Vol 1 n° 1 - Bipolar Disorders
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Linkage studies have defined at least five bipolar (BP) disorder susceptibility loci that meet suggest- ed guidelines for initial identification and subse- quent confirmation. These loci, found on 18p11, 18q22, 21q21, 4p16, and Xq26, are targets for BP candidate gene investigations. Molecular dissec- tion of expressed sequences for these regions is likely to yield specific BP susceptibility alleles in most cases. In all probability, these BP susceptibili- ty alleles will be common in the general popula- tion, and, individually, will be neither necessary nor sufficient for manifestation of the syndrome. Additive   or   multiplicative   oligogenic   models involving several susceptibility loci appear most reasonable at present. It is hoped that these BP susceptibility genes will increase understanding of many   mysteries   surrounding   these   disorders, including drug response, cycling patterns, age-of- onset, and modes of transmission. Keywords: genetics; bipolar disorder; linkage; susceptibility ipolar (BP) disorders are common, chronic, recur- rent, and episodic mood disturbances, associated with vari- able dysfunctions in sleep, appetite, libido, activity, and cog- nition. These disorders are typically so severe that they impair occupational functioning.  Bipolar disorders are char- acterized by recurrent episodes of mania and depression, both of which are defined below. Mania represents a state of persistently elevated (predomi- nantly euphoric) mood with increased activity, intrusive social behavior, irritability (unpredictable angry outbursts are common), decreased need for sleep, grandiosity, exces- sive   energy,   increased   libido,   spending   sprees,   racing thoughts, and poor judgement (inability to perceive possible adverse consequences of dangerous behavior). Mania repre- sents a more severe syndrome than hypomania, and is often accompanied by psychotic symptoms, including hallucina- tions and delusions. Hypomania is a less severe form of mania.  Mania causes impairment in functioning, whereas hypomania (by definition) does not.  Untreated episodes of mania or hypomania are typically 1 to 3 months in length, although this duration is quite variable.   Depression  represents a state of persistent and pervasive sadness, accompanied by crying spells, decreased energy, suicidal ideation, decreased libido, anhedonia (inability to experience pleasure), decreased cognitive ability, sleep dys- function (insomnia or hypersomnia), and appetite distur- bance (with or without weight change). The duration of an untreated episode of depression is typically 6 to 9 months.   Bipolar disorder is characterized by repeated manic or hypo- manic episodes and recurrent depressive episodes. Two sub- types of BP  disorder are recognized: the BP  II category is reserved for persons who have never had an episode of frank mania,  but  have  experienced  hypomania  with  recurrent episodes of depression; the BP I category describes individu- als with the full syndrome of manic and depressive episodes. Individuals with BP disorder have a median of 10 episodes of illness during their lifetime, even with treatment. The diagno- sis of unipolar disorder describes individuals who have recur- rent episodes of depression but no (hypo)manic episodes. Persons  with  unipolar  (UP)  illness  have  a  median  of  4 episodes during their lifetime.  The mean age at onset for BP Molecular linkage studies of bipolar disorder Wade H. Berrettini, MD, PhD B a s i c   r e s e a r c h B From: the department of Psychiatry and the Center for Neurobiology and Behavior, University of Pennsylvania, USA
Address for correspondence: Dr Wade H. Berrettini, Department of Psychiatry and the Center for Neurology Behavior, University of Pennsylvania, 415 Curie Boulevard, Room 111, Philadelphia, PA 19107, USA
E-mail: wadeb@mail.med.upenn.edu
 1 2 Wade H. BERRETTINI