonia/induzido quimicamente , Clozapina/efeitos adversos , Síndrome de Abstinência a Substâncias/psicologia , Suspensão de Tratamento , Idoso , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Colinérgicos/efeitos adversos , Clozapina/uso terapêutico , Humanos , MasculinoRESUMO
OBJECTIVE: Hypothyroidism is a well-documented consequence of lithium treatment. Less well known is a possible association between lithium therapy and hyperthyroidism. This may have clinical implications as rapid changes in thyroid hormones may worsen a person's affective state, while symptoms of hyperthyroidism can mimic those of mania. We therefore systematically reviewed the published literature for evidence of lithium-induced hyperthyroidism. METHODS: We searched PubMed, Embase and CINAHL for articles where individuals developed biochemically confirmed hyperthyroidism (with or without clinical symptoms), while on lithium therapy for an affective illness. We included case reports, case series, cross-sectional, case control and cohort studies. RESULTS: We included 52 studies, 39 of which were individual case reports and 3 were case series. There were 10 cross-sectional or case control or cohort studies. All the research designs suggested an association between the prescription of lithium and hyperthyroidism. However, these findings were limited by the quality of the included studies, small number of participants and the general lack of either a clear temporal relationship or dose response. CONCLUSION: Hyperthyroidism is an uncommon side-effect of lithium compared to hypothyroidism but may have clinical implications. However, large prospective studies are required to clarify this association and to further inform the management of patients treated with lithium where hyperthyroidism occurs.
Assuntos
Transtorno Bipolar/tratamento farmacológico , Hipertireoidismo/induzido quimicamente , Hipotireoidismo/induzido quimicamente , Compostos de Lítio/efeitos adversos , Transtornos Psicóticos/tratamento farmacológico , HumanosRESUMO
Considering the changes in moral principles, human behavior and behavioral values through the ages, in Egill Skallagrimsson's Saga, Egill presents us with altered mental status. This is in terms of what at present is considered symptoms of an anti-social personality, and bipolar affective disorder. Egill Skallagrimsson is considered one of the most famous Vikings in the Icelandic Sagas. Archaeological findings mentioned in Egill's Saga indicate disfigurement of his skull, which has led many authors to suggest that Egill suffered from skeletal dysplasia. The primary assumption in the literature is that Egill Skallagrimsson was affected by Paget's disease of bone. This consideration is additionally based on the scholar's interpretation of the Saga text. The unique storytelling style in the Saga of Egill Skallagrimsson is evident; however, the question of the story's truthfulness remains open. In this article, we investigate Egill Skallagrimsson's assumed Paget's disease of bone, based on the physical and mental symptoms disclosed in the Saga of Egill Skallagrimsson. Associated with the assumption, the author's hermeneutics of Egill's Saga in the context of modern-day knowledge of Paget's disease of bone, brings forward the probability estimate to the range of permille. In Scandinavian folklore and mythology, a tale by Saxo Grammaticus of a notorious shield-maiden named Visna, reminds of Egill, as noted by Snorri Sturluson. Hence, in reference to Egill Skallagrimsson's mental status and physical appearance as listed in Egill's Saga, the authors recommend the name for his condition to be "Visna of Egill Skallagrimsson".
Assuntos
Transtorno da Personalidade Antissocial/história , Transtorno Bipolar/história , Saúde Mental/história , Osteíte Deformante/história , Transtorno da Personalidade Antissocial/diagnóstico , Transtorno da Personalidade Antissocial/psicologia , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , História Medieval , Humanos , Islândia , Narração/história , Osteíte Deformante/diagnóstico , Osteíte Deformante/psicologiaRESUMO
BACKGROUND: A challenge of understanding the mechanisms underlying cognition including neurodevelopmental and neuropsychiatric disorders is mainly given by the potential severity of cognitive disorders for the quality of life and their prevalence. However, the field has been focused predominantly on protein coding variation until recently. Given the importance of tightly controlled gene expression for normal brain function, the goal of the study was to assess the functional variation including non-coding variation in human genome that is likely to play an important role in cognitive functions. To this end, we organized and utilized available genome-wide datasets from genomic, transcriptomic and association studies into a comprehensive data corpus. We focused on genomic regions that are enriched in regulatory activity-overlapping transcriptional factor binding regions and repurpose our data collection especially for identification of the regulatory SNPs (rSNPs) that showed associations both with allele-specific binding and allele-specific expression. We matched these rSNPs to the nearby and distant targeted genes and then selected the variants that could implicate the etiology of cognitive disorders according to Genome-Wide Association Studies (GWAS). Next, we use DeSeq 2.0 package to test the differences in the expression of the certain targeted genes between the controls and the patients that were diagnosed bipolar affective disorder and schizophrenia. Finally, we assess the potential biological role for identified drivers of cognition using DAVID and GeneMANIA. RESULTS: As a result, we selected fourteen regulatory SNPs locating within the loci, implicated from GWAS for cognitive disorders with six of the variants unreported previously. Grouping of the targeted genes according to biological functions revealed the involvement of processes such as 'posttranscriptional regulation of gene expression', 'neuron differentiation', 'neuron projection development', 'regulation of cell cycle process' and 'protein catabolic processes'. We identified four rSNP-targeted genes that showed differential expression between patient and control groups depending on brain region: NRAS-in schizophrenia cohort, CDC25B, DDX21 and NUCKS1-in bipolar disorder cohort. CONCLUSIONS: Overall, our findings are likely to provide the keys for unraveling the mechanisms that underlie cognitive functions including major depressive disorder, bipolar disorder and schizophrenia etiopathogenesis.
Assuntos
Transtorno Bipolar/genética , Transtorno Depressivo Maior/genética , Predisposição Genética para Doença , Esquizofrenia/genética , Regulação da Expressão Gênica , Loci Gênicos , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo Único , TranscriptomaRESUMO
Bipolar affective disorder type I imparts significant morbidity and disease burden in the population. It is characterized by occurrence of one or more manic episodes which may be preceded or followed by a depressive or hypomanic phase. About half of these manic episodes are characterized by the presence of psychotic features. The condition is further complicated when the patient has multiple comorbid conditions. We report here the case of a Caucasian woman, aged 66 years, previously diagnosed with Bipolar disorder who developed treatment refractory mania with psychotic feature after being on the immunosuppressive agent, tacrolimus, after kidney transplantation.
Assuntos
Transtorno Bipolar/induzido quimicamente , Rejeição de Enxerto/prevenção & controle , Imunossupressores/efeitos adversos , Transplante de Rim , Psicoses Induzidas por Substâncias/etiologia , Tacrolimo/efeitos adversos , Idoso , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Feminino , Humanos , Imunossupressores/uso terapêutico , Ácido Micofenólico/uso terapêutico , Prednisona/uso terapêutico , Psicoses Induzidas por Substâncias/tratamento farmacológico , Transtornos Psicóticos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Research suggests that maintaining treatment during pregnancy for women with bipolar affective disorder reduces the risk of relapse. However, one of the key questions for women and clinicians during pregnancy is whether there are implications of exposure to mood stabilizers for longer term child development. Despite these concerns, there are few recent systematic reviews comparing the impact on child developmental outcomes for individual mood-stabilizing agents to inform clinical decisions. OBJECTIVES: To examine the strengths and limitations of the existing data on child developmental outcomes following prenatal exposure to mood stabilizers and to explore whether there are any differences between agents for detrimental effects on child development. METHOD: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a rigorous systematic search was carried out of four electronic databases from their respective years of inception to September 2016 to identify studies which examined the effects of mood stabilizers including sodium valproate, carbamazepine, lamotrigine, lithium and second-generation antipsychotics on child developmental outcomes. RESULTS: We identified 15 studies for critical review. Of these, 10 examined antiepileptic drugs, 2 studied lithium and 3 studied second-generation antipsychotics. The most consistent finding was a dose-response relationship for valproate with higher doses associated with poorer global cognitive abilities compared to other antiepileptic drugs. The limited data available for lithium found no adverse neurodevelopmental outcomes. The limited second-generation antipsychotic studies included a report of a transient early neurodevelopmental delay which resolved by 12 months of age. CONCLUSION: This review found higher neurodevelopmental risk with valproate. While the existing data on lithium and second-generation antipsychotics are reassuring, these data are both limited and lower quality, indicating that further research is required. The information from this review is relevant for patients and clinicians to influence choice of mood-stabilizing agent in childbearing women. This must be balanced against the known risks associated with untreated bipolar affective disorder.
Assuntos
Anticonvulsivantes/efeitos adversos , Antimaníacos/efeitos adversos , Antipsicóticos/efeitos adversos , Transtorno Bipolar/tratamento farmacológico , Desenvolvimento Infantil/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Criança , Feminino , Humanos , GravidezRESUMO
BACKGROUND: Impairments in key neuropsychological domains (e.g. working memory, attention) and social cognitive deficits have been implicated as intermediate (endo) phenotypes for bipolar disorder (BD), and should therefore be evident in unaffected relatives. METHOD: Neurocognitive and social cognitive ability was examined in 99 young people (age range 16-30 years) with a biological parent or sibling diagnosed with the disorder [thus deemed to be at risk (AR) of developing BD], compared with 78 healthy control (HC) subjects, and 52 people with a confirmed diagnosis of BD. RESULTS: Only verbal intelligence and affective response inhibition were significantly impaired in AR relative to HC participants; the BD participants showed significant deficits in attention tasks compared with HCs. Neither AR nor BD patients showed impairments in general intellectual ability, working memory, visuospatial or language ability, relative to HC participants. Analysis of BD-I and BD-II cases separately revealed deficits in attention and immediate memory in BD-I patients (only), relative to HCs. Only the BD (but not AR) participants showed impaired emotion recognition, relative to HCs. CONCLUSIONS: Selective cognitive deficits in the capacity to inhibit negative affective information, and general verbal ability may be intermediate markers of risk for BD; however, the extent and severity of impairment in this sample was less pronounced than has been reported in previous studies of older family members and BD cases. These findings highlight distinctions in the cognitive profiles of AR and BD participants, and provide limited support for progressive cognitive decline in association with illness development in BD.
Assuntos
Atenção , Transtorno Bipolar/psicologia , Filho de Pais com Deficiência/psicologia , Endofenótipos , Irmãos , Percepção Social , Adolescente , Adulto , Transtorno Bipolar/genética , Estudos de Casos e Controles , Cognição , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Memória de Curto Prazo , Testes Neuropsicológicos , Adulto JovemRESUMO
PURPOSE: People with severe mental illnesses (SMI) experience a 17- to 20-year reduction in life expectancy. One-third of deaths are due to cardiovascular disease. This study will establish the relationship of SMI with cardiovascular disease in ethnic minority groups (Indian, Pakistani, Bangladeshi, black Caribbean, black African and Irish), in the UK. METHODS: E-CHASM is a mixed methods study utilising data from 1.25 million electronic patient records. Secondary analysis of routine patient records will establish if differences in cause-specific mortality, cardiovascular disease prevalence and disparities in accessing healthcare for ethnic minority people living with SMI exist. A nested qualitative study will be used to assess barriers to accessing healthcare, both from the perspectives of service users and providers. RESULTS: In primary care, 993,116 individuals, aged 18+, provided data from 186/189 (98 %) practices in four inner-city boroughs (local government areas) in London. Prevalence of SMI according to primary care records, ranged from 1.3-1.7 %, across boroughs. The primary care sample included Bangladeshi [n = 94,643 (10 %)], Indian [n = 6086 (6 %)], Pakistani [n = 35,596 (4 %)], black Caribbean [n = 45,013 (5 %)], black African [n = 75,454 (8 %)] and Irish people [n = 13,745 (1 %)]. In the secondary care database, 12,432 individuals with SMI over 2007-2013 contributed information; prevalent diagnoses were schizophrenia [n = 6805 (55 %)], schizoaffective disorders [n = 1438 (12 %)] and bipolar affective disorder [n = 4112 (33 %)]. Largest ethnic minority groups in this sample were black Caribbean [1432 (12 %)] and black African (1393 (11 %)). CONCLUSIONS: There is a dearth of research examining cardiovascular disease in minority ethnic groups with severe mental illnesses. The E-CHASM study will address this knowledge gap.
Assuntos
Transtorno Bipolar/etnologia , Doenças Cardiovasculares/etnologia , Etnicidade/psicologia , Disparidades nos Níveis de Saúde , Grupos Minoritários/psicologia , Transtornos Psicóticos/etnologia , Esquizofrenia/etnologia , Adulto , Povo Asiático/psicologia , Povo Asiático/estatística & dados numéricos , População Negra/psicologia , População Negra/estatística & dados numéricos , Região do Caribe/etnologia , Etnicidade/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Grupos Minoritários/estatística & dados numéricos , Prevalência , Pesquisa Qualitativa , Fatores Socioeconômicos , Reino Unido/epidemiologia , População Branca/psicologia , População Branca/estatística & dados numéricosRESUMO
Schizophrenia (SCH) is a complex, psychiatric disorder affecting 1 % of population. Its clinical phenotype is heterogeneous with delusions, hallucinations, depression, disorganized behaviour and negative symptoms. Bipolar affective disorder (BD) refers to periodic changes in mood and activity from depression to mania. It affects 0.5-1.5 % of population. Two types of disorder (type I and type II) are distinguished by severity of mania episodes. In our analysis, we aimed to check if clinical and demographical characteristics of the sample are predictors of symptom dimensions occurrence in BD and SCH cases. We included total sample of 443 bipolar and 439 schizophrenia patients. Diagnosis was based on DSM-IV criteria using Structured Clinical Interview for DSM-IV. We applied regression models to analyse associations between clinical and demographical traits from OPCRIT and symptom dimensions. We used previously computed dimensions of schizophrenia and bipolar affective disorder as quantitative traits for regression models. Male gender seemed protective factor for depression dimension in schizophrenia and bipolar disorder sample. Presence of definite psychosocial stressor prior disease seemed risk factor for depressive and suicidal domain in BD and SCH. OPCRIT items describing premorbid functioning seemed related with depression, positive and disorganised dimensions in schizophrenia and psychotic in BD. We proved clinical and demographical characteristics of the sample are predictors of symptom dimensions of schizophrenia and bipolar disorder. We also saw relation between clinical dimensions and course of disorder and impairment during disorder.
Assuntos
Transtorno Bipolar/psicologia , Depressão/psicologia , Esquizofrenia , Psicologia do Esquizofrênico , Estresse Psicológico/psicologia , Ideação Suicida , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polônia , Análise de Regressão , Fatores Sexuais , Adulto JovemRESUMO
We studied the efficacy of umbilical cord blood cells in the therapy of treatment-resistant depressive states in women. Concentrated umbilical cord blood cells were administered in a dose of 250 millions cells (4 injections at 1-week intervals). The control group received placebo. In both groups, reduction of depressive disorders and the decrease in hypothymia severity were observed. Infusions of cell concentrate contributed to delayed correction of treatment resistance and reduced the severity of depression to moderate. In the main group, significant, persistent, and long-term positive dynamics was observed in the cognitive sphere. The therapeutic potential of umbilical cord blood cell concentrate can be used to overcome treatment resistance formed in depressive patients.