RESUMEN
BACKGROUND: Identifying clinical features that predict conversion to bipolar disorder (BD) in those at high familial risk (HR) would assist in identifying a more focused population for early intervention. METHOD: In total 287 participants aged 12-30 (163 HR with a first-degree relative with BD and 124 controls (CONs)) were followed annually for a median of 5 years. We used the baseline presence of DSM-IV depressive, anxiety, behavioural and substance use disorders, as well as a constellation of specific depressive symptoms (as identified by the Probabilistic Approach to Bipolar Depression) to predict the subsequent development of hypo/manic episodes. RESULTS: At baseline, HR participants were significantly more likely to report ⩾4 Probabilistic features (40.4%) when depressed than CONs (6.7%; p < .05). Nineteen HR subjects later developed either threshold (n = 8; 4.9%) or subthreshold (n = 11; 6.7%) hypo/mania. The presence of ⩾4 Probabilistic features was associated with a seven-fold increase in the risk of 'conversion' to threshold BD (hazard ratio = 6.9, p < .05) above and beyond the fourteen-fold increase in risk related to major depressive episodes (MDEs) per se (hazard ratio = 13.9, p < .05). Individual depressive features predicting conversion were psychomotor retardation and ⩾5 MDEs. Behavioural disorders only predicted conversion to subthreshold BD (hazard ratio = 5.23, p < .01), while anxiety and substance disorders did not predict either threshold or subthreshold hypo/mania. CONCLUSIONS: This study suggests that specific depressive characteristics substantially increase the risk of young people at familial risk of BD going on to develop future hypo/manic episodes and may identify a more targeted HR population for the development of early intervention programs.
Asunto(s)
Síntomas Conductuales/fisiopatología , Trastorno Bipolar/fisiopatología , Trastorno Depresivo Mayor/fisiopatología , Progresión de la Enfermedad , Predisposición Genética a la Enfermedad , Adolescente , Adulto , Niño , Femenino , Humanos , Estudios Longitudinales , Masculino , Riesgo , Adulto JovenRESUMEN
This meta-analysis aimed to update existing data on the comparison of prevalence rates of psychopathology primarily among offspring with at least one parent with bipolar disorder (BD) and offspring of parents without psychiatric illness. Seventeen studies were derived from a systematic search of PsychInfo, Medline, Scopus and Embase. Inclusion criteria were use of a control offspring group, standardized diagnostic procedures and reporting of clear frequency data. Risk of psychopathology was estimated by aggregating frequency data from selected studies. Compared to control offspring, high-risk BD offspring are nine times more likely to have a bipolar-type disorder, almost two and a half times more likely to develop a non-BD affective disorder and over two times more likely to develop at least one anxiety disorder. High-risk offspring also showed a significant increased risk of other non-mood psychopathology such as attention deficit hyperactivity disorder (ADHD), any type of behavioral disorder and substance use disorder (SUDs). Risk of developing a broad range of affective and non-affective psychopathology is significantly higher in high-risk BD offspring. Identifying clinical presentations of this genetically high-risk cohort is important in establishing appropriate preventative treatment.
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Trastorno Bipolar/psicología , Psicopatología/métodos , Adolescente , Niño , Femenino , Humanos , Masculino , Prevalencia , Factores de Riesgo , HermanosRESUMEN
OBJECTIVE: Disruptive mood dysregulation disorder is a newly proposed childhood disorder included in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition to describe children ⩽18 years of age with chronic irritability/temper outbursts. This study aimed to examine the prevalence of disruptive mood dysregulation disorder, severe mood dysregulation and chronic irritability in an Australian study of young people at increased familial risk of developing bipolar disorder ('HR' group) and controls ('CON' group). METHODS: A total of 242 12- to 30-year-old HR or CON subjects were administered the severe mood dysregulation module. Of these, 42 were aged ⩽18 years at the time of assessment, with 29 subjects in the HR group and 13 in the CON group. RESULTS: No subjects ⩽18 years - in either group - fulfilled current or lifetime criteria for disruptive mood dysregulation disorder or severe mood dysregulation, the precursor to disruptive mood dysregulation disorder. Similarly, no subjects in either group endorsed the severe mood dysregulation/disruptive mood dysregulation disorder criteria for irritable mood or marked excessive reactivity. One HR participant endorsed three severe mood dysregulation criteria (distractibility, physical restlessness and intrusiveness), while none of the comparison subjects endorsed any criteria. Exploratory studies of the broader 12- to 30-year-old sample similarly found no subjects with severe mood dysregulation/disruptive mood dysregulation disorder in either the HR or CON group and no increased rates of chronic irritability, although significantly more HR subjects reported at least one severe mood dysregulation/disruptive mood dysregulation disorder criterion (likelihood ratio = 6.17; p = 0.013); most of the reported criteria were severe mood dysregulation 'chronic hyper-arousal' symptoms. CONCLUSION: This study comprises one of the few non-US reports on the prevalence of disruptive mood dysregulation disorder and severe mood dysregulation and is the first non-US study of the prevalence of these conditions in a high-risk bipolar disorder sample. The failure to replicate the finding of higher rates of disruptive mood dysregulation disorder and chronic irritability in high-risk offspring suggests that these are not robust precursors of bipolar disorder.
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Trastorno Bipolar/epidemiología , Trastornos de la Conducta Infantil/epidemiología , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Genio Irritable , Trastornos del Humor/epidemiología , Adolescente , Adulto , Australia/epidemiología , Niño , Trastornos de la Conducta Infantil/clasificación , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Trastornos del Humor/clasificación , Riesgo , Adulto JovenRESUMEN
OBJECTIVE: Although there is clear evidence that reproductive cycle events are associated with mood episodes for women with bipolar disorder, few studies have examined for relationships between these and specific clinical characteristics of the disorder. This study aimed to explore the relationship between mood symptoms associated with reproductive cycle events and features of the disorder indicative of a more severe lifetime course. METHOD: Totally, 158 women of at least 18 years of age participated in the study. Subjects were recruited through a specialist clinic at the Black Dog Institute, Sydney, Australia. RESULTS: In total, 77% of women reported increases in mood symptoms during perimenstrual, postnatal or menopausal periods. These women had an earlier age of onset for depressive and hypo/manic episodes and a greater likelihood of comorbid anxiety disorders, rapid cycling and mixed mood compared to those who did not report such reproductive cycle-associated mood changes. Women who experienced postnatal episodes were also more likely to experience worse mood symptoms perimenstrually and menopausally. CONCLUSION: First, reproductive cycle event-related worsening of mood was associated with a more severe lifetime course of bipolar disorder, and, second, it appears that some women have a greater propensity to mood worsening at each of these reproductive cycle events. If replicated, these findings provide important information for clinicians treating women with reproductive cycle event mood changes and highlight the need for improved therapeutics for such presentations.
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Trastorno Bipolar/fisiopatología , Menopausia , Menstruación , Periodo Posparto , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Adulto JovenRESUMEN
The emotional and cognitive vulnerabilities that precede the development of bipolar disorder are poorly understood. The inferior frontal gyrus-a key cortical hub for the integration of cognitive and emotional processes-exhibits both structural and functional changes in bipolar disorder, and is also functionally impaired in unaffected first-degree relatives, showing diminished engagement during inhibition of threat-related emotional stimuli. We hypothesized that this functional impairment of the inferior frontal gyrus in those at genetic risk of bipolar disorder reflects the dysfunction of broader network dynamics underlying the coordination of emotion perception and cognitive control. To test this, we studied effective connectivity in functional magnetic resonance imaging data acquired from 41 first-degree relatives of patients with bipolar disorder, 45 matched healthy controls and 55 participants with established bipolar disorder. Dynamic causal modelling was used to model the neuronal interaction between key regions associated with fear perception (the anterior cingulate), inhibition (the left dorsolateral prefrontal cortex) and the region upon which these influences converge, namely the inferior frontal gyrus. Network models that embodied non-linear, hierarchical relationships were the most strongly supported by data from our healthy control and bipolar participants. We observed a marked difference in the hierarchical influence of the anterior cingulate on the effective connectivity from the dorsolateral prefrontal cortex to the inferior frontal gyrus that is unique to the at-risk cohort. Non-specific, non-hierarchical mechanisms appear to compensate for this network disturbance. We thus establish a specific network disturbance suggesting dysfunction in the processes that support hierarchical relationships between emotion and cognitive control in those at high genetic risk for bipolar disorder.
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Trastorno Bipolar/fisiopatología , Cognición , Emociones , Familia , Giro del Cíngulo/fisiopatología , Corteza Prefrontal/fisiopatología , Adulto , Trastorno Bipolar/genética , Encéfalo/fisiopatología , Estudios de Casos y Controles , Miedo , Femenino , Neuroimagen Funcional , Predisposición Genética a la Enfermedad , Humanos , Imagen por Resonancia Magnética , Masculino , Vías Nerviosas/fisiopatología , Dinámicas no Lineales , Percepción , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Recent studies have revealed the polygenic nature of bipolar disorder (BP), and identified common risk variants associated with illness. However, the role of common polygenic risk in multiplex families has not previously been examined. The present study examined 249 European-ancestry families from the NIMH Genetics Initiative sample, comparing subjects with narrowly defined BP (excluding bipolar II and recurrent unipolar depression; n = 601) and their adult relatives without BP (n = 695). Unrelated adult controls (n = 266) were from the NIMH TGEN control dataset. We also examined a prospective cohort of young (12-30 years) offspring and siblings of individuals with BPI and BPII disorder (at risk; n = 367) and psychiatrically screened controls (n = 229), ascertained from five sites in the US and Australia and assessed with standardized clinical protocols. Thirty-two disease-associated SNPs from the PGC-BP Working Group report (2011) were genotyped and additive polygenic risk scores (PRS) derived. We show increased PRS in adult cases compared to unrelated controls (P = 3.4 × 10(-5) , AUC = 0.60). In families with a high-polygenic load (PRS score ≥32 in two or more subjects), PRS distinguished cases with BPI/SAB from other relatives (P = 0.014, RR = 1.32). Secondly, a higher PRS was observed in at-risk youth, regardless of affected status, compared to unrelated controls (GEE-χ(2) = 5.15, P = 0.012). This report is the first to explore common polygenic risk in multiplex families, albeit using only a small number of robustly associated risk variants. We show that individuals with BP have a higher load of common disease-associated variants than unrelated controls and first-degree relatives, and illustrate the potential utility of PRS assessment in a family context.
Asunto(s)
Trastorno Bipolar/genética , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Familia , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Persona de Mediana Edad , Herencia Multifactorial , Linaje , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVES: In a relatively small number of previous studies, childhood abuse has been found to be associated with more severe symptom course, earlier onset, greater comorbidity, and greater suicidality in those diagnosed with bipolar disorder. There have been no prior reports looking for any association between childhood abuse and cognitive style. This study aimed to examine the relationship between cognitive factors, such as response styles to depressed mood and dysfunctional attitudes, clinical features, and childhood physical and sexual abuse in this population. METHODS: A total of 157 adult participants diagnosed with DSM-IV bipolar disorder I or II were assessed on clinical features of this condition and measures of childhood sexual and physical abuse. Participants also completed self-report questionnaires covering areas such as symptom measures of depression, anxiety and stress, dysfunctional attitudes, and response styles to depressed mood. RESULTS: Seventy-four participants (37%) reported having experienced either sexual or physical abuse. Those who reported physical or sexual abuse were significantly more likely to report self-harm or suicidal behaviors and showed higher stress scores. Specifically, those who reported sexual abuse were more likely to have simple phobias, to have attempted suicide, and to have had more hospitalizations for depression. After controlling for current mood severity, there were no significant differences on the self-report cognitive style measures for those who reported childhood sexual or physical abuse compared to those who did not report abuse. CONCLUSIONS: Cognitive styles were not found to be associated with childhood sexual or physical abuse in participants with bipolar disorder. Stress may be important to target in psychological interventions, whilst special attention should also be paid to those with a history of sexual abuse given the greater likelihood of suicide attempt.
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Trastorno Bipolar/complicaciones , Trastorno Bipolar/psicología , Maltrato a los Niños/psicología , Trastornos del Conocimiento/etiología , Adulto , Análisis de Varianza , Distribución de Chi-Cuadrado , Niño , Maltrato a los Niños/clasificación , Preescolar , Trastornos del Conocimiento/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , Adulto JovenRESUMEN
OBJECTIVES: Recent neuroimaging studies support the contention that depression, pain distress, and rejection distress share the same neurobiological circuits. In two recently published studies we confirmed the hypothesis that the perception of increased pain during both treatment-refractory depression (predominantly unipolar) and difficult-to-treat bipolar depression was related to increased state rejection sensitivity (i.e., rejection sensitivity when depressed). In the present study, we aimed to compare the correlates of pain and rejection sensitivity in individuals with bipolar versus unipolar depression and test the hypothesis that bipolar disorder may be distinguished from unipolar depression both by an increased perception of pain and heightened rejection sensitivity during depression. METHODS: We analyzed data from 113 bipolar and 146 unipolar depressed patients presenting to the Black Dog Institute, Sydney, Australia. The patients all met DSM-IV criteria for bipolar disorder or unipolar depression (major depressive disorder). RESULTS: Bipolar disorder predicted a major increase in state rejection sensitivity when depressed (p = 0.001), whereas trait rejection sensitivity (i.e., a long-standing pattern of rejection sensitivity) was not predicted by polarity. A major increase in the experience of headaches (p = 0.007), chest pain (p < 0.001), and body aches and pains (p = 0.02) during depression was predicted by a major increase in state rejection sensitivity for both bipolar and unipolar depression. CONCLUSIONS: State, but not trait, rejection sensitivity is significantly predicted by bipolar depression, suggesting that this might be considered as a state marker for bipolar depression and taken into account in the clinical differentiation of bipolar and unipolar depression.
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Trastorno Bipolar/psicología , Trastorno Depresivo/psicología , Dolor/psicología , Rechazo en Psicología , Adolescente , Adulto , Anciano , Trastorno Bipolar/complicaciones , Trastorno Depresivo/complicaciones , Femenino , Humanos , Acontecimientos que Cambian la Vida , Masculino , Persona de Mediana Edad , Dolor/etiología , Valor Predictivo de las Pruebas , Escalas de Valoración Psiquiátrica , Estadísticas no Paramétricas , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: The prevention of intimate partner transmission of HIV remains an important component of comprehensive HIV prevention strategies. In this paper we examine the sexual practices of people living with HIV on antiretroviral therapy (ART) in Papua New Guinea (PNG). METHOD: In 2008, a total of 374 HIV-positive people over the age of 16 and on ART for more than two weeks were recruited using a non-probability, convenience sampling methodology. This accounted for around 18% of adults on ART at the time. A further 36 people participated in semi-structured interviews. All interviews were thematically analysed using NVivo qualitative data analysis software. RESULTS: Less than forty per cent (38%) of participants reported having had sexual intercourse in the six months prior to the survey. Marital status was by far the most important factor in determining sexual activity, but consistent condom use during vaginal intercourse with a regular partner was low. Only 46% reported consistent condom use during vaginal intercourse with a regular partner in the last six months, despite 77% of all participants reporting that consistent condom use can prevent HIV transmission. Consistent condom use was lowest amongst married couples and those in seroconcordant relationships. The vast majority (91.8%) of all participants with a regular heterosexual partner had disclosed their status to their partner. Qualitative data reinforced low rates of sexual activity and provided important insights into sexual abstinence and condom use. CONCLUSIONS: Considering the importance of intimate partner transmission of HIV, these results on the sexual practices of people with HIV on ART in PNG suggest that one-dimensional HIV prevention messages focussing solely on condom use fail to account for the current practices and needs of HIV-positive people, especially those who are married and know their partners' HIV status.
RESUMEN
BACKGROUND: Although genetic epidemiological studies have confirmed increased rates of major depressive disorder among the relatives of people with bipolar affective disorder, no report has compared the clinical characteristics of depression between these two groups. AIMS: To compare clinical features of depressive episodes across participants with major depressive disorder and bipolar disorder from within bipolar disorder pedigrees, and assess the utility of a recently proposed probabilistic approach to distinguishing bipolar from unipolar depression. A secondary aim was to identify subgroups within the relatives with major depression potentially indicative of 'genetic' and 'sporadic' subgroups. METHOD: Patients with bipolar disorder types 1 and 2 (n = 246) and patients with major depressive disorder from bipolar pedigrees (n = 120) were assessed using the Diagnostic Interview for Genetic Studies. Logistic regression was used to identify distinguishing clinical features and assess the utility of the probabilistic approach. Hierarchical cluster analysis was used to identify subgroups within the major depressive disorder sample. RESULTS: Bipolar depression was characterised by significantly higher rates of psychomotor retardation, difficulty thinking, early morning awakening, morning worsening and psychotic features. Depending on the threshold employed, the probabilistic approach yielded a positive predictive value ranging from 74% to 82%. Two clusters within the major depressive disorder sample were found, one of which demonstrated features characteristic of bipolar depression, suggesting a possible 'genetic' subgroup. CONCLUSIONS: A number of previously identified clinical differences between unipolar and bipolar depression were confirmed among participants from within bipolar disorder pedigrees. Preliminary validation of the probabilistic approach in differentiating between unipolar and bipolar depression is consistent with dimensional distinctions between the two disorders and offers clinical utility in identifying patients who may warrant further assessment for bipolarity. The major depressive disorder clusters potentially reflect genetic and sporadic subgroups which, if replicated independently, might enable an improved phenotypic definition of underlying bipolarity in genetic analyses.
Asunto(s)
Trastorno Bipolar/diagnóstico , Trastorno Depresivo Mayor/diagnóstico , Adulto , Trastorno Bipolar/epidemiología , Trastorno Bipolar/genética , Análisis por Conglomerados , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/genética , Diagnóstico Diferencial , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Entrevista Psicológica , Modelos Logísticos , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Intento de Suicidio/estadística & datos numéricosRESUMEN
OBJECTIVES: Little is known regarding the correlates of pain in bipolar disorder. Recent neuroimaging studies support the contention that depression, as well as pain distress and rejection distress, share the same neurobiological circuits. In a recently published study, we confirmed the hypothesis that perception of increased pain during treatment-refractory depression, predominantly unipolar, was related to increased rejection sensitivity. In the present study, we aimed to test this same hypothesis for bipolar depression. METHODS: The present study analysed data from 67 patients presenting to the Black Dog Institute Bipolar Disorders Clinic in Sydney, Australia. The patients all met DSM-IV criteria for bipolar disorder and had completed a self-report questionnaire regarding perceived pain and rejection sensitivity during depression. RESULTS: A significant increase in the experience of headaches (p=0.003) as well as chest pain (p=0.004) during bipolar depression was predicted by a major increase in rejection sensitivity when depressed, i.e., state rejection sensitivity. Being rejection sensitive in general, i.e., trait rejection sensitivity, did not predict pain during depression. CONCLUSIONS: The experience of increased headaches and chest pain during bipolar depression is related to increased rejection sensitivity during depression. Research to further elucidate this relationship is required.
Asunto(s)
Trastorno Bipolar/psicología , Dolor/psicología , Rechazo en Psicología , Adulto , Anciano , Australia , Trastorno Bipolar/complicaciones , Trastorno Bipolar/diagnóstico , Dolor en el Pecho/complicaciones , Dolor en el Pecho/psicología , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Cefalea/complicaciones , Cefalea/psicología , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Autoinforme , Encuestas y Cuestionarios , Adulto JovenRESUMEN
This paper examines condom use in intimate relationships amongst Papua New Guineans on antiretroviral therapy (ART). These findings are from a mixed-method study in six provinces throughout Papua New Guinea (PNG). A total of 374 HIV-positive adult Papua New Guineans, over the age of 16 and on ART for more than two weeks were recruited using a non-probability, convenience sampling methodology. Participants were recruited through ART prescribing sites, People Living with HIV/AIDS (PLWHA) drop-in clinics and support groups. A small number (36) also participated in in-depth interviews. Of the sample 226 (60.4%) were women and 148 (39.6%) were men. The majority of the sample was aged below 40 years, with a median age of 30 years. Of the sample who were in a regular relationship 64.7% identified themselves as being in a relationship where both they and their partner were HIV-positive (seroconcordant). Smaller proportions (21.0%) reported being in a relationship with a HIV-negative partner (serodiscordant), or in a relationship where they were not aware of their partner's HIV status (14.3%). The majority of participants who reported having a regular partner also reported having disclosed their HIV serostatus to their partner (91.8%). A significantly greater proportion of participants who reported being in relationships where they did not know the status of their partner, also reported living in the Southern Region of PNG (52.9%), while the majority of those in seroconcordant relationships lived in the Highlands Region (71.2%). There did not appear to be any differences in sexual practice of using condoms between the three groups. Knowledge of serostatus is important for "positive prevention".
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Condones/estadística & datos numéricos , Seropositividad para VIH/psicología , Conducta Sexual/psicología , Parejas Sexuales/psicología , Adolescente , Adulto , Anciano , Antirretrovirales/uso terapéutico , Femenino , Seropositividad para VIH/epidemiología , Conocimientos, Actitudes y Práctica en Salud , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Papúa Nueva Guinea/epidemiología , Investigación Cualitativa , Asunción de Riesgos , Conducta Sexual/estadística & datos numéricos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Concern internationally that young gay men are at increased risk of HIV infection has not been reflected in earlier findings in Australia where younger men have not been found to be at increased likelihood to engage in unprotected anal intercourse with casual partners (UAIC). There has, however, been little attention paid to the issue of age in relation to HIV risk behaviour in Australia in recent years. In 2007, among men who completed Gay Community Periodic Survey questionnaires in Sydney, Melbourne and Brisbane, Australia, younger men were more likely to report being in relatively short-term monogamous relationships than were their older counterparts. They were also less likely to know their own or their partners' HIV serostatus. Men aged less than 25 years reported fewer recent partners and were less likely to report sex with casual male partners in the previous six months (p<0.001). Younger men were also less likely to engage in group sex. Approximately, one-quarter of the sample reported engaging in any UAIC in the previous six months during each year of the survey. Younger men were no less likely to report UAIC overall, but they were somewhat more likely to report taking the receptive position during UAIC. While age is a consideration in the assessment of risk of HIV transmission among gay men, this risk is dependent upon the context in which it occurs: Age mixing may be an important consideration in understanding HIV risk among young gay men.
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Infecciones por VIH/psicología , Homosexualidad Masculina/psicología , Adulto , Factores de Edad , Australia , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Asunción de Riesgos , Conducta Sexual/psicología , Parejas Sexuales , Encuestas y Cuestionarios , Sexo Inseguro/psicología , Adulto JovenRESUMEN
BACKGROUND: Increased white matter hyperintensities (WMHs) is one of the most consistent imaging findings amongst participants with bipolar disorder (BD). This study investigated WMHs in a young population at high genetic risk for bipolar disorder (HR). METHODS: MRI scans were conducted at baseline in HR individuals (nâ¯=â¯131), patients with BD (nâ¯=â¯47) and controls (CON) (nâ¯=â¯108). Most of the HR (nâ¯=â¯77) and CON (nâ¯=â¯74) group completed scans after two years. Scans were examined for the presence of WMHs. RESULTS: There were significantly more periventricular WMHs in the BD compared to the CON group at baseline (pâ¯=â¯.04). Although the prevalence of periventricular WMHs was intermediate in the HR group, there were no significant differences between the HR and CON or BD participants. Deep WMHs did not differ significantly between the groups. Over time, there was a significant increase in the prevalence of periventricular WMHs in both the HR and CON groups (pâ¯=â¯.02). LIMITATIONS: The use of a visual rating scale to examine WMHs is subjective. As the gradings were collapsed into 'present' or 'absent', we could not ascertain whether the severity of hyperintensities worsened over time. CONCLUSIONS: Periventricular WMHs are more prevalent in young individuals with BD than controls. As these are not more prevalent in HR individuals, it is possible that these are either secondary to the development of bipolar disorder, its treatment, or resulting changes in lifestyle. In a novel finding, there were similar increases in the prevalence of WMHs in controls and HR youth over the 2-year period.
Asunto(s)
Trastorno Bipolar/diagnóstico por imagen , Imagen por Resonancia Magnética/estadística & datos numéricos , Sustancia Blanca/diagnóstico por imagen , Adolescente , Adulto , Trastorno Bipolar/genética , Trastorno Bipolar/patología , Niño , Femenino , Predisposición Genética a la Enfermedad , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Tamaño de los Órganos , Prevalencia , Factores de Riesgo , Sustancia Blanca/patología , Adulto JovenRESUMEN
BACKGROUND: Schizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects. METHODS: We performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects. RESULTS: FDRs-BD had significantly larger ICV (d = +0.16, q < .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = -0.12, q < .05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d < -0.09, q < .05 corrected); and third ventricle was larger (d = +0.15, q < .05 corrected). The findings were not explained by psychopathology in the relatives or control subjects. CONCLUSIONS: Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct.
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Trastorno Bipolar , Encéfalo/patología , Predisposición Genética a la Enfermedad , Esquizofrenia , Adulto , Trastorno Bipolar/genética , Trastorno Bipolar/patología , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esquizofrenia/genética , Esquizofrenia/patología , Adulto JovenRESUMEN
BACKGROUND: The aim of this study was to examine the relationship between family environment (cohesion and parental bonding), high-risk status, and psychopathology (internalizing and externalizing problems) among offspring of parents with bipolar disorder (BD), from the perspective of both offspring and their parents. We further tested if family environment mediated the relationship between bipolar risk status and internalizing and externalizing problems. METHOD: High-risk (n = 90) BD offspring and control (n = 56) offspring aged 12-21 years old, and their parents, completed questionnaires on family cohesion and offspring internalizing and externalizing problems. Offspring also completed a parental bonding questionnaire. Group differences were examined, followed by multi-level mediation analysis with maximum likelihood and robust standard errors. RESULTS: Both offspring and parents in the high-risk group reported higher levels of internalizing and externalizing problems than controls. According to offspring reports, high-risk status, lower maternal and paternal care in parental bonding, was independently associated with internalizing problems. Lower maternal care alone predicted externalizing problems. Family environment did not mediate the relationship between bipolar risk status, and offspring problems. LIMITATIONS: Due to rates of missing data from parent reports of offspring psychopathology, mediation analysis was completed using offspring reports. CONCLUSIONS: The offspring-report data presented indicate that low parental warmth and connection were associated with internalizing and externalizing problems as an independent risk factor, in addition to bipolar risk status. The parent-child relationship therefore warrants attention as a potential target for prevention strategies with such families.
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Trastorno Bipolar/psicología , Hijo de Padres Discapacitados/psicología , Relaciones Familiares , Relaciones Padres-Hijo , Psicopatología , Adolescente , Adulto , Niño , Hijo de Padres Discapacitados/estadística & datos numéricos , Relaciones Familiares/psicología , Padre , Femenino , Humanos , Relaciones Interpersonales , Masculino , Apego a Objetos , Encuestas y CuestionariosRESUMEN
BACKGROUND: Bipolar disorder (BD) is characterized by a dysregulation of affect and impaired integration of emotion with cognition. These traits are also expressed in probands at high genetic risk of BD. The inferior frontal gyrus (IFG) is a key cortical hub in the circuits of emotion and cognitive control, and it has been frequently associated with BD. Here, we studied resting-state functional connectivity of the left IFG in participants with BD and in those at increased genetic risk. METHODS: Using resting-state functional magnetic resonance imaging we compared 49 young BD participants, 71 individuals with at least one first-degree relative with BD (at-risk), and 80 control subjects. We performed between-group analyses of the functional connectivity of the left IFG and used graph theory to study its local functional network topology. We also used machine learning to study classification based solely on the functional connectivity of the IFG. RESULTS: In BD, the left IFG was functionally dysconnected from a network of regions, including bilateral insulae, ventrolateral prefrontal gyri, superior temporal gyri, and the putamen (p < .001). A small network incorporating neighboring insular regions and the anterior cingulate cortex showed weaker functional connectivity in at-risk than control participants (p < .006). These constellations of regions overlapped with frontolimbic regions that a machine learning classifier selected as predicting group membership with an accuracy significantly greater than chance. CONCLUSIONS: Functional dysconnectivity of the IFG from regions involved in emotional regulation may represent a trait abnormality for BD and could potentially aid clinical diagnosis.
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Trastorno Bipolar/genética , Trastorno Bipolar/fisiopatología , Encéfalo/fisiopatología , Corteza Prefrontal/fisiopatología , Adolescente , Adulto , Mapeo Encefálico/métodos , Femenino , Predisposición Genética a la Enfermedad , Humanos , Sistema Límbico/fisiopatología , Aprendizaje Automático , Imagen por Resonancia Magnética , Masculino , Vías Nerviosas/fisiopatología , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVE: Bipolar disorder (BD) is one of the most heritable psychiatric conditions and is associated with high suicide risk. To explore the reasons for this link, this study examined the interaction between traumatic stress and BD polygenic risk score in relation to suicidal ideation, suicide attempt, and nonsuicidal self-injury (NSSI) in adolescent and young adult offspring and relatives of persons with BD (BD-relatives) compared with adolescent and young adult offspring of individuals without psychiatric disorders (controls). METHOD: Data were collected from 4 sites in the United States and 1 site in Australia from 2006 through 2012. Generalized estimating equation models were used to compare rates of ideation, attempts, and NSSI between BD-relatives (n = 307) and controls (n = 166) and to determine the contribution of demographic factors, traumatic stress exposure, lifetime mood or substance (alcohol/drug) use disorders, and BD polygenic risk score. RESULTS: After adjusting for demographic characteristics and mood and substance use disorders, BD-relatives were at increased risk for suicidal ideation and attempts but not for NSSI. Independent of BD-relative versus control status, demographic factors, or mood and substance use disorders, exposure to trauma within the past year (including bullying, sexual abuse, and domestic violence) was associated with suicide attempts (p = .014), and BD polygenic risk score was marginally associated with attempts (p = .061). Importantly, the interaction between BD polygenic risk score and traumatic event exposures was significantly associated with attempts, independent of demographics, relative versus control status, and mood and substance use disorders (p = .041). CONCLUSION: BD-relatives are at increased risk for suicide attempts and ideation, especially if they are exposed to trauma and have evidence of increased genetic vulnerability.
Asunto(s)
Trastorno Bipolar/genética , Trastorno Bipolar/psicología , Predisposición Genética a la Enfermedad , Trauma Psicológico/genética , Trauma Psicológico/psicología , Conducta Autodestructiva/genética , Conducta Autodestructiva/psicología , Adolescente , Trastorno Bipolar/diagnóstico , Estudios de Casos y Controles , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Modelos Estadísticos , Polimorfismo de Nucleótido Simple , Escalas de Valoración Psiquiátrica , Trauma Psicológico/diagnóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Conducta Autodestructiva/diagnóstico , Ideación Suicida , Intento de Suicidio/psicología , Adulto JovenRESUMEN
OBJECTIVE: In a prior study of bipolar disorder pedigrees, we demonstrated distinct clinical differences between depressive episodes in bipolar disorder and major depressive disorder (MDD), including differentiation between these conditions using the Probabilistic Approach to Bipolar Depression. The aim of this retrospective study was to compare the phenomenology of the most severe lifetime depressive episodes between bipolar I (BP-I) and II (BP-II) disorder subtypes and MDD in these pedigrees. METHOD: Patients with DSM-IV diagnoses of BP-I (n = 202), BP-II (n = 44), and MDD (n = 120) from bipolar disorder pedigrees were assessed using the Diagnostic Interview for Genetic Studies between 1998 and 2012. Multivariate logistic regression was used to identify distinguishing clinical features. The utility of the Probabilistic Approach in distinguishing BP-I and BP-II depression from MDD was assessed. RESULTS: BP-I differed from MDD in terms of greater rates of psychomotor retardation (P < .05) and psychotic features (P < .05). BP-II was distinguished from MDD (P < .01) by the greater likelihood of mixed features. Patients with BP-II had a greater likelihood of mixed features (P < .001) and a lesser likelihood of psychomotor retardation (P < .05) compared to those with BP-I. The Probabilistic Approach significantly differentiated both BP-I and BP-II from MDD (P < .01 to P < .001, depending on cutoff) but did not robustly distinguish between BP-I and BP-II. CONCLUSIONS: First, the differentiation of BP-II from both BP-I depression and MDD in terms of the presence of mixed symptoms is of particular interest given the current debate over "mixed specifiers" for these conditions in DSM-5. Second, the Probabilistic Approach to Bipolar Depression was demonstrated for the first time to significantly distinguish both bipolar disorder subtypes from MDD.