Neurology_Adams

Neurology_Adams. Intense outbursts of anger and physical violence are also features of the diagnostic category of borderline personality disorder, the other manifestations of which include “a pervasive pattern of instability of mood, interpersonal relationships, and self-image.” Besides propranolol, lithium, carbamazepine, and phenytoin have been found to be helpful in controlling and preventing the explosive attacks. We have noted the recent increased use by psychiatrists of serotonergic antidepressants in these patients, but have no way to judge their effect.


Neurology_Adams

Neurology_Adams. Anorexia nervosa is a behavioral disorder of previously healthy girls and young women living in affluent societies, mainly from upper and middle social classes, who become emaciated as a result of voluntary starvation. It is rare in Asian and African American women, and very uncommon in males. Herzog and Becker remind us that it was Richard Morton who first described the condition in 1649, under the title of “nervous phthisis,” a “nervous consumption” resulting from “sadness and anxious cares”—a title that embodied enigmatic roots in psychologic derangements. Bulimia (literally ox-hunger), to which it is closely related, was not identified as an eating disorder until the latter part of the 19th century.


Neurology_Adams

Neurology_Adams. As a rule, anorexia nervosa begins shortly after puberty—sometimes later, but seldom after 30 years of age. Some of the patients were overweight in childhood, especially in the prepubertal period. Dieting is much talked about and may have been encouraged, especially by mothers who want their daughters to be more attractive. In epochs such as the current one, where dieting and female thinness are considered normative and desirable, the illness seems to be more common and lesser but transient forms of the disorder are rampant in high school-and college-age young women. Sometimes there appears to be a precipitating event, such as leaving home, disruption of family life, or other stress. Whatever the provocation, it leads to an obsessive refusal to eat. What is more important, the abnormal eating habits persist even when the patient has become painfully thin, and when counseled to eat normally she will use every artifice to starve herself. Food is hidden instead of being eaten, vomiting


Neurology_Adams

Neurology_Adams. habits persist even when the patient has become painfully thin, and when counseled to eat normally she will use every artifice to starve herself. Food is hidden instead of being eaten, vomiting may be provoked after a meal, or the bowel may be emptied by laxatives. The patient shows no concern about her obvious emaciation and remains active. If left alone, these patients waste away, and approximately 5 percent have succumbed to some intercurrent infection or other medical complication, placing it among the most lethal of psychiatric conditions.


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Neurology_Adams. One is struck with the degree of emaciation; it exceeds that of most of the known wasting diseases. Often 30 percent or more of the body weight will have been lost by the time the patient’s family insists on medical consultation. Bradycardia and hypotension are indicators for hospitalization. A fine lanugo covers the face, body, and limbs. The skin is thin and dry, without its normal elasticity, and the nails are brittle. The dental enamel is eroded. Pubic hair and breast tissue (except for loss of fat) are normal, and, in this respect, anorexia nervosa is unlike hypopituitary cachexia (Simmonds disease). Surprisingly, however, there are no neurologic signs of nutritional deficiency. The patient is alert and cheerfully indifferent to her condition. Any suggestion that she is unattractively thin or seriously depleted is rejected.


Neurology_Adams

Neurology_Adams. Amenorrhea is practically always present and may precede the extreme weight loss. Luteinizing hormone (LH) concentrations are reduced to pubertal or prepubertal levels. Clomiphene citrate fails to stimulate a rise in LH, as it does normally. Administration of gonadotropic-releasing factor raises the LH and follicle-stimulating hormone (FSH) levels, suggesting a hypothalamic disorder. The basal metabolic rate is low; triiodothyronine (T3) and thyroxine (T4) are low, while levels of physiologically inactive 3,3,5-triiodothyronine (reverse T3) are normal or increased. Plasma thyrotropin (thyroid-stimulating hormone [TSH]) and growth hormone levels are normal. Serum cortisol levels are usually normal; excretion of 17-hydroxysteroids is slightly reduced. In sum, there is evidence of hypothalamic–pituitary dysfunction, but this is probably secondary to starvation, as indicated by the study of Scheithauer and colleagues who found no definite changes in the pituitary gland in 12 fatal cases.


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Neurology_Adams. dysfunction, but this is probably secondary to starvation, as indicated by the study of Scheithauer and colleagues who found no definite changes in the pituitary gland in 12 fatal cases. These endocrine abnormalities, most of which are probably secondary effects of weight loss, are summarized in the review by Becker and colleagues. Brain imaging shows slight to moderate enlargement of the lateral and third ventricles, which return to normal size when the illness subsides.


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Neurology_Adams. The etiology of anorexia nervosa is unknown, although there is no lack of hypotheses. Holland and coworkers reported a high concordance in monozygotic twins as compared with dizygotic twins. Earlier signs of hysterical tendencies, obsessional personality traits, and depression are mentioned as being frequent in some series, but not in others. Certain polymorphisms in the serotonin transporter gene, of types different from those that have been tentatively attached to anxiety and to obsessive traits, have also been reported. These findings are difficult to interpret. A functional imaging study has shown activation of the left insula, amygdala, and cingulate when high-calorie drinks were imbibed by anorectic women (Ellison et al), but this conceivably may have reflected anxiety that the authors termed calorie fear rather than a specific biologic feature of the disease.


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Neurology_Adams. Reports concerning the percentage of first-degree relatives of anorectic patients with bipolar disease are also inconsistent. An increased prevalence of neurosis or alcoholism has been noted in other members of the family. However, psychiatrists seem to agree that the patient does not have symptoms that conform to any of the major neuroses or psychoses. Certainly loss of appetite, lack of self-esteem and interest in personal appearance, and self-destructive behavior—common features of anorexia nervosa—are also symptoms of depressive illness, yet most of the patients do not look or admit to being dejected. Moreover, endogenous depression affects both sexes. The pathologic fear of becoming fat and the obsession with weight might be interpreted as a phobic or obsessional neurosis.


Neurology_Adams

Neurology_Adams. That anorexia nervosa is practically confined to females must figure in any acceptable explanation of the syndrome. Among psychiatric disorders, only hysteria has this sex predilection. Probably important is that anorexia nervosa has its onset in relation to menarche, at a time when the female exhibits rather large fluctuations in appetite and weight. This has suggested to some an imbalance between the satiety center, believed to lie in the ventromedial hypothalamus, and the feeding center, in the lateral hypothalamus.


Neurology_Adams

Neurology_Adams. An association of anorexia with structural disease involving the appetite centers has not been established, although the cases of acquired anorexia reported by Lewin and colleagues and of White and Hain are informative. Martin and Reichlin, in citing these rare cases, attribute the anorexia and cachexia to lesions of the lateral hypothalamus. A disorder of infants described under the title of “diencephalic syndrome” causes progressive and ultimately fatal emaciation (“failure to thrive”) despite normal food intake in an otherwise alert and cheerful infant. The causative lesion has usually proved to be a low-grade astrocytoma of the anterior hypothalamus or optic nerve region (Burr et al). Also interesting is a case in which profound and long-standing anorexia nervosa resolved after a left thalamic stroke (Dusoir et al). See Chap. 26 for further discussion and references.


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Neurology_Adams. Treatment Treatment at the moment consists of winning the patient’s confidence, supportive psychotherapy, assignment of one individual to sit with the patient as each meal is eaten, and a gradual increase of a balanced diet (Anderson). Extreme cases require hospitalization. If the patient refuses to eat, tube feeding is the only alternative. As weight is gained over several weeks, the patient usually becomes more normal in her attitude toward eating and will continue to recover on this regimen at home. The menses do not return until considerable weight has been gained (approximately 10 percent above the weight at the time of the menarche). Our colleagues report better success with such a regimen when imipramine or fluoxetine is added. Others have found these drugs to be ineffective except in patients with prominent symptoms of depression.


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Neurology_Adams. Becker and colleagues emphasized the potentially devastating medical complications to which severely anorectic patients are prone and the need to evaluate and treat these problems at the same time that nutritional therapy is undertaken. In particular, an electrocardiogram is essential in order to exclude a prolonged QT interval—the presence of which contraindicates the use of tricyclic antidepressants and increases the risk of ventricular tachycardia.


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Neurology_Adams. On average, 50 percent of patients recover completely or almost completely (Steinhausen and Seidel). In the remainder, the outcome is quite unfavorable. They either relapse after an initial period of improvement or remain chronically anorectic. Many patients are said to lapse into a chronic dysfunctional state characterized by a persistent preoccupation with food, weight, and dieting. It is not generally appreciated that chronic anorexia nervosa significantly shortens life; after a mean followup period of 12 years, 11 percent of a group of 84 patients had died (Deter and Herzog), and 15 percent after 20 years (Ratnasuriya et al). Suicide is a major contributor to this high mortality rate (Sullivan). The addition of antidepression drugs to a behavioral regimen has been tried with generally disappointing results.


Neurology_Adams

Neurology_Adams. The few adolescent boys who we have seen with this syndrome recovered on antidepressant medication. Cases caused by tumors within the hypothalamus were mentioned earlier and in Chap. 26. In general, the therapeutic benefit of these drugs is considerably greater in cases of bulimia than it is in anorexia nervosa. A review of the problem of bulimia nervosa, binge eating followed by purging, is given by Mehler. The medical complications of either component disorder may be seen but particularly hypokalemia and alkalosis. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 5th ed (DSM-5). Arlington, VA, American Psychiatric Publishing, 2013. Anderson AE: Practical Comprehensive Treatment of Anorexia Nervosa and Bulimia. Baltimore, Johns Hopkins University Press, 1985. Andreasen NC, Black DW: Introductory Textbook of Psychiatry, 3rd ed. Washington, DC, American Psychiatric Press, 2001.


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Neurology_Adams. Andreasen NC, Black DW: Introductory Textbook of Psychiatry, 3rd ed. Washington, DC, American Psychiatric Press, 2001. Baxter LR: Neuroimaging in obsessive-compulsive disorder: Seeking the mediating neuroanatomy. In: Jenike MA, Baer L, Minichiello WE (eds): Obsessive-Compulsive Disorders: Theory and Management, 2nd ed. Chicago, Mosby-Year Book, 1990, pp 167–188. Beard G: Neurasthenia, or nervous exhaustion. Boston Med Surg J 18:270, 1868. Becker AE, Grinspoon SK, Klibanski A, Herzog DB: Eating disorders. N Engl J Med 340:1092, 1999. Berthier ML, Kulisevsky J, Gironell A, et al: Obsessive-compulsive disorder associated with brain lesions: Clinical phenomenology, cognitive function and anatomic correlates. Neurology 47:353, 1996. Briquet P: Traite Clinique et Therapeutique a l’Hysterie. Paris, Ballière, 1859. Burr IM, Slonim AE, Danish RK: Diencephalic syndrome revisited. J Pediatr 88:429, 1976.


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Neurology_Adams. Briquet P: Traite Clinique et Therapeutique a l’Hysterie. Paris, Ballière, 1859. Burr IM, Slonim AE, Danish RK: Diencephalic syndrome revisited. J Pediatr 88:429, 1976. Cadoret RJ: Psychopathology in adopted-away offspring of biologic parents with antisocial behavior. Arch Gen Psychiatry 35:176, 1978. Cadoret RJ, Leve LD, Devor E: Genetics of aggressive and violent behavior. Psychiatr Clin North Am 20:301, 1997. Carothers JC: Hysteria, psychopathy and the magic word. Mankind Q 16:93, 1975. Carson AJ, Brown R, David AS, et al: Functional (conversion) neurological symptoms: Research since the millennium. J Neurol Neurosurg Psychiat 83:842, 2013. Christiansen KO: Crime in a Danish twin population. Acta Genet Med Gemellol (Roma) 19:323, 1970. Cleckley H: The Mask of Sanity. St. Louis, Mosby, 1955. Cloninger CR, Adolfsson R, Svrakic NM: Mapping genes for human personality. Nat Genet 12:3, 1996.


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Neurology_Adams. Cleckley H: The Mask of Sanity. St. Louis, Mosby, 1955. Cloninger CR, Adolfsson R, Svrakic NM: Mapping genes for human personality. Nat Genet 12:3, 1996. Cloninger CR, Guze SB: Psychiatric illness and female criminality: The role of sociopathy and hysteria in the antisocial woman. Am J Psychiatry 127:303, 1970. Cloninger CR, Reich T, Guze SB: The multifactorial model of disease transmission: III. Familial relationship between sociopathy and hysteria (Briquet’s syndrome). Br J Psychiatry 127:23, 1975. Cohen ME, White PD: Life situations, emotions, and neurocirculatory asthenia (anxiety neurosis, neurasthenia, effort syndrome). Res Publ Assoc Res Nerv Ment Dis 29:832, 1949. Cohen ME, White PD, Johnson RE: Neurocirculatory asthenia, anxiety neurosis or the effort syndrome. Arch Intern Med 81:260, 1948. Couprie W, Wijdicks EFM, Rooijmans HGM, Van Gijn J: Outcome in conversion disorder: A follow-up study. J Neurol Neurosurg Psychiatry 58:750, 1995.


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Neurology_Adams. Couprie W, Wijdicks EFM, Rooijmans HGM, Van Gijn J: Outcome in conversion disorder: A follow-up study. J Neurol Neurosurg Psychiatry 58:750, 1995. Deter H-C, Herzog W: Anorexia nervosa in a long-term perspective: Results of the Heidelberg-Mannheim study. Psychosom Med 56:20, 1994. Dusoir H, Owens C, Forbes RB, et al: Anorexia nervosa remission following left thalamic stroke. J Neurol Neurosurg Psychiatry 76:144, 2005. Elliott FA: Propranolol for the control of belligerent behavior following acute brain damage. Ann Neurol 1:489, 1977. Ellison Z, Foong J, Howard R, et al: Functional anatomy of calorie fear in anorexia nervosa. Lancet 352:1192, 1998. Gatfield PD, Guze SB: Prognosis and differential diagnosis of conversion reactions: A follow-up study. Dis Nerv Syst 23:623, 1962. Gesell A (ed): The First Five Years of Life: A Guide to the Study of the Pre-School Child. New York, Harper & Row, 1940.


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Neurology_Adams. Gesell A (ed): The First Five Years of Life: A Guide to the Study of the Pre-School Child. New York, Harper & Row, 1940. Ghaffar O, Staines R, Feinstein A: Unexplained neurologic symptoms: An fMRI study of sensory conversion disorder. Neurology 67:2036, 2006. Goodwin DW, Guze SB: Psychiatric Diagnosis, 5th ed. New York, Oxford University Press, 1996. Gunderson JG: Borderline personality disorder. N Engl J Med 364:2037, 2011. Guze SB, Goodwin DW, Crane JB: Criminal recidivism and psychiatric illness. Am J Psychiatry 127:832, 1970. Herzog DB, Becker AE: Eating disorders. In: Nicholi AM (ed): The New Harvard Guide to Psychiatry, 3rd ed. Cambridge, MA, Belknap Harvard University Press, 1999, pp 400–414. Hinson VK, Haren WB: Psychogenic movement disorders. Lancet Neurol 5:695, 2006. Holland AJ, Sicotte N, Treasure J: Anorexia nervosa: Evidence for a genetic basis. J Psychosom Res 32:561, 1988. Ireland P, Sapira JD, Templeton B: Munchausen’s syndrome. Am J Med 43:579, 1967.


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Neurology_Adams. Holland AJ, Sicotte N, Treasure J: Anorexia nervosa: Evidence for a genetic basis. J Psychosom Res 32:561, 1988. Ireland P, Sapira JD, Templeton B: Munchausen’s syndrome. Am J Med 43:579, 1967. Jenkins SC, Maruta T: Therapeutic use of propranolol for intermittent explosive disorders. Mayo Clin Proc 62:204, 1987. Jones AB, Llewellyn LJ: Malingering. Philadelphia, Lippincott, 1918. Judd FK, Brurrows GD, Norman TR: The biological basis of anxiety: An overview. J Affect Disord 9:271, 1985. Kandel ER: A new intellectual framework for psychiatry. Am J Psychiatry 155:457, 1998. Keane JR: Hysterical gait disorders: 60 cases. Neurology 39:586, 1989. Kurlan R: Tourette’s syndrome: Current concepts. Neurology 39:1625, 1989. Lazare A: Conversion symptoms. N Engl J Med 305:745, 1981. Lesch K-P, Bengel D, Heils A, et al: Association of anxiety-related traits with polymorphism in the serotonin transporter gene regulatory region. Science 274:1527, 1996.


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Neurology_Adams. Lesch K-P, Bengel D, Heils A, et al: Association of anxiety-related traits with polymorphism in the serotonin transporter gene regulatory region. Science 274:1527, 1996. Lewin K, Mattingly D, Millis RR: Anorexia nervosa associated with hypothalamic tumour. Br Med J 10:629, 1972. Lewis A: Psychopathic personality: A most elusive category. Psychol Med 4:133, 1974. Lieb K, Zanarini MC, Schmal C, et al: Borderline personality disorder. Lancet 364:453, 2004. Liebowitz MR, Fryer AJ, Goerman JM, et al: Lactate provocation of panic attacks. Arch Gen Psychiatry 41:764, 1984. Mallet L, Polosan M Jaafari N, et al: Subthalamic nucleus stimulation in severe obsessive compulsive disorder. N Engl J Med 359:2121, 2008. Martin JB, Reichlin S: Clinical Neuroendocrinology, 2nd ed. Philadelphia, Davis, 1987. McCord W, McCord J: The Psychopath. Princeton, NJ, Van Nostrand, 1964. Mehler PS: Bulimia nervosa. N Engl J Med 349:875, 2003.


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Neurology_Adams. Philadelphia, Davis, 1987. McCord W, McCord J: The Psychopath. Princeton, NJ, Van Nostrand, 1964. Mehler PS: Bulimia nervosa. N Engl J Med 349:875, 2003. Merskey H: The Analysis of Hysteria. London, Ballière Tindall, 1979. Modlin HC: Postaccident anxiety syndrome: Psychosocial aspects. Am J Psychiatry 123:1008, 1967. Nemiah JC: The psychodynamic basis of psychopathology. In: Nicholi AM Jr (ed): The Harvard Guide to Psychiatry. Cambridge, MA, Belknap Harvard University Press, 1999, pp 203–219. Noyes R, Clarkson C, Crowe R, et al: A family study of generalized anxiety disorder. Am J Psychiatry 144:1019, 1987. Purtell JJ, Robins E, Cohen ME: Observations on clinical aspects of hysteria. JAMA 146:902, 1951. Raskin M, Talbott JA, Meyerson AT: Diagnosis of conversion reactions: Predictive value of psychiatric criteria. JAMA 197:530, 1966.


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Neurology_Adams. Raskin M, Talbott JA, Meyerson AT: Diagnosis of conversion reactions: Predictive value of psychiatric criteria. JAMA 197:530, 1966. Ratnasuriya RH, Eisler I, Szmukler GJ, Russell GFM: Anorexia nervosa: Outcome and prognostic factors after 20 years. Br J Psychiatry 158:495, 1991. Reid W (ed): The Psychopath: A Comprehensive Study of Antisocial Disorders and Behaviors. New York, Brunner-Mazel, 1978. Robins E, Purtell JJ, Cohen ME: Hysteria in men. N Engl J Med 246:677, 1952. Robins LN: Deviant Children Grown Up: A Sociological and Psychiatric Study of Sociopathic Personality. Huntington, NY, Krieger, 1974. Ropper AH, Burrell BD: How the Brain Lost Its Mind. New York, Avery, Penguin Press, 2019. Scheithauer BW, Kovacs KT, Jariwala LK, et al: Anorexia nervosa: An immunohistochemical study of the pituitary gland. Mayo Clin Proc 63:23, 1988.


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Neurology_Adams. Scheithauer BW, Kovacs KT, Jariwala LK, et al: Anorexia nervosa: An immunohistochemical study of the pituitary gland. Mayo Clin Proc 63:23, 1988. Slater B, Shields J: Genetical aspects of anxiety. In: Lader MH (ed): Studies of Anxiety. London, Royal Medico-Psychological Association, 1969, pp 62–71. Spence SA, Crimlisk HL, Cope H, et al: Discrete neurophysiological correlates in prefrontal cortex during hysterical and feigned disorder of movement. Lancet 355:1243, 2000. Stein DJ: Obsessive-compulsive disorder. Lancet 360:397, 2002. Steinhausen HC, Seidel R: The Berlin follow-up study of eating disorders in adolescence, Part 2: Intermediate-term catamnesis after 4 years. Nervenarzt 65:26, 1994. Stone J, Carson A, Duncan R, et al: Symptoms “unexplained by organic disease” in 1144 new neurology out-patients: How often does the diagnosis change at follow-up? Brain. 132:2878, 2009.


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Neurology_Adams. Stone J, Carson A, Duncan R, et al: Symptoms “unexplained by organic disease” in 1144 new neurology out-patients: How often does the diagnosis change at follow-up? Brain. 132:2878, 2009. Stone J, Edwards M: Trick or treat? Showing patients with functional (psychogenic) motor symptoms their physical signs. Neurology 79:282, 2013a. Stone J, Reuber M, Carson A: Functional symptoms in neurology. Pract Neurol 13:104, 2013b. Stone J, Sharpe M, Carson A, et al: Are functional motor and sensory symptoms really more common on the left? A systematic review. J Neurol Neurosurg Psychiatry 73:578, 2002a. Stone J, Sharpe M, Rothwell PM, et al: The 12 year prognosis of unilateral functional weakness and sensory disturbance. J Neurol Neurosurg Psychiatry 74:591, 2003. Stone J, Zeman A, Sharpe M: Functional weakness and sensory disturbance. J Neurol Neurosurg Psychiatry 73:241, 2002b. Sullivan PE: Mortality in anorexia nervosa. Am J Psychiatry 152:1073, 1995.


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Neurology_Adams. Stone J, Zeman A, Sharpe M: Functional weakness and sensory disturbance. J Neurol Neurosurg Psychiatry 73:241, 2002b. Sullivan PE: Mortality in anorexia nervosa. Am J Psychiatry 152:1073, 1995. Terracciano A, Abdel-Khalek AM, Ádám N, et al: National character does not reflect mean personality trait levels in 49 cultures. Science 310:96, 2005. Tyrer P: New approaches to the diagnosis of psychopathy and personality disorder. J R Soc Med 97:371, 2004. Wheeler EO, White PD, Reed EW, Cohen ME: Neurocirculatory asthenia (anxiety neurosis, effort syndrome, neurasthenia): A twenty year follow-up study of one hundred and seventy-three patients. JAMA 142:878, 1950. White LF, Hain RF: Anorexia in association with a destructive lesion of the hypothalamus. Arch Pathol 68:275, 1959. Winokur G, Coryell W: Anxiety disorders: The magnitude of the problem. In: Coryell W, Winokur G (eds): The Clinical Management of Anxiety Disorders. New York, Oxford University Press, 1991, pp 3–9.


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Neurology_Adams. Winokur G, Coryell W: Anxiety disorders: The magnitude of the problem. In: Coryell W, Winokur G (eds): The Clinical Management of Anxiety Disorders. New York, Oxford University Press, 1991, pp 3–9. Chapter 47 Anxiety Disorders, Hysteria, and Personality Disorders disease may be dominated by depressions, with manic or hypomanic episodes appearing as only a minor or background problem. Foremost among the reasons to consider them separately, however, are differences that have been highlighted in response to treatment. In keeping with modern notions, endogenous depression and bipolar disorder are presented separately in this chapter but an understanding of either one is incomplete without knowledge of the other.


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Neurology_Adams. Another important reason why all physicians should be knowledgeable about depressive illness in all its forms is the danger of suicide, which may be attempted and successfully accomplished before the depression is recognized. Timely diagnosis may prevent such a tragedy—one that is all the more regrettable as some depressive illnesses can be successfully treated.


Neurology_Adams

Neurology_Adams. As remarked in Chap. 23, the term depression embraces more than a feeling of sadness and unhappiness. It stands for a complex of disturbed feelings (called mood or affective disorder)—which may include aspects of despair, hopelessness, sense of worthlessness, and thoughts of self-harm—associated with decreased energy and libido, loss of interest in personal affairs, impaired concentration, various abnormalities of behavior and appearance, and sometimes, prominent physical complaints. The most important of these include anxiety, insomnia, anorexia or overeating, headache, and various types of regional pain. At one extreme are depressive symptoms of psychotic proportions that incorporate paranoid or somatic delusions, which create chaos in the lives of patients and those close to them. At the other extreme are the common feelings of unhappiness, anhedonia (loss of pleasurable responses), discouragement, and resentment that may occur in almost everyone as a reaction to the


Neurology_Adams

Neurology_Adams. to them. At the other extreme are the common feelings of unhappiness, anhedonia (loss of pleasurable responses), discouragement, and resentment that may occur in almost everyone as a reaction to the disappointments of everyday life such as loss of employment, failure to gain recognition, or unsuccessful social adjustment.


Neurology_Adams

Neurology_Adams. The place in this nosology of the special case of postpartum depression has not been clear, and it is discussed in this chapter as well in the next one, as it is sometimes difficult to differentiate it from postpartum psychosis, a more dramatic and well-defined disorder. Some authors question the primacy of a primary biologic entity that is tied to the postpartum period (see summary by Brockington) but this diverges markedly from the general experience, in which varying degrees of depression are quite common in the weeks after delivery and cannot simply be attributed to psychosocial factors or sleep deprivation.


Neurology_Adams

Neurology_Adams. As a purely phenomenological observation, an abnormally elevated mood, or mania, is about one-third as frequent as depression. It may develop as a relatively pure, recurrent clinical state, or more often may alternate or be intertwined with depression, in which case it was referred to as manic-depressive disease (now, bipolar disorder in the classification of the Diagnostic and Statistical Manual of Mental Disorders (see under American Psychiatric Association in references). Hypomania and cyclothymic disorder are the names given to milder forms of mania and bipolar disorder, respectively. The DSM classifications also acknowledge the existence of a mixed schizoaffective state in which attributes of depression and schizophrenia are combined. Distinguishing these various types of depressive illnesses is of therapeutic as well as theoretical importance insofar as a particular type may respond better to one form of treatment than to another. Finally, the neurologist should bear in mind the


Neurology_Adams

Neurology_Adams. is of therapeutic as well as theoretical importance insofar as a particular type may respond better to one form of treatment than to another. Finally, the neurologist should bear in mind the possibility of an incipient dementia presenting as a depression, although the reverse, a masked depression causing difficulty with thinking and memory (pseudodementia) is more common in general practice.


Neurology_Adams

Neurology_Adams. Patients reacting to a medical or neurologic illness seldom express feelings of sadness or despair without mentioning physical accompaniments such as easy fatigability, anxiety, headaches, dizziness, loss of appetite, reduced interest in life and love, trouble in falling asleep, or premature awakening. It follows that whenever these symptoms become manifest in the course of medical disease, they should arouse suspicion of a depressive reaction (Table 48-1). Chronic pain is a frequent somatic manifestation of depression. The pain may be based on an attendant disease but is prolonged, disabling, sometimes vague in nature, and recalcitrant to straightforward medical and surgical approaches. Furthermore, depressed mood exacerbates and prolongs pain of any type. All patients with chronic pain syndromes should be evaluated psychiatrically, as pointed out in Chap. 7.


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Neurology_Adams. In a number of major medical illnesses depressive symptoms occur with such frequency as to become almost part of the disease. Contrariwise, in certain chronic and occult diseases, symptoms such as lassitude and fatigue may resemble and be mistaken for a depressive reaction. Hypothyroidism, infectious mononucleosis, hepatitis, lymphoma, myeloma, metastatic carcinoma, malnutrition, polymyalgia rheumatica, and frontal lobe tumors, especially meningiomas, may simulate depression for weeks or months before the diagnosis becomes evident. A special relationship to occult pancreatic or other abdominal cancers has been suggested but is difficult to understand. Sedative drugs, beta-adrenergic blocking agents, beta-interferons used for the treatment of multiple sclerosis and hepatitis, and the phenothiazines may also evoke a depressive reaction; corticosteroids can induce a peculiar psychiatric state in which confusion, insomnia, and either an elevation of mood or depression are combined, even


Neurology_Adams

Neurology_Adams. may also evoke a depressive reaction; corticosteroids can induce a peculiar psychiatric state in which confusion, insomnia, and either an elevation of mood or depression are combined, even to the point of psychoses. A depressed mood may also emerge during the tapering-off period of corticosteroid medication (a hypomanic state is more common in our experience during active use).


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Neurology_Adams. Of particular significance is the reactive depression that occurs on learning of a serious medical or neurologic disease. Often such an emotional reaction, which the physician may tend to ignore, is the dominant manifestation of a disease that threatens the life pattern and independence of the patient. Recognition by the patient that he has suffered a stroke or that he has cancer, multiple sclerosis, amyotrophic lateral sclerosis, or Parkinson disease, is almost always followed by some degree of reactive depression, often with an element of anxiety. A prime example is depression that follows myocardial infarction (Wishnie et al). Usually it begins toward the end of the patient’s stay in the hospital and attracts little attention. Once the patient is home, fatigability that approaches exhaustion may be the main complaint and interfere with accustomed activities and rehabilitation. It may be described as weakness and falsely attributed to heart failure. Symptoms of irritability,


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Neurology_Adams. exhaustion may be the main complaint and interfere with accustomed activities and rehabilitation. It may be described as weakness and falsely attributed to heart failure. Symptoms of irritability, anxiety, and despondency are next in order of frequency, followed by insomnia and feelings of aimlessness and boredom. Although most of these patients ultimately recover without medical assistance the depression exacts a high toll in terms of mental suffering and some surveys suggest a relation of depression to poorer cardiovascular outcomes.


Neurology_Adams

Neurology_Adams. Depression following stroke and with degenerative neurologic disease An analogous depressive reaction occurs in some patients after stroke. Some studies have indicated that patients with left anterior cerebral lesions, involving predominantly the lateral frontal cortex or basal ganglia, have a greater frequency and severity of depression than do patients with lesions in other locations (Starkstein et al, 1987; Robinson). According to these authors, lesions of the right hemisphere do not show this correlation with depression but have a higher association with pathologic cheerfulness or mania. However, House and colleagues, in a British community-based study of stroke survivors, failed to confirm these findings, perhaps because the infarcts were small in size (more than half the patients had never been admitted to hospital) and many patients were examined for the first time only at 6 and 12 months after their strokes. Our colleagues Levine and Finkelstein reported the occurrence of


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Neurology_Adams. had never been admitted to hospital) and many patients were examined for the first time only at 6 and 12 months after their strokes. Our colleagues Levine and Finkelstein reported the occurrence of psychotic depression with hallucinations and delusions in patients with right temporoparietal infarcts. Our own experience suggests an unsurprising relationship between the degree of motor and language disability and the severity of poststroke depression, but a less predictable relationship to the location of the lesion. The possible predisposing effects of minor previous episodes of depression, family history of depressive illness, and medications have not been studied systematically. These issues are also incorporated into Chap. 33.


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Neurology_Adams. With regard to emotional reactions in degenerative brain diseases, Parkinson disease is complicated by a depressive reaction in approximately one-quarter of cases. Weakness and fatigability, already aspects of the motor syndrome, are added to the principal psychologic manifestations and the resulting therapeutic problem becomes formidable. Another hazard in Parkinson and in Lewy-body disease is the tendency for l-dopa itself to provoke a depression in a limited number of patients, sometimes with suicidal tendencies, paranoid ideation, and psychotic episodes. Huntington chorea is quite often associated with depression, even before the movement disorder and dementia become conspicuous. In one series, 10 of 101 patients with Huntington disease either committed suicide or attempted it, and this outcome is commented on in almost all large series of that disease. Alzheimer disease may be accompanied by depressive symptoms, in which instance it is difficult or impossible early in the illness


Neurology_Adams

Neurology_Adams. outcome is commented on in almost all large series of that disease. Alzheimer disease may be accompanied by depressive symptoms, in which instance it is difficult or impossible early in the illness to evaluate the relative contributions of the mood disorder and the dementia. In later stages, the overt signs of depression usually abate.


Neurology_Adams

Neurology_Adams. Depression during and after pregnancy The main risk for depression during pregnancy is a history of previous depressions. Certain epidemiologic factors also come into play including a family history of depression, single motherhood, cigarette smoking, low income, youth, and domestic violence. The implications, however, of depression during and after pregnancy are great in that the fetus and neonate are at risk of suffering due to inadequate prenatal and postnatal care and there is an increased rate of miscarriage. Several pieces of controversial evidence suggest that maternal depression may affect fetal growth and infant temperament. Furthermore, postpartum depression is also more common in women with prenatal depression and may lead to similar difficulties with infant care.


Neurology_Adams

Neurology_Adams. The treatment of depression during pregnancy has attracted considerable attention because of the potential risks to the fetus of the class of serotonin reuptake inhibitors. This is discussed in a later section. The clinical aspects of depression during pregnancy have been summarized by Stewart. Clinical Presentation of Depression


Neurology_Adams

Neurology_Adams. Clinical Presentation of Depression Fully developed endogenous depression may evolve within a few days, or more often, it emerges gradually, on a background of vague prodromal symptoms that had been present for months. Chapter 23 provides a detailed description of the symptoms and signs of depression. Here it need only be repeated that the patient expresses feelings of sadness, unhappiness, discouragement, hopelessness, and despondency, with loss of self-esteem. Reduced energy and activity, typically expressed as mental and physical exhaustion, is almost always present, to the point of catatonia in the most severe cases. Indeed, as emphasized in Chap. 23, the most common cause in general practice of symptoms relating to reduced psychic and physical energy and drive (conation) is depression. There is usually heightened irritability, most often reported by a spouse or friends, as well as a lack of interest in activities that formerly were pleasurable.


Neurology_Adams

Neurology_Adams. According to DSM, an abstract of the essential diagnostic criteria of endogenous depression (“major depressive syndrome”) consist of a dysphoric mood or loss of interest or pleasure in all usual activities (including sexual activity) in combination with at several of the following symptoms: (1) disturbance of appetite and change in weight; (2) sleep disorder; (3) psychomotor retardation or agitation; (4) decreased energy and fatigue; (5) self-reproach, feelings of worthlessness or guilt; (6) indecisiveness, complaints of memory loss and difficulty in concentrating; and (7) thoughts of death or suicide or actual suicide attempts. In this diagnostic scheme, each of the 4 diagnostic symptoms should have been present for at least 2 weeks and the state should represent a departure from previous functioning. This is a useful listing but simply recapitulates the well-described emotional, conative, and physical aspects of endogenous depression. Several formalized diagnostic criteria have been


Neurology_Adams

Neurology_Adams. functioning. This is a useful listing but simply recapitulates the well-described emotional, conative, and physical aspects of endogenous depression. Several formalized diagnostic criteria have been devised for both screening and diagnosis of major depression (Table 48-2). These codify the clinical features discussed in previous paragraphs but separate major depression from bipolar disorder by requiring the absence of elements that suggest a manic or hypomanic episode and further exclude depression that is plausibly connected to personal distress or grieving due to a loss, or the effects of a drug or toxic substance.


Neurology_Adams

Neurology_Adams. The depressed patient tends to move slowly, sighing is frequent, and speech is reduced. The mental life of such an individual may narrow to a single-minded concern about physical or mental health. In dialogue, the patient’s responses become so stereotyped that the listener can soon predict exactly what is going to be said. There is a poverty of ideation and sometimes a notable absence of insight. Consciousness is clear, and although there is no evidence of a schizophrenic type of thought disorder, delusional ideas, and less often hallucinations, may be prominent in some patients, justifying the term depressive psychosis. The delusions are generally congruent with the patient’s mood and are not as fixed or bizarre as those of schizophrenia or paranoia. In our experience, delusions are more common in older patients and tend to appear only after weeks or months of more typical symptoms of depression. Common ones in experience with our patients have been gas poisoning in the house,


Neurology_Adams

Neurology_Adams. more common in older patients and tend to appear only after weeks or months of more typical symptoms of depression. Common ones in experience with our patients have been gas poisoning in the house, unaccustomed suspiciousness, alleged home break ins, having inadequate money, or being stolen from or cheated. (Some of these arise in early dementia as well.) Hallucinations, when they occur, are usually transitory, vocal, and only vaguely accusatory; their presence should always raise the possibility of an associated structural brain disease, drug intoxication, or alcoholic auditory hallucinosis.


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Neurology_Adams. Frequently, agitation or irritability rather than physical inactivity and mental slowness are the principal behavioral abnormalities. The source of the agitation appears usually to be related to an underlying anxiety state. Pacing the floor and wringing the hands, particularly in the early morning hours, are characteristic. Such patients tend to be overly talkative and vexed in their manner of expression, irritable, short-tempered, impatient, and intolerant of minor problems—changes noted mainly by family members. Attempts at reassurance may meet with initial success, only to be dispelled in the next rush of doubts. These patients remain impervious to reason and logic with respect to their symptoms, even though they are reasonable and logical in other areas of their lives. At its worst, the illness takes the form of a depressive stupor; the patient becomes mute, indifferent to nutritional needs, and neglectful even of bowel and bladder functions (anergic depression). The condition in


Neurology_Adams

Neurology_Adams. illness takes the form of a depressive stupor; the patient becomes mute, indifferent to nutritional needs, and neglectful even of bowel and bladder functions (anergic depression). The condition in this extreme form is a catatonic depression. Such patients must be fed and their other needs attended to until therapy (usually electroconvulsive therapy [ECT]) brings about improvement.


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Neurology_Adams. The most important concern in patients with midand late-life depression is suicide, a topic addressed again further on. Because many of these individuals have reputations for being sound, dependable, and stable and deny being depressed, one’s inclination is to doubt the possibility of self-destruction. Such patients should nonetheless be questioned forthrightly on this subject: Do they feel that life is not worthwhile? Have there been thoughts of suicide? Do they think themselves capable of committing suicide? Have they made such plans or made suicide attempts before? Is there a family history of suicide? Do they own a firearm? Are they fearful of dying? Do they have a strongly held religious view that proscribes suicide? These questions relate to features that have been shown to put depressed individuals at risk (or less risk) of suicide but none are infallible guides to the risk of suicide. If, from their answers, they are judged to carry an imminent risk of suicide, they should be


Neurology_Adams

Neurology_Adams. individuals at risk (or less risk) of suicide but none are infallible guides to the risk of suicide. If, from their answers, they are judged to carry an imminent risk of suicide, they should be directed to a psychiatrist and generally admitted to a hospital. In recent years, it has come to be appreciated that the elderly are increasingly prone to suicide and that older white men have the highest rates of completed suicides (mainly with firearms).


Neurology_Adams

Neurology_Adams. In some depressions, hypochondriacal preoccupation with bowel and digestive functions accounts for repeated visits to the physician. In one study, 21 of 120 such patients were subsequently diagnosed as being depressed. Persistent insomnia may be the major complaint of the depressed patient. Early awakening is typical, and the morning hours are then the worst period of the day for the low emotional state. Other patients have difficulty falling asleep, especially if there is an associated anxiety state. A complaint in the male of loss of libido and erectile dysfunction is another monosymptomatic presentation; only with probing inquiry about other disturbances common to depression will the diagnosis become evident.


Neurology_Adams

Neurology_Adams. Adherence to the aforementioned or similar diagnostic criteria (see Table 48-1) undoubtedly facilitates diagnosis, but not infrequently a single one of these symptoms so dominates the clinical picture as to suggest the diagnosis of another disease state and obscure the presence of an underlying depression. As mentioned earlier, depressed patients who are referred to the neurologist tend to complain inordinately of physical and cognitive symptoms and to minimize or deny the emotional ones. Complaints of fatigue, weakness, malaise, or widespread aches and pains, for example, suggest a variety of medical diseases, such as anemia, Addison disease, hypothyroidism, chronic infection, polymyositis, or early rheumatoid arthritis. Quite often the fatigue state is misinterpreted as muscular weakness, and this directs a medical search for neuromuscular disease. Similarly, complaints of persistent headache may suggest the presence of intracranial disease. Complaints of poor memory, inability to


Neurology_Adams

Neurology_Adams. and this directs a medical search for neuromuscular disease. Similarly, complaints of persistent headache may suggest the presence of intracranial disease. Complaints of poor memory, inability to concentrate, and other cognitive impairments raise the question of a dementia until it is found, by careful examination, that mental competence belies the patient’s appraisal of his own defects.


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Neurology_Adams. A number of psychologic scales are used to score the severity of depression. Although they are of value mainly for clinical studies, several of them can be helpful in clinical work since they are sensitive to one or another aspect of depression. They do not supplant the clinical examination in determining if an individual is depressed or suicidal but they may be helpful in differentiating depression from dementia and in detecting depression in cases where physical complaints are more prominent than psychic ones. The tests most familiar to neurologists are the Hamilton and the Beck scales, but others are as valid and widely used.


Neurology_Adams

Neurology_Adams. Bipolar disease is a disorder of mood consisting of prolonged episodes of depression, interrupted by, or coexistent with episodes of mania. It was given the name manic-depressive disease by Kraepelin in 1896, and it was with him that our current clinical concept of this disorder originated. He viewed the manic and depressive attacks as opposite poles of the same underlying process and pointed out that, unlike dementia praecox (the prevalent name at the time, given by Pick, for schizophrenia), bipolar psychosis entails no intellectual deterioration. A traditional view of this disease was that of a periodic or cyclic condition in which one major mood swing was followed by an equal but opposite excursion. This is seldom the case, however. Episodes of depression are more than twice as frequent as manic ones, and according to current experts, the most common form of the illness is characterized by episodic depression alone with many patients having several episodes of depression before


Neurology_Adams

Neurology_Adams. as manic ones, and according to current experts, the most common form of the illness is characterized by episodic depression alone with many patients having several episodes of depression before their first period of mania.


Neurology_Adams

Neurology_Adams. Recurrence of episodes of pure mania without interspersed episodes of depression is known but relatively less common. As a consequence, bipolar psychosis has been divided into two subtypes: the unipolar group, in which only an endogenous depressive illness occurs, and a bipolar group, in which one or more bouts of mania occur with or without depression. The bipolar variety occurs in approximately 10 percent of patients with affective disorder. The biologic accuracy of this classification has not been critically determined. There has been an arbitrary further subdivision of bipolar I to denote at least one episode of full mania, and bipolar II when the process entails an episode of hypomania.


Neurology_Adams

Neurology_Adams. In addition, there are mixed affective states, in which symptoms of both depression and mania occur within a single episode of the illness. A so-called “rapid-cycling” form of bipolar disease has also been recognized in which four or more circumscribed cycles of manias and depression occur in a year. Like other variants of the disease, it tends to have an aberrant or unpredictable response to medication. Still other patients with affective elements of depression present with atypical features; for example, instead of anorexia, weight loss, and insomnia, they sleep and eat excessively.


Neurology_Adams

Neurology_Adams. The prevalence of bipolar disease cannot be stated with precision, mainly because of varying criteria used for diagnosis. Certainly depression and depressive episodes are ubiquitous and mania is less common. The apparent increase of the disease in the past 50 years probably reflects a growing awareness of the condition among both physicians and the laity. Studies of large groups of patients from relatively isolated areas of Iceland and the Danish islands of Bornholm and SamsØ indicated that 5 percent of men and 9 percent of women developed symptoms of major depression, mania, or both at some time during their lives (Goodwin and Guze). More recent studies, such as the one conducted by the National Comorbidity Survey, report lifetime prevalence for bipolar disorder in the United States as 4.5 percent (Merikangas et al). According to the Global Burden of Disease Study, the incidence of bipolar disease increased by about 50 percent between 1990 and 2013 but it is still considered rare by


Neurology_Adams

Neurology_Adams. percent (Merikangas et al). According to the Global Burden of Disease Study, the incidence of bipolar disease increased by about 50 percent between 1990 and 2013 but it is still considered rare by comparison to depression and to other medical diseases (Ferrari).


Neurology_Adams

Neurology_Adams. Bipolar disease occurs most frequently in middle and later adult years, with a peak age of onset between 55 and 65 for both sexes. However, a significant proportion of patients experience the first attack in childhood, adolescence, or early adult life. Depression is also a major problem in the elderly. Blazer and Williams, who studied 997 persons older than age 65 years in North Carolina, found symptoms of a major depressive illness in 3.7 percent. The disease was 2 or 3 times more frequent among women. There is no known explanation for this gender difference, but some have speculated that just as many men are depressed, only they deny it or turn to alcohol. Patients in the bipolar group have an earlier age of onset, more frequent and shorter cycles of illness, and a greater prevalence of affective disorder among their relatives than do patients with unipolar depression (Winokur).


Neurology_Adams

Neurology_Adams. The manic state is in most ways the opposite of the depressed state, being characterized by a euphoric flight of ideas, motor and speech hyperactivity, and an increased appetite and sex urge. When such a state is fully developed, it qualifies as a psychosis. After a minimum of sleep, the patient awakes with enthusiasm and expectation. The manic individual appears to possess great drive and confidence yet lacks the ability to carry out plans. Often headstrong, impulsive, socially intrusive behavior is characteristic. Judgment may be so impaired that reckless investments are made; fortunes are spent in gambling or on extravagant shopping sprees. Setbacks do not perturb the patient, but rather act as goads to new activities. Euphoria and expansiveness sometimes bubble over into delusions of power and grandeur, which, in turn, may make the patient offensively aggressive. Up to a point, the patient’s mirth and good spirits may be contagious, and others may join in; however, if the patient


Neurology_Adams

Neurology_Adams. power and grandeur, which, in turn, may make the patient offensively aggressive. Up to a point, the patient’s mirth and good spirits may be contagious, and others may join in; however, if the patient is thwarted, the warmth and good humor can suddenly change to anger. Irritability rather than elation may become the prevailing mood. The threshold for paranoid thinking is low, which makes the patient sensitive and suspicious.


Neurology_Adams

Neurology_Adams. Personal neglect may reach the point of dishevelment and poor hygiene. In its most advanced form, a condition described as “delirious mania,” the patient becomes totally incoherent and altogether disorganized in behavior. (Such were the descriptions in some of the great literature of the 19th and early 20th centuries depicting the mania of neurosyphilis.) At this stage visual and auditory hallucinations and paranoid delusions may be rampant.


Neurology_Adams

Neurology_Adams. Hypomania describes a milder degree of the disorder but this term is also used loosely to depict behavior in a normally functioning individual who is unusually energetic and active. In this latter sense, hypomania is a personality trait found in many talented and productive persons and need not arouse concern unless it is excessive and out of character for the individual. As Belmaker noted, a number of highly creative individuals have had bipolar disorders, but full-blown mania is uniformly destructive of careers and personal relationships. Such individuals are actually more creative when treated with appropriate medications. Even though many authors, such as Thomas Mann in his character of Adrian Leverkühn in Doctor Faustus, romanticized a link between madness and creativity, the linkage in reality goes only so far.


Neurology_Adams

Neurology_Adams. First attacks of either depression or mania last an average of 6 months if untreated, although the duration varies greatly. With treatment, this can be reduced according to some trials by more than half in many patients. Although most attacks of bipolar disease subside in a matter of months, a significant number, remain chronically ill for long periods. According to Winokur and colleagues, 14 percent of their bipolar patients had not recovered after 2 years and 5 percent had not recovered after 5 years. Comparative figures for primary unipolar patients were 19 and 12 percent, respectively. The majority of depressed patients have one or more recurrences. Variables that are predictive of an unfavorable outcome are high degrees of anxiety, strongly positive family history of a similar psychiatric illness, and presence of depression-provoking circumstances (Hirschfeld et al). Perhaps most important is the duration of illness before treatment, that is, earlier treatment is generally


Neurology_Adams

Neurology_Adams. psychiatric illness, and presence of depression-provoking circumstances (Hirschfeld et al). Perhaps most important is the duration of illness before treatment, that is, earlier treatment is generally associated with a more favorable prognosis.


Neurology_Adams

Neurology_Adams. Mania presenting as an encephalopathy The manic patient may be disoriented and slightly agitated, with a clouded sensorium. This extreme is not frequently encountered but we have several times admitted patients to the neurology service with mania that presented in a manner suggesting an encephalopathy and global confusional state. The patient conducted himself pleasantly, without psychosis, pressured speech or overactive motor behavior but with an inattentive, confusion as the dominant feature. Conditions such as herpes encephalitis, alcohol or drug withdrawal, stroke, and paraneoplastic encephalitis were considered until the patient began filling notebooks with writing, manifesting insomnia, and making connections between ideas and events that were individually valid but just outside the realm of likelihood. One insisted that one of us was also his wife’s cardiologist and another, that one of the authors had scored a winning touchdown at a college football game at which he was


Neurology_Adams

Neurology_Adams. the realm of likelihood. One insisted that one of us was also his wife’s cardiologist and another, that one of the authors had scored a winning touchdown at a college football game at which he was present. Stories about public figures were factually correct but attached to the wrong person. The patient sat near the door to his hospital room and incessantly but pleasantly attracted our attention to speak to him every time one of us was in sight. At the same time, performance on orientation, arithmetic, and language tasks were normal. Such an individual is depicted in Reaching Down the Rabbit Hole by Ropper and Burrell.


Neurology_Adams

Neurology_Adams. The following are the main theories, not mutually exclusive, that have been proposed to explain the origin of depression; for a detailed review of the subject, the reader is referred to the review by Belmaker and Agam.


Neurology_Adams

Neurology_Adams. The capacity to experience sadness and depression is common to all people but there is no question that some individuals are more liable to depression than others who are subjected to similar psychosocial forces. It has been estimated, using various genetic techniques, that as much as 40 percent of the risk of depression is heritable (lower than for schizophrenia and bipolar disease). Adopted children whose biologic parents had affective disorder are at greater risk of developing this disease than are adoptees whose biologic parents were not affected (Mendlewicz and Rainer; Cadoret). The frequency of these illnesses is greatly increased in the relatives of affected patients (prevalence rate of 14 to 25 percent in first-degree relatives). Similarly, the risk of depression among first-degree relatives is increased (15 percent, in comparison to 1 to 2 percent risk in the general population). If several twin studies are taken together, 72 percent of monozygotic twins are concordant for


Neurology_Adams

Neurology_Adams. relatives is increased (15 percent, in comparison to 1 to 2 percent risk in the general population). If several twin studies are taken together, 72 percent of monozygotic twins are concordant for bipolar disease, compared with 14 percent of same-sex dizygotic twins; comparative figures for unipolar disease are 40 percent and 11 percent, respectively (see Goodwin and Guze). All of these findings indicate a strong genetic factor. The genes for bipolar disease remain to be discovered, and current thinking holds that several are likely to be involved. One indication that specific genes may alter the susceptibility to depression has been presented by Ogilvie and colleagues; they and others have found allelic variations in the serotonin transporter gene (the main target of the selective serotonin antidepressants) that were associated with a sevenfold increased risk of major depression. Not all studies agree on these points. This result has been reinforced by Caspi and colleagues who


Neurology_Adams

Neurology_Adams. serotonin antidepressants) that were associated with a sevenfold increased risk of major depression. Not all studies agree on these points. This result has been reinforced by Caspi and colleagues who reported that a variant in the serotonin transporter correlates with an increase in depression in response to stress. Other hypotheses have postulated various susceptibility loci but again, a single gene locus seems unlikely (see Sanders et al).


Neurology_Adams

Neurology_Adams. Several lines of study, including those employing functional imaging, indicate that a few regions of the brain are implicated in the pathogenesis of the complex symptomatology of depression (Drevets). Hypometabolism in the left frontal cortex is among the most consistent findings. Also prominent in many studies are metabolic changes in the cingulate and orbitofrontal cortices, related parts of the medial limbic system, and the hippocampus. As with all functional imaging studies, it is difficult to know if the observed changes are the cause or simply the representation of activity that corresponds to the depressive state.


Neurology_Adams

Neurology_Adams. An intriguing observation, and one that does not entirely accord with the above, has been made by Bejjani and colleagues in the course of deep brain stimulation for the treatment of Parkinson disease. One of their patients displayed transient but dramatic manifestations of depression only when high-frequency stimulation was delivered to the left substantia nigra. Positron emission tomography imaging during stimulation showed activation in the left orbitofrontal cortex and, less consistently, in the left amygdala, globus pallidus, thalamus, and right parietal lobe. In 2 other cases with no prior psychiatric symptoms, deep brain stimulation of the subthalamic nucleus induced a reversible manic state (Herzog et al; Kulisevsky et al). Fisher noted a hypomanic episode in the early stages of herpes encephalitis, and numerous cases of temporary secondary mania have been reported after stroke and after brain trauma, the latter affecting most often the right temporal lobe. It is likely that


Neurology_Adams

Neurology_Adams. herpes encephalitis, and numerous cases of temporary secondary mania have been reported after stroke and after brain trauma, the latter affecting most often the right temporal lobe. It is likely that the structures implicated in these cases are part of a larger and widely distributed network that is activated during depression.


Neurology_Adams

Neurology_Adams. On the histologic level, several studies have shown a depletion of and changes in the pyramidal neurons of the CA3 region of the hippocampus in both depression and stress, but the meaning of these findings is unclear (Sapolsky). They are referred to later in relation to neurogenesis (the appearance in adults of new neurons) in the temporal lobe and recovery from depression. These ideas regarding neurogenesis, which are still speculative, are discussed in Chap. 28. Interestingly, in a rodent model of depression, neurogenesis was required for the beneficial effects of antidepressants to take place (Santarelli). Based in part on this observation, a relationship has been suggested between depressive illness and the later development of dementia. The reviews of Starkstein (1987, 1991) and Robinson, and that of Belmaker and Agam mentioned earlier, may be consulted for further information on anatomic lesions that cause changes in affect. Evolving work on alterations in the brain connectome


Neurology_Adams

Neurology_Adams. and that of Belmaker and Agam mentioned earlier, may be consulted for further information on anatomic lesions that cause changes in affect. Evolving work on alterations in the brain connectome in mania have give varied results but focus on decreased activity between various brain hubs that are considered “rich” in connectivity and between the hemispheres (Collin et al) but these are not easily applicable concepts and will probably change as more investigation is performed.


Neurology_Adams

Neurology_Adams. It has been evident for several years that the biogenic monoamines (norepinephrine, serotonin, and dopamine) are in some way involved in the biology of depression. However, most of the neurochemical theories of depression suffer from the weakness that they have been the result of backward reasoning from the effects of antidepressants on various neurotransmitters to the putative mechanisms of the disease. Following the observations that the tricyclic antidepressants and the monoamine oxidase (MAO) inhibitors exerted their effect by increasing norepinephrine and serotonin at central adrenergic receptor sites in the limbic system and hypothalamus and that depression-provoking drugs (such as reserpine) deplete biogenic amines at these sites, it was proposed that naturally occurring depressions might be associated with a deficiency of these substances. Furthermore, depressed patients and their first-degree relatives, as well as healthy individuals, develop a depressed mood after dietary


Neurology_Adams

Neurology_Adams. might be associated with a deficiency of these substances. Furthermore, depressed patients and their first-degree relatives, as well as healthy individuals, develop a depressed mood after dietary depletion of the monoamine precursor tryptophan, and concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG), a metabolite of norepinephrine, are reduced in the cerebrospinal fluid during endogenous depression and the levels are elevated in manic states. Some neurochemical imaging studies corroborate these findings and others do not. Along similar lines, 5-hydroxyindoleacetic acid (5-HIAA), a deaminated metabolite of serotonin, is reduced in the cerebrospinal fluid of depressed patients (Carroll et al).


Neurology_Adams

Neurology_Adams. Certain of the newer antidepressants act as selective serotonin reuptake inhibitors (SSRIs) and apparently produce their salutary effects by increasing the amount of serotonin that is functionally active in the synapse (they also raise the concentrations of norepinephrine). For these reasons, serotonin and its neuronal pathways are also currently implicated in the genesis of depression. However, the reader should be reminded that only 2 decades ago it was widely held that depletion of norepinephrine fulfilled this role. It is also not yet clear which neurochemical alterations are primary and which modulate other systems. For example, reports suggest that substance P plays an important role in the causation of depression (Kramer et al) and that blockade of substance P receptors has antidepressant effects. Why there is a delay of several weeks in the improvement of depression related to the taking of the various antidepressants is unexplained by any of the neurochemical models.


Neurology_Adams

Neurology_Adams. Another set of observations that has continued to capture interest implicates a disorder of hypothalamic–pituitary–adrenal axis function (summarized by Schlesser et al). It had been found several decades ago that the parenteral administration of 1 to 2 mg of dexamethasone failed to suppress serum cortisol secretion while the patient was ill with endogenous depression, but did so after recovery. In a comparable series of reactive depressions, there was a normal suppression of cortisol secretion. Originally, the dexamethasone suppression test was believed to separate the 2 large groups of depressed patients and to predict the response to drug therapy. However, subsequent studies have shown that the specificity of this test was far less than earlier reports had indicated (Amsterdam et al; Insel et al). Accumulated evidence indicates that 50 percent of severely depressed patients do not show suppression of cortisol secretion, and a positive test can be obtained in a significant number of


Neurology_Adams

Neurology_Adams. et al). Accumulated evidence indicates that 50 percent of severely depressed patients do not show suppression of cortisol secretion, and a positive test can be obtained in a significant number of patients with other psychiatric disorders.


Neurology_Adams

Neurology_Adams. The failure of dexamethasone suppression has been attributed to hyperactivity in the hypothalamic pituitary axis and a corresponding increase in secretion of corticotropin-releasing hormone, adrenocorticotropic hormone (ACTH), and glucocorticoids. Elevated levels of glucocorticoids have been theorized to impede neurogenesis in the medial temporal lobe, and perhaps to explain or exaggerate the loss of hippocampal neurons demonstrated in some studies of the brains of deceased depressed patients. A proposal that ECT acts by elevating levels of neurotrophic factors is at least consistent with this view and with the hypothesis that one component of recovery from depression is in some way associated with restoration of normal neuronal architecture in regions of the hippocampus and the hypothalamus (Chen). Although highly speculative, perhaps some of these changes explain the delay in improvement after the administration of antidepression drugs.


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Neurology_Adams. At the present time, it must also be conceded that there is no reliable biologic test for depression. One must resort to clinical analysis not only for diagnosis but also for the differentiation of special types of depressive reactions.


Neurology_Adams

Neurology_Adams. Many experienced psychiatrists have emphasized the importance of psychosocial factors in the genesis of depressive illness. Among patients with primary depressive disorders, life events of a stressful nature were found to have occurred more frequently in the months preceding the onset of depression than in matched control groups. In the study by Thomson and Hendrie, this was equally true of patients with a positive family history of depression and of those without such a history. Nor did patients with endogenous depression differ in this respect from those with reactive depression. Left unanswered is the question of why some individuals are subject to a reactive depression. Are they predisposed by psychologic, personality, or genetically transmitted factors of heightened vulnerability to the effects of psychosocial stress? One is tempted to conclude that many depressions attributed to psychosocial stress are contaminating a group of endogenous depressions. Psychiatrists have also


Neurology_Adams

Neurology_Adams. to the effects of psychosocial stress? One is tempted to conclude that many depressions attributed to psychosocial stress are contaminating a group of endogenous depressions. Psychiatrists have also failed to find a consistent correlation between depressive illness and personality type or a particular psychodynamic mechanism. The biopsychosocial theories of mental illness have the most appeal in explaining depression but which elements are operative in any individual are difficult to discern.


Neurology_Adams

Neurology_Adams. The use of medications for depression is now so widespread that all physicians should be familiar with them. It must be acknowledged, however, that the magnitude of the effect on depression of these medications has been dominated by a few clinical trials. Meta-analyses of several large studies on the therapeutic effects of antidepressants suggest that clinical improvement attributable to the drugs themselves occurs in approximately 50 percent of patients; remarkably, an additional improvement in up to 25 percent is attributable to a placebo effect or, more likely, to the natural course of the disease. The remainder fails to improve in a timely manner or relapse while on medication. The incremental value of certain forms of psychotherapies is discussed further on.


Neurology_Adams

Neurology_Adams. Those untrained in psychiatry would be unwise to undertake the management of bipolar disease or a serious endogenous depression without the advice or assistance of a psychiatrist. On the other hand, if the symptoms are primarily neurologic (e.g., chronic headache, generalized weakness, and fatigability) and if there is a low risk of suicide, it may be appropriate for the experienced neurologist to institute treatment with antidepressant medication. In the management of bipolar and depressive disease, six main categories of drugs are in general use—the tricyclic antidepressants, the “atypical” or nontricyclic group of compounds, the MAO inhibitors, serotonin agonists (reuptake inhibitors), antiepileptic drugs, and lithium. The pharmacologic properties and modes of action of these drugs were considered in the context of their side effects in Chap. 41. Additional points of interest are mentioned here.


Neurology_Adams

Neurology_Adams. Most psychiatrists currently prefer to begin treatment with one of the functional serotonin agonists (SSRIs)—fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), citalopram (Celexa), escitalopram (Lexapro), and others, or one of a related group (serotonin-norepienphrine reuptake inhibitors), exemplified by venlafaxine (Effexor) and nefazodone (Serzone). New drugs of similar type are appearing yearly. These drugs have less sedating and anticholinergic effects than the tricyclic antidepressants discussed below, and may have a slightly faster onset of effect against depression. Fluoxetine has a tendency to produce insomnia and weight loss, making it particularly useful in the treatment of depressions that are characterized by overeating and hypersomnia. Some female patients have experienced an opposite effect, that is, weight gain. Patients with anorexia, insomnia, and high levels of anxiety may do better with a more sedating medication, such as amitriptyline. Fluoxetine would


Neurology_Adams

Neurology_Adams. an opposite effect, that is, weight gain. Patients with anorexia, insomnia, and high levels of anxiety may do better with a more sedating medication, such as amitriptyline. Fluoxetine would be a reasonable choice for patients in whom lethargy is a prominent complaint.


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Neurology_Adams. Certain side effects such as loss of libido and erectile dysfunction occur in a proportion of patients and are difficult to differentiate from the signs of depression. Other side effects occur in a proportion of patients, including gastrointestinal upset, increased anxiety as discussed in Chap. 47, blurred vision, dizziness, among many others (see Chap. 41).


Neurology_Adams

Neurology_Adams. The contentious issues of (1) inducing mania, (2) precipitating suicide soon after the institution of these medications, and (3) the use of these drugs in children are important ones that can only be addressed here cursorily. Ryan summarizes these problems and points out that the overall rates of suicide among adolescents are decreasing at the time of increasing use of SSRI agents. The precipitation of a manic episode by serotonergic antidepressants in some patients with bipolar disorder seems a regular enough occurrence that this risk is no longer a point in question. Also to be emphasized is an increased risk of pulmonary hypertension in the babies of mothers exposed to SSRI during the pregnancy.


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Neurology_Adams. The tricyclic antidepressants comprise amitriptyline, imipramine, desipramine, doxepin, clomipramine, and trimipramine, and the closely related drugs nortriptyline and protriptyline. Among this group, most psychiatrists start with imipramine or amitriptyline because of their relative safety. In general, all of these drugs are equally effective, although an individual patient may have a better response or tolerance to one than to another. The starting dose for amitriptyline or imipramine is 25 mg/d, which is then raised by 25 mg q3–4d as needed up to 150 mg/d. These drugs, taken at bedtime, are also very helpful in alleviating the insomnia that accompanies depression. The therapeutic effect of tricyclic medication is generally not evident for 2 to 4 weeks after treatment has been initiated, and it is important that this be explained to the patient and family. Common side effects are orthostatic hypotension, dry mouth, constipation, tachycardia, urinary hesitancy or retention


Neurology_Adams

Neurology_Adams. initiated, and it is important that this be explained to the patient and family. Common side effects are orthostatic hypotension, dry mouth, constipation, tachycardia, urinary hesitancy or retention (especially in patients with prostatic hypertrophy), tremor, and drowsiness. Closed-angle glaucoma may decompensate. Caution should be exercised in elderly patients with cardiac disorders of all types because of the possibility of causing heart block or arrhythmia. For such patients, the serotonin drugs or one of a group of nontricyclic antidepressant drugs—bupropion and trazodone—may be preferable, but the latter causes orthostatic hypotension and sedation in doses required for consistent antidepression effects. The non-trycyclic drugs appear to be as effective as the tricyclic agents in the treatment of depression without the adverse anticholinergic and cardiotoxic effects.


Neurology_Adams

Neurology_Adams. If one of the SSRI or tricyclic and related drugs given in full doses for 4 to 6 weeks does not produce the desired effect, or as often happens, the patient is intolerant of the given drug, an alternative group, for example, an MAO inhibitor, may be tried. In one of the many new “effectiveness” trials sponsored by the National Institutes of Mental Health, as distinguished from “efficacy” in randomized trials, failure of citalopram to accomplish remission of depression, by changing to bupropion, sertraline, or venlafaxine was successful in 25 percent of cases (Rush et al). After discontinuing SSRIs, there must be a drug-free interval of 1 to 2 weeks before instituting an MAO inhibitor in order not to provoke a serotonin syndrome. Some studies suggest that MAO inhibitors are superior in depression with atypical features such as increased appetite. Phenelzine, isocarboxazid, and tranylcypromine are in this category, of which the first is said to be the least likely to produce serious


Neurology_Adams

Neurology_Adams. depression with atypical features such as increased appetite. Phenelzine, isocarboxazid, and tranylcypromine are in this category, of which the first is said to be the least likely to produce serious side effects. The usual starting dose is 15 mg tid, which is gradually increased as needed to a maximum of 45 mg tid. The most serious risk of MAO inhibitors is the occurrence of a hypertensive crisis; consequently, these drugs should be dispensed with caution in patients with hypertension and with cardiovascular or cerebrovascular disease. Patients taking these drugs should avoid foods with a high tyramine content (aged cheese, many pickled foods, chicken liver, beer, wines, yeast extract) as well as medications containing sympathomimetic agents or l-dopa (decongestants, amphetamines, caffeine) and the aforementioned serotonin agonists. The use of the MAOI (monoamine oxidase inhibitor)-B drugs for Parkinson disease (see Chap. 38) is also interdicted.


Neurology_Adams

Neurology_Adams. Supplementation of antidepressants with the administration of an antiepileptic medication as a “mood stabilizer” is a popular approach with many psychiatrists. Valproate or gabapentin are used, but also used are carbamazepine or phenytoin. There are few credible studies by which to judge the value of this strategy, but these drugs may provide some additional benefit, if only as antianxiety agents. More persuasive are the data suggesting that antiepileptic drugs are useful in treatment of the manic state.


Neurology_Adams

Neurology_Adams. Because many depressed patients are responsive to one of the tricyclic drugs, MAO inhibitors, or serotonin agonists but not to all of them, the clinician is greatly aided by information regarding which of these drugs has been helpful in past episodes. As mentioned, response to antidepressant drugs is not expected for several weeks. Treatment, if successful, should be continued for 6 to 9 months and generally combined with some type of psychotherapy. The premature discontinuation of medications is a major source of relapse. The dosage of medication may then be reduced slowly over a period of weeks. Rapid reduction may result in withdrawal symptoms (nausea, vomiting, malaise, and muscular pains). If depressive symptoms recur upon withdrawal, the effective dose should be gradually reinstituted. Mann (2005) provides a thorough review of the medical treatment of depression; the side effects of each are given in tabular form and adapted for Table 48-3.


Neurology_Adams

Neurology_Adams. What used to be called infelicitously “electroshock” therapy continues to be a highly effective treatment for severe endogenous depression and can also be used to interrupt manic episodes. The technique is relatively simple and, in properly supervised clinics, quite safe. The patient is anesthetized by an intravenous injection of a short-acting barbiturate, benzodiazepine, or propofol, and is also medicated with a muscle relaxant (succinylcholine). In the conventional method, an electrode is placed over each temple and a current of about 400 mA and 70 to 120 V is passed between them for 0.1 to 0.5 s. The machine itself has as the essential element a large capacitor that is discharged to produce an electrographic seizure. The succinylcholine prevents strong and injurious muscle spasms. The patient is awake within 5 to 10 min and is up and about in 30 min. The mechanism by which ECT produces its effects is unknown. Treatments are usually given every other day for 6 to 14 sessions. The


Neurology_Adams

Neurology_Adams. patient is awake within 5 to 10 min and is up and about in 30 min. The mechanism by which ECT produces its effects is unknown. Treatments are usually given every other day for 6 to 14 sessions. The only absolute contraindication is the presence of increased intracranial pressure, as may occur with a neoplasm or intracranial hematoma. Whether epilepsy is precipitated or worsened by ECT is still debated but the presence of epilepsy is generally considered a contraindication. This treatment should also be used cautiously in the presence of uncontrolled systemic hypertension or with a known sensitivity to the anesthetic agents that are used as premedication.


Neurology_Adams

Neurology_Adams. The major drawback of ECT is the production of a transient impairment of recent memory for the period of treatment and for the days that follow, the degree of impairment related to the number of treatments given. Placing both electrodes on the nondominant side (unilateral ECT) or using lower amounts of current and a briefer pulse rather than a sine wave produces less memory disturbance and has been adopted because it is almost as effective against the depression.


Neurology_Adams

Neurology_Adams. With the recognition that transcranial magnetic motor stimulation sometimes produced an elevation of mood, its use as a substitute for ECT is being introduced. The magnetic technique has the advantage of being free of any but minor physical effects, and because it produces no loss of consciousness, anesthesia and neuromuscular paralysis are not needed. Brief pulses of high-frequency stimuli are used. Few controlled studies have as yet been performed and this technique could conceivably replace ECT, but the initial sense is that it is not as effective against severe or prolonged depressions and probably not at all for catatonia. Related methods, such as direct current stimulation of the cortex have met with mixed but generally negative results (Brunoni et al).


Neurology_Adams

Neurology_Adams. Until the advent of the antidepressant drugs, ECT was the treatment of choice for the agitated depression of middle and late life and for catatonia. Following a course of 6 to 14 treatments, close to 90 percent of patients recovered within 2 months or less. Prior to the use of ECT, this type of depression might last for 2 years or longer before remission or suicide occurred. In cases of catatonia or severe psychotic depression most psychiatrists favor the initial use of one of the newer antipsychosis agents, followed by a trial of an antidepressant before resorting to ECT. Following ECT therapy, maintenance therapy with an antidepressant or lithium is necessary to prevent relapse. Deep brain stimulation is under study for refractory depression. Treatment of Bipolar Disease


Neurology_Adams

Neurology_Adams. This has for decades, until very recently, been the drug of choice in treating the manic phase of bipolar disease and it is useful in preventing relapses of depression in some patients. Certain of the newer antipsychotic drugs, discussed in the next chapter, have overtaken lithium for the treatment of bipolar disease, with little evidence that they are superior. During an acute manic attack, hospitalization may be required to protect the manic patient from impulsive and aggressive behavior that might cause personal and interpersonal difficulty or jeopardize a career. Haloperidol (Haldol), or one of the newer antipsychosis agents discussed in Chap. 49—or electroconvulsive therapy (ECT, see further on) if these drugs are ineffective—can be used to control the mania until lithium carbonate becomes effective, usually a matter of 4 or 5 days. The usual dosage of lithium is 1,200 to 2,400 mg daily in divided oral doses, which produces a desired serum level of 0.9 to 1.4 mEq/L. The serum


Neurology_Adams

Neurology_Adams. becomes effective, usually a matter of 4 or 5 days. The usual dosage of lithium is 1,200 to 2,400 mg daily in divided oral doses, which produces a desired serum level of 0.9 to 1.4 mEq/L. The serum level of lithium must be checked frequently, both to ensure that a therapeutic dose is being taken and to guard against toxicity (see later).


Neurology_Adams

Neurology_Adams. The side effects of lithium are nausea and vomiting, diarrhea (especially if the dose is increased too rapidly), a feeling of mental dullness, action tremor, weakness, ataxia, slurred speech, blurred vision, dizziness, nystagmus (especially vertical or down beating), stupor, and coma. A confusional psychosis with polymyoclonus and ataxia-simulating Creutzfeldt-Jakob disease (including periodic sharp waves in the electroencephalogram) may occur at toxic levels. In patients who do not tolerate lithium, carbamazepine, valproate, or another antiepileptic may be substituted. A combination of lithium and a tricyclic or SSRI medication at the lowest effective level has been one of the most often used long-term preventive therapies for bipolar disease, and the same combination is useful for patients with mixed bipolar disorder in which depressive and manic manifestations occur within a single episode of illness.


Neurology_Adams

Neurology_Adams. Perhaps the most marked change in the treatment of bipolar disease is to initiate one of the approved antipsychotic medications (quetiapine, fluoxetine) rather than lithium to bring both the depression and episodic cycling into mania under control. Failing this, a “mood stabilizing” drug such as lamotrigine or divalproex has been used. As mentioned earlier, there is scant evidence that these approaches are superior to lithium. The point to be made is that the use of conventional antidepressants is currently less popular because of the risk of worsening depression to the point of a suicidal state or of inducing mania. Other combinations have been used such as olanzapine with a serotonergic antidepressant (e.g., fluoxetine). These are summarized in the review by Frye. Taken together the effectiveness of these new approaches serve to emphasize the importance of proper diagnosis of bipolar disease in contrast to unipolar depression. Haloperidol may be necessary to control a dangerous


Neurology_Adams

Neurology_Adams. effectiveness of these new approaches serve to emphasize the importance of proper diagnosis of bipolar disease in contrast to unipolar depression. Haloperidol may be necessary to control a dangerous manic episode while one of these medications becomes effective.


Neurology_Adams

Neurology_Adams. In all patients with depression or bipolar disease, careful explanations of the patient’s illness, reassurance that the illness is self-limited, and encouragement and instruction of the family are of value in helping both the patient and family to understand the illness and cope with it. At the same time, there should be vigilance for suicidality, admittedly a difficult task given its unpredictability. As a general rule, bipolar illness is best managed by a physician who is willing to follow the patient over a long period of time and is available to reevaluate the patient on suspicion of a relapse. Although the prognosis for any individual attack is relatively good, it is wise to arrange for a plan of action that will be set in operation at the first hint of a recurrence.


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Neurology_Adams. Tomes have been written about various psychodynamic approaches to psychotherapy and the authors are unable to comment authoritatively on them. A structured and problem-oriented approach to psychotherapy using “cognitive-behavioral” and “interpersonal” strategies has gained considerable popularity since its introduction in the 1970s by Beck. It draws to a limited extent on psychoanalytic and other psychodynamic theories and has been used in patients with depression and in those with anxiety, chronic pain, and other disorders. According to Blenkiron, cognitive-behavioral therapy is most effective in patients with mild to moderate (not chronic) depression, generalized anxiety and panic disorder, and obsessive-compulsive and phobic disorders. Essentially, in the short term, the therapist provides the patient with information on the nature of the illness, its common symptoms, and the active interventions that are to be undertaken by the patient with the aid of the therapist to alter the


Neurology_Adams

Neurology_Adams. the patient with information on the nature of the illness, its common symptoms, and the active interventions that are to be undertaken by the patient with the aid of the therapist to alter the specific misperceptions and the dysfunctional behaviors that spring from them. In difficult chronic forms of depression, Keller and colleagues compared an antidepression drug (nefazodone), cognitive-behavioral therapy, or the combination, and found remissions in approximately 50 percent of each of the first 2 groups and in 85 percent of the combined treatment cohort by 12 weeks. This stands as one of the better demonstrations of the value of modern, result-oriented psychotherapy. One popular derivative approach is “Acceptance and Commitment Therapy” (ACT), which aids in accepting the difficulties of life. The interested reader can find discussion of this subject in the current edition of Kaplan and Sadock’s Comprehensive Textbook of Psychiatry (Sadock and Sadock). Noteworthy is the opinion of


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Neurology_Adams. of life. The interested reader can find discussion of this subject in the current edition of Kaplan and Sadock’s Comprehensive Textbook of Psychiatry (Sadock and Sadock). Noteworthy is the opinion of Gabbard that behavioral-cognitive psychotherapy has been shown to be no better or worse than other forms of psychotherapy, but it has the virtues of relative brevity, uniformity of application, and straightforwardness that avoids blaming the patient, family, environment, or other external forces.


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Neurology_Adams. Some 30,000 suicides are recorded annually in the United States, and attempted suicides exceed this number by approximately 10 times. All psychiatrists agree that these are conservative figures. Suicide is the eighth leading cause of death among adults in the United States and the second leading cause among persons between the ages of 15 and 24 years, figures that emphasize the importance of recognizing depression that has a high potential for self-destruction. Every physician should be familiar with the few clues we possess to identify those patients who intend to end their lives. Some of the questions that may be broached in the interview regarding depression were listed earlier, but particularly, “Do you think of hurting yourself or taking your own life?” and the follow-through query, “Do you have a plan?” Physicians should also be aware that the majority of suicides are accomplished by taking an overdose of prescribed medications, for which reason caution needs to be exercised in


Neurology_Adams

Neurology_Adams. “Do you have a plan?” Physicians should also be aware that the majority of suicides are accomplished by taking an overdose of prescribed medications, for which reason caution needs to be exercised in their distribution and administration in depressed patients.


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Neurology_Adams. Some views, summarized by Mann (1998), are that suicidal intent represents a special form of depression, or an important variant of it, and that certain individuals are by nature susceptible as a result of biologic factors. In other words, suicide is not simply a cognitive response to extreme stress or despondency. Certainly impulsivity, a frontal lobe phenomenon, seems to be an element of the suicidal act in many cases but this also is difficult to anticipate and prevent. There is no way for the authors to judge these views, but proponents have pointed to particular indices of serotonin function that differ between depressed individuals who attempt suicide and those who do not. It has also been observed that the inception of modern antidepressant medications has not greatly altered the rate of suicide among depressed patients. Bipolar illness, endogenous depression, depression resulting from a debilitating disease (particularly Huntington disease, cancer, and HIV), pathologic grief,


Neurology_Adams

Neurology_Adams. of suicide among depressed patients. Bipolar illness, endogenous depression, depression resulting from a debilitating disease (particularly Huntington disease, cancer, and HIV), pathologic grief, and depression in an alcoholic or schizophrenic, all carry the risk of suicide. In bipolar disease and endogenous depression, the risk of suicide over the lifetime of the patient is approximately 15 percent (Guze and Robins). In Robins’ series of 134 patients who committed suicide, 47 percent had a known depressive illness and 25 percent were alcoholic. Other series have recorded even higher rates of depression, alcoholism, and drug abuse (see Andreasen and Black).


Neurology_Adams

Neurology_Adams. Despite the above comments regarding impulsivity, most suicides are planned. Furthermore, the intention of committing suicide is more often than not communicated to someone significant in the patient’s life. The message may be in the form of a direct verbal statement of intent, or it may be indirect, such as giving away a treasured possession or revising a will. It is known that successful suicide is 3 times more common in men than in women and particularly common among men older than 40 years of age. Patients with a history of suicide in either mother or father carry a higher risk than those without such a history. A previous suicide attempt adds to the risk. As alluded to earlier, important deterrents to suicide are devout Catholicism or comparable religious belief against suicide, concern about the suffering it would cause the family, and fear of death sincerely expressed by the patient. However, no single one of these attributes stands out as entirely predictive of suicide. As a


Neurology_Adams

Neurology_Adams. about the suffering it would cause the family, and fear of death sincerely expressed by the patient. However, no single one of these attributes stands out as entirely predictive of suicide. As a consequence, one is left with clinical judgment and an index of suspicion as the main guides. The only rule of thumb is that all suicidal threats are to be taken seriously and all patients who threaten to kill themselves should be evaluated quickly by a psychiatrist.


Neurology_Adams

Neurology_Adams. In our experience, the following are some of the common and troublesome clinical situations in which it may prove difficult to recognize an underlying depression: 1. Patients with chronic pain. The association of chronic pain and depression has long been appreciated. This is far from a homogeneous group. The special case of chronic headache, confronted often by neurologists, is discussed below and in Chap. 9. In some patients with chronic pain, the symptoms and signs of depression are quite apparent. If the pain has been present for less than 1 year and had its onset at the same time as other depressive symptoms, response to antidepressant treatment is likely to be favorable. Far more difficult to understand, and to manage, are patients with persistent pain as the only complaint; the head, face, and lower back are the most common loci. Weeks or months of unremitting daily tension-type headaches in the context of a normal examination are highly suggestive of depression at any age. If


Neurology_Adams

Neurology_Adams. face, and lower back are the most common loci. Weeks or months of unremitting daily tension-type headaches in the context of a normal examination are highly suggestive of depression at any age. If an exhaustive search for the source of the pain proves unsuccessful, the conclusion is finally reached that the pain is “psychogenic.” This attribution of pain to some obscure psychologic mechanism is hardly helpful. Nevertheless, in a fair proportion of such patients, that pain will be alleviated by antidepressant drugs is suggestive of a linkage of the pain and depression. The problem may have been made even more difficult by repeated surgical operations as well as dependency on analgesic drugs, which in themselves deplete energy and have other adverse effects. Such patients are to be found among those disabled after multiple operations for ruptured intervertebral disc or arthritic hips or those with atypical facial pain.


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Neurology_Adams. 2. Depression and alcoholism. These are commonly associated, and it is important to determine which is primary and which is secondary. A depressive syndrome developing for the first time on a background of alcoholism is a common clinical occurrence. In a large series of alcoholic patients studied by Cadoret and Winokur, a secondary depression occurred in 30 of 61 females and in 41 of 112 males; moreover, once the alcoholism was established, depression became evident much earlier in the women than in the men. The opposite occurrence (i.e., the development of alcoholism on the background of a primary depression) is less common. Again, women are disproportionately affected. As mentioned earlier, these differences may be spurious; Winokur’s family studies (1991) suggest that the same genetic predisposition leads to depression in females and alcoholism and sociopathy in men. Whether there is a similar linkage between depression and drug addiction, for example to opiates, is not clear but


Neurology_Adams

Neurology_Adams. predisposition leads to depression in females and alcoholism and sociopathy in men. Whether there is a similar linkage between depression and drug addiction, for example to opiates, is not clear but it seems not, in our experience.


Neurology_Adams

Neurology_Adams. 3. Depression in childhood and adolescence. We have observed depressive states in children and they have often been misdiagnosed by both pediatricians and psychiatrists. The common manifestations have been chronic headache, refusal to go to school, withdrawal from social activities, anorexia, vomiting and weight loss, and scholastic failure. Puberty is a time of onset in many cases and the disorder is frequent in late childhood and in high school and college students. It is a tragic mistake not to appreciate this fact and to treat the patient for some presumed nonaffective nervous symptoms, only to have the patient commit suicide.