Leverich, Gabriele S.

Introduction Instead of the typical assessment of risk of illness in the offspring based on a parent with bipolar disorder, we explored the potential multigenerational conveyance across several disorders of the vulnerability to illness in the offspring of a patient with bipolar disorder. Methods A total of 968 outpatients (average age 41 years) with bipolar illness gave informed consent and filled out a detailed questionnaire about a family history in their parents, grandparents, and offspring of: depression; bipolar disorder; alcohol abuse; substance abuse; suicide attempt; or “other” illness. Of those with children, 346 were from the USA and 132 were from Europe. Amount and type of illness in progenitors in two and three previous generations were related to offspring illness. Results The type of illness seen in both prior generations was associated with the same type of illness in the offspring of a bipolar patient, including depression, bipolar disorder, alcohol and substance abuse and “other” illness, but not suicide attempts. There was an impact of multiple generations, such that depression in grandparents and/or great‐grandparents increased the risk of depression in the offspring from 12.6% to 41.4%. Conclusions A family history of illness burden in prior generations was previously related to an earlier age of onset of bipolar illness in our adult patients with bipolar disorder and is now also found to be related to the incidence of multiple psychiatric illnesses in their offspring. Genetic and epigenetic mechanisms deserve consideration for this multigenerational conveyance of illness vulnerability, and clinical and public health attempts to prevent or slow this transmission are indicated.

AbstractObjectivesA high incidence of Axis II personality disorders is described in patients with bipolar disorder; however, their relationship to mood state remains uncertain.MethodsA total of 966 outpatients with bipolar disorder gave informed consent and filled out the Personality Disorder Questionnaire, 4th edition (PDQ4) and a questionnaire on demographics and course of illness prior to Bipolar Treatment Outcome Network entry at average age 41 years. Patients were rated at each visit for depression on the Inventory of Depressive Symptoms‐Clinician version (IDS‐C) and for mania on the Young Mania Rating Scale (YMRS). In a subgroup, the PDQ4 was retaken during periods of depression and euthymia.ResultsPatients met criteria for most personality disorders at a much higher rate when they took the PDQ4 while depressed compared to while euthymic, and scores were significantly related to the severity of depression (IDS) and of mania (YMRS) assessed within 2 weeks of taking the PDQ. Even when euthymic, more than quarter to half of the patients met criteria for a cluster A, B or C personality disorder.ConclusionsA wide range of personality disorders occur in bipolar patients, but are highly dependent on filling out the form while depressed compared to while euthymic. How this relates to having a personality disorder assessed using a structured clinical interview remains to be tested. However, higher PDQ4 scores are related to an earlier age of onset of bipolar disorder and other factors portending a more difficult course of bipolar disorder, and the optimal treatment of these patients remains to be illuminated.

ObjectiveEarly‐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.MethodParental 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.ResultsAfter 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.ConclusionParental 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.