How to study psychological mechanisms of mania? A systematic review on the methodology of experimental studies on manic mood dysregulation of leading theories on bipolar disorder.

INTRODUCTION: Although there are several psychological theories on bipolar disorders (BD), the empirical evidence on these theories through experimental studies is still limited. The current study systematically reviews experimental methods used in studies on the main theories of BD: Reward Hypersensitivity Theory (RST) or Behavioral Activation System (BAS), Integrative Cognitive Model (ICM), Positive Emotion Persistence (PEP), Manic Defense theory (MD), and Mental Imagery (MI). The primary aim is to provide an overview of the used methods and to identify limitations and suggest areas of improvement. METHODS: A systematic search of six databases until October 2023 was conducted. Study selection involved two independent reviewers extracting data on experimental study design and methodology. RESULTS: A total of 84 experimental studies were reviewed. BAS and RST were the most frequently studied theories. The majority of these experimental studies focus on mechanisms of reward sensitivity. Other important elements of the reviewed theories, such as goal setting and-attainment, situation selection (avoidance or approach), activation, affective/emotional reactivity, and regulatory strategies, are understudied. Self-report and neuropsychological tasks are most often used, while mood induction and physiological measures are rarely used. CONCLUSION: There is a need for more consensus on the operationalization of psychological theories of mania. Standardization of test batteries could improve comparability among studies and foster a more systematic approach to experimental research. Research on affective (activated) states is still underrepresented in comparison with studies on trait vulnerabilities.

[Tapering maintenance treatment for bipolar disorders]. / Hoogste tijd voor onderzoek naar het afbouwen van onderhoudsbehandeling voor bipolaire stoornissen.

BACKGROUND: In bipolar disorder (BD) preventive maintenance treatment is the rule, yet the scientific evidence supporting this is limited. AIM: To argue the need for research into the gradual discontinuation of maintenance treatment for (BD). METHOD: A narrative review of evidence regarding the effectiveness of maintenance treatment for (BD), supplemented by exploration of potential reasons behind the predominant reliance on pharmacological interventions. RESULTS: Evidence for maintenance treatment primarily focuses on clinical effectiveness, while individuals with bipolar disorder may prioritize other outcome measures. Much research on (BD) centers on neurobiological or genetic aspects. CONCLUSION: A non-pharmacologic approach for longterm treatment in BD has been understudied. The desire of many individuals with bipolar disorder to managing their vulnerability with minimal (or no) medication necessitates thorough research on who, when, and how maintenance medication can be successfully tapered.

[Mental disorders in a dental practice. Psychomood disorders]. / Serie: Psychische stoornissen in de mondzorgpraktijk. Stemmings­stoornissen.

Individuals with a depressive or bipolar mood disorder have a higher prevalence of somatic comorbidities, including dental problems. This is partly due to impaired self-care, smoking, alcohol use, and an unhealthy diet, and partly due to the often long-term use of medication. Depression has a negative impact on concentration and motivation and increases anxiety and avoidant behavior. In addition, there are indications for an interaction between stress, psychopathology, neuro-inflammatory processes and somatic health. These (temporary) factors must be taken into consideration in dental care for persons suffering from depression. Also, one must be alert for interactions between psychiatric medications and medications used in dental care. Especially in chronic psychiatric disorders, a coordinated care between dentist, general practitioner, and psychiatrist is of importance.

A cognitive behavioural group therapy for bipolar disorder using daily mood monitoring.

BACKGROUND AND AIM: This study investigated the effects of group cognitive behavioural therapy (CBT) for patients with bipolar disorder. The development of CBT for this disorder is relatively under-explored. METHOD: Participants with bipolar I or II disorder were treated with group CBT in addition to treatment as usual. The effectiveness of the protocol was explored through sequence analysis of daily mood monitoring prior to, during and after the intervention. Also, a repeated measures design was used assessing symptomatology, dysfunctional attitudes, sense of mastery, psychosocial functioning, and quality of life at start and end of intervention, and at follow-up 2 and 12 months later. RESULTS: The results indicate that variation in mood states diminished over the course of the intervention. Also, there was a change from depressive states to more euthymic states. Greater number of reported lifetime depressive episodes was associated with greater diversity of mood states. There was an increase in overall psychosocial functioning and self-reported psychological health following the intervention. Improvement continued after treatment ended until follow-up at 2 months, and measured 1 year later, for outcomes representing depression, general psychosocial functioning and self-reported psychological health. Due to small sample size and the lack of a control group the results are preliminary. CONCLUSIONS: The results of this pilot study suggest that both offering CBT in group interventions and sequence analysis of time series data are helpful routes to further explore when improving standard CBT interventions for patients suffering from bipolar disorder.

[Carbamazepine and quetiapine: a neglected, but highly relevant interaction]. / Carbamazepine en quetiapine: een onderbelichte, maar zeer relevante interactie.

We describe a case of concomitant use of carbamazepine and quetiapine, with a highly relevant interaction that requires attention. The combination of these drugs can be prescribed in psychiatry, for example in bipolar disorder, but also in other disciplines. Pharmacotherapy is one of the cornerstones in the treatment of bipolar disorders, and a combination of drugs is frequently used. Carbamazepine, an anti-epileptic drug that is effective as a mood stabilizer, and quetiapine, a second-generation antipsychotic, are both recommended in the Dutch guideline. Besides monotherapy is a combination of both drugs possible. It is striking that carbamazepine and quetiapine have a strong pharmacokinetic interaction via the metabolizing liver enzyme, CYP3A4. This interaction results in a factor 10 reduction of quetiapine blood levels. This may result in a possible loss of clinical efficacy of quetiapine.

Study protocol of a multicenter randomized controlled trial of mindfulness-based cognitive therapy and treatment as usual in bipolar disorder.

BACKGROUND: Despite multiple pharmacological interventions, many people with bipolar disorder (BD) experience substantial residual mood symptoms, even in the absence of severe mood episodes, which have a negative impact on the course of illness and quality of life. Limited data are available on how to optimize treatment for BD, especially for those who suffer from persistent and residual depressive symptoms. Preliminary evidence suggests Mindfulness-Based Cognitive Therapy (MBCT) as a psychological treatment option for BD. This study aims to investigate whether adding MBCT to treatment as usual (TAU) will result in symptomatic and functional improvements in adults with BD compared to TAU alone. METHODS/DESIGN: This study is a prospective, evaluator blinded, multicenter, randomized controlled trial of MBCT + TAU and TAU alone in 160 adults with bipolar type I and type II. Assessments will be conducted at baseline (T0), mid-treatment (Tmid), and at 3 (T1), 6 (T2), 9 (T3), 12 (T4), and 15 (T5) months follow-up. Primary outcome is post-treatment severity of depressive symptoms (Inventory of Depressive Symptomatology- Clinician administered). Secondary outcomes are severity of (hypo) manic symptoms, anxiety, relapse rates, overall functioning, positive mental health, and cost-effectiveness. As possible mediators will be assessed rumination of negative affect, dampening and rumination of positive affect, mindfulness skills, and self-compassion. DISCUSSION: This study will provide valuable insight into the (cost-)effectiveness of MBCT on clinician- and self-rated symptoms of BD, relapse rates, positive mental health, and overall functioning. TRIAL REGISTRATION: NCT03507647 . Registered 25th of April 2018.

[Earlier recognition of bipolar disorder - necessity and advice for clinical practice]. / Tijdige herkenning van bipolaire stoornissen; noodzaak en praktijkadviezen.

BACKGROUND: There is an average 10-year delay in diagnosing bipolar disorder, hampering the application of effective therapeutic interventions.
AIM: To investigate factors contributing to early recognition.
METHOD: We give a stage-oriented overview of the opportunities for early recognition.
RESULTS: Recognition in stage 0 (at-risk) and stage 1 (prodromal) is yet impossible. In stage 2 (syndromal) there are opportunities for better recognition in patients presenting with depression by conducting a thorough (collateral) psychiatric assessment, family history and by applying additional screening tools. CONCLUSIONS There are opportunities for better recognition of bipolar disorder in the syndromal stage.

Evaluation of clarity of presentation and applicability of monitoring instructions for patients using lithium in clinical practice guidelines for treatment of bipolar disorder.

OBJECTIVES: Clinical practice guidelines (CPGs) for treatment of bipolar disorder (BD) aim to provide guidance to health care professionals on monitoring of patients using lithium. The aim was to assess the clarity of presentation and applicability of monitoring instructions for patients using lithium in CPGs for treatment of BD. METHODS: CPGs for treatment of BD were selected from acknowledged professional organizations from multiple continents. CPGs were rated on the clarity of presentation and applicability of lithium monitoring instructions using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool. The applicability of monitoring instructions was assessed according to the Systematic Information for Monitoring (SIM) score. Monitoring instructions were considered applicable when a SIM score of ≥3 was found. RESULTS: The clarity of presentation for six out of the nine CPGs was good (>70%) using the AGREE II tool. Only one CPG scored >70% on applicability. Descriptions of the resource implications and facilitators of and barriers to monitoring were most often missing. All CPGs contained instructions for monitoring of lithium serum levels and renal and thyroid function. Information provided in monitoring instructions (n = 247) was in general applicable to clinical practice (77%) based on the SIM score. Overall, a median SIM score of 3 (interquartile range 3-4) was found. CONCLUSIONS: Improvement of the applicability of CPGs is recommended, and can be achieved by describing the resource implications and facilitators of and barriers to monitoring. In addition, information on critical values and instructions on how to respond to aberrant monitoring parameters are needed. With such improvements, CPGs may better aid health care professionals to monitor patients using lithium.

[Bipolar disorder and alcohol use disorder: practical recommendations for treatment, based on a literature review]. / Bipolaire stoornissen en alcoholafhankelijkheid; praktische aanbevelingen voor behandeling op basis van een systematische literatuurstudie.

BACKGROUND: A fairly large proportion (25-50%) of patients with bipolar disorder (bd) also suffer from comorbid alcohol use disorder (aud). However, little is known how this type of morbidity should be treated. It is also unclear whether the current guidelines on bd have been influenced by aud.
AIM: To provide an overview of recent literature concerning the diagnosis and treatment of comorbid bd and aud.
METHOD: We systematically reviewed studies that have addressed three treatment options for this group of patients: pharmaco-therapy, psychological interventions and self-management techniques.
RESULTS: If health professionals decide to treat bd using a pharmaco-therapeutic intervention, they must proceed with caution because the patient may also be suffering from aud. From the very limited number of published articles on this subject, we conclude that the best solution to the problem is to add valproate to the lithium-based treatment. There is also limited evidence that other effective treatments may include the use of integrated psychological interventions, cognitive behavioural therapy and self-management techniques, but these possibilities need further investigation.
CONCLUSION: Treatment of patients suffering from both bd and aud should always focus on both disorders, either simultaneously or separately. If this approach is successful it is vitally important that care is better organised and that there is cooperation between institutions involved in treating addiction disorders and departments that specialise in the care of bd. These improvements are likely to lead to further developments and to more research into new forms of integrated treatment.

[The effects of pharmacological and psychotherapeutic treatment of comorbid anxiety disorders in patients with bipolar disorder]. / De effectiviteit van medicamenteuze en psychotherapeutische behandeling van comorbide angststoornissen bij patiënten met bipolaire stoornis.

BACKGROUND: The co-occurrence of bipolar disorder and anxiety disorder is associated with a worse prognosis. Clinical guidelines do not give clear therapeutic recommendations on this subject.
AIM: To review the evidence on the effectiveness of both psychotherapy and pharmacotherapy for anxiety disorders in patients with a bipolar disorder.
METHOD: A systematic search in PubMed, Embase, Cochrane en Psycinfo and subsequent screening of potential studies resulted in 11 included studies.
RESULTS: Five studies examined the effect of pharmacotherapy on treatment of comorbid anxiety disorders. One of these studies showed that both olanzapine and lamotrigine provided positive results in treating the anxiety disorders, with olanzapine being the more effective of the two. Conflicting results were found for quetiapine and valproic acid. The conclusion of one study was that risperidone was not effective. No studies were found researching the effect of psychotherapy on treatment of comorbid anxiety disorders. However, two case studies and four studies that included patients with mixed diagnoses, including bipolar disorder, proposed evidence that behavioral and cognitive behavioral therapy (cbt) had a positive effect on treatment of the comorbid anxiety disorder.
CONCLUSION: There is little evidence on the treatment of comorbid anxiety disorders in people with bipolar disorder. Psychotherapy is preferred due to the uncertainty of the effects of pharmacotherapy and the associated risk of causing side effects. Pharmacotherapy can be considered in cases where this is insufficiently effective.

High educational performance is a distinctive feature of bipolar disorder: a study on cognition in bipolar disorder, schizophrenia patients, relatives and controls.

BACKGROUND: Schizophrenia is associated with lower intelligence and poor educational performance relative to the general population. This is, to a lesser degree, also found in first-degree relatives of schizophrenia patients. It is unclear whether bipolar disorder I (BD-I) patients and their relatives have similar lower intellectual and educational performance as that observed in schizophrenia. METHOD: This cross-sectional study investigated intelligence and educational performance in two outpatient samples [494 BD-I patients, 952 schizophrenia spectrum (SCZ) patients], 2231 relatives of BD-I and SCZ patients, 1104 healthy controls and 100 control siblings. Mixed-effects and regression models were used to compare groups on intelligence and educational performance. RESULTS: BD-I patients were more likely to have completed the highest level of education (odds ratio 1.88, 95% confidence interval 1.66-2.70) despite having a lower IQ compared to controls (ß = -9.09, S.E. = 1.27, p < 0.001). In contrast, SCZ patients showed both a lower IQ (ß = -15.31, S.E. = 0.86, p < 0.001) and lower educational levels compared to controls. Siblings of both patient groups had significantly lower IQ than control siblings, but did not differ on educational performance. IQ scores did not differ between BD-I parents and SCZ parents, but BD-I parents had completed higher educational levels. CONCLUSIONS: Although BD-I patients had a lower IQ than controls, they were more likely to have completed the highest level of education. This contrasts with SCZ patients, who showed both intellectual and educational deficits compared to healthy controls. Since relatives of BD-I patients did not demonstrate superior educational performance, our data suggest that high educational performance may be a distinctive feature of bipolar disorder patients.

[Fatal aortarupture following electroconvulsive therapy]. / Aortaruptuur als fatale complicatie bij elektroconvulsietherapie.

Electroconvulsive therapy (ect) is a highly effective and safe form of treatment in psychiatry. However, fatal cardiovascular complications are rarely discussed in the literature. We describe the case of a 49-year old man who died from a ruptured aorta following treatment with ect.

[The general practitioner in charge of treatment of patients with bipolar disorder: an exploratory study]. / De huisarts als primaire behandelaar van patiënten met een bipolaire stoornis: een exploratief onderzoek.

BACKGROUND: The role of the general practitioner (gp) in the treatment of severe psychiatric disorders, including bipolar disorder (bd), is under discussion. AIM: To investigate how many patients with a recognised bd are being treated for their illness exclusively in the setting of primary care and to find out how many patients are registrated as having bd on their gp's file. METHOD: We made an exploratory study in a gp's database containing data for 14,254 Dutch adult patients in the Amsterdam over a period of 3.5 years (2010-2013). RESULTS: We found that the gp was in charge of the treatment of bd in less than one patient per practice. The percentage of patients officially recognised as having bd in the database we studied was 0.15%, a percentage that is much lower than the percentage of bd in the Dutch population as a whole. There are several possible explanations for this discrepancy. CONCLUSION: Given these low numbers, it is unlikely that the gps can have adequate experience of giving their bd patients the latest type of treatment. In view of the increasing role played by gps in the treatment of bd, it is important that there is strong collaboration with specialised mental health care, and that a low threshold prevails for consultation and referral.

Clinical malaria diagnosis in pregnancy in relation to early perinatal mother-to-child transmission of HIV: a prospective cohort study.

OBJECTIVES: We prospectively investigated fever symptoms and maternal diagnosis of malaria in pregnancy (MIP) in relation to child HIV infection among 2368 pregnant HIV-positive women and their infants, followed up from pregnancy until 6 weeks post-delivery in Tanzania. METHODS: Doctors clinically diagnosed and treated MIP and fever symptoms during prenatal health care. Child HIV status was determined via DNA polymerase chain reaction (PCR). Multivariable logistic regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for HIV mother-to-child transmission (MTCT) by the 6th week of life. RESULTS: Mean gestational age at enrolment was 22.2 weeks. During follow-up, 16.6% of mothers had at least one MIP diagnosis, 15.9% reported fever symptoms and 8.7% had both fever and MIP diagnosis. Eleven per cent of HIV-exposed infants were HIV-positive by 6 weeks. The RR of HIV MTCT was statistically similar for infants whose mothers were ever vs. never clinically diagnosed with MIP (RR 1.24; 95% CI 0.94-1.64), were diagnosed with one vs. no clinical MIP episodes (RR 1.07; 95% CI 0.77-1.48) and had ever vs. never reported fever symptoms (RR 1.04; 95% CI 0.78-1.38) in pregnancy. However, the HIV MTCT risk increased by 29% (95% CI 4-58%) per MIP episode. Infants of women with at least two vs. no MIP diagnoses were 2.1 times more likely to be HIV infected by 6 weeks old (95% CI 1.31-3.45). CONCLUSIONS: Clinical MIP diagnosis, but not fevers, in HIV-positive pregnant women was associated with an elevated risk of early HIV MTCT, suggesting that malaria prevention and treatment in pregnant HIV-positive women may enhance the effectiveness of HIV prevention in MTCT programmes in this setting. Future studies using a laboratory-confirmed diagnosis of malaria are needed to confirm this association.

Increased parental history of bipolar disorder in the United States: association with early age of onset.

OBJECTIVE: Early-onset bipolar (BP) disorder and other poor prognosis characteristics are more prevalent in patients from the United States than from the Netherlands and Germany (abbreviated as Europe). We explored the impact of parental loading for affective illness on onset and other characteristics of BP disorder. METHOD: Parental history for unipolar (UP) and bipolar (BP) depression and course of illness characteristics were obtained from self-report in adults (average age 42) with BP disorder. Illness characteristics were examined by χ2 and multinomial logistic regression in relationship to the degree of parental loading: i) both parents negative; ii) one UP disorder; iii) one with BP disorder; and iv) both affected. RESULTS: After controlling for many poor prognosis factors, compared with those from Europe, patients from the United States had more iii) one parent with BP disorder and iv) both parents affected. An early age of onset of BP disorder was independently associated with this increased parental loading for affective disorder. CONCLUSION: Parental history of BP disorder and both parents with a mood disorder were more common in the United States than Europe and were associated with an early onset of bipolar disorder and other poor prognosis characteristics. These findings deserve replication and exploration of the potential mechanisms involved and their therapeutic implications.

Staging systems in bipolar disorder: an International Society for Bipolar Disorders Task Force Report.

OBJECTIVE: We discuss the rationale behind staging systems described specifically for bipolar disorders. Current applications, future directions and research gaps in clinical staging models for bipolar disorders are outlined. METHOD: We reviewed the literature pertaining to bipolar disorders, focusing on the first episode onwards. We systematically searched data on staging models for bipolar disorders and allied studies that could inform the concept of staging. RESULTS: We report on several dimensions that are relevant to staging concepts in bipolar disorder. We consider whether staging offers a refinement to current diagnoses by reviewing clinical studies of treatment and functioning and the potential utility of neurocognitive, neuroimaging and peripheral biomarkers. CONCLUSION: Most studies to date indicate that globally defined late-stage patients have a worse overall prognosis and poorer response to standard treatment, consistent with patterns for end-stage medical disorders. We believe it is possible at this juncture to speak broadly of 'early'- and 'late'-stage bipolar disorder. Next steps require further collaborative efforts to consider the details of preillness onset and intermediary stages, and how many additional stages are optimal.

[Forcing patients with bipolar disorder to make a financial contribution to secondary psychiatric care may make them forsake care completely]. / Vraaguitval bij poliklinische patiënten met een bipolaire stoornis als gevolg van de eigen bijdrage in de tweedelijns-ggz.

BACKGROUND: In 2012 patients were required to make a personal financial contribution for secondary mental health care over and above their standard insurance fee. According to current guidelines, the majority of patients with bipolar disorder must be treated as outpatients at psychiatric clinics. It was to be expected that some patients would decide to discontinue their outpatient treatment on account of the newly imposed personal financial contribution. AIM: To obtain insight into the size and characteristics of the group of patients with bipolar disorder who were thinking about giving up treatment or had already decided to give it up because of the imposition of the personal financial contribution; also to find out which factors influenced patients' decisions and to discover how patients perceived the role of the GP as the provider of subsequent psychiatric care. METHOD: We conducted an exploratory study by sending a survey to all outpatients receiving treatment at three clinics specialising in the treatment of bipolar disorder. RESULTS: 640 patients responded to the survey (55% response); 15% of these patients were thinking about giving up treatment or had already decided to stop their treatment. They were influenced primarily by financial considerations. Two-thirds of the respondents did not consider that the GP was as a suitable alternative to outpatient care at a clinic. Even patients with moderate to serious symptoms were considering leaving secondary care. CONCLUSION: The obligatory financial contribution for secondary mental health care could have considerable consequences for a small number of patients with severe mood disorder who are currently treated as outpatients in secondary facilities. The increase in the compulsory & squo;own risk' insurance fee as from 2013 could have similar consequences.

Risk of psychiatric treatment for mood disorders and psychotic disorders among migrants and Dutch nationals in Utrecht, The Netherlands.

PURPOSE: While there are consistent reports of a high psychosis rate among certain groups of migrants in Europe, there is little information on their risk for mood disorders. The aim of this study was to investigate the risk of receiving psychiatric treatment for mood disorders or psychotic disorders, comparing migrants and Dutch nationals in an ethnically mixed catchment area. A second aim was to calculate the 1-year prevalence rates of psychotic disorders in first-generation migrants. METHOD: A psychiatric registry provided information on treatments at all in- and outpatient facilities. Statistics Netherlands provided annual population figures. RESULTS: The risk of receiving treatment for unipolar depressive disorder was increased for the Turkish-Dutch (first and second generation combined; age- and sex-adjusted relative risk 4.9; 95% CI: 4.4-5.5), Moroccan-Dutch (RR = 3.6; 3.3-4.0) and Surinamese-Dutch (RR=1.8; 1.5-2.2). The risk of being treated for bipolar disorder was not significantly increased for any group, except for the Turkish-Dutch of the second generation. The risk of treatment for non-affective psychotic disorder was very high for the Turkish-Dutch, Moroccan-Dutch and Surinamese-Dutch of the second generation. There was a large difference in the relative risk of this disorder between the Turkish-Dutch of the first (RR = 1.3; 1.0-1.8) and the second generation (RR = 8.7; 5.5-13.9). The 1-year prevalence rates of treated psychotic disorders were highest for Surinamese-Dutch (2.1%) and Moroccan-Dutch males (1.2%) of the first generation. Migrants from western-European countries were not at increased risk for any of these disorders. CONCLUSIONS: The stressful position of non-Western migrants in Dutch society has negative consequences on their mental health.

[Staging and profiling in bipolar disorders]. / Stagering en profilering bij bipolaire stoornissen.

BACKGROUND: Bipolar disorders are expressed in a wide variety of forms and last for different lengths of time. This has a major influence on diagnosis and treatment and on the interpretation of research findings. AIM: To propose and describe a method for staging and profiling of bipolar disorders. METHOD: We searched the literature for evidence of attempts to define stages of illness progression and risk factors that determine the course of illness. RESULTS: The staging of bipolar disorders evolves from a symptom-free phase with high-risk conditions to a treatment-resistent chronic mood disorder. A family history of recurrent mood disorder, affective symptoms in childhood and depression in adolescence strongly predict future bipolar disorder. The profiling system that we propose incorporates not only clinical phenomenology in accordance with current classification but also clinically relevant predictors for an unfavorable course of illness. These predictors include age at onset, cognitive profiles, comorbidity, traumatic life events, psychosis, suicidality, insight into illness, and respons to treatment. There is some emerging evidence for genetic or other biological markers. CONCLUSION: Staging and profiling may contribute to early diagnosis, preventive strategies, and personalised treatment and may provide guidance for further research.