How self-reflection and self-certainty are related to neurocognitive functioning: an examination of cognitive insight in bipolar disorder

Introduction. The pattern of associations between clinical insight, cognitive insight, and neurocognitive functioning was assessed in bipolar disorder patients.

Methods. Data from 42 bipolar disorder patients were examined. Cognitive insight was measured using the Beck Cognitive Insight Scale (BCIS). The BCIS is a 15-item self-report instrument consisting of two subscales, self-reflectiveness and self-certainty. Clinical insight was measured by the use of the item G12 of the Positive and Negative Syndrome Scale. Neurocognitive functioning was assessed using the International Society for Bipolar Disorders-Battery for Assessment of Neurocognition.

Results. Correlation analyses revealed significant positive associations between self-reflectiveness and speed of processing, attention, working memory, visual learning, and reasoning and problem solving. The subscale self-certainty was negatively correlated to working memory, however, this correlation disappeared when we controlled for confounding variables. No correlations between clinical insight and neurocognition were found. In addition, there was no association between cognitive insight and clinical insight.

Conclusion. Better neurocognitive functioning was more related to higher levels of self-reflectiveness than to diminished self-certainty.     

Polymorphisms of BDNF and CACNA1C are not associated with cognitive functioning in bipolar disorder or healthy controls

Introduction: The cause of cognitive dysfunction in bipolar disorder (BD) is not well understood. BDNF and CACNA1C are two susceptibility genes for the disorder that have also been reported to be associated with cognitive deficits in the disorder, but the studies have been small and with conflicting results. We therefore attempted to replicate an association between cognitive dysfunction with the most commonly studied single nucleotide polymorphisms rs6265 and rs1006737.

Methods: Regression models with five aggregated cognitive domains derived from a comprehensive test battery and IQ score were run using directly genotyped risk variants of SNPs rs6265 and rs1006737 as predictors with covariates as appropriate. Models were performed in a clinical sample of Swedish patients with BD (N?=?114) and sex- and age-matched population controls (N?=?104).

Results: No significant associations (regardless of correction for multiple testing) between the BDNF and CACNA1C risk variants and cognitive functioning were found in either patients or controls.

Conclusions: Our results do not support that the common genetic risk variants in rs6265 and rs1006737 are associated with cognitive dysfunction.     

Improving functional outcome in bipolar disorder: A pilot study on metacognitive training

Background

Effective group psychological interventions in bipolar disorder are rare. In this study, we present “metacognitive training (MCT) for bipolar disorder”—an adaption of a group intervention that has proven effective in other severe psychiatric disorders. MCT is a structured, interactive approach that addresses cognitive biases, social cognition, and self‐esteem. In this pilot study, we investigated psychosocial functioning as primary outcome measure, as well as the feasibility of MCT and its acceptance among bipolar patients.

Methods

Thirty‐four outpatients with bipolar disorder were recruited. Inclusion criteria were euthymia and psychosocial functioning with a score >11 assessed by the Functional Assessment Short Test. The subjects received eight weekly MCT sessions. Before and after the intervention, psychosocial functioning, quality of life (QoL), and patient views were assessed.

Results

Patients improved significantly in global psychosocial functioning, with a large effect size from baseline to post‐treatment. Over the intervention period, patient QoL improved significantly in terms of their physical health, however not for other QoL subdomains. Treatment adherence was 80%, and patients' appraisal of the training was positive.

Limitations

As this study lacks a control group, it is not possible to ascertain whether the positive treatment effects are attributable to MCT. Additionally, it is unclear whether gains in psychosocial functioning would have been maintained long term.

Conclusions

This pilot trial conclusively shows that MCT is feasible and provides preliminary evidence for both the acceptance and efficacy of MCT. Further studies with larger samples and control condition will be necessary to build on these findings.     

Genetics of bipolar disorder

Bipolar disorder (also known as manic depressive illness) is a complex genetic disorder in which the core feature is pathological disturbance in mood (affect) ranging from extreme elation, or mania, to severe depression usually accompanied by disturbances in thinking and behaviour. The lifetime prevalence of 1% is similar in males and females and family, twin, and adoption studies provide robust evidence for a major genetic contribution to risk. There are methodological impediments to precise quantification, but the approximate lifetime risk of bipolar disorder in relatives of a bipolar proband are: monozygotic co-twin 40-70%; first degree relative 5-10%; unrelated person 0.5-1.5%. Occasional families may exist in which a single gene plays the major role in determining susceptibility, but the majority of bipolar disorder involves the interaction of multiple genes (epistasis) or more complex genetic mechanisms (such as dynamic mutation or imprinting). Molecular genetic positional and candidate gene approaches are being used for the genetic dissection of bipolar disorder. No gene has yet been identified but promising findings are emerging. Regions of interest identified in linkage studies include 4p16, 12q23-q24, 16p13, 21q22, and Xq24-q26. Chromosome 18 is also of interest but the findings are confusing with up to three possible regions implicated. To date most candidate gene studies have focused on neurotransmitter systems influenced by medication used in clinical management of the disorder but no robust positive findings have yet emerged. It is, however, almost certain that over the next few years bipolar susceptibility genes will be identified. This will have a major impact on our understanding of disease pathophysiology and will provide important opportunities to investigate the interaction between genetic and environmental factors involved in pathogenesis. This is likely to lead to major improvements in treatment and patient care but will also raise important ethical issues that will need to be addressed.     

Parental reflective functioning and executive functioning in mothers with substance use disorder

Having a substance use disorder (SUD) may adversely affect caregiving capacities. Reflective functioning (RF) and executive functioning (EF) are both important capacities for sensitive parenting, and are often impaired in a SUD. Only a few studies have explored the possible association between the two phenomena. In this study, we used a neuropsychological test battery to assess EF, and the Parent Development Interview to assess RF in a sample of mothers with a SUD (N = 43). Although parental RF (PRF) was associated with EF, when controlled for intelligence (IQ) and mental health, there was no significant association between EF and PRF. Mental health, however, showed a significant negative association with PRF. Splitting the group in two based on PRF level, mothers with a negative to low PRF exhibited more severe difficulties in SUD-related aspects, as well as in several EF components, compared to mothers with an adequate to high PRF, highlighting the association between EF and PRF. The results from this study contribute to enhance our understanding of the dynamics underlying vulnerability in PRF that mothers with small children may experience. We suggest EF to be a prerequisite for adequate PRF, and for interventions to be customized accordingly regarding parents with a SUD.     

Interpersonal functioning in borderline personality disorder: A systematic review of behavioral and laboratory-based assessments

It is widely accepted that interpersonal problems are a central area of difficulty for those with borderline personality disorder (BPD). However, empirical elucidation of the specific behaviors, or patterns of behaviors, characterizing interpersonal dysfunction or dissatisfaction with relationships in BPD is limited. In this paper, we review the literature on interpersonal functioning of individuals with BPD by focusing on studies that include some assessment of interpersonal functioning that is not solely self-report; that is, studies with either behavioral laboratory tasks or manipulation of interpersonal stimuli in a controlled laboratory setting were included. First, we review the literature relevant to social cognition, including perceptual biases, Theory of Mind/empathy, and social problem-solving. Second, we discuss research that assesses reactivity to interpersonal stressors and interpersonal aggression in BPD. Next, we review the literature on trust and cooperation among individuals with BPD and controls. Last, we discuss the behavior of mothers with BPD in interactions with their infants. In conclusion, we specify areas of difficulty that are consistently identified as characterizing the interpersonal behaviors of those with BPD and the relevant implications. We also discuss the difficulties in synthesizing this body of literature and suggest areas for future research.     

Genetic linkage study of bipolar disorder and the serotonin transporter

The serotonin transporter (HTT) is an important candidate gene for the genetic transmission of bipolar disorder. It is the site of action of many antidepressants, and plays a key role in the regulation of serotonin neurotransmission. Many studies of affectively ill patients have found abnormalities in serotonin metabolism, and dysregulation of the transporter itself. The human serotonin transporter has been recently cloned and mapped to chromosome 17. We have identified a PstI RFLP at the HTT locus, and here report our examination of this polymorphism for possible linkage to bipolar disorder. Eighteen families were examined from three populations: the Old Order Amish, Iceland, and the general North American population. In addition to HTT, three other microsatellite markers were examined, which span an interval known to contain HTT. Linkage analyses were conducted under both dominant and recessive models, as well as both narrow (bipolar only) and broad (bipolar + recurrent unipolar) diagnostic models. Linkage could be excluded to HTT under all models examined. Linkage to the interval spanned by the microsatellites was similarly excluded under the dominant models. In two individual families, maximum lod scores of 1.02 and 0.84 were obtained at D17S798 and HTT, respectively. However, these data overall do not support the presence of a susceptibility locus for bipolar disorder near the serotonin transporter. © 1996 Wiley-Liss, Inc.     

Parent-child interactions in pediatric bipolar disorder

Parent-child relationships may have a significant effect on illness characteristics of children with pediatric bipolar disorder (PBD), and these relationships may, in turn, be affected by the child's illness. We characterized maternal reports of parent-child relationships using the five-factor Parent-Child Relationship Questionnaire (PCRQ) in 60 families (30 PBD youth and 30 matched controls). Data on child proband and parental psychopathology were also obtained. Compared to controls, parent-child relationships in the PBD group were characterized by significantly less warmth, affection, and intimacy, and more quarreling and forceful punishment. Among PBD participants, elevated symptoms of mania, comorbid ADHD, an earlier age of illness onset, living in a single parent home, and the presence of a parental mood disorder were associated with greater parent-child relationship difficulties. These findings have implications for the development of interventions that focus on the quality of parent-child relationships, in addition to symptom management, in the treatment of PBD.     

Lithium responsive bipolar disorder,unilineality, and chromosome 18: A linkage study

Over the last three years several studies have investigated the hypothesis of linkage between bipolar disorder and markers on chromosome 18. Although independent groups have reported positive results, it is still not clear how these should be interpreted, as linkage spans a considerably large segment of the chromosome. In this study we have investigated linkage with chromosome 18 markers in 19 families of lithium-responsive bipolar patients, as a way to select a more homogeneous population. In addition, we have investigated whether there is evidence of a parent-of-origin effect as suggested by previous studies. Eleven markers spanning the whole chromosome were typed and linkage analysis was carried out using parametric and nonparametric methods. Analysis of the whole sample provided nonsignificant linkage results. However, when the sample included only unilineal families, and was further stratified according to parental origin, two chromosomal regions provided modestly positive lod scores. Maximum lod scores of 1.04 (P = 0.001) at D18S53 and 0.87 (P = 0.045) at D18S61 were observed for maternal and paternal pedigrees, respectively. Nonparametric analysis yielded similar results. In conclusion, our results are congruent with previous reports that suggest an advantage of unilineal pedigrees in linkage analysis of bipolar disorder and cannot rule out a parent-of-origin effect in this genomic region. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:411–415, 1999. © 1999 Wiley-Liss, Inc.     

Genome‐wide association study of cognitive performance in U.S. veterans with schizophrenia or bipolar disorder

Cognitive impairment is a frequent and serious problem in patients with various forms of severe mental illnesses (SMI), including schizophrenia (SZ) and bipolar disorder (BP). Recent research suggests genetic links to several cognitive phenotypes in both SMI and in the general population. Our goal in this study was to identify potential genomic signatures of cognitive functioning in veterans with severe mental illness and compare them to previous findings for cognition across different populations. Veterans Affairs (VA) Cooperative Studies Program (CSP) Study #572 evaluated cognitive and functional capacity measures among SZ and BP patients. In conjunction with the VA Million Veteran Program, 3,959 European American (1,095 SZ, 2,864 BP) and 2,601 African American (1,095 SZ, 2,864 BP) patients were genotyped using a custom Affymetrix Axiom Biobank array. We performed a genome‐wide association study of global cognitive functioning, constructed polygenic scores for SZ and cognition in the general population, and examined genetic correlations with 2,626 UK Biobank traits. Although no single locus attained genome‐wide significance, observed allelic effects were strongly consistent with previous studies. We observed robust associations between global cognitive functioning and polygenic scores for cognitive performance, intelligence, and SZ risk. We also identified significant genetic correlations with several cognition‐related traits in UK Biobank. In a diverse cohort of U.S. veterans with SZ or BP, we demonstrate broad overlap of common genetic effects on cognition in the general population, and find that greater polygenic loading for SZ risk is associated with poorer cognitive performance.     

Polygenic prediction of bipolar disorder in a Latin American sample

To date, bipolar disorder (BD) genetic studies and polygenic risk scores (PRSs) for BD are based primarily on populations of European descent (EUR) and lack representation from other ancestries including Latin American (LAT). Here, we describe a new LAT cohort from the Mayo Clinic Bipolar Biobank (MCBB), a multisite collaboration with recruitment sites in the United States (EUR; 1,443 cases and 777 controls) and Mexico and Chile (LAT; 211 cases and 161 controls) and use the sample to explore the performance of a BD-PRS in a LAT population. Using results from the largest genome-wide association study of BD in EUR individuals, PRSice2 and LDpred2 were used to compute BD-PRSs in the LAT and EUR samples from the MCBB. PRSs explained up to 1.4% (PRSice) and 4% (LDpred2) of the phenotypic variance on the liability scale in the LAT sample compared to 3.8% (PRSice2) and 3.4% (LDpred2) in the EUR samples. Future larger studies should further explore the differential performance of different PRS approaches across ancestries. International multisite studies, such as this one, have the potential to address diversity-related limitations of prior genomic studies and ultimately contribute to the reduction of health disparities.     

Premorbid functioning in adolescent onset bipolar I disorder: a preliminary report from an ongoing study

BACKGROUND: This study reports on premorbid academic and peer functioning and psychiatric illness in a rigorously diagnosed sample (N = 28) of adolescent onset bipolar I patients. METHODS: Premorbid functioning was assessed by parental report and review of the Ontario School Record (OSR). Premorbid psychiatric diagnoses were assigned on the basis of all information gathered. RESULTS: Overall, findings suggest that this cohort demonstrates good to excellent peer and academic functioning prior to illness onset. Rates of premorbid psychiatric illnesses were similar to that described in epidemiologic samples. CONCLUSIONS: Results are discussed in relation to current understanding of early onset bipolar illness and directions for future research.     

Early childhood temperament in pediatric bipolar disorder and attention deficit hyperactivity disorder

Recent theories suggest that children with pediatric bipolar disorder (PBD) may exhibit more difficult temperaments premorbidly, including traits such as behavioral disinhibition and difficulty with emotion regulation. We investigated temperament characteristics retrospectively during infancy and toddlerhood in subjects with PBD (n=25), attention-deficit/hyperactivity disorder (ADHD; n=25), and healthy controls (n=25). Children with PBD were reported to experience increased difficult temperament in both infancy and toddlerhood compared to children with ADHD. Several characteristics of difficult temperament were associated with residual symptoms of mania and depression. Difficult premorbid temperament characteristics may be a specific indicator of a bipolar diathesis, or might signal underlying dysfunction in affective processes that significantly increase risk for a mood disorder.     

Meditation for treating adults with bipolar disorder II: A multi‐city study

There is a need to generate evidence on whether meditation's core aspect of building and nurturing calm and peace serves as a mood stabilizer for current and recurrent episodes of depression through the acute and maintenance phases of treating bipolar disorder II affected patients. A 2‐year longitudinal multi‐city randomized controlled trial experiment was conducted comprising 311 bipolar disorder II affected patients in the intervention and control group respectively across eight African and Asian cities. The Bipolar Depression Rating Scale (BDRS) was administered with the intervention and control groups that were equal at baseline. Meditation had a positive impact on the intervention group. Post intervention BDRS scores were significantly lower for patients from Asian cities, men, Hindus and Buddhists, middle class, and married patients as well as those who attended all the meditation rounds and regularly self‐practiced. Within the BDRS outcome measure, depressive symptoms were impacted the most as compared with mixed symptoms. Meditation helped alleviate guilt, depressed mood, and helplessness–hopelessness. The meditation programme can be used as a combination therapy along with pharmacological treatment to treat mood instability and depression among patients with bipolar disorder II.     

Unrecognised bipolar disorder among UK primary care patients prescribed antidepressants: an observational study

Background

Bipolar disorder is not uncommon, is associated with high disability and risk of suicide, often presents with depression, and can go unrecognised.

Aim

To determine the prevalence of unrecognised bipolar disorder among those prescribed antidepressants for depressive or anxiety disorder in UK primary care; whether those with unrecognised bipolar disorder have more severe depression than those who do not; and the accuracy of a screening questionnaire for bipolar disorder, the Mood Disorder Questionnaire (MDQ), in this setting.

Design and setting

Observational primary care study of patients on the lists of 21 general practices in West Yorkshire aged 16–40 years and prescribed antidepressant medication.

Method

Participants were recruited using primary care databases, interviewed using a diagnostic interview, and completed the screening questionnaire and rating scales of symptoms and quality of life.

Results

The prevalence of unrecognised bipolar disorder was 7.3%. Adjusting for differences between the sample and a national database gives a prevalence of 10.0%. Those with unrecognised bipolar disorder were younger and had greater lifetime depression. The predictive value of the MDQ was poor.

Conclusion

Among people aged 16–40 years prescribed antidepressants in primary care for depression or anxiety, there is a substantial proportion with unrecognised bipolar disorder. When seeing patients with depression or anxiety disorder, particularly when they are young or not doing well, clinicians should review the life history for evidence of unrecognised bipolar disorder. Some clinicians might find the MDQ to be a useful supplement to non-standardised questioning.     

A narrative review of cross-sectional and prospective associations between self-schemas and bipolar disorder

The role of self-concept in bipolar disorder (BD) has not been well understood. The present review utilizes the notion of self-schema and interrogates existing research concerning evidence for cross-sectional and prospective associations between four schema-like constructs (i.e. trait self-esteem, dysfunctional beliefs concerning contingent self-worth, early maladaptive schemas and implicit self-esteem) and various facets of BD. Existing findings demonstrate various types of involvement of self-schemas in BD. Of particular clinical relevance, the present review suggests that low trait self-esteem and dysfunctional beliefs concerning contingent self-worth are risk factors for ongoing BD symptoms and mood episodes. The present review also yields important yet unaddressed questions with respect to the evaluative content of self-schemas associated with the hypo/manic phase of BD.     

Symptom-related attributional biases in schizophrenia and bipolar disorder

Introduction: Biases in causal attributions and evidence integration have been implicated in delusions, but have not been investigated simultaneously to examine additive or multiplicative effects. It was hypothesised that paranoid delusions would correlate with self-serving and personalising biases (“defence” model of paranoia), particularly when these biases were disconfirmed.

Methods: Constrained principal component analysis was used to investigate differences between schizophrenia patients (paranoid vs. non-paranoid), bipolar disorder patients, and healthy controls, as well as to examine the extent to which psychotic symptoms could predict patterns of responding on a novel attributional bias task (Attributional Style BADE, or ASB) that requires integrating contextual information.

Results: Although no group differences were found, disorganisation and manic symptoms correlated with situation attributions and self-blame when such attributions were unsupported by the available evidence, and depression and anxiety correlated with other-person and self attributions (not situation attributions) when confirmed by the available evidence, regardless of diagnosis.

Conclusions: While group differences accounted for little variance in responses on the ASB task, a transdiagnostic association between symptoms of psychosis and the ASB task was observed. This highlights the importance of considering symptom profiles rather than diagnostic groupings when investigating cognitive biases and related non-pharmacological treatments.     

Suicidal risk in young adult offspring of mothers with bipolar or major depressive disorder: a longitudinal family risk study

Recent evidence has highlighted suicidal risk associated with bipolar disorder (BD). Using a family risk approach, the goal of this study was to evaluate suicidal thoughts and behaviors longitudinally from childhood to young adulthood in children of mothers with BD, Major depressive disorder (MDD), and well mothers. Few group differences were found for cross-sectional assessments of suicidal thoughts and behavior in young adulthood; the offspring of MDD demonstrate an earlier onset and more persistent suicidality than other groups, but by young adulthood, BD offspring appear to be comparable to MDD offspring in their rates of suicidality. The longitudinal assessments reveal a pattern of higher suicidal risk in MDD offspring, more intermediate risk in BD offspring, and lower risk in well offspring. Precursors and correlates of suicidal thoughts and behaviors were also examined. These findings suggest diverse developmental trajectories based on family risk and have implications for planning preventive intervention.