[Paleopsych] SW: On Generalized Anxiety Disorder

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Medical Biology: On Generalized Anxiety Disorder
http://scienceweek.com/2004/sa041022-3.htm

    The following points are made by Gregory Fricchione (New Engl. J. Med.
    2004 351:675):
    1) Anxiety disorders are the most prevalent psychiatric conditions in
    the US aside from disorders involving substance abuse.(1) Generalized
    anxiety disorder has a lifetime prevalence of 5 percent. The onset is
    usually before the age of 25 years, and the incidence in men is half
    that in women. Untreated, the typical course is chronic, with a low
    rate of remission and a moderate recurrence rate.(3)
    2) Risk factors for generalized anxiety disorder include a family
    history of the condition, an increase in stress, and a history of
    physical or emotional trauma.(4,5) An association has also been
    reported between smoking and anxiety, and the risk of generalized
    anxiety disorder among adolescents who smoke heavily is five to six
    times the risk among nonsmokers. Traits such as nervousness and social
    discomfort may predispose people to both nicotine dependence and
    anxiety. Medical illnesses are often associated with anxiety. For
    example, generalized anxiety disorder occurs in 14 percent of patients
    with diabetes.
    3) Major depression is the most common coexisting psychiatric illness
    in patients with generalized anxiety disorder, occurring in almost two
    thirds of such patients. Panic disorder occurs in a quarter of
    patients with generalized anxiety disorder, and alcohol abuse in more
    than a third.(1) Studies of twins suggest a shared genetic propensity
    to both generalized anxiety disorder and major depression, and a
    recent report suggests that a genetic variant of the
    serotonin-transporter gene may predispose people to both conditions.
    In prospective studies, anxiety almost always appears to be the
    primary disorder and to increase the risk of depression. Patients who
    have generalized anxiety disorder along with coexisting psychiatric
    illnesses have more impairment, seek more medical attention, and have
    a poorer response to treatment than those without coexisting
    illnesses.
    4) Patients with generalized anxiety disorder often have physical
    symptoms, and it may be difficult to distinguish the symptoms from
    those of medical illnesses that are associated with anxiety. Factors
    suggesting that anxiety is the symptom of a medical disorder include
    an onset of the symptoms after the age of 35 years, no personal or
    family history of anxiety, no increase in stress, little or no
    avoidance of anxiety-provoking situations, and a poor response to
    antianxiety medication. A physical cause should be suspected when
    anxiety follows recent changes in medication or accompanies signs and
    symptoms of a new disease.(2)
    References (abridged):
    1. Kessler RC, McGonagle KA, Zhao S, et al. Lifetime and 12-month
    prevalence of DSM-III-R psychiatric disorders in the United States:
    results from the National Comorbidity Survey. Arch Gen Psychiatry
    1994;51:8-19
    2. Diagnostic and statistical manual of mental disorders, 4th ed.:
    DSM-IV. Washington, D.C.: American Psychiatric Association, 1994:435-6
    3. Wittchen HU, Carter RM, Pfister H, Montgomery SA, Kessler RC.
    Disabilities and quality of life in pure and comorbid generalized
    anxiety disorder and major depression in a national survey. Int Clin
    Psychopharmacol 2000;15:319-328
    4. Brantley PJ, Mehan DJ Jr, Ames SC, Jones GN. Minor stressors and
    generalized anxiety disorders among low-income patients attending
    primary care clinics. J Nerv Ment Dis 1999;187:435-440
    5. Brown ES, Fulton MK, Wilkeson A, Petty F. The psychiatric sequelae
    of civilian trauma. Compr Psychiatry 2000;41:19-23
    New Engl. J. Med. http://www.nejm.org
    --------------------------------
    Related Material:
    ON SEROTONIN AND ANXIETY
    The following points are made by Solomon H. Snyder (Nature 2002
    416:377):
    1) Perhaps one of the best known of neurotransmitters, serotonin has a
    role in many different neurobiological processes. For example, it
    helps to regulate our moods -- a fact that has been well established
    since the 1950s, with the discovery that drugs that deplete serotonin
    precipitate depression whereas increasing serotonin levels has
    antidepressant effects. The idea that serotonin might also affect
    anxiety was first suspected in the 1980s following the serendipitous
    finding that buspirone, a drug developed to treat psychotic patients,
    is also useful for treating anxiety disorders, and stimulates a type
    of serotonin-detecting molecule in the body, the serotonin-1A
    receptor. Later came the discovery that mice that have been
    genetically engineered to lack this receptor, and so cannot respond
    normally to serotonin, show increased "anxiety-like" behavior(2-4).
    2) But the underlying mechanisms have been elusive. For instance, the
    relevant brain regions have not been delineated. Moreover, the
    findings in receptor-deficient mice appear to contradict observations
    that compounds that block serotonin-1A receptors do not cause anxiety
    in adult mice. Gross et al.(1) have substantially clarified these
    issues: By using mice in which the serotonin-1A receptor can be
    knocked out at will, they have shown that the absence of the receptor
    in newborns does indeed lead to anxiety-like behavior, whereas its
    knockout during adult life has no effect. Gross et al. also
    discriminate between the role of the receptors in the hindbrain and in
    forebrain structures such as the hippocampus and cerebral cortex.
    3) Conventional gene-knockout techniques are powerful tools for
    working out what a protein does. But they have major limitations
    compared with using drugs (which might, for example, activate or
    inhibit the protein of interest). Genes tend to be knocked out during
    embryonic life, generally affecting the whole organism throughout its
    lifetime. By contrast, a drug can be administered at any time and, in
    the brain, can be injected into specific areas. The approach adopted
    by Gross et al.1 is an ingenious way of addressing the shortcomings of
    gene knockouts, providing time-and tissue-specific deletion and
    restoration of serotonin-1A receptors. To achieve time-specific
    knockouts, Gross et al. produced mice in which expression of the
    serotonin-1A-receptor gene was under the control of the antibiotic
    doxycycline. The gene could be switched off -- with a certain time lag
    -- simply by feeding mice the antibiotic.
    References (abridged):
    1. Gross, C. et al. Nature 416, 396-400 (2002)
    2. Parks, C. L., Robinson, P. S., Sibille, E., Shenk, T. & Toth, M.
    Proc. Natl Acad. Sci. USA 95, 10734-10739 (1998)
    3. Ramboz, S. et al. Proc. Natl Acad. Sci. USA 95, 14476-14481 (1998)
    4. Heisler, L. K. et al. Proc. Natl Acad. Sci. USA 95, 15049-15054
    (1998)
    5. D'Amato, R. J. et al. Proc. Natl Acad. Sci. USA 84, 4322-4326
    (1987)
    Nature http://www.nature.com/nature
    --------------------------------
    Related Material:
    EMOTION, COGNITION, AND BEHAVIOR
    The following points are made by R. J. Dolan (Science 2002 298:1191):
    1) An ability to ascribe value to events in the world, a product of
    evolutionary selective processes, is evident across phylogeny (1).
    Value in this sense refers to an organism's facility to sense whether
    events in its environment are more or less desirable. Within this
    framework, emotions represent complex psychological and physiological
    states that, to a greater or lesser degree, index occurrences of
    value. It follows that the range of emotions to which an organism is
    susceptible will, to a high degree, reflect on the complexity of its
    adaptive niche. In higher order primates, in particular humans, this
    involves adaptive demands of physical, socio-cultural, and
    interpersonal contexts.
    2) The importance of emotion to the variety of human experience is
    evident in that what we notice and remember is not the mundane but
    events that evoke feelings of joy, sorrow, pleasure, and pain. Emotion
    provides the principal currency in human relationships as well as the
    motivational force for what is best and worst in human behavior.
    Emotion exerts a powerful influence on reason and, in ways neither
    understood nor systematically researched, contributes to the fixation
    of belief. A lack of emotional equilibrium underpins most human
    unhappiness and is a common denominator across the entire range of
    mental disorders from neuroses to psychoses, as seen, for example, in
    obsessive-compulsive disorder (OCD) and schizophrenia. More than any
    other species, we are beneficiaries and victims of a wealth of
    emotional experience.
    3) Progress in emotion research mirrors wider advances in cognitive
    neurosciences where the idea of the brain as an information processing
    system provides a highly influential metaphor. An observation by the
    19th-century psychologist, William James (1842-1910), questions the
    ultimate utility of a purely mind-based approach to human emotion.
    James surmised that "if we fancy some strong emotion, and then try to
    abstract from our consciousness of it all the feelings of its bodily
    symptoms, we find we have nothing left behind, no mind-stuff out of
    which the emotion can be constituted, and that a cold and neutral
    state of intellectual perception is all that remains" (2). This
    quotation highlights the fact that emotions as psychological
    experiences have unique qualities, and it is worth considering what
    these are. First, unlike most psychological states emotions are
    embodied and manifest in uniquely recognizable, and stereotyped,
    behavioral patterns of facial expression, comportment, and autonomic
    arousal. Second, they are less susceptible to our intentions than
    other psychological states insofar as they are often triggered, in the
    words of James, "in advance of, and often in direct opposition of our
    deliberate reason concerning them" (2). Finally, and most importantly,
    emotions are less encapsulated than other psychological states as
    evident in their global effects on virtually all aspects of cognition.
    This is exemplified in the fact that when we are sad the world seems
    less bright, we struggle to concentrate, and we become selective in
    what we recall. These latter aspects of emotion and their influences
    on other psychological functions are addressed here.
    4) In summary: Emotion is central to the quality and range of everyday
    human experience. The neurobiological substrates of human emotion are
    now attracting increasing interest within the neurosciences, motivated
    to a considerable extent by advances in functional neuroimaging
    techniques. An emerging theme is the question of how emotion interacts
    with and influences other domains of cognition, in particular
    attention, memory, and reasoning. The psychological consequences and
    mechanisms underlying the emotional modulation of cognition provide
    the focus of much new research.(3-5)
    References (abridged):
    1. K. J. Friston, et al., Neuroscience 59, 229 (1994)
    2. W. James, The Principles of Psychology (Holt, New York, 1890)
    3. A. Ohman, et al., J. Exp. Psychol. Gen. 130, 466 (2001)
    4. J. L. Armony, et al., Neuropsychologia 40, 817 (2002)
    5. K. Mogg, et al., Behav. Res. Ther. 35, 297 (1997)
    Science http://www.sciencemag.org