International Journal of Bipolar Disorders最新文献

Background: A surrogate marker (a substitute indicator of the true outcome) is needed to predict subgroups of long-term lithium users at risk of end-stage kidney disease (ESKD). In this narrative review the aim is to determine the optimal surrogate endpoint for ESKD in long-term lithium users in a scientific context. MAIN: In a literature search in long-term lithium users, no studies on surrogate measurements on ESKD were identified. Therefore, comparable ESKD populations were sought, based on baseline eGFR, age, somatic comorbidity and sex. Articles were scored on comparability and risk of bias. Seventeen studies were included; ten studies evaluated a percentual decline (between 20 and 50% decline in eGFR) and seven studies focused upon a declining slope (from 1.63 to 6 ml/min/1,73m² decline per year), using an interval of one to five years. Study populations mostly included patients with cardiovascular disease and chronic kidney disease.

Conclusion: Currently, the most appropriate marker for ESKD in long term lithium users appears a 30% decline in eGFR in at least one year. In order to confirm this hypothesis, further research in a cohort of long-term lithium users is needed. Better feasible research on lithium induced nephropathy could result in more knowledge about the risk on kidney function decline in lithium users and guide clinical decision making on lithium use.

Background: Patients with bipolar disorder (BD) are at increased risk of dementia. The underlying mechanisms are debated. FDG-PET elucidates glucose metabolic reductions due to altered neuronal activity in the cerebral cortex, allowing detection and identification of neurodegenerative processes. This study aims to investigate cerebral glucose metabolism in cognitively impaired elderly patients with BD using FDG-PET imaging, to elucidate potential underlying mechanisms and improve diagnostic accuracy.

Methods: We conducted a retrospective analysis of FDG-PET scans from 32 cognitively impaired elderly patients with BD (mean age 70.4 years). These were compared with scans from 35 non-degenerative controls (NDC) and patients diagnosed with Alzheimer's disease (AD, n = 27), frontotemporal dementia (FTD, n = 26), and dementia with Lewy bodies (DLB, n = 18). Voxel-wise statistical analysis was performed using SPM software, adjusting for age and sex.

Results: No significant cortical hypometabolism was found in patients with BD compared to NDC. In contrast, typical patterns of hypometabolism were observed in the AD, FTD, and DLB groups. The findings suggest that late-life cognitive impairment in patients with BD is not due to a single common neurodegenerative process.

Conclusion: The absence of abnormal cortical metabolism in cognitively impaired elderly patients with BD suggests that cognitive impairment in this population may not be driven by a common neurodegenerative pathway. Further studies using other biomarkers are needed to investigate the brain processes involved, which could lead to improved understanding and management of cognitive impairment in patients with BD.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a common neuro-developmental disorder that often persists into adulthood. Moreover, it is frequently accompanied by bipolar disorder (BD) as well as borderline personality disorder (BPD). It is unclear whether these disorders share underlying pathomechanisms, given that all three are characterized by alterations in affective states, either long or short-term. BD is characterized by infrequent but intense mood shifts, while ADHD and BPD involve more dynamic emotional fluctuations. It is yet to be determined whether these disorders represent distinct phenomena or different points on a spectrum of affective dysregulation.

Methods: This study seeks to distinguish the emotional dysregulation of BPD, ADHD, and BD by using digital phenotyping, a measurement burst electronic-diary method with different sampling rates, and accelerometry to measure participants' activity. Our study will include 480 participants aged 14 to 50 (120 each from BPD, ADHD, BD, and healthy control groups) from five European sites. Participants' smartphones will provide continuous data on their digital phenotypes, i.e., by indicators of physical activity and communication, for one year, along with daily evening ratings of mood and sleep. Moreover, five intensive measurement periods of five days each, called measurement bursts, will occur throughout the year, with electronic diaries asking participants to report on mood, self-esteem, impulsivity, life events, social interactions, and dysfunctional behaviors ten times a day. Moreover, participants will wear activity sensors during the five measurement bursts. Statistical analysis aims to identify whether affective dysregulation aspects share or differ across disorders. Specifically, data analysis aims to investigate the differences in parameters of affect fluctuation such as attractor strength and variability between disorders and to test the association of genetic risk factors for psychiatric disorders and resilience factors with critical parameters of affect modulation.

Discussion: The results of this study offer the potential to link patients' external exposures with their affective state, reduce misdiagnosis, and determine the best timing for therapeutic interventions. Potential limitations of the study include insufficient recruitment of patients and drop-outs due to various protocol violations.

Trial registration: Study code: DRKS00028917, registered 27.07.2022, https://drks.de/search/de/trial/DRKS00028917 .

Background: The rate of suicide attempts by patients with bipolar disorder is high. In addition to patient and country specific factors, environmental factors may contribute to suicidal behavior. Sunlight has multiple diverse impacts on human physiology and behavior. Solar insolation is defined as the electromagnetic energy from the sun striking a surface area on earth. We previously found that a large change in solar insolation between the minimum and maximum monthly values was associated with an increased risk of suicide attempts in patients with bipolar I disorder.

Methods: The association between solar insolation and a history of suicide attempts in bipolar disorder was again investigated using an international database with 15% more data and more sites at diverse locations and countries.

Results: Data were available from 5641 patients with bipolar I disorder living at a wide range of latitudes in 41 countries in both hemispheres. A large change in solar insolation between the minimum and maximum monthly values was associated with a history of suicide attempts in patients with bipolar I disorder, a replication of our prior analysis. The estimated model also associated state sponsored religion in the onset country, female gender, a history of alcohol or substance abuse, and being part of a younger birth cohort with a history of suicide attempts.

Conclusions: A large change between the minimum and maximum monthly values of solar insolation was associated with a history of suicide attempts in bipolar I disorder, replicating our prior research. Physicians should be aware that daylight has wide ranging physiological and psychiatric impacts, and that living with large changes in solar insolation may be associated with an increased suicide risk.

Background: The Hypomania Checklist-32 is widely used to screen for bipolar disorder, but its length can be challenging for adolescents with manic symptoms. This study aimed to develop a shortened version of the HCL-32 tailored for adolescents using machine learning techniques.

Methods: Data from 2,850 adolescents (mean age 15.50 years, 68.81% female) who completed the HCL-32 were analyzed. Random forest (RF) and gradient boosting machine (GBM) algorithms were employed for feature selection. The area under the curve (AUC) was used to evaluate model performance. Receiver operating characteristic (ROC) analysis was conducted to determine optimal cutoff points for the shortened scale.

Results: An 8-item version of the HCL-32 was derived, maintaining high predictive accuracy (AUC = 0.97). The selected items captured core symptoms of adolescent mania, including increased energy, risk-taking, and irritability. Two cutoff points were identified: a score of 3 offered high specificity (0.98) and positive predictive value (0.98), while a score of 4 provided balanced sensitivity (0.87) and specificity (0.94) with the highest overall accuracy (0.91).

Conclusions: The machine learning-driven 8-item version of the HCL-32 demonstrates strong diagnostic utility for adolescent bipolar disorder, offering a more efficient screening tool without sacrificing clinical sensitivity. This shortened scale may improve assessment feasibility and accuracy in clinical settings, addressing the unique challenges of diagnosing bipolar disorder in adolescents.

Background: Cognitive impairment is frequently observed in bipolar disorder (BD). Previous findings indicated that predominant polarity could have an effect on cognitive deficits. This study aimed to examine the association between predominant polarity and cognitive impairments in BD.

Materials and methods: Euthymic BD patients with manic (MPP, n = 31), depressive (DPP, n = 25), undetermined predominant polarity (UPP, n = 28), and healthy controls (HC, n = 27) participated in the study. A battery of neurocognitive and social cognitive tests was implemented. Neurocognitive domains were identified via principal component analysis.

Results: The MPP group performed worse in the Controlled Oral Word Association Test (COWAT), Reading the Mind in the Eyes Test (RMET), and Hinting Test (HT) compared to the DPP group and reasoning/problem-solving skills compared to the UPP group. Both MPP and UPP groups showed impairments in processing speed compared to HC. Among patient groups, there was no significant difference in working memory, attention, processing speed, verbal, and visual domain scores. The MPP group had poorer scores compared to controls in most of the social cognitive and neurocognitive domains in the study, while the overall cognitive impairment in the DPP group was relatively milder.

Conclusions: Although our sample size was relatively small, the MPP group yielded more severe cognitive impairment in verbal fluency and social cognition tests compared to DPP. Patients with MPP are particularly vulnerable to cognitive impairment, making them a priority for cognitive enhancement interventions. Future studies should focus on the outcomes of cognitive and pharmacological interventions in these polarity subgroups.

Background: Lithium is our oldest continuously prescribed medication in psychopharmacology, with its history as an agent for treating mood disorders extending from the 19th century. Although clinicians prescribe it less frequently than in the past, its utility in treating bipolar disorder is unquestionable. Novel potential indications for its use in psychiatry have created excitement about broader roles for lithium in treating and preventing other disorders.

Content: Lithium is effective both in treating acute mania, as an adjunctive antidepressant, and as a maintenance treatment in bipolar disorder. Lithium has also shown some efficacy in treating and preventing unipolar depression, but less clearly than for bipolar maintenance treatment and acute mania. Common side effects include nausea, polyuria, tremor, weight gain and cognitive dulling. These side effects are typically manageable with reasonable clinical strategies. Lithium affects renal, thyroid and parathyroid function. With clinical monitoring, these effects are easily managed although infrequent cases of severe renal insufficiency may occur with long term use. Although not all studies are positive, a consistent database suggests the efficacy of lithium in decreasing suicide attempts and suicides, likely due to its effect on impulsivity and aggression as well as its prophylaxis against depressive and manic recurrences. Recent data have suggested lithium's potential efficacy for a number of new clinical indications. Lithium's neuroprotective effects suggest potential efficacy in preventing mild cognitive impairment (MCI) and dementia as well as in aiding recovery from strokes. Higher (but still trace) lithium levels in drinking water are associated with lower rates of dementia. It is still not clear how much lithium-and what serum lithium levels- are required for either of these effects. Other preliminary research suggests that lithium may also have antiviral effects and may decrease cancer risk.

Conclusions: Lithium continues to be the mainstay treatment of mood disorders in general and in bipolar disorder specifically. Other potential clinical uses for lithium in psychiatry have re-invigorated excitement for research in other areas such as suicide, preventing cognitive impairment and possibly preventing viral infections and diminishing cancer risk.

Background: Diagnosing bipolar disorder (BD) is challenging, and adequate treatment is of major importance to minimalize the consequences of the illness. Early recognition is one way to address this. Although in clinical research the prodromal phase of BD is gaining interest, the perspective of patients with BD and their caregivers on prodromal symptoms is still lacking. The aim of this study is to gain insights in prodromal symptoms of patients with BD and their caregivers before the onset of a first manic episode.

Methods: A qualitative research method was used to investigate prodromal symptoms one year prior to a first manic episode. In-depth interviews were conducted with patients with BD type I and their caregivers. Only patients with a first manic episode in the previous five years were included.

Results: The prodromal symptoms from patients' and caregivers' perspectives could be clustered into seven themes, with underlying subthemes: behavior (increased activity, destructive behavior, disinhibited behavior, inadequate behavior, changes in appearance), physical changes (changes in sleep, physical signals, differences in facial expression), communication (reciprocity, process, changes in use of social media), thought (process and content), cognition (changes in attention and concentration, forgetfulness), emotions (positive emotions, more intense emotions, mood swings), and personality (more pronounced manifestation of existing personality traits).

Conclusion: Patients with bipolar I disorder and their caregivers described subsyndromal manic features one year prior to a first manic episode. In addition, they recognized mood lability, physical changes and more pronounced manifestation of existing personality traits. The results of this study confirm the presence of a prodromal phase. In clinical practice, monitoring of prodromal symptoms of BD can be useful in patients with depression, especially those with a familial risk of BD.

Background: Increased awareness of the factors contributing to the diagnostic disparities seen in bipolar disorder between individuals of different heritage is needed to achieve equity in diagnosis and treatment. One such inequity is the provision of earlier treatment. Earlier treatment of patients diagnosed with bipolar disorder may prolong time to recurrence of mood episodes and reduce functional impairment and other poor outcomes associated with disease progression. The aim of this post hoc analysis was to study the efficacy and safety of long-acting injectable aripiprazole once-monthly 400 mg (AOM 400) in patients with earlier-stage bipolar I disorder (BP-I). Data from a 52-week multicenter, double-blind, placebo-controlled, randomized withdrawal trial of AOM 400 versus placebo in patients with BP‑I (NCT01567527) were analyzed. Those patients in the lowest quartiles for age (18-≤32 years; n = 70) or disease duration (0.13-≤4.6 years; n = 67) at baseline were categorized with earlier-stage BP-I. The primary endpoint was time from randomization to recurrence of any mood episode. Other endpoints included proportion of patients with recurrence of any mood episode, and change from baseline in Young Mania Rating Scale (YMRS) and Montgomery-Åsberg Depression Rating Scale (MADRS) total scores.

Results: Maintenance treatment with AOM 400 significantly delayed time to recurrence of any mood episode versus placebo in patients aged 18-≤32 years (hazard ratio [HR]: 2.46 [95% confidence interval (CI) 1.09, 5.55]; p = 0.0251) or with disease duration 0.13-≤4.6 years (HR: 3.21 [95% CI 1.35, 7.65]; p = 0.005). This was largely driven by a lower proportion of patients in the AOM 400 group with YMRS total score ≥15 or clinical worsening. Changes from baseline in MADRS total score in both earlier-stage groups indicated AOM 400 did not worsen depression versus placebo. The safety profile of AOM 400 was consistent with the original study. Note that the original study included patients who had previously been stabilized on AOM 400 monotherapy, which may have enriched the population with patients who respond to and tolerate AOM 400.

Conclusions: In this post hoc analysis, AOM 400 prolonged time to recurrence of any mood episode versus placebo in earlier-stage BP-I. These findings support early initiation of maintenance treatment with AOM 400.