Prevalence of psychopathology in bipolar high-risk offspring and siblings: a meta-analysis.

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.

Family environment and psychopathology in offspring of parents with bipolar disorder.

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.

Functional Dysconnection of the Inferior Frontal Gyrus in Young People With Bipolar Disorder or at Genetic High Risk.

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.

What clinical features precede the onset of bipolar disorder?

Despite a growing number of reports, there is still limited knowledge of the clinical features that precede the onset of bipolar disorder (BD). To explore this, we investigated baseline data from a prospectively evaluated longitudinal cohort of subjects aged 12-30 years to compare: first, lifetime rates of clinical features between a) subjects at increased genetic risk for developing BD ('AR'), b) participants from families without mental illness ('controls'), and c) those with established BD; and, second, prior clinical features that predict the later onset of affective disorders in these same three groups. This is the first study to report such comparisons between these three groups (though certainly not the first to compare AR and control samples). 118 AR participants with a parent or sibling with BD (including 102 with a BD parent), 110 controls, and 44 BD subjects were assessed using semi-structured interviews. AR subjects had significantly increased lifetime risks for depressive, anxiety and behavioural disorders compared to controls. Unlike prior reports, preceding anxiety and behavioural disorders were not found to increase risk for later onset of affective disorders in the AR sample, perhaps due to limited sample size. However, preceding behavioural disorders did predict later onset of affective disorders in the BD sample. The findings that i) AR subjects had higher rates of depressive, anxiety and behavioural disorders compared to controls, and ii) prior behavioural disorders increased the risk to later development of affective disorders in the BD group, suggest the possibility of therapeutic targeting for these disorders in those at high genetic risk for BD.

Cognitive styles and clinical correlates of childhood abuse in bipolar disorder.

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.

Rejection sensitivity and pain in bipolar versus unipolar depression.

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.

Anxiety, stress and perfectionism in bipolar disorder.

BACKGROUND: Previous reports have highlighted perfectionism and related cognitive styles as a psychological risk factor for stress and anxiety symptoms as well as for the development of bipolar disorder symptoms. The anxiety disorders are highly comorbid with bipolar disorder but the mechanisms that underpin this comorbidity are yet to be determined. METHOD: Measures of depressive, (hypo)manic, anxiety and stress symptoms and perfectionistic cognitive style were completed by a sample of 142 patients with bipolar disorder. Mediation models were used to explore the hypotheses that anxiety and stress symptoms would mediate relationships between perfectionistic cognitive styles, and bipolar disorder symptoms. RESULTS: Stress and anxiety both significantly mediated the relationship between both self-critical perfectionism and goal attainment values and bipolar depressive symptoms. Goal attainment values were not significantly related to hypomanic symptoms. Stress and anxiety symptoms did not significantly mediate the relationship between self-critical perfectionism and (hypo)manic symptoms. LIMITATIONS: 1. These data are cross-sectional; hence the causality implied in the mediation models can only be inferred. 2. The clinic patients were less likely to present with (hypo)manic symptoms and therefore the reduced variability in the data may have contributed to the null findings for the mediation models with (hypo) manic symptoms. 3. Those patients who were experiencing current (hypo)manic symptoms may have answered the cognitive styles questionnaires differently than when euthymic. CONCLUSION: These findings highlight a plausible mechanism to understand the relationship between bipolar disorder and the anxiety disorders. Targeting self-critical perfectionism in the psychological treatment of bipolar disorder when there is anxiety comorbidity may result in more parsimonious treatments.

Clinical and demographic features associated with the detection of early warning signs in bipolar disorder.

AIM: The detection of early warning signs is a major component of many psychological interventions for assisting in the management of bipolar disorder. The aim of this study was to assess whether the ability to detect early warning signs was associated with clinical and demographic characteristics in a bipolar disorder clinic sample. METHOD: Two-hundred-and-one participants with DSM-IV bipolar I or II disorder aged over 18 years of age were recruited through a specialized bipolar disorder clinic. Participants were administered a structured interview by psychiatrists asking participants about any early warning signs, and features of the phenomenology, course and treatment of bipolar disorder. RESULTS: Participants were significantly more likely to recognise both hypo/manic and depressive early warning signs rather than only one type of mood episode. The ability to detect signs of both hypo/mania and depression was greater in younger participants. The ability to detect signs of depression was associated with more prior depressive episodes and a lesser likelihood of prior hospitalisations whilst a history of mixed mood was associated with a greater likelihood of detecting depressive symptoms. The ability to recognise signs of hypo/mania was greater in those reporting a history of visual hallucinations (during depressive and/or manic episodes). LIMITATIONS: Cross-sectional design and previous experience with psychotherapy was not assessed. CONCLUSION: These findings provide useful clinical data pertinent to psychological interventions for bipolar disorder. Longitudinal studies are needed to further examine how the ability to recognise early warning signs may be associated with longer term outcome.