Bipolar disorder - from endophenotypes to treatment

There are a lot of unresolved issues associated with the classification, diagnosis, clinical management and understanding of the underlying pathogenic mechanisms of bipolar affective disorder.

To search for discrete endophenotypes in BAD.

We studied various bipolar I and II and recurrent depression patient samples and healthy controls using descriptive data, self and clinician-rated scales for neurological and psychopathological symptoms, neurocognitive instruments, and inventories for temperamental and characterological features. We also looked into the efficacy, tolerability and cost/benefit ratio of sodium valproate in the treatment of acute mania.

BAD patients display deficits in the domains of memory, selective attention, working memory and psychomotor speed. Sensory, motor and complex neurological soft signs can be considered part and parcel of the symptomatology of BAD. The evidence linking hyperthymic temperament to the bipolar spectrum is not supported, while cyclothymia seems to be a marker of vulnerability to affective psychopathology. In contrast to others, we found significantly lower self-transcendence in BAD patients compared to controls. Early age of onset, abrupt onset, lability of mood and energy with late-day brightening and activation, discriminate bipolar from unipolar depression. Sodium valproate (especially if started intravenously) is a highly efficacious, cost-effective treatment approach for acute mania.

The discovery of BAD endophenotypes can enhance early diagnosis, prevent errors in treatment and help elucidate the genetic vulnerability for this grave disease.