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OBJECTIVE: To provide up-to-date clinical guidance on the efficacy of lamotrigine in bipolar disorder (BD). METHODS: Eligible studies were identified during a systematic literature search according to PRISMA-guidelines. We included randomized controlled trials (RCTs) and cohort studies that quantitatively assessed lamotrigine's efficacy in BD. We divided the included studies into three groups: 1. acute treatment of depression, 2. acute treatment of mania and hypomania, and 3. maintenance treatment. Analyses were stratified by control group (placebo vs active comparator) and treatment strategy (monotherapy vs add-on treatment). RESULTS: We included 20 RCTs (n = 1166 lamotrigine users) and 20 cohort studies (n = 11,141 lamotrigine users). Twenty-four of these studies were included in meta-analyses. During depressive episodes, greater decreases in depressive symptomatology were associated with initiation of lamotrigine as add-on treatment than with placebo (SMD -0.30 [95% CI = -0.51, -0.10], df = 3, p = 0.004). Decreases in depressive symptomatology did not differ significantly between lamotrigine and the active comparator (SMD -0.28 [95% CI = -1.06, 0.50], df = 3, p = 0.488). As a maintenance treatment, lamotrigine was associated with a significantly lower relapse/recurrence rate than placebo (risk ratio (RR) 0.84 [95% CI = 0.71, 0.99], df = 2, p = 0.037). Relapse/recurrence rates did not differ significantly between lamotrigine and lithium (RR 1.06 [95% CI = 0.89, 1.25], df = 2, p = 0.513). A qualitative assessment of high-quality register-based studies found that lamotrigine was associated with lower hospital admission rates than other commonly used treatment regimes. CONCLUSIONS: There is substantial evidence for the efficacy of lamotrigine in BD, specifically as add-on treatment during acute depressive episodes and as maintenance treatment for preventing relapse and recurrence.
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Trastorno Bipolar , Lamotrigina , Triazinas , Lamotrigina/uso terapéutico , Humanos , Trastorno Bipolar/tratamiento farmacológico , Triazinas/uso terapéutico , Antimaníacos/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Anticonvulsivantes/uso terapéuticoRESUMEN
Reactions on 'The effectiveness of monoamine oxidase inhibitors in treatment-resistant depressive disorders in clinical practice; a retrospective open-label study'.
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Trastorno Depresivo Resistente al Tratamiento , Inhibidores de la Monoaminooxidasa , Trastorno Depresivo Resistente al Tratamiento/tratamiento farmacológico , Humanos , Monoaminooxidasa , Inhibidores de la Monoaminooxidasa/uso terapéutico , Estudios RetrospectivosRESUMEN
BACKGROUND: Testosterone has been implicated in suicidality in cross-sectional studies. Stress that coincides with a suicide attempt may alter androgen levels, so prospective studies are needed to exclude reverse causation. We aimed to examine the associations of plasma androgens with concurrent and future suicidality, and if present, whether these associations were mediated by a behavioral trait like reactive aggression. METHODS: Baseline plasma levels of total testosterone, 5α-dihydrotestosterone, and androstenedione were determined with liquid chromatography-tandem mass spectrometry, and dehydroepiandrosterone-sulphate with a radioimmunoassay. Suicidality was assessed using the Suicidal Ideation Scale at baseline and after 2-, 4-, 6-, and 9-year follow-up. Men and women were analyzed separately, and potential confounders were considered. RESULTS: Participants (N = 2861; 66.3% women) had a mean age of 42.0 years (range 18-65) and almost half (46.9%) fulfilled criteria for a major depressive or anxiety disorder. At baseline 13.2% of men and 11.2% of women reported current suicidal ideation. In participants who were non-suicidal at baseline, slightly more men than women reported suicidal ideation during follow-up (14.7% vs. 12.5%), whereas the reverse pattern was observed for suicide attempts (3.6% vs. 4.2%). None of the associations between androgens and current and future suicidality were significant. LIMITATIONS: Androgens were determined once, which may have been insufficient to predict suicidality over longer periods. DISCUSSION: The lack of associations between plasma levels of androgens determined by 'gold-standard' laboratory methods with suicidality do not support previous cross-sectional and smaller studies in adult men and women with values within the physiological range.
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Trastorno Depresivo Mayor , Suicidio , Adolescente , Adulto , Anciano , Andrógenos , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Plasma , Estudios Prospectivos , Factores de Riesgo , Ideación Suicida , Adulto JovenRESUMEN
BACKGROUND: Despite the existence of several pathophysiological theories about bipolar disorder, it has so far been difficult to find diagnostic biomarkers and to develop new pharmacologic treatments based on the more novel theories. AIM: To reflect on the causes and consequences of problems that beset pathophysiological research into psychiatric disorders in general and bipolar disorder in particular. METHOD: In this essay we address the problems facing professionals engaged in research into bipolar disorder and we interpret these problem in the light of brain complexity. RESULTS: The complexity of the brain can be divided into two types: spatial complexity, which reflects the various physiological levels of the central nervous system (genetic, molecular, cellular, neuronal circuits and phenomenological levels), and temporal complexity, i.e. neurodevelopment. We discuss the consequences of these two types of complexity and make suggestions relating to clinical practice and pathophysiological psychiatric research. CONCLUSION: To achieve further progress in the field of brain research, we need to acquire a deeper understanding of the spatial and temporal complexity of the brain and consider the possible consequences of such knowledge for the pathophysiology and treatment of psychiatric illnesses such as bipolar disorder.
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Trastorno Bipolar/diagnóstico , Trastorno Bipolar/fisiopatología , Encéfalo/fisiopatología , Biomarcadores , Humanos , PsicopatologíaRESUMEN
OBJECTIVE: To identify the early signs of mood disorder development, specifically bipolar disorder (BD), in a population at familial risk for BD. METHOD: The sample included 107 Dutch adolescent bipolar offspring (age 12-21) followed into adulthood (age 22-32). Lifetime DSM-IV axis I diagnoses were examined at baseline, 1-, 5-, and 12- year follow-up. Symptoms were assessed at baseline on a 3-point Likert scale at baseline with the K-SADS-PL and were analyzed using symptom and sum scores. As observed in previous studies, BD typically starts with other mood disorders. Therefore, the sample was stratified in offspring with a mood diagnosis (n = 29) and without (n = 78) at baseline. RESULTS: Subthreshold manic experiences proved the strongest predictor of BD conversion (n = 10; HR2.16, CI95% 1.23-3.78). At symptom level, elated mood, decreased need of sleep, racing thoughts, suicidal ideation, and middle insomnia were significantly associated with BD conversion. Depressive symptoms proved the strongest predictor for first mood episode onset (n = 28; HR1.27, CI95% 1.02-1.58). CONCLUSION: This study extends our knowledge of prodromal manifestations of BD in a high-risk population. Although preliminary, findings of this study provide potential targets for early identification and underscore the importance of detailed assessment of manic symptomatology in bipolar offspring.
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Trastorno Bipolar/diagnóstico , Trastorno Bipolar/fisiopatología , Hijo de Padres Discapacitados/psicología , Adolescente , Adulto , Trastornos Psicóticos Afectivos/diagnóstico , Trastornos Psicóticos Afectivos/fisiopatología , Edad de Inicio , Femenino , Estudios de Seguimiento , Humanos , Países Bajos , Adulto JovenRESUMEN
Immune dysregulation plays a role in the vulnerability for mood disorders. Immune growth factors, such as Stem Cell Factor (SCF), Insulin-like Growth Factor-Binding Protein-2 (IGF-BP2), Epidermal Growth Factor (EGF), IL-7 and sCD25 have repeatedly been reported altered in patients with mood disorders. The aim of this study was to investigate levels of these factors in serum of adolescent bipolar offspring, who have a heightened risk for mood disorder development and to also analyze the data combined with previously published data. Growth factors were assessed by CBA/ELISA in adolescent bipolar offspring (n=96, mean age=16years) and in age- and gender-matched healthy controls (n=50). EGF belonged to a mutually correlating cluster of mainly neurotrophic compounds including S100B and BDNF, which were in general decreased in serum. IL-7, SCF, IGF-BP2 and sCD25, belonged to a different mutually correlating cluster of immune growth factors, which were in general increased: IGF-BP2 significantly in serum of offspring without a mood disorder, IL-7 and SCF in serum of offspring who had experienced a mood episode. This pattern of de- and increases was not different between bipolar offspring that developed or did not develop a mood disorder over time, apart from the IGF-BP2 level, which was near significantly higher in offspring later developing a mood disorder. Correlations with the previously published immune-cellular abnormalities were not found. In conclusion non-affected adolescents at familial mood disorder development risk were characterized by a distinct pattern of a series of compounds operating in a network of hematopoiesis, neurogenesis and inflammation.
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Trastorno Bipolar/sangre , Trastorno Bipolar/inmunología , Péptidos y Proteínas de Señalización Intercelular/sangre , Péptidos y Proteínas de Señalización Intercelular/inmunología , Adolescente , Trastorno Bipolar/complicaciones , Factor Neurotrófico Derivado del Encéfalo/sangre , Factor Neurotrófico Derivado del Encéfalo/inmunología , Hijo de Padres Discapacitados , Factor de Crecimiento Epidérmico/sangre , Factor de Crecimiento Epidérmico/inmunología , Femenino , Humanos , Inflamación/complicaciones , Inflamación/inmunología , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/inmunología , Interleucina-7/sangre , Interleucina-7/inmunología , Masculino , Subunidad beta de la Proteína de Unión al Calcio S100/sangre , Subunidad beta de la Proteína de Unión al Calcio S100/inmunología , Factor de Células Madre/sangre , Factor de Células Madre/inmunologíaRESUMEN
BACKGROUND: Previous studies of our group among bipolar offspring and bipolar twins showed significant higher prevalence's and levels of antithyroid peroxidase antibodies (TPO-Abs) in offspring and co-twins (without a mood disorder) compared to controls, suggesting that TPO-Abs might be considered as vulnerability factor (trait marker) for BD development. OBJECTIVES: Here we elucidate, in the same cohorts, but now after 12- and 6-year follow-up, whether TPO-abs should be considered as a 'trait' marker for BD. The present study aims to investigate whether TPO-Abs (1) are stable over time, (2) are associated with lithium-exposure, (3) share a common genetic background with BD and are related to psychopathology. RESULTS: In bipolar offspring and twins, the prevalence of TPO-Abs is stable over time (r s = .72 p < .001 resp. r s = .82, p < .001) and not associated with lithium use. At follow-up, an increased prevalence of TPO-abs was again observed in bipolar offspring (10,4% versus 4%) and higher TPO-abs titers were still present in co-twins of bipolar cases compared to control twins [mean 1.06 IU/ml (SD .82) versus mean .82 IU/ml (SD .67)], although statistical significance was lost. CONCLUSIONS: Although our results show a trend toward an increased inherited risk of the co-occurrence of BD and thyroid autoimmunity, large-scale studies can only draw final conclusions. Nationwide epidemiological and GWAS studies reach such numbers and support the view of a possible common (autoimmune) etiology of severe mood disorders and chronic recurrent infections and autoimmunity, including thyroid autoimmunity.
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OBJECTIVE: To validate the Seven Up Seven Down (7U7D), an abbreviated version of the General Behavior Inventory (GBI), as screener for mood disorders and test its ability to predict mood disorders over time in individuals at risk for bipolar disorder (BD). METHODS: Bipolar offspring (n=108) were followed from adolescence into adulthood and assessed at baseline, 1-, 5- and 12 years follow-up (T1-T4 respectively). Offspring were assessed using the Schedule for Affective Disorders and Schizophrenia for School-Age Children--Present and Lifetime Version, Structured Clinical Interview for DSM-IV Axis I Disorders and the GBI. RESULTS: Performance of the GBI and 7U7D was functionally similar for the depression (7D) scale, but variable for the mania (7U) scale. As screener for mood disorders (T4), the 7D showed fair diagnostic efficiency (area under the curve (AUC) 0.68, p<0.01, OR 1.53, 95% CI 1.15-2.03). The discriminative validity for BD and unipolar disorder was only close to significant (7D AUC 0.66, p=0.078; 7U AUC 0.67, p=0.067). In terms of prediction of mood disorder onset between T1 and T4, the 7D, but not the 7U, was associated with new onset (AUC 0.67, p<0.05; HR 1.14, 95% CI 1.07-1.23). The 7U7D did not achieve significant prediction of BD. LIMITATIONS: Relative small sample size and limited generalizability. CONCLUSIONS: Based on the current study, the 7U7D shows limited potential as screening instrument for mood disorders in bipolar offspring. The clinical utility of the 7U7D needs further exploration for use in clinical and research settings.
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Trastorno Bipolar/diagnóstico , Hijo de Padres Discapacitados/psicología , Trastorno Depresivo/diagnóstico , Adolescente , Área Bajo la Curva , Trastorno Bipolar/psicología , Niño , Trastorno Depresivo/psicología , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Masculino , Tamizaje Masivo , Trastornos del Humor/diagnóstico , Trastornos del Humor/psicología , Países Bajos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
This is the first longitudinal twin study examining genetic and environmental contributions to the association between liability to bipolar disorder (BD) and changes over time in global brain volumes, and global and regional measures of cortical surface area, cortical thickness and cortical volume. A total of 50 twins from pairs discordant or concordant for BD (monozygotic: 8 discordant and 3 concordant pairs, and 1 patient and 3 co-twins from incomplete pairs; dizygotic: 6 discordant and 2 concordant pairs, and 1 patient and 7 co-twins from incomplete pairs) underwent magnetic resonance imaging twice. In addition, 57 twins from healthy twin pairs (15 monozygotic and 10 dizygotic pairs, and 4 monozygotic and 3 dizygotic subjects from incomplete pairs) were also scanned twice. Mean follow-up duration for all twins was 7.5 years (standard deviation: 1.5 years). Data were analyzed using structural equation modeling software OpenMx. The liability to BD was not associated with global or regional structural brain changes over time. Although we observed a subtle increase in cerebral white matter in BD patients, this effect disappeared after correction for multiple comparisons. Heritability of brain changes over time was generally low to moderate. Structural brain changes appear to follow similar trajectories in BD patients and healthy controls. Existing brain abnormalities in BD do not appear to progressively change over time, but this requires additional confirmation. Further study with large cohorts is recommended to assess genetic and environmental influences on structural brain abnormalities in BD, while taking into account the influence of lithium on the brain.
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Trastorno Bipolar/diagnóstico por imagen , Trastorno Bipolar/epidemiología , Encéfalo/diagnóstico por imagen , Interacción Gen-Ambiente , Adulto , Antimaníacos/uso terapéutico , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/genética , Encéfalo/efectos de los fármacos , Enfermedades en Gemelos , Femenino , Estudios de Seguimiento , Humanos , Compuestos de Litio/uso terapéutico , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Tamaño de los Órganos , Factores Socioeconómicos , Gemelos Dicigóticos , Gemelos MonocigóticosRESUMEN
OBJECTIVES: T cell abnormalities have been repeatedly reported in adult patients with mood disorders, suggesting a role of these cells in the pathogenesis of these disorders. In the present study, we explored the dynamics of circulating T cell subsets over time in a population at high familial risk for developing a mood disorder. METHODS: Children of a parent with bipolar disorder (bipolar offspring, N=140) were assessed at three time-points: adolescence, young adulthood and adulthood. We carried out a detailed fluorescence-activated cell sorting (FACS) analysis to determine various T cell subsets from frozen stored peripheral blood mononuclear cells of bipolar offspring and age- and gender-matched healthy controls at each time-point. RESULTS: Throughout the period of observation reduced levels of CD3+ and CD3+ CD4+ T cells were observed. In bipolar offspring Th1, Th2, Th17 and natural T regulatory cells (Tregs) followed a dynamic course over time with reduced levels of Tregs in adolescence and a reduced relative number of Th1, Th17 cells in young adulthood. In post hoc analysis Tregs were inversely associated with the pro-inflammatory monocyte state determined previously (rs=-0.220, p=0.001). Significant associations between T cell subset abnormalities and psychopathology such as mood disorders were not found. CONCLUSIONS: A subtle partial T cell defect was present in bipolar offspring from adolescence through adulthood. Within this defect the dynamic change of inflammatory and regulatory T cell subsets suggests a high inflammatory state during adolescence, a reduced inflammatory state during young adulthood and a virtually normalized state at adulthood.
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Trastornos del Humor/genética , Trastornos del Humor/inmunología , Subgrupos de Linfocitos T/metabolismo , Adolescente , Trastorno Bipolar/genética , Niño , Femenino , Expresión Génica , Predisposición Genética a la Enfermedad , Humanos , Inflamación/complicaciones , Inflamación/inmunología , Células Asesinas Naturales/metabolismo , Masculino , Monocitos/metabolismo , Trastornos del Humor/complicaciones , Adulto JovenRESUMEN
BACKGROUND: Increasingly, health insurance companies are asking for treatment results in mental health care to be expressed in actual numbers. They base their request on the data supplied by sbg (Stichting Benchmark ggz) and the procedures that sbg has followed. For the purpose of benchmarking, the sbg has accepted a limited number of questionnaires. These tools are not suitable for performing routine outcome monitoring (rom) in clinical practice. There is a urgent need for these questionnaires to be replaced by a widely-used depression questionnaire, namely the ids. AIM: To present arguments supporting the view that the ids is an excellent and useful instrument that the sbg should accept as a measuring tool. METHOD: We discuss the quality of the ids by reviewing the literature. RESULTS: The ids is a high quality instrument well suited for measuring the severity of depressions and also is sufficiently sensitive for measuring mood improvements.
CONCLUSION: The ids is an excellent tool for performing rom measurements and is available free of charge. The authors argue that the sbg should accept this questionnaire as a suitable instrument for benchmarking.
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Benchmarking , Depresión/diagnóstico , Depresión/terapia , Evaluación de Resultado en la Atención de Salud , Escalas de Valoración Psiquiátrica/normas , Depresión/clasificación , Medicina Basada en la Evidencia , Humanos , Servicios de Salud Mental/normas , Países Bajos , Psicometría/instrumentación , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: This study aimed to examine whether inflammatory gene expression was a trait or a state marker in patients with bipolar disorder (BD). METHODS: 69 healthy controls (HC), 82 euthymic BD patients and 8 BD patients with a mood episode (7 depressed, 1 manic) were included from the MOODINFLAME study. Six of the eight patients who had a mood episode were also investigated when they were euthymic (6 of the 82 euthymic patients). Of these participants the expression of 35 inflammatory genes was determined in monocytes using quantitative-polymerase chain reaction, of which a total gene expression score was calculated as well as a gene expression score per sub-cluster. RESULTS: There were no significant differences in inflammatory monocyte gene expression between healthy controls and euthymic patients. Patients experiencing a mood episode, however, had a significantly higher total gene expression score (10.63 ± 2.58) compared to healthy controls (p = .004) and euthymic patients (p = .009), as well as when compared to their own scores when they were euthymic (p = .02). This applied in particular for the sub-cluster 1 gene expression score, but not for the sub-cluster 2 gene expression score. CONCLUSIONS: Our study indicates that in BD inflammatory monocyte, gene expression is especially elevated while in a mood episode compared to being euthymic.
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BACKGROUND: Life events are an established risk factor for the onset and recurrence of unipolar and bipolar mood episodes, especially in the presence of genetic vulnerability. The dynamic interplay between life events and psychological context, however, is less studied. In this study, we investigated the impact of life events on the onset and recurrence of mood episodes in bipolar offspring, as well as the effects of temperament, coping and parenting style on this association. METHOD: Bipolar offspring (n = 108) were followed longitudinally from adolescence to adulthood. Mood disorders were assessed with: the Kiddie Schedule of Affective Disorders and Schizophrenia - Present and Lifetime Version or the Structured Clinical Interview for DSM-IV Axis I disorders; life events with the Life Events and Difficulties Schedule; and psychological measures using the Utrecht Coping List, Temperament and Character Inventory and short-EMBU (memories of upbringing instrument). Anderson-Gill models (an extension of the Cox proportional hazard model) were utilized. RESULTS: Life events were associated with an increased risk for first and, although less pronounced, subsequent mood episodes. There was a large confounding effect for the number of previous mood episodes; findings suggest a possible kindling effect. Passive coping style increased the risk of mood episode onset and recurrent episodes, but also altered the effect of life events on mood disorders. Harm avoidance temperament was associated with mood episode recurrence. CONCLUSIONS: Life events are especially a risk factor in the onset of mood disorders, though less so in recurrent episodes. Psychological features (passive coping and harm-avoidant temperament) contribute to the risk of an episode occurring, and also have a moderating effect on the association between life events and mood episodes. These findings create potential early intervention strategies for bipolar offspring.
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Trastorno Bipolar/epidemiología , Trastorno Bipolar/psicología , Predisposición Genética a la Enfermedad/epidemiología , Acontecimientos que Cambian la Vida , Adaptación Psicológica , Adolescente , Adulto , Hijo de Padres Discapacitados/psicología , Femenino , Humanos , Estudios Longitudinales , Masculino , Países Bajos/epidemiología , Escalas de Valoración Psiquiátrica , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: The severity of bipolar disorder can be assessed using the daily prospective National Institute of Mental Health׳s Life Chart Method (LCM-p). Also for scientific research the LCM-p, has been used frequently. However, processing and analyzing the LCM-p for research purposes, are challenging because of the multitude of complex measures that can be derived from the data. In the current paper we review the different LCM-p course variables (mood episodes, average severity, proportion of time ill and mood switches) and their definitions. Strengths and limitations and the impact of the use of different LCM-p course measures and definitions on the research results are described. METHOD: A systematic review of original papers on the LCM was conducted using 9 electronic databases for literature between January 1996 and December 2014. Papers using other prospective charting procedures were not evaluated in the current study. RESULTS: The initial literature search led to 1352 papers of which 21 were eventually selected. A relatively wide variety of definitions of LCM-p course variables was used across the studies. Especially for the calculation of number of episodes and mood switch no univocal definition seems to exist. Across studies several different durations and severity criteria are applied to calculate these variables. We describe which variables and definitions are most suitable for detecting specific bipolar disease course characteristics and patterns. CONCLUSION: In the absence of a golden standard for the calculation of LCM-p course variables, researchers should report the exact method they applied to their LCM-p data, and clearly motivate why this is their method of first choice considering their research aim.
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Trastorno Bipolar/diagnóstico , Evaluación de Resultado en la Atención de Salud , Escalas de Valoración Psiquiátrica , Investigación/instrumentación , Humanos , National Institute of Mental Health (U.S.) , Escalas de Valoración Psiquiátrica/normas , Estados UnidosRESUMEN
BACKGROUND: The risk of developing bipolar disorder (BD) has been linked to structural brain abnormalities. The degree to which genes and environment influence the association of BD with cortical surface area remains to be elucidated. In this twin study, genetic and environmental contributions to the association between liability to develop BD and surface area, thickness and volume of the cortex were examined. METHOD: The study cohort included 44 affected monozygotic (nine concordant, 12 discordant) and dizygotic (four concordant, 19 discordant) twin pairs, and seven twins from incomplete discordant monozygotic and dizygotic discordant twin pairs. In addition, 37 monozygotic and 24 dizygotic healthy control twin pairs, and six twins from incomplete monozygotic and dizygotic control pairs were included. RESULTS: Genetic liability to develop BD was associated with a larger cortical surface in limbic and parietal regions, and a thicker cortex in central and parietal regions. Environmental factors related to BD were associated with larger medial frontal, parietal and limbic, and smaller orbitofrontal surfaces. Furthermore, thinner frontal, limbic and occipital cortex, and larger frontal and parietal, and smaller orbitofrontal volumes were also associated with environmental factors related to BD. CONCLUSIONS: Our results suggest that unique environmental factors play a prominent role in driving the associations between liability to develop BD and cortical measures, particularly those involving cortical thickness. Further evaluation of their influence on the surface and thickness of the cortical mantle is recommended. In addition, cortical volume appeared to be primarily dependent on surface and not thickness.
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Trastorno Bipolar/genética , Trastorno Bipolar/fisiopatología , Corteza Cerebelosa/fisiopatología , Interacción Gen-Ambiente , Adolescente , Adulto , Algoritmos , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad/genética , Humanos , Entrevistas como Asunto , Sistema Límbico/fisiopatología , Modelos Lineales , Masculino , Persona de Mediana Edad , Neuroimagen , Gemelos Dicigóticos/genética , Gemelos Monocigóticos/genética , Adulto JovenRESUMEN
Palmar and finger dermatoglyphics are formed between the 10th and the 17th weeks of gestation and their morphology can be influenced by genetic or environmental factors, interfering with normal intrauterine development. As both the skin and the brain develop from the same embryonal ectoderm, dermatoglyphic alterations may be informative for early abnormal neurodevelopmental processes in the brain. We investigated whether dermatoglyphic alterations are related to structural brain abnormalities in bipolar disorder and to what extent they are of a genetic and of an environmental origin. Dermatoglyphics and volumetric data from structural MRI were obtained in 53 twin pairs concordant or discordant for bipolar disorder and 51 healthy matched control twin pairs. Structural equation modeling was used. Bipolar disorder was significantly positively associated with palmar a-b ridge count (ABRC), indicating higher ABRC in bipolar patients (rph=.17 (CI .04-.30)). Common genes appear to be involved because the genetic correlation with ABRC was significant (rph-A=.21 (CI .05-.36). Irrespective of disease, ABRC showed a genetically mediated association with brain volume, indicated by a significant genetic correlation rph-A of respectively -.36 (CI -.52 to -.22) for total brain, -.34 (CI -.51 to -.16) total cortical volume, -.27 (CI -.43 to -.08) cortical gray matter and -.23 (CI -.41 to -.04) cortical white matter. In conclusion, a genetically determined abnormal development of the foetal ectoderm between the 10th and 15th week of gestation appears related to smaller brain volumes in (subjects at risk for) bipolar disorder.
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Trastorno Bipolar/genética , Trastorno Bipolar/patología , Encéfalo/patología , Dermatoglifia , Gemelos Dicigóticos/genética , Gemelos Monocigóticos/genética , Adolescente , Adulto , Trastorno Bipolar/psicología , Estudios de Casos y Controles , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neuroimagen , Tamaño de los Órganos , Gemelos Dicigóticos/psicología , Gemelos Monocigóticos/psicología , Adulto JovenRESUMEN
BACKGROUND: There is some controversy but growing evidence that childhood onset bipolar disorder may be more prevalent and run a more difficult course in the United States than some European countries. METHODS: We update and synthesize course of illness data from more than 960 outpatients with bipolar disorder (average age 40) from 4 sites in the U.S. and 3 sites in Netherlands and Germany. After giving informed consent, patients reported on parental history, childhood and lifetime stressors, comorbidities, and illness characteristics. RESULTS: Almost all aspects of bipolar disorder were more adverse in patients from the US compared with Europe, including a significantly higher prevalence of: bipolar disorder in one parent and a mood disorder in both parents; childhood verbal, physical, or sexual abuse; stressors in the year prior to illness onset and the last episode; childhood onsets of bipolar illness; delay to first treatment; anxiety disorder, substance abuse, and medical comorbidity; mood episodes and rapid cycling; and nonresponse to prospective naturalistic treatment. LIMITATIONS: Selection bias in the recruit of patients cannot be ruled out, but convergent data in the literature suggest that this does not account for the findings. Potential mechanisms for the early onset and more adverse course in the U.S. have not been adequately delineated and require further investigation. CONCLUSIONS: The data suggest the need for earlier and more effective long-term treatment intervention in an attempt to ameliorate this adverse course and its associated heavy burden of psychiatric and medical morbidity.
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Trastorno Bipolar/epidemiología , Trastorno Bipolar/terapia , Política de Salud , Adulto , Edad de Inicio , Estudios Transversales , Femenino , Alemania/epidemiología , Humanos , Entrevista Psicológica , Masculino , Países Bajos/epidemiología , Estados Unidos/epidemiologíaRESUMEN
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.
Asunto(s)
Síntomas Afectivos , Trastorno Bipolar , Hijo de Padres Discapacitados/psicología , Padres/psicología , Adulto , Síntomas Afectivos/diagnóstico , Síntomas Afectivos/etnología , Edad de Inicio , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/etnología , Trastorno Bipolar/psicología , Comparación Transcultural , Trastorno Depresivo , Salud de la Familia/etnología , Femenino , Alemania/epidemiología , Humanos , Masculino , Países Bajos/epidemiología , Prevalencia , Pronóstico , Escalas de Valoración Psiquiátrica , Factores de Riesgo , Autoinforme , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Knowledge of the risk of recurrence after recovery from major depressive disorder (MDD) in the general population is scarce. METHOD: Data were derived from 687 subjects in the general population with a lifetime DSM-III-R diagnosis of MDD but without a current major depressive episode (MDE) or dysthymia. Participants had to be at least 6 months in remission, and were recruited from The Netherlands Mental Health Survey and Incidence Study (NEMESIS), using the composite international diagnostic interview (CIDI). Recency and severity of the last MDE were assessed retrospectively at baseline. Recurrence of MDD was measured prospectively during the 3-year follow-up. Kaplan-Meier survival curves were used to measure time to recurrence. Determinants of time to recurrence were analyzed using proportional hazard models. RESULTS: The estimated cumulative recurrence of MDD was 13.2% at 5 years, 23.2% at 10 years and 42.0% at 20 years. In bivariate analysis, the following variables predicted a shorter time to recurrence: younger age, younger age of onset, higher number of previous episodes, a severe last depressive episode, negative youth experiences, ongoing difficulties before recurrence and high neuroticism. Multivariably, younger age, a higher number of previous episodes, a severe last depressive episode, negative youth experiences and ongoing difficulties remained significant. CONCLUSIONS: In this community sample, the long-term risk of recurrence was high, but lower than that found in clinical samples. Subjects who had had an MDE had a long-term vulnerability for recurrence. Factors predicting recurrence included illness- and stress-related factors.
Asunto(s)
Trastorno Depresivo Mayor/epidemiología , Adolescente , Adulto , Estudios de Cohortes , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Salud Mental , Persona de Mediana Edad , Países Bajos/epidemiología , Personalidad/fisiología , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Recurrencia , Índice de Severidad de la Enfermedad , Factores de Tiempo , Adulto JovenRESUMEN
OBJECTIVE: To identify moderators of synchrony of change between depression severity and disability. METHOD: From a large cohort study with 2 years of follow-up, patients with major depressive disorder at baseline who decreased at least 25% in depression severity after 2 years (n = 245) were selected. We measured overall and domain-specific disability at baseline, and at 1- and 2-year follow-up. Possible moderators, among which several demographic, clinical, personality, and contextual factors, were measured at baseline. We used linear mixed models to analyze the data. RESULTS: Decrease in depression severity correlated strongly with reductions of overall disability (r = 0.54). Synchrony of change for the disability domains ranged from 0.13 for self-care to 0.47 for participation. From the possible moderators, only age and work stress moderated the association between change in depression severity and disability, with stronger synchrony of change among younger patients and patients who experienced moderate work stress. CONCLUSION: Strong synchrony of change exists between depression severity and disability. Perhaps, because of the strength of this synchrony, few contextual characteristics moderated the association. Clinicians should be aware of the risk of slower or incomplete functional recovery in older people and those without a job or those experiencing low work stress.