Cognitive functioning and its heritability in bipolar I disorder

Bipolar I disorder is a severe psychiatric disorder characterized by episodic mood alterations that can be manic, depressive or mixed. Bipolar disorder seems to be highly genetic, but the etiology of this complex disorder has remained elusive. In recent years, studies have found that euthymic patients with bipolar disorder may have impairments particularly in executive functioning, verbal learning and memory. These impairments may be present also among some of the relatives of these patients, who may be vulnerable to the disorder. Using neuropsychological variables as endophenotypes, i.e. intermediate phenotypes between genes and the phenotypes, has been suggested to aid search for the etiological background of the disorder, but evidence is sparse on whether these variables fulfill the criteria for endophenotypes. The present thesis is part of the Genetic Epidemiology and Molecular Genetics of Severe Mental Disorders in Finland project. The specific aim was to investigate whether neuropsychological test variables would indicate genetic liability to the disorder and could therefore be regarded as endophenotypes. Thus, cognitive functions and their heritability were studied in bipolar I disorder patients and in their unaffected first-degree relatives from a population-based sample of families, comparing them to a population-based control group. In order to add homogeneity to the subgroups of bipolar disorder patients and their relatives, cognitive functions and their heritability were further studied in a group of families affected by bipolar I disorder only (bipolar families) and another group of families affected by both bipolar I disorder and schizophrenia or schizoaffective disorders (mixed families). Finally, the effect of processing speed on other cognitive functions was investigated. The study showed that especially executive functioning and processing speed fulfilled the endophenotype criteria. Impairments in these functions were found in bipolar patients and in their relatives irrespective of other severe psychopathology in the family. These functions were highly heritable in these families. Study also showed that generalized impairment in verbal memory may associate more with bipolar disorder than to vulnerability to other psychotic disorders, and be more related to fully developed disease; impairments in verbal learning and memory were found only in patients, and they were not found to be highly heritable. Finally, the most potential endophenotype, i.e. processing speed, seemed to contribute to a range of other cognitive dysfunctions seen in bipolar disorder patients. Processing speed, in particular, has also been shown to be a valid endophenotype in subsequent association analyses in psychiatric genetics in Finland and internationally. Information concerning cognitive impairments and their association with the psychosocial consequences of bipolar disorder is important in planning treatment. It is also important to understand and acknowledge that patients may have cognitive impairments that affect their everyday life. Psychosocial interventions and neuropsychological rehabilitation may supplement other conventional treatments for bipolar patients.

Prevalencia y factores asociados a la no adherencia en el tratamiento farmacológico de mantenimiento en adultos con trastorno afectivo bipolar

La prevalencia de no adherencia en el tratamiento de mantenimiento en el Trastorno Afectivo Bipolar esta en los rangos de 20% y un 60%, interviniendo diversos factores relacionados con el paciente, la enfermedad, el tratamiento, y la relación con el terapeuta, asociándose a una mayor morbilidad, mortalidad y riesgo de reingresos hospitalarios. Objetivos: Determinar la prevalencia y factores asociados a la no adherencia en tratamiento de mantenimiento de pacientes adultos con diagnóstico de trastorno afectivo bipolar. Métodos: Estudio de corte transversal incluyo 124 paciente que asistieron a consulta los meses de noviembre y diciembre , se aplicó cuestionario estructurado, que contenía las variables de factores asociados, demográficos, relacionadas con el paciente, con la enfermedad, el tratamiento, relación terapéutica y el sistema de salud, relacionados con la familia; la Escala de Impresión Global Para el Trastorno Bipolar Modificado (CGI – BPM -M) y apgar familiar Resultados: La prevalencia de no adherencia al tratamiento farmacológico de mantenimiento fue del 29.8%. Siendo esta mayor para las mujeres (64.9%) que para los hombres (35.1%), aunque esta diferencia no fue estadísticamente significativa (p= 0.17). Los factores asociados que estadísticamente significativos fueron mayor gravedad de la enfermedad OR 1.9 , antecedente de no adherencia (38% P=0.001), percepción negativa del terapeuta, menor insight( 87% RP4.65), mayor estigma(50% RP 6.2), no tener familiar que le recuerde toma del medicamento(73%). Conclusiones: La prevalencia estuvo en el rango de otros estudios realizados por Scott, Vieta et al, los factores asociados como estigma, antecedente de no adherencia, no tener apoyo familiar, un insight pobre y el habito de fumar ,pueden ser identificados desde el abordaje del paciente y modificados para mejorar la adherencia terapéutica

Affective disorder in the parents of a clinic sample of children with anxiety disorders

Background: Family history studies in adults reveal strong familiality for the anxiety disorders with some specificity. The aim of the current study was to establish whether there was an elevated rate of anxiety disorders in the parents of children with anxiety disorders, and whether there was intergenerational specificity in the form of disorder. Methods: The mental state of a clinic sample of 85 children with anxiety disorder and their parents was systematically assessed, together with a comparison sample of 45 children with no current disorder and their parents. Results: Compared to the rate of anxiety disorder amongst parents of comparison children, the rate of current anxiety disorder in mothers of anxious children was significantly raised, as was the lifetime rate of anxiety disorder for both mothers and fathers. The mothers of children with generalised anxiety disorder, social phobia, specific phobia and separation anxiety disorder all had raised lifetime rates of the corresponding disorder, but also raised rates of others disorders. Limitations: Only 60% of the fathers of the anxious children were assessed. Conclusions: Strong familiality of anxiety disorders was confirmed, especially between child and maternal anxiety disorder. All child anxiety disorders were associated with several forms of anxiety disorder in the mother. Some specificity in the form of anxiety disorder in the child and the mother was apparent for social phobia and separation anxiety disorder. The findings have implications for the management of child anxiety. (c) 2006 Elsevier B.V. All rights reserved.

Sadness in mothers’ ‘baby-talk’ predicts affective disorder in adolescent offspring

‘Baby-talk’ is common across cultures. It underpins infant vocal preferences, and helps regulate infant engagement. Its longer-term significance is unclear. In a longitudinal study, we found indications of ‘sadness’ in postnatally depressed mothers’ baby-talk statistically mediated effects of maternal depression on offspring adolescent affective disorder.

Maternal affective disorder and children’s representation of their families

Children’s perceptions of family relationship are related to their later emotional and social adjustment. This is of particular relevance in the context of family stressors such as maternal affective disorder. This study investigated the effects of maternal postnatal depression and anxiety on children’s family representations. In our sample of postnatally depressed mothers we also explored marital conflict as mediator between maternal psychopathology and children’s representations. Family drawings of 235 4–5 year-old children (93 control, 53 depressed and 89 anxious) were examined. When compared to controls, children of depressed, but not of anxious mothers, were more likely to draw themselves as less prominent than other family members and to represent a dysfunctional family, less likely to represent themselves with a happy face and showed a greater tendency of drawing bizarre pictures. Marital conflict mediated the association between maternal depression and dysfunctionality in drawings.

Bipolar II disorder : a review

Objectives: To review the current knowledge of bipolar II disorder.

Methods: Literature was reviewed after conducting a Medline search and a hand search of relevant literature.

Results: Bipolar II disorder is a common disorder, with a prevalence of approximately 3–5%. Distinct clinical features of bipolar II disorder have been described. The key to diagnosis is the recognition of past hypomania, while depression is the typical presenting feature of the illness. This is responsible for a significant rate of missed diagnosis, and consequent management according to unipolar guidelines. It is unclear if bipolar II disorder is over-represented amongst resistant depression populations and if abrupt offset of antidepressant action is a phenomenon over represented in bipolar II disorder, reflecting induction of predominantly depressive cycling. A few mood-stabilizer studies available provide provisional suggestion of utility. A supportive role for psychosocial therapies is suggested, however, there is a sparsity of published studies specific to bipolar II disorder cohorts. A small number of short-term antidepressant trials have suggested efficacy, however, compelling long-term maintenance data is absent.

Conclusions: An emerging literature on the specific clinical signature and management of the disorder exists, however, this is disproportionately small relative to the epidemiology and clinical significance of the disorder.

A prospective study of the impact of subthreshold mixed states on the 24-month clinical outcomes of bipolar I disorder or schizoaffective disorder

Objectives: Subthreshold mixed states are common, yet their clinical significance is unclear. This study investigated the clinical outcomes of subthreshold mixed states in participants with bipolarI disorder or schizoaffective disorder, using the Cassidy and Benazzi criteria for manic and depressive mixed states, respectively.

Methods: The Bipolar Comprehensive Outcomes Study (BCOS) is a prospective observational study of treatment and outcomes for patients with bipolar I or schizoaffective disorder, bipolar type. Participants (N=239) were grouped based on study entry clinical presentation as having pure depression (n=63) if they satisfied DSM-IV-TR criteria for a Major Depressive Episode (MDE), depressive mixed state (DMX) if they also had at least three concurrent hypomanic symptoms (n=33), or not depressed (n=143) if they did not satisfy the criteria for MDE. Participants were similarly grouped as having pure mania (n=3) if they satisfied DSM-IV criteria for a Manic Episode, manic mixed state (MMX) if they also had at least two concurrent depressive symptoms (n=33), or not manic (n=203). Clinical data were collected by interview every 3-months over a 24-month period.

Results: Measures of quality of life, mental and physical health over the 24-month period were significantly worse for participants who were classified as having mixed states at study entry on most outcome measures compared to participants who were not in an illness episode at study entry. DMX was predictive of greater manic symptomatology over the 24 months compared to participants with pure depression.

Conclusion: In participants with a current episode of mood disorder, the presence of subthreshold symptoms of opposite polarity was associated with poorer clinical outcomes over a 24-month period.

Meta-analytic review of neurocognition in bipolar II disorder

Objective: The clinical distinction between bipolar II disorder (BD II) and bipolar I disorder (BD I) is not clear-cut. Cognitive functioning offers the potential to explore objective markers to help delineate this boundary. To examine this issue, we conducted a quantitative review of the cognitive profile of clinically stable patients with BD II in comparison with both patients with BD I and healthy controls.
Method: Meta-analytical methods were used to compare cognitive functioning of BD II disorder with both BD I disorder and healthy controls.
Results: Individuals with BD II were less impaired than those with BD I on verbal memory. There were also small but significant difference in
visual memory and semantic fluency. There were no significant differences in global cognition or in other cognitive domains. Patients with BD II performed poorer than controls in all cognitive domains.
Conclusion: Our findings suggest that with the exception of memory and semantic fluency, cognitive impairment in BD II is as severe as in BD I. Further studies are needed to investigate whether more severe deficits in BD I are related to neurotoxic effects of severe manic episodes on medial temporal structures or neurobiological differences from the onset of the illness.

Influence of birth cohort on age of onset cluster analysis in bipolar I disorder

Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database.