Melancholia

Normally, dietary tyramine is broken down in the gastrointestinal tract by MAO and is not absorbed. In the presence of MAOI, however, all of its potent sympathomimetic actions are seen. Other side effects of MAOI include excessive CNS stimulation, orthostatic hypotension, weight gain, and in rare cases hepatotoxicity. Because the monoamine oxidase inhibitors exhibit greater toxicity, yet no greater therapeutic response than other, newer agents, clinical use has been markedly curtailed. The primary use for MAOIs is in the treatment of atypical depressions, eg, those associated with increased appetite, phobic anxiety, hypersomnolence, and fatigues, but not melancholia (2). 

Depression and mania are both affective disorders but their symptoms and treatments are quite distinct. Mania is expressed as heightened mood, exaggerated sense of self-worth, irritability, aggression, delusions and hallucinations. In stark contrast, the most obvious disturbance in depression is melancholia that often co-exists with behavioural and somatic changes (Table 20.1). Some individuals experience dramatic mood swings between depression and mania. This is known as "bipolar disorder which, like mania itself, is treated with lithium salts or neuroleptics. 

In the past several decades there has been increased incidence of depression, which motivated Gerald Klerman to describe this era as the age of melancholia [5], The lifetime prevalence of depression in the U.S. is higher in women (21.3%) than in men (12.7%). Although the rates of major depression vary across the world, data from fifty countries support the notion that this disease is the fourth leading cause of disability worldwide (second in developed countries) [3]. Longitudinal studies verify that the typical course of the disease is recurrent, with periods of recovery and periods of depression symptoms however, approximately 17% of patients have a chronic unremitting disease [6], Depression is the major cause of suicidal behavior and the rate of suicidal attempts has been estimated to be around 56% in depressed patients [7]. 

The authors wanted to select indicators that specifically tap melancholic depression. To evaluate this construct, a principal components analysis of the joint pool of K-SADS and BDI items was performed. Two independent statistical tests suggested a two-component solution, but the resulting components appeared to reflect method factors, rather than substantive factors. Specifically, all of the BDI items loaded on the first component (except for three items that did not load on either component) and nearly all of the K-SADS items loaded on the second component. In fact, the first component correlated. 98 with the BDI and the second component correlated. 93 with the K-SADS. Ambrosini et al., however, concluded that the first component reflected depression severity and the second component reflected melancholic depression. This interpretation was somewhat at odds with the data. Specifically, the second component included some K-SADS items that did not tap symptoms of melancholia (e.g., irritability and anger) and did not include some BDI items that measure symptoms of melancholia (e.g., loss of appetite). 

The conclusion seems to be that depression is a very broad, heterogeneous construct and a general depression taxon probably does not exist. However, taxa may be found in this domain if the researchers carefully select indicators to evaluate distinct constructs, such as melancholia. It is important to note that use of specific markers may permit clearer differentiation of the target taxon from other psychiatric problems and from other depression taxa, if they exist. The taxometrics of depression is a complex and interesting area that requires well-defined questions accompanied by careful research. 

It also seems likely that some mental disorders (perhaps major depressive disorder) in their present form will fail to show evidence of taxonicity, but definitional refinement would help elucidate underlying taxa (e.g., melancholia). Thus, taxometrics may be able to serve as an impetus and a guide for revising the diagnostic system. Of course, taxometric methods alone are not sufficient to tackle this task and should be used in conjunction with dimensional methods, such as exploratory factor analysis. Dimensions provide the building blocks for construction of taxa, and research on the structure of psychopathology should integrate dimensional and taxometric methods. 

Ambrosini, P., Bennett, D. S., Cleland, C. M., Haslam, N. (2002). Taxonicity of adolescent melancholia A categorical or dimensional construct Journal of Psychiatric Research, 36, 247-256. 

However, there is a time-delay phenomenon between causes being set in motion in the inner world and their effects appearing, fully manifest, in the outer world. This needs to be taken into account so that you do not become disheartened or fall prey to melancholia, as the old alchemical books term it. Lama Anagarika Govinda explains this delay between causation and result in his book, Foundations of Tibetan Mysticism ... 

My purpose in comparing Alchemy and Tibetan Buddhist Yoga is twofold. First, the old European alchemists refered to their melancholia, meaning the depression that besets till spiritual practitioners from time to time. In Alchemy this depression is pronounced and common, because its practitioners, more often than not, work in isolation and in a nonsupportive culture. Tibetan Buddhism on the other hand, has a continuous lineage of practitioners who have attained signs of accomplishment, thereby giving assurance to others that the Goal is attainable. Tibet also has a culture where the fruits of the spirit are valued above all else. 

Carroll BJ, Feinberg M, Greden JF, Tarika J, Albala AA, Haskett RF, James NM, Kronfol Z, Lohr N, Steiner M, et al. (1981). A specific laboratory test for the diagnosis of melancholia. Standardization, validation, and clinical utility. Arch Gen Psychiatry. 38(1) 15-22. 

Euphorics. In the 19th century, euphoria-inducing substances such as cocaine were recommended for the treatment of melancholia. Although these substances... 

The diagnosis of mania is made on the basis of clinical history plus a mental state examination. Key features of mania include elevated, expansive or irritable mood accompanied by hyperactivity, pressure of speech, flight of ideas, grandiosity, hyposomnia and distractibility. Such episodes may alternate with severe depression, hence the term "bipolar illness", which is clinically similar to that seen in patients with "unipolar depression". In such cases, the mood can range from sadness to profound melancholia with feelings of guilt, anxiety, apprehension and suicidal ideation accompanied by anhedonia (lack of interest in work, food, sex, etc.). 

Manic-depressive illness connotes a psychotic disorder of affect that occurs episodically without external cause. In endogenous depression (melancholia), mood is persistently low. Mania refers to the opposite condition (p. 234). Patients may oscillate between these two extremes with interludes of normal mood. Depending on the type of disorder, mood swings may alternate between the two directions (bipolar depression, cyclothymia) or occur in only one direction (unipolar depression). 

FIGURE 7. Albrecht Diirer, Melancholia, 1514, Inv. B.74-II. Photo Jorg P. Anders. Kupferstichkabinett, Staadiche Museen zu Berlin, Berlin, Germany. Photo credit Bildarchiv Preussischer Kulturbesitz / Art Resource, NY. 

Diirer s St. ]erome in His Study of 1514 (Figure 8) is another example of the composition type in consideration here. It is from the same period as his Knight, Death and the Devil (1513) and his Melancholia (1514) (Figure 7). 

Depression and mania are described in Chapter 16 they are mentioned here because of their close relation to reward and punishment systems. The passive anhedonia of melancholia, with inability to derive pleasure from usual enjoyments and general lack of motivation, indicates underactivity in reward... 

Bipolar disease, or recurrent unipolar disease may be manic-depressive illness. This disease can manifest as typical bipolar disease, with alternating depressive and manic episodes, or as recurrent depression (or more rarely recurrent mania). The age of onset and frequency of recurrence may be highly variable, with at best a single episode, where the disease may be suspected from family history. The intensity of individual episodes may vary from the maximal intensities of depression, also called melancholia, or mania justifying rapid hospitalisation to barely pathological mood swings, where it is an alternation and... 

Prog Neuropsychopharmacol Biol Psychiatry 25 141-166 Henn FA, Johnson J, Edwards E, Anderson D (1985) Melancholia in rodents neurobiology and pharmacology. Psychopharmacol Bull 21 443-446 Henn FA, Edwards E, Muneyyird J (1993) Animal models in depression. Clin Nemosci 1 152-156... 

Carroll, B.J. (1982) The dexamethasone suppression test for melancholia. Br J Psychiatry 140 292-304. 

Overall, the clinical picture of childhood MDD parallels the symptoms of adult MDD (Birmaher et ak, 1996b). There are some developmental differences, however. Symptoms of melancholia (e.g., lack of appetite, insomnia, lack of interest in anything), delusions, suicide attempts, especially high-lethality ones, are all less prevalent in young children and increase with age. In contrast, symptoms of anxiety, behavioral problems, and perhaps auditory and visual hallucinations seem to occur more frequently in children (AA-CAP, 1998 Birmaher et ah, 1996a). Also, it appears that the rate of onset of bipolar disorder is higher in... 

Severity of Illness. J. M. Roberts (1959] originally reported that higher symptom scores at baseline predicted better ECT response. In contrast, Andrade et al. (1988] and Sackeim et al. (1987a] found no differences between responders and nonresponders in initial severity, while others reported that ECT nonresponders had greater initial severity of depression (Kindler et al. 1991 Pande et al. 1988]. Thus, there is no consensus on how symptom severity, independent of the presence of psychosis or melancholia, is predictive of ECT response. 

Clerc GE, Ruimy P, Verdeau Pailles J A double-bhnd comparison of venlafaxine and fluoxetine in patients hospitabzed for major depression and melancholia the Venlafaxine Erench Inpatient Study Group. Int Clin Psychopharmacol 9 139-143, 1994... 

Guelfi JD, White AG, Hackett D, et al Effectiveness of venlafaxine in hospitalized patients with major depression and melancholia. J Chn Psychiatry 56 450-458, 1995... 

Roose SP, Glassman AH, Walsh BT, et al Tricyclic nonresponders phenomenology and treatment. Am J Psychiatry 143 345-348, 1986 Roose SP, Glassman AH, Attia E, et al Comparative efficacy of selective serotonin reuptake inhibitors and tricyclics in the treatment of melancholia. Am J Psychiatry 151 1735-1739, 1994... 

Tignol J, Stoker MJ, Dunbar GC Paroxetine in the treatment of melancholia and severe depression. Int Clin Psychopharmacol 7 91-94, 1992 Tilders FJH, Schmidt ED, Van Dijken HH, et al Adaptive changes in hypothalamic CRH-neurons in experimental animals and man (abstract). American College of Neuropsychopharmacology Annual Meeting, San Juan, Puerto Rico, December 1994... 

TCAs derive their name from their chemical structure aU tricyclics have a three-ring nucleus. Currently, most clinicians are moving away from using TCAs as first-line drugs relative to the newer antidepressants, they tend to have more side effects, to require gradual titration to achieve an adequate antidepressant dose, and to be lethal in overdose. Some data suggest that TCAs may be more effective than SSRIs in the treatment of major depression with melancholic features (Danish University Antidepressant Group 1990 Perry 1996) however, many skilled clinicians and researchers continue to prefer the newer antidepressants, even for patients with melancholia, for the aforementioned reasons. Newer medications that affect both norepinephrine and serotonin (e.g., venlafaxine and mirtazapine) also may have superior efficacy in severely iU depressed patients or when remission is defined as the outcome (Thase et al. 2001). 

Clerc, G.E., Ruimy, P., Verdeau-Pailles, J., et ah A double-blind comparison of venlafaxine and fluoxetine in patients hospitalized for major depression and melancholia. Int. Clin. Psvchopharmacol. 9, 139-143, 1994. 

Although hypomanic and manic episodes are discussed comprehensively in Chapter 9, it is important to note that the disturbance in mania (and hypomania), as well as in depression, includes the same core symptoms, differing only in the direction of change. Complicating the diagnosis, unipolar patients may also present with classic melancholia or atypical (nonclassic) symptoms. The latter, in particular, can overlap considerably with hypomania. Similarly, bipolar patients in a depressive phase may demonstrate classic or nonclassic symptoms (Table 6-5). 

There are three subtypes of MDD melancholia, or classic depression atypical, or nonclassic depression and psychotic depression. These three subtypes have construct validity based on differences in the following ... 

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