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We sought to determine whether premenstrual mood symptoms exhibit familial aggregation in bipolar disorder or major depression pedigrees. Two thousand eight hundred seventy-six women were interviewed with the Diagnostic Interview for Genetic Studies as part of either the NIMH Genetics Initiative Bipolar Disorder Collaborative study or the Genetics of Early Onset Major Depression (GenRED) study and asked whether they had experienced severe mood symptoms premenstrually. In families with two or more female siblings with bipolar disorder (BP) or major depressive disorder (MDD), we examined the odds of having premenstrual mood symptoms given one or more siblings with these symptoms. For the GenRED MDD sample we also assessed the impact of personality as measured by the NEO-FFI. Premenstrual mood symptoms did not exhibit familial aggregation in families with BP or MDD. We unexpectedly found an association between high NEO openness scores and premenstrual mood symptoms, but neither this factor, nor NEO neuroticism influenced evidence for familial aggregation of symptoms. Limitations include the retrospective interview, the lack of data on premenstrual dysphoric disorder, and the inability to control for factors such as medication use.

Despite compelling evidence that genetic factors contribute to bipolar disorder (BP), attempts to identify susceptibility genes have met with limited success. This may be due to the genetic heterogeneity of the disorder. We sought to identify susceptibility loci for BP in a genome-wide linkage scan with and without clinical covariates that might reflect the underlying heterogeneity of the disorder. We genotyped 428 subjects in 98 BP families at the Center for Inherited Disease Research with 402 microsatellite markers. We first carried out a non-parametric linkage analysis with MERLIN, and then reanalyzed the data with LODPAL to incorporate clinical covariates for age at onset (AAO), psychosis and comorbid anxiety. We sought to further examine the top findings in the covariate analysis in an independent sample of 64 previously collected BP families. In the non-parametric linkage analysis, three loci were nominally significant under a narrow diagnostic model and seven other loci were nominally significant under a broader model. The top findings were on chromosomes 2q24 and 3q28. The covariate analyses yielded additional evidence for linkage on 3q28 with AAO in the primary and independent samples. Although none of the linked loci were genome-wide significant, their congruence with prior results and, for the covariate analyses, their identification in two separate samples increases the likelihood that they are true positives and deserve further investigation. These findings further demonstrate the value of considering clinical features that may reflect the underlying heterogeneity of disease in order to facilitate gene mapping.

Since the time of the ancient Greeks, physicians have recognized a certain relatedness between the mental states of depression and mania. In the mid-Nineteenth century, French alienists proposed a 'double' or 'circular' illness consisting of alternating depressed and manic episodes and at the beginning of the twentieth century, Emil Kraepelin introduced the term 'manic-depressive insanity.' Kraepelin's broad clinical experience resulted in compelling descriptions of the symptoms of mood disorders that have arguably never been surpassed. The Kraepelinian nosology continues to provide a touchstone for modern classification systems of the mood disorders.

The biological mechanisms underlying the major psychiatric disorders remain mysterious, resulting in a lack of precision in diagnosis and controversies in nosology. This is especially true for the mood disorders. This issue of the International Review of Psychiatry reviews several of these controversies with special attention to syndromic manifestations of affective disorder that are often missing in modern nosological systems.

The modern dichotomous divide between unipolar and bipolar depressive disorders derives from several monographs that appeared in the mid-twentieth century. Studies of illness course and differing symptomatic profiles in unipolar and bipolar illness support this interpretation, but more recent descriptions of ‘bipolar spectrum disorders’ and genetic findings suggest otherwise. Whether these illnesses represent categories or points on a continuum remains an unresolved question.

With the release of new medications into the armamentarium for the treatment of bipolar disorder, clinicians are required to make prudent treatment decisions in light of insufficient research data for patients with a difficult-to-control illness. Increasingly, clinicians are turning toward a combination or adjunctive treatment out of necessity. Many studies suggest effectiveness of add-on agents in patients with mania who are unresponsive to one or more drugs, while only a limited number of controlled trials actually compare one particular combination regimen to another. Despite this lack of data, there has been no lack of advice for the clinician from clinical recommendations in the form of expert treatment guidelines to case reports describing suggestive findings from the off-label use of newer agents. With a particular emphasis on the treatment of mania, this article reviews the clinical data on the individual agents of foreseeable use in combination treatment for bipolar disorder. We suggest beginning with an agent of established effectiveness when combining medications for the treatment of bipolar disorder.

Of 20 patients receiving ECT, those with high anticholinergic drug levels after ECT were at greater risk for developing post-ECT confusional states than were patients with low levels.