[Paleopsych] SW: On Bipolar Disorder

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Medical Biology: On Bipolar Disorder

    The following points are made by R.H. Belmaker (New Engl. J. Med. 2004
    1) Bipolar disorder is one of the most distinct syndromes in
    psychiatry and has been described in numerous cultures over the course
    of history.(1) The unique hallmark of the illness is mania. Mania is,
    in many ways, the opposite of depression. It is characterized by
    elevated mood or euphoria, overactivity with a lack of need for sleep,
    and an increased optimism that usually becomes so extreme that the
    patient's judgment is impaired. For example, a person with mania may
    decide to purchase 500 television sets if he or she believes that
    their price will go up. Drives such as sexual desire are also
    enhanced; manic patients are disinhibited in their speech about sexual
    matters, joking or talking about subjects not normally allowed in
    their culture. Manic patients are sometimes disinhibited in their
    sexual actions as well, and they may endanger their marriage or
    relationship as a result.
    2) A key point is that manic behavior is distinct from a patient's
    usual personality, but its onset may be gradual with weeks or months
    passing before the syndrome becomes full-blown. In the absence of
    effective treatment, a manic episode, although ultimately
    self-limited, could last months or years.(2) Before effective
    treatment was available, even after a long manic episode, patients
    were known to recover to a state closely approximating, if not
    identical with, their personality before the illness developed.(3)
    3) The depression that alternates with manic episodes (bipolar
    depression) is characterized by more familiar symptoms. A single manic
    episode is sufficient for the diagnosis of bipolar illness, as long as
    the manic symptoms are not due to a general medical condition such as
    amphetamine abuse or pheochromocytoma.(4) Some patients may have one
    manic episode at a young age and frequent depressive episodes
    thereafter, others may have alternating episodes of mania and
    depression on a yearly basis, and still others may have a manic
    episode every five years but never have a depressive episode.
    4) Approximately 50 percent of patients with bipolar illness have a
    family history of the disorder, and in some families, known as
    multiplex families, there are many members with the disease across
    several generations. Studies of twins suggest that the concordance for
    bipolar illness is between 40 percent and 80 percent in monozygotic
    twins and is lower (10 to 20 percent) in dizygotic twins, a difference
    that suggests a genetic component to the disorder. There is no
    mendelian pattern, however, and statistical analysis suggests
    polygenic inheritance.
    5) The advent of molecular genetics opened a new era in genetic
    studies of bipolar disorder. DNA markers have been sought throughout
    the genome in large pedigrees in which many family members have the
    illness and, with the use of the transmission disequilibrium test, in
    patients with bipolar disorder and their parents. Linkage studies have
    identified markers, which have been replicated in more than one study,
    particularly on chromosomes 18 and 22. However, no single locus has
    been consistently replicated, and the contribution of any identified
    locus appears small. Progress in genomic medicine offers the hope that
    specific genes that confer an elevated risk of bipolar illness will be
    References (abridged):
    1. Clinical description. In: Goodwin FK, Jamison KR. Manic-depressive
    illness. New York: Oxford University Press, 1990:15-55
    2. Beers C. A mind that found itself. Garden City, N.Y.: Doubleday,
    3. Kraepelin E. Manic-depressive insanity and paranoia. Chicago:
    University of Chicago Press, 2002
    4. Diagnostic and statistical manual of mental disorders, 4th ed.:
    DSM-IV. Washington, D.C.: American Psychiatric Association, 1994
    5. Baldessarini RJ. A plea for integrity of the bipolar disorder
    concept. Bipolar Disord 2000;2:3-7
    New Engl. J. Med. http://www.nejm.org
    Related Material:
    The following points are made by D.A. Brent and B. Birmaher (New Engl.
    J. Med. 2002 347:667):
    1) In children and adolescents, depression is not always characterized
    by sadness, but instead by irritability, boredom, or an inability to
    experience pleasure. Depression is a chronic, recurrent, and often
    familial illness that frequently first occurs in childhood or
    adolescence. Any child can be sad, but depression is characterized by
    a persistent irritable, sad, or bored mood and difficulty with
    familial relationships, school, and work(1). In the absence of
    treatment, a major depressive episode lasts an average of eight
    months. The risk of recurrence is approximately 40 percent at two
    years and 72 percent at five years.(2) Longer depressive episodes
    occur in patients who have a dysthymic disorder (a milder, but chronic
    and insidious form of depression) that gradually evolves into major
    depression. More prolonged episodes are also associated with
    coexisting psychiatric conditions, parental depression, and
    parent-child discord.(2)
    2) At least 20 percent of those with early-onset depressive disorders
    (those beginning in childhood or adolescence) are at risk for bipolar
    disorder, particularly if they have a family history of bipolar
    disorder, psychotic symptoms, or a manic response to antidepressant
    treatment.(2,3) Bipolar disorder is characterized by depressive
    episodes that alternate with periods of mania, defined by a decreased
    need for sleep, increased energy, grandiosity, euphoria, and an
    increased propensity for risk-taking behavior. Often in children and
    adolescents, mania and depression occur as "mixed states", in which
    the lability of mania is combined with depression, or there is rapid
    cycling between depression and mania over a period of days or even
    3) Suicidal behavior is closely associated with depression. Risk
    factors for suicide during a depressive episode include chronic
    depression, coexisting substance abuse, impulsivity and aggression, a
    history of physical or sexual abuse, same-sex attraction and sexual
    activity, a personal or family history of a suicide attempt, and
    access to an effective means of suicide, such as a gun.(5) Girls are
    more likely to attempt suicide, and boys to complete suicide. Among
    adolescents, the annual rate of suicide attempts requiring medical
    attention is 2.6 percent. Completed suicide is much rarer: among
    15-to-19-year-olds, the rates in 1998 were 14.6 per 100,000 in boys
    and 2.9 per 100,000 in girls.
    4) Depression is present in about 1 percent of children and 5 percent
    of adolescents at any given time. Before puberty, boys and girls are
    at equal risk for depression, whereas after the onset of puberty, the
    rate of depression is about twice as high in girls. Having a parent
    with a history of depression increases a child's risk of a depressive
    episode by a factor of 2 to 4.7 Anxiety, particularly social phobia,
    may be a precursor of depression.
    References (abridged):
    1. Diagnostic and statistical manual of mental disorders, 4th ed.:
    DSM-IV. Washington, D.C.: American Psychiatric Association, 1994.
    2. Birmaher B, Ryan ND, Williamson DE, et al. Child and adolescent
    depression: a review of the past 10 years. J Am Acad Child Adolesc
    Psychiatry 1996;35:1427-1439.
    3. Geller B, Zimerman B, Williams M, Bolhofner K, Craney JL. Bipolar
    disorder at prospective follow-up of adults who had prepubertal major
    depressive disorder. Am J Psychiatry 2001;158:125-127.
    4. Geller B, Zimerman B, Williams M, et al. Diagnostic characteristics
    of 93 cases of a prepubertal and early adolescent bipolar disorder
    phenotype by gender, puberty and comorbid attention deficit
    hyperactivity disorder. J Child Adolesc Psychopharmacol
    5. Brent DA. Mood disorders and suicide. In: Green M, Haggerty RJ,
    eds. Ambulatory pediatrics. 5th ed. Philadelphia: W.B. Saunders,
    New Engl. J. Med. http://www.nejm.org
    Related Material:
    The following points are made by Christopher K. Varley (J. Am. Med.
    Assoc. 2003 290:1091):
    1) An increasing body of knowledge confirms that depression is a
    common and serious illness in youth, affecting 3% to 8% of children
    and adolescents. Moreover, rates of depression increase dramatically
    as children move into adolescence. An estimated 20% of adolescents
    have had at least 1 episode of major depressive disorder (MDD) by age
    18 years, while 65% report transient, less severe depressive symptoms.
    2) Depression compromises the developmental process; feelings of
    worthlessness, low self-esteem, and thoughts of suicide are common, as
    are difficulties with concentration and motivation. As many as 20% of
    adolescents each year have suicide ideation and 5% to 8% attempt
    suicide. While the majority of attempts are not lethal, suicide is a
    leading cause of death in adolescents and is a major health care
    concern. One of the major risk factors associated with suicide is
    3) Depressive disorders in children and adolescents can be chronic and
    recurrent. The mean length of a major depressive episode in youth aged
    6 to 17 years is 7 to 9 months, with remittance commonly occurring
    over a 1- to 2-year period. Longitudinal studies suggest a strong
    potential for recurrence; 48% to 60% of this age group have recurrence
    of major depression after an initial MDD episode within 5 years.
    4) Although depression in youth is now recognized as a significant
    health concern, identification of safe and effective treatment has
    been challenging. The recent study by Wagner et al (2003) is the
    fourth published double-blind, placebo-controlled study demonstrating
    efficacy in the treatment of MDD in children and adolescents; all
    studies included selective serotonin uptake inhibitors (SSRIs). A
    number of psychotropic medications established as safe and effective
    in the treatment of MDD in adults have been investigated in youth but
    may not be effective, including tricyclic antidepressants, monoamine
    oxidase inhibitors, and venlafaxine. There are also safety concerns
    regarding the use of tricyclic antidepressants in children and
    adolescents, including lethality in overdose and cardiac conduction
    delays (and possibly increased risk of sudden death) in therapeutic
    J. Am. Med. Assoc. http://www.jama.com

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