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عدد الرسائل : 4046
العمل/الترفيه : طبيب أختصاصي طب الأطفال وحديثي الولادة
المزاج : الحمد لله جيد
تاريخ التسجيل : 15/09/2008
 | موضوع: Depression: Pathophysiology, clinical manifestations, and diagnosis part2  الأربعاء أكتوبر 01, 2008 4:52 pm | |
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ETIOLOGY AND PATHOGENESIS – Our understanding of the pathogenesis of major depression is still at a theoretical stage. We have increasing radiographic, genetic, and neurochemical data that are converging on a biological understanding. Some theorists argue that, even though the recent pharmacologic advances in the treatment of depression point to the involvement of norepinephrine, serotonin, and dopamine in the biology of depression, the ultimate common pathway may be mediated through hormonal mechanisms. It is likely that both genetic and environmental influences play a role in the pathogenesis of this disorder [8].
A biologic basis for depression is suggested by the following observations:
• Genetic studies have found significantly higher rates of depression in first-degree relatives of depressed patients. Twin studies have also shown a high rate of concordance.
• Medical therapy results in a rapid response of major depressive symptoms.
• Electroconvulsive therapy (ECT) is effective for the treatment of major depression. ECT is thought to act via an induced seizure, which in turn releases increased amounts of norepinephrine, serotonin, and dopamine in the brain stem.
Severe symptoms of major depression generally require some biologic intervention, either with antidepressants or ECT.
There is currently no biologic marker for depression, although the following may be seen in depressed individuals:
• Early REM latency (dreaming as soon as falling asleep)
• Early morning awakening
• Poor appetite
• Weight loss
• Pseudodementia (diminished cognitive performance that resolves with successful treatment of depressive symptoms)
Conditions associated with depression – A number of medical conditions may present with depression, including stroke, diabetes, dementia, cancer, hypothyroidism, chronic fatigue syndrome (see Fatigue below), fibromyalgia, systemic lupus erythematosus, coronary heart disease, corticosteroid use, and anxiety and panic disorders. Some medications other than corticosteroids are also associated with depression. A causal link has not been established in all circumstances, although depression may resolve with treatment of the underlying medical conditions. Limited laboratory testing in patients with depression to rule out some of these disorders includes measurement of thyroid function (TSH), electrolytes, folate, vitamin B12, and an electrocardiogram.
Hypothyroidism – Several studies suggest that subclinical hypothyroidism is associated with neuropsychiatric disease. In one report, for example, the prevalence of hypothyroidism was 14.8 percent in patients with neurotic depression, 2.3 percent in those with senile and multi-infarct dementia, and 1.9 percent in nonpsychiatric inpatients [9]. The following additional findings have been noted. (See "Subclinical hypothyroidism"):
• Patients with depression and subclinical hypothyroidism have a higher prevalence of associated panic disorder, and a poorer response to antidepressant drugs than euthyroid depressed patients [10].
• Patients with subclinical hypothyroidism have a higher lifetime frequency of depression than euthyroid subjects [11].
• Women with subclinical hypothyroidism who presented to a clinic for assessment of goiter were found to have increased rates of free-flowing anxiety, somatic complaints, depressive features, hysteria, and abnormal psychometric testing as compared with euthyroid patients with goiter [12]. These problems improved with T4 treatment.
Fibromyalgia – Depression is more common in patients with fibromyalgia than in normal controls or patients with rheumatoid arthritis [13]. Approximately 25 percent of patients with fibromyalgia have current major depression, and 50 percent have a lifetime history. Furthermore, many of the symptoms of depression such as fatigue, lack of energy, and sleep disturbances are identical to the symptoms of fibromyalgia, leading some authors to propose that fibromyalgia is actually a manifestation of depression. However, the observation that 75 percent of patients with fibromyalgia do not have current depression speaks against this theory. (See "Differential diagnosis of fibromyalgia").
Systemic lupus erythematosus – The most common psychologic symptom in patients with systemic lupus erythematosus (SLE) is depression. Depressive symptoms usually begin acutely [14]. They reflect the patient's reaction to chronic illness and the significant lifestyle limitations that must be endured, including difficulties with pregnancy, fatigue, limited sun exposure, and chronic medication use. There may also be an organic basis in some cases. Some depressed patients, for example, have elevated levels of certain autoantibodies [14-16] or are more prone to have associated illnesses (eg, neuropsychiatric lupus or Sj[size=16]ِgren's syndrome) [17]. (See "Psychiatric manifestations of systemic lupus erythematosus").
Cardiovascular disease – There is mounting evidence that depressive symptoms are associated with increased cardiovascular risk. However, it remains uncertain whether the symptoms are playing a causative role or whether they are primarily a marker or prodrome of an evolving event. (See "The role of psychosocial factors in acute myocardial infarction").
Corticosteroid use – Many patients taking corticosteroids note a slight increase in their overall sense of well-being that appears to be independent of any improvement in their underlying disease. The development of a sense of euphoria is a common clinical observation.
However, some patients develop disturbing psychiatric symptoms, which can occur quickly (within a few days). In one prospective but uncontrolled study of 50 patients, for example, large doses of corticosteroids induced hypomanic symptoms in about 30 percent and depressive symptoms in about 10 percent by the end of one week [18]. Patients with a family history of depression or alcoholism are at increased risk for affective diseases when given corticosteroids [19]. (See "Major side effects of corticosteroids").
Depression has also been associated with endogenous overproduction of cortisol in Cushing's syndrome. (See "Clinical manifestations of Cushing's syndrome").
Anxiety and panic disorder – Depression is common in patients with generalized anxiety disorder. (See "Overview of generalized anxiety disorder"). In addition, one-third to one-half of patients with panic disorder also meet DSM-IV criteria for major depression at the initial presentation, while 60 to 90 percent have had one or more lifetime episodes of major depression [20-24]. (See "Overview of panic disorder").
Other disorders – Other disorders associated with depression include:
• Hypercalcemia (see "Clinical manifestations of hypercalcemia")
• Sjِgren's syndrome (see "Clinical manifestations of Sjِgren's syndrome")
• Major depression may be associated with seizure disorders in older adults [25]
• Major depression may be associated with increased bone loss [26]
SYMPTOMS AND CLASSIFICATION OF DEPRESSIVE DISORDERS – The three subgroups of depressive disorder are major depression, dysthymia, and atypical depression or depression not otherwise specified (NOS) (show figure 1). These need to be differentiated from grief and bereavement, which are normal responses to a loss. Seasonal affective disorder is not a separate mood disorder; it is classified as a specifier to major depression [27]. A large population of depressed patients do not meet any of the existing criteria [28]; they may respond to collaborative therapy (psychiatrist or therapist with primary care physician) and a careful trial of antidepressants. (See "Treatment of depression-I"). Even mild depressive symptoms can contribute to increasing disability in older individuals [29].
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