Treatment Of Bipolar Disorder Research Articles

SPIRAL MRI for in vivo lithium-7 imaging: a feasibility study in mice after oral lithium treatment

Lithium has been the frontline treatment for bipolar disorder for over 60 years. However, its mode of action and distribution in the brain is still incompletely understood. The primary isotope of lithium, lithium-7 (7Li), is a magnetic resonance (MR) active, spin-3/2 nucleus. However, its low MR sensitivity and the small brain size of mice make 7Li MR imaging (MRI) difficult in preclinical research. We tested four MRI sequences (FLASH, RARE, bSSFP, and SPIRAL) on lithium-containing phantoms, and bSSFP and SPIRAL on orally lithium-treated adult C57BL/6 mice. 7Li MR spectroscopy was acquired weekly at 9.4T to monitor the lithium uptake. The in vivo T1 relaxation time of 7Li was estimated in four mice. 4-h SPIRAL 7Li MRI was acquired in ten mice at a resolution of 2 × 2 × 3 mm3. SPIRAL MRI provided the highest signal-to-noise ratio (SNR) per unit acquisition time and the best image quality. We observed a non-homogeneous distribution of lithium in the mouse brain, with the highest concentrations in the cortex, ventricles, and basal brain regions. Almost no lithium signal was detected in the olfactory bulb and the cerebellum. We showed that in vivo 7Li MRI in mice is feasible, although with limited spatial resolution and SNR.

Weight change following diagnosis with psychosis: a retrospective cohort study in Greater Manchester, UK

IntroductionWeight gain in the months/years after diagnosis/treatment of severe enduring mental illness (SMI) is a major predictor of future diabetes, dysmetabolic profile and increased risk of cardiometabolic diseases. There is limited data on the longer-term profile of weight change in people with a history of SMI and how this may differ between individuals. We here report a retrospective study on weight change over the 5 years following an SMI diagnosis in Greater Manchester UK, an ethnically and culturally diverse community, with particular focus on comparing non-affective psychosis (NAP) vs affective psychosis (AP) diagnoses.MethodsWe undertook an anonymised search in the Greater Manchester Care Record (GMCR). We reviewed the health records of anyone who had been diagnosed for the first time with first episode psychosis, schizophrenia, schizoaffective disorder, delusional disorder (non-affective psychosis = NAP) or affective psychosis (AP). We analysed body mass index (BMI) change in the 5-year period following the first prescription of antipsychotic medication. All individuals had taken an antipsychotic agent for at least 3 months. The 5-year follow-up point was anywhere between 2003 and 2023.ResultsWe identified 9125 people with the diagnoses above. NAP (n = 5618; 37.3% female) mean age 49.9 years; AP (n = 4131; 60.5% female) mean age 48.7 years. 27.0% of NAP were of non-White ethnicity vs 17.8% of AP individuals. A higher proportion of people diagnosed with NAP were in the highest quintile of social disadvantage 52.4% vs 39.5% for AP. There were no significant differences in baseline BMI profile. In a subsample with HbA1c data (n = 2103), mean HbA1c was higher in NAP at baseline (40.4 mmol/mol in NAP vs 36.7 mmol/mol for AP). At 5-year follow-up, there was similarity in both the overall % of individuals in the obese ≥ 30 kg/m2 category (39.8% NAP vs 39.7% AP), and % progressing from a normal healthy BMI transitioned to obese/overweight BMI (53.6% of NAP vs 55.6% with AP). 43.7% of those NAP with normal BMI remained at a healthy BMI vs 42.7% with AP. At 5-year follow-up for NAP, 83.1% of those with BMI ≥ 30 kg/m2 stayed in this category vs 81.5% of AP.ConclusionThe results of this real-world longitudinal cohort study suggest that the changes in BMI with treatment of non-affective psychosis vs bipolar disorder are not significantly different, while 43% maintain a healthy weight in the first 5 years following antipsychotic prescription.

Gene Expression Differences and Similarities between Bipolar Disorder and Gliomas Studied by Brain Expression Data

Both bipolar disorder and glioma are highly prevalent diseases. Bipolar disorder is a significant mental illness, while glioma constitutes 46% of intracranial tumors. By conducting differential expression analysis, Weighted Gene Coexpression Network Analysis, and Gene Ontology enrichment analysis on brain expression data of bipolar disorder and glioma, it was found that these two conditions share three terms: protein localization to organelle, organelle localization, and protein maturation. Exploring targeted therapy and drug-targeting research on these three terms can offer novel insights for the treatment of both bipolar disorder and glioma.

Prof. Tarhan: "Diagnosis and treatment of bipolar disorder and attention deficit disorder have become easier"

President of Üsküdar University, Psychiatrist Prof. Nevzat Tarhan evaluated the topic of brain mapping in the treatment of psychiatric diseases.

Bipolar affective disorder occurring with psychopharmacotherapy-induced manic phases

To analyze the stages of development of the problem, identify the evolution of views and the main directions of current research in the field of bipolar affective disorder, which occurs with psychopharmacotherapy-induced manic phases, the search for publications by keywords «pharmaco-induced mania»", «bipolar affective disorder» was carried out in the PubMed/MEDLINE, Russian Citation index and other sources from the mid-19th century to the present. The issue of adequate treatment of bipolar depression became relevant back in the 20th century; numerous observations indicated the presence of associated risks when using antidepressants in patients with bipolar affective disorder, namely, the likelihood of affect inversion and aggravation of the course of the disease (accelerated cyclicity, continuum). In recent years, due to the expansion of research capabilities and the introduction of biological psychiatry, works have appeared that consider this problem from both clinical and pharmacodynamic, genetic and neurophysiological aspects, which opens up the prospect of developing advanced methods of personalized medicine for the diagnosis and treatment of bipolar disorder, taking into account the need to minimize iatrogenic effects.

拉莫三嗪治疗双相障碍致罕见延迟皮疹1例

拉莫三嗪治疗双相障碍致罕见延迟皮疹1例

Lithium and exercise ameliorate insulin-deficient hyperglycemia by independently attenuating pancreatic α-cell mass and hepatic gluconeogenesis.

As in type 1 diabetes, the loss of pancreatic β-cells leads to insulin deficiency and the subsequent development of hyperglycemia. Exercise has been proposed as a viable remedy for hyperglycemia. Lithium, which has been used as a treatment for bipolar disorder, has also been shown to improve glucose homeostasis under the conditions of obesity and type 2 diabetes by enhancing the effects of exercise on the skeletal muscles. In this study, we demonstrated that unlike in obesity and type 2 diabetic conditions, under the condition of insulin-deficient type 1 diabetes, lithium administration attenuated pancreatic a-cell mass without altering insulin-secreting β-cell mass, implying a selective impact on glucagon production. Additionally, we also documented that lithium downregulated the hepatic gluconeogenic program by decreasing G6Pase protein levels and upregulating AMPK activity. These findings suggest that lithium's effect on glucose metabolism in type 1 diabetes is mediated through a different mechanism than those associated with exerciseinduced metabolic changes in the muscle. Therefore, our research presents the novel therapeutic potential of lithium in the treatment of type 1 diabetes, which can be utilized along with insulin and independently of exercise.

Lithium treatment for affective disorders in old age

Lithium is considered the gold standard for the treatment of bipolar affective disorder for the prevention of recurrence of manic and depressive episodes and for augmentation treatment in unipolar severe depressive episodes. The indications for treatment with lithium do not differ for older or younger patients. Nevertheless, there are anumber of aspects to be considered with respect to drug safety in the group of old patients. The aim was to give an overview of the current literature on lithium treatment in old age and from this to derive recommendations for action. Aselective literature review on lithium treatment in old age was conducted to answer questions on drug safety, monitoring (particularly with respect to comorbidities) and potential alternatives to lithium. Lithium is an effective and, if used correctly, safe drug also in old people; however, with respect to somatic comorbidities that increase with age, special caution is required when using lithium in order to prevent nephropathy and intoxication.

Mortality risk and mood stabilizers in bipolar disorder: a propensity-score-weighted population-based cohort study in 2002-2018.

Accumulating studies have assessed mortality risk associated with mood-stabilizers, the mainstay treatment for bipolar disorder (BD). However, existing data were mostly restricted to suicide risk, focused on lithium and valproate and rarely adequately adjusted for potential confounders. This study aimed to assess comparative mortality risk with all, natural and unnatural causes between lithium, valproate and three frequently prescribed second-generation antipsychotics (SGA), with adjustment for important confounders. This population-based cohort study identified 8137 patients with first-diagnosed BD, who had exposed to lithium (n = 1028), valproate (n = 3580), olanzapine (n = 797), quetiapine (n = 1975) or risperidone (n = 757) between 2002 and 2018. Data were retrieved from territory-wide medical-record database of public healthcare services in Hong Kong. Propensity-score (PS)-weighting method was applied to optimize control for potential confounders including pre-existing chronic physical diseases, substance/alcohol use disorders and other psychotropic medications. PS-weighted Cox proportional-hazards regression was conducted to assess risk of all-, natural- and unnatural-cause mortality related to each mood-stabilizer, compared to lithium. Three sets of sensitivity analyses were conducted by restricting to patients with (i) length of cumulative exposure to specified mood-stabilizer ≥90 days and its medication possession ratio (MPR) ≥90%, (ii) MPR of specified mood-stabilizer ≥80% and MPR of other studied mood-stabilizers <20% and (iii) monotherapy. Incidence rates of all-cause mortality per 1000 person-years were 5.9 (95% confidence interval [CI]: 4.5-7.6), 8.4 (7.4-9.5), 11.1 (8.3-14.9), 7.4 (6.0-9.2) and 12.0 (9.3-15.6) for lithium-, valproate-, olanzapine-, quetiapine- and risperidone-treated groups, respectively. BD patients treated with olanzapine (PS-weighted hazard ratio = 2.07 [95% CI: 1.33-3.22]) and risperidone (1.66 [1.08-2.55]) had significantly higher all-cause mortality rate than lithium-treated group. Olanzapine was associated with increased risk of natural-cause mortality (3.04 [1.54-6.00]) and risperidone was related to elevated risk of unnatural-cause mortality (3.33 [1.62-6.86]), relative to lithium. The association between olanzapine and increased natural-cause mortality rate was consistently affirmed in sensitivity analyses. Relationship between risperidone and elevated unnatural-cause mortality became non-significant in sensitivity analyses restricted to low MPR in other mood-stabilizers and monotherapy. Valproate- and lithium-treated groups did not show significant differences in all-, natural- or unnatural-cause mortality risk. Our data showed that olanzapine and risperidone were associated with higher mortality risk than lithium, and further supported the clinical guidelines recommending lithium as the first-line mood-stabilizer for BD. Future research is required to further clarify comparative mortality risk associated with individual SGA agents to facilitate risk-benefit evaluation of alternative mood-stabilizers to minimize avoidable premature mortality in BD.

Potential Stem Cell Treatment for Alzheimer’s Disease with Possible Applications of Lithium Therapy

Alzheimer’s disease is characterized by progressive cognitive decline, including memory loss, impaired judgment, and changes in behavior. It is the most common cause of dementia and is known to generate pathological changes in the brain, such as amyloid plaques and neurofibrillary tangles which contribute to the symptoms. This disease affects over 55 million people worldwide and is known to frequently develop around the age of 65 and older. Bipolar disorder is characterized by extreme mood swings that include periods of mania involving heightened energy, euphoria, and depressive episodes leading to a loss of interest in many activities. These mood shifts can significantly impact the daily life and functioning of the affected person. There are more than 18 million people in the United States affected by this disease, and it is also known to be associated with the later development of neurodegenerative disorders like Alzheimer’s disease. Lithium has been used as a treatment for bipolar disorder for 60+ years while also being known to show effects decreasing the incidence of neurodegenerative disorders in a variety of patients. Regarding the treatment of Alzheimer’s disease, there is no present therapy approved to decrease the rate of development or cure the morbid disease after it has been diagnosed in individuals. Stem cell treatment is currently being studied through animal models to find a way to regenerate the loss of important neurological functions and combat the development of Alzheimer’s disease. Research has shown that lithium induces the proliferation of stem cells, including pluripotential stem cells and is a potent inhibitor of the biochemical process that results in the hyperphosphorlyation of Tau protein that is responsible for neurofibril tangles and neurological dysfunction observed in Alzheimer’s patients.

Drug repurposing and personalized treatment strategies for bipolar disorder using transcriptomics: an exploratory study.

The present study combined transcriptomic data and computational techniques based on gene expression signatures to identify new bioactive compounds or Food and Drug Administration-approved drugs for the treatment of bipolar disorder (BD). Five transcriptomic datasets containing 165 blood samples from individuals with BD were selected from the Gene Expression Omnibus (GEO). The number of participants varied from six to 60, with a mean age between 35 and 48 years and a gender difference between them. Most of these patients were receiving pharmacological treatment. Master regulator analysis (MRA) and gene set enrichment analysis (GSEA) were performed to identify genes that were significantly different between patients with BD and healthy controls and their associations with mood states in patients with BD. In addition, molecules that could reverse the transcriptomic profiles of BD-altered regulons were identified from the Library of Network-Based Cellular Signatures Consortium (LINCS) and the Broad Institute Connectivity Map Drug Repurposing Database (cMap) databases. MRA identified 59 candidate master regulators (MRs) that modulate regulatory units enriched with BD-altered genes. In contrast, GSEA identified 134 enriched genes and 982 regulons whose activation state was determined. Both analyses revealed genes exclusively associated with mania, depression, or euthymia, and some genes were shared among these three mood states. We identified bioactive compounds and licensed drug candidates, including antihypertensives and antineoplastic agents, as promising candidates for the treatment of BD. However, experimental validation is essential to confirm these findings in further studies. Although our data are still preliminary, they provide some insights into the biological patterns of different mood states in patients with BD and their potential therapeutic targets. The strategy of transcriptomics plus bioinformatics offers a way to advance drug discovery and personalized medicine by using gene expression information.

Real-world clinical determinants of alcohol dependence in outpatients with bipolar disorder: a multicenter treatment survey for bipolar disorder in psychiatric outpatient clinics with 2,392 participants.

Bipolar disorder is a psychiatric disorder characterized by mood swings between manic and depressed states that causes psychosocial problems. Cognitive function deteriorates with each recurrence, making it important to maintain remission through continued treatment. Bipolar disorder often co-occurs with alcohol dependence, which is known to lead to decreased treatment adherence and increased suicide risk. However, the real-world clinical determinants of alcohol dependence in outpatients with bipolar disorder in Japan remain unclear. We conducted an observational study targeting 2392 patients with bipolar disorder using data from the MUSUBI study, a joint project of the Japanese Association of Neuro-Psychiatric Clinics and the Japanese Society of Clinical Neuropsychopharmacology. After determining the prevalence of alcohol dependence and the sociodemographic characteristics of patients with bipolar disorder, multivariate analysis was performed to identify risk factors for alcohol comorbidity. The prevalence of alcohol dependence among outpatients with bipolar disorder in this study was 5.7%. The prevalence was 7.6% for males and 3.1% for females. The results of the binomial logistic regression analysis revealed that bipolar I disorder, manic state, comorbidities with other psychiatric disorders, male sex, and suicidal ideation were significantly associated with alcohol dependence. Stratified analysis by gender showed that alcohol dependence was more strongly associated with the presence of suicidal ideation in women than in men. First, because this was an observational study with a cross-sectional design, causal relationships between factors cannot be determined. In addition, this study included outpatients in Japan but lacked information on inpatients. Therefore, it was considered necessary to conduct the study on a larger population in order to generate more robust evidence. We found that outpatients with bipolar disorder, especially men, had higher rates of alcohol dependence overall than the general population in Japan. In addition, the relationship between alcohol dependence and suicidal ideation was stronger in women than in men with bipolar disorder. There was a strong association between manic states and alcohol dependence in outpatients with bipolar disorder. These results are useful to clinicians because they reinforce real-world clinical evidence for the treatment of bipolar disorder and co-occurring alcohol dependence.

Monoclonal antibody precision therapy targeting inflammation for bipolar disorder: a narrative review.

Bipolar disorder (BD) is a severe mental disorder with various hypotheses regarding its pathogenesis. This article provides a summary of numerous studies on the variations in inflammatory cytokine levels in patients with BD and the effects of treatment with antipsychotics, mood stabilizers, and antidepressants on these levels. In addition, patients with autoimmune diseases who use anti-inflammatory monoclonal antibodies experience symptoms, such as depression, anxiety, and insomnia. These pieces of evidence suggest a potential association between immune inflammation and BD and offer new possibilities for therapy. Building upon this relationship, the authors propose an innovative approach for treating BD through individualized and precise therapy using anti-inflammatory monoclonal antibody drugs. To support this proposal, the authors compile information on pharmacological effects and relevant studies, including trials of various anti-inflammatory therapeutic monoclonal antibody drugs (e.g. infliximab, tocilizumab, and canakinumab) for the potential treatment of BD and its associated side effects in psychiatry. The authors categorize these anti-inflammatory monoclonal antibody drugs into levels I-IV through a comprehensive analysis of their advantages and disadvantages. Their potential is examined, and the need for further exploration of their pharmaceutical effects is established.

Discussion on pathological diagnosis of psychoanalysis and psychiatry: bipolar disorder as an example

In this article, the significance of pathological diagnosis in psychoanalysis is explored. It goes from structure to understanding the individual, the certainty of diagnosis and the benefits of the effects of treatment, the exploration of relationship and prognosis. At the same time, a psychiatric diagnosis standard is introduced on the basis of the evolution of psychodynamics to the present taxonomy of symptoms. Whether the relationship between the two is a conflict or convergence is discussed. Furthermore, pathological diagnosis in Freudian psychoanalytic theory and the diagnostic content of DSM-5 of bipolar disorder are discussed in detail. By combining the situation of the author's clinical cases, the different pathological diagnosis methods of bipolar disorder within theories of psychiatry and psychoanalysis and the possible influence on the treatment are discussed in detail, in order to summarise the suggestions conducive to the diagnosis and treatment of bipolar disorder, and to provide reference for the development of clinical psychological work.

Aspects of the Use of Lithium Particles in the Treatment of Bipolar Disorder

Bipolar Disorder (BD) is characterized by chronic and complex disturbances, featuring periods of depression and phases of mania or hypomania. Considering the studies already conducted, it is important to highlight the efficacy of lithium in individuals, especially in relapse prophylaxis, acute mani a phases, and suicide prevention. Thus, this article aims to address various aspects related to the intrinsic relationship between Bipolar Disorder and the use of lithium, specifically for the maintenance therapy of this condition; to explore the mechanism of action of lithium, demonstrating the benefits of this therapy so that professionals and students in the field can gain a clearer understanding of the subject and evaluate the effectiveness of continuous lithium particle use in treatment. This work is based on a literature review conducted on the Pubmed and Scielo databases from 2018 to 2023. The descriptors used were lithium, treatment, and bipolar disorder. In this context, the review of studies on lithium is essential for healthcare proof essionals and the families of individuals to understand the importance of this substance in maintaining mood stability in patients.

Experiences of Interpersonal Emotion Regulation for People with Heightened Emotions: An Examination in People with Bipolar Disorder and Those with High Aggression

Most research on interpersonal emotion regulation (IER) has focused on nonclinical samples. On one hand, people with clinically significant emotion, mood, or interpersonal difficulties may encounter more challenges with IER. On the other hand, IER could potentially be a useful resource for addressing challenges related to intrapersonal emotion dysregulation. We analyzed data from two samples characterized by heightened emotionality: people who self-reported a history of bipolar disorder (N = 51) and people seeking treatment for aggression and emotional impulsivity (N = 199). For comparison, we analyzed data from two samples recruited without regard to clinical status: undergraduates (N = 389) and online respondents (N = 116). We assessed multiple aspects of participants’ experiences of intrinsic IER, including frequency of seeking and receiving IER, perceptions of provider responsiveness and provider hostility, perceptions of helpfulness, and reports of feeling ashamed due to receiving IER. We used two complementary methods: participants were first asked to report on their general experiences of seeking and receiving IER and were then asked to recall a rate a recent instance of receiving IER. Results were largely consistent across the two methods and the two comparison samples, providing a replication in-kind. Relative to the comparison samples, the aggression sample reported more negative experiences of IER, on average, including more difficulty obtaining IER, receiving less responsive support, encountering more hostility, and perceiving IER as less helpful. In contrast, the bipolar disorder sample appeared to be less distinct from the comparison samples. We discuss the implications of this apparent divergence.

Nicotine Addiction, Alcohol Use Disorder and Bipolar Disorder

Bipolar affective disorder has a wide range of effects on human health and is extremely harmful, and the mortality rate of patients continues to grow. Meanwhile, most people, especially those with mental illness, tend to numb themselves by smoking and drinking. Unfortunately, tobacco and alcohol abuse are also extremely harmful to human health, moreover, the cost of living will be increased due to addiction of these things. At the same time, the unconscious mind after using alcohol and tobacco has also brought great uneasiness to society, thus leading to increased burden on individuals and society. This review discusses the genetics, comorbidity, and treatment of nicotine dependence, alcohol use disorder, and bipolar disorder, and finds that the severity of bipolar disorder patients is positively correlated with the severity of alcohol use disorder and nicotine dependence. Both patients with bipolar disorder and alcohol use disorder exhibit mutations in the BDNF gene, and an age peak in bipolar disorder coincides with a peak in nicotine dependence. In the end, it is believed that the interaction between comorbidities may become a breakthrough in the diagnosis or treatment of bipolar disorder in the future, and the easy-to-observe alcohol and nicotine intake can be used to assist in judging the current state of patients.

Invited commentary to Professor Belmaker's letter on lithium treatment for bipolar disorder.

Invited commentary to Professor Belmaker's letter on lithium treatment for bipolar disorder.

Ciddi Nörolojik Bulgularla Birlikte Giden Lityum Zehirlenmesi Olgusu

Lithium is used for the treatment of bipolar disorder and some other psychiatric disorders. Due to the narrow therapeutic range, intoxications are common. In this case, chronic lithium intoxication with severe neurological symptoms was discussed in light of the literature. A 72-year-old female patient. The patient had been receiving psychiatric treatment for 7 years with the diagnosis of unipolar depression. In the 6th month of lithium use, she was brought by her relatives with complaints of drowsiness, tremor, muscle twitching, and difficulty walking. On examination, consciousness was confused, there was no cooperation orientation and there was general rigidity, tremor, fasciculations, and ataxic gait. Vital signs; blood pressure 147/92 mmHg, heart rate 69 bpm, SpO2: 94%. The laboratory tests: lithium 2.98 mEq/L, potassium 5.8 mmol/l, sodium 129 mmol/l, creatinine 1.66 mg/dl, urea 166 mg/dl. The patient was transferred to the internal medicine clinic with the diagnosis of lithium intoxication. Lithium treatment was discontinued. On the 7th day, her neurological symptoms improved with supportive treatment, and biochemical parameters returned to normal. A lithium concentration of more than 3.5 mEq/L was defined as severe poisoning. Neurological findings are prominent in severe poisonings. Especially, geriatric population is at greater risk. In our case; age, use of three different groups of diuretics as antihypertensive treatment, and urinary tract infection were defined as factors that predispose to poisoning. In this case, it's emphasized that although the lithium blood level isn't very high, severe neurological symptoms can be seen clinically in the presence of risk factors.

BIPOLAR DISORDER MANIC EPISODE WITH PSYCHOSIS : A CASE REPORT

Bipolar disorder (BD) is a psychiatric disorder that presents with manic and depressive episodes. The mood episodes appear as random and unpredictable episodes. The frequency and course of manic and depressive episodes may vary in each case and be determined by environmental factors as well as patient susceptibility.. A 25-year-old man, looks age appropriate, lacks self-care. He was taken to the emergency room because he was making noise about recommendations since 1 week before he was admitted to the hospital. 3 days before came to hospital was confused, easily emotional and had difficulty sleeping, talking to herself, having difficulty communicating, including being in a trance and starting to borrow and owe money to other people. Patients also see and hear sounds that other people do not hear. Further studies are needed for the evaluation of patients with bipolar disorder with psychosis and to acknowledge the treatment options with psychosocial educations as the support the treatment of bipolar disorder.