mes. Lae Moot Disorders ad Suicide CHAPTER 7 the following case. ‘A Successful “Total Failure” Margaret, a prominent businesswoman inher ate-oties, noted for her energy and productivity, was unexpectedly deserted by her husband fora younger woman. Following her inital shock and rage, she began to have uncontrol lable weeping spells and doubts about her business acu- men. Decision making became an ordeal. Her spirits rapidly sank, and she began to spend more and more | time in bed, reusing to deal with anyone. Her alcohol © consumption increased to the point where she was sel: dom entirely sober. Within period of weeks, she had suf- {fered serious financial losses owing to her inability, or | refusal, to keep her affairs in order. She felt she was a | total filur,” even when reminded of her considerable “personal and professional achievements; indeed, her -selfcricism gradually spread to all aspects of her life andher persona history. Finally, alarmed members ofher ily essentially forced her to accept an appointment witha clinical psychologist. ‘Was something “wrong” with Margaret, ot was she merely ‘experiencing normal human emotions because of her hus- band’s deserting her? The psychologist concluded that she ‘was suffering from a serious mood disorder and initiated treatment. The diagnosis, based on the severity of the symptoms and the degree of impairment, was. major ‘depressive disorder, Secondarily, she had also developed a serious drinking problem—a condition that frequently co- ‘occurs with major depressive disorder. exam, not getting into o,, palling 2 o seo ine NE yp th 9 ang it depress rate school, ane 28 depressed Mood in man | 1 of us 8 : ert enoice of colle that severe alterations in my i a involv isturbances ner are all ext igorders IV ch cases the disturbane of moog a] people. However ‘ time, In UCT PT Gaptive, and often lead tose, and for much Ln 5 cleat mace. In facts it as been ex ‘ istent e ; intense and persistent ak peerage eal ond gus problems in rlatlONST | ranked aMMOnE orld except Africa, and it vag mated that 2000 OEP in all ats OF eg States, FMRI abOvE hag terms of years lost R health condition in the roe Preease-burden” of depres the numberone such Healt) <1" vera the rreatment 2 nding direct costs ture deaths) —totalleg fase and stroke (Ustll : is, the total ee ‘ciety—that i, the and P esha mised oe disap yr eo percent ofthe reported cos : lone, : $83.1 billion in ee Smonkplace (Greenbers, Kessler et al» 2003). Consider resulting from problet erse in nature, asisillustrated by e gnized in the DSM-IV-TR semanytypesof depression recognized int thor we wll discus Nevertheless, int all mood disorders ive disorders), extremes of emotion v merly called affective disorders), extrem ie ition or deep depression—dominate cor affect soaring el of Uisieal picture, other symptoms are also present, but the abnormal mapd is the defining feature. Wuat ARE Moop DISORDERS? “The two key moods involved in mood disorders are mania, often characterized by intense and unrealistic feelings of excitement and euphoria, and depression, which usually involves feelings of extraordinary sadness and dejection. Some people experience both of these kinds of moods at ‘one time or another, but other people experience only the depression. These mood states are often conceived to beat opposite ends of mood continuum, with normal mood in the middle. although this concept is accurate t0 ¢ eres, sometimes patient may have symptoms pf manit sed orion during the same time period (In thes le cases, the person experiences rapidly altet~ ‘aUingmoodssuchassadness, cuporia, and eabiy al ren gime ead floes the el ist discuss the unipolar disorders, in which wwe wil diane ences only depressive episodes, and thet xpress Cat bipolar disorders, in which the pero® tinction is saaine ic and depressive episodes. This dis tnpolerarereminent in DSM-1V-TR, and although the holy co POL forms of mood disorder may not be arate and distinct, there are notable difference ‘Mood disorders are divcors,and treatm ~ yoms caus flerentiate amor rents. As . “n Weill see, iat costomiry te ng the mood ‘ior, Perms OY Severin A tans j ies the rau dete of impairment evi. Fhose areas and DY duration —whether thea, 4 esa clonic, of intermittent (with periods ot BE oral functioning between the episodes of | ei 080 ted, diagnosing unipolar or bipolar disorder Jefe diagnosing what kind of mood episode the ints with. The most common form of mood { se Fiat people present with is a major depressi le pressive ge Pe dealed in the DSM-IV-TR table, Criteris for Fypressive Episode, to receive this diagnosis, the sfineest in pleasurable activities) for most of every od for most days for at least 2 weeks. In addition, he must show at least three or four other symptoms ijt of five) that range from cognitive symptoms (issteings of worthlessness or guilt and thoughts of Gate to behavioral symptoms (such as fatigue or phy ‘agiation), to physical symptoms (such as changes in setteand sleep patterns). ‘The other primary kind of mood episode is a manic aiode, in which the person shows markedly elevated; phair expansive mood, often interrupted by occa- ged outbursts of intense irritability or even violence— pialarly when others refuse to go along with the ‘atic person’s wishes and schemes. These extreme sods ust persist for at least a week for this diagnosis to txmale In addition, three or more additional symptoms tzatoccurin the same time period, ranging from behav- ial symptoms (such as a notable increase in goal- Sxcted activity, often involving loosening of personal ‘odcaltural inhibitions as in multiple sexual, political, or tgous activities), to mental symptoms where self- xen becomes grossly inflated and mental activity may sredup (uch as a “fight of ideas” or “racing thoughts”), “»physical symptoms (such as a decreased need for sleep, ‘ythomotor agitation). (See the DSM-IV-TR table, Ci ‘ti fora Manic Episode on p. 228.) Research suggests that mild mood disturbances are on ‘ame continuum as the more severe disorders. That is, dferences seem to be chiefly of degree, not of kind, a ion supported in several large studies examining yt 8Kendler & Gardner, 1998; Ruscio & Ruscio, However, there is also considerable heterogeneity in sit it which the mood disorders manifest them- yattthere are multiple different subtypes of both i and bipolar disorders, and somewhat different Nelyeand treatments are important for different . sg important to remember that suicide is a di Sey) feguent outcome (and always a potential out, Sue Bhificant depressions, both unipolar and fact, as discussed in the latter part of this chap- MS ptf be markedly depressed (or show a marked fof Criteria for Major Depressive Episode A. Five (or more) ofthe fllowing symptoms have been present dung the same 2-veek period and represent @ Change from previous functioning: atleast one of the Symptoms is either 1) depressed mood or 2) loss of les interest or pleasure. WS SEiessed most of the day, nearly every day. as Cis eo indented by ether subjective reports or observation P29 made by thers, (2) Markedly diminished interest or pleasure in all, or almost al, activities most ofthe day, nearly every day. (3) Significant weight loss (when not dieting) or weight sain. (@) Insomnia or hypersomnia nearly every day. (5) Psychomotor agitation or retardation nearly every day. (@ Fatigue or loss of energy nearly every day. (7) Feelings of worthlessness or excessive or guilt nearly every day. shed ability to think or concentrate, oF iveness, nearly every day. (9) Recurrent thoughts of death or suicide, or recurrent suicidal ideation without a plan, ora suicide attempt or plan. B. The symptoms do not meet criteria for a Mixed Episode, C. The symptoms cause clinically significant distress or impairment. ter, depressive episodes are clearly the most common of the predisposing causes leading to suicide. The Prevalence of Mood Disorders Major mood disorders occur with alarming frequency—at least 15 to 20 times more frequently than schizophrenia, for example, and at almost the same rate as all the anxiety disorders taken together. Of the two types of serious mood disorders, unipolar major depression is much more com- mon, and its occurrence has apparently increased in recent decades (Kaelber, Moul, & Farmer, 1995; Kessler, Berglund, et al, 2003). The most recent epidemiological results from the National Comorbidity Survey-Replication study found lifetime prevalence rates of unipolar major depression at nearly 17 percent (12-month prevalence rates were nearly 7 percent) (Kessler, Chiu, et al, 2005), Moreover, rates for unipolar depression are always much higher for women than for men (tisually about 2:1), similar to the sex differ. ences for most anxiety disorders (see Chapter 6). The issue of sex differences in unipolar depression will be discussed ppropriateDysthymic Disorder The point at which mood disturbance becomes a diagnos” able mood disorder is a matter of clinical judgment and usually concerns the degree of impairment in functioning that the individual experiences. Dysthymic disorder is considered to be of mild to moderate intensity, but its pri- mary hallmark is its chronicity. To qualify for a diagnosis of dysthymic disorder (or dysthymia), a person must have a persistently depressed mood most of the day, for more days than not, for at least 2 years (1 year for children and adolescents). In addition, individuals with dysthymic dis- order must have at least two of six additional symptoms when depressed (see the DSM-IV-TR table, Criteria for Dysthymic Disorder). Periods of normal mood may occur briefly, but they usually last for only a few days to a few weeks (and for a maximum of 2 months). These intermit- tently normal moods are one of the most important char- acteristics distinguishing dysthymic disorder from major depressive disorder. Dysthymia is also quite common, with a lifetime prevalence estimated between 2.5 and 6 percent (Kessleret al., 2005), erglunds ne The aver 5 years, but it can persist gee 1, 1997) Chronic stress hash, y of symptoms overa 7.5, yx Klein, & Davila, 2004), Rd n cover from dysthymia wig apse within an average of a, h half may Fel : eat Swartz, Rose, & Leader, 2000), San + the teenage YeATS AME OVET 50 perce before age 21- g case is typi 1 of this disorder, a as,yearold junior executive. ...complained of being gepressed” about everyting: her job, her husband, and her prospects forthe future...-Her complaints were of vorsistent feelings of depressed mood, inferiority, and pessimism, which she claims to have had since she was fe or 27 years old. Although she did reasonably well in ‘college, she constantly ruminated about those students ‘who were “genuinely intelligent.” She dated during col- lege and graduate school but claimed that she would never go after a guy she thought was “special,” always feeling inferior and intimidated... Just after graduation, she had married the man she ‘was going out with at the time. She thought of him as rea- sonably desirable, though not “special,” and married him primarily because she felt she “needed a husband” for ‘companionship. Shortly after their marriage, the couple started to bicker, She was very critical of his clothes, his job, and his parents; and he, in turn, found her rejecting, controlling, and moody. She began to feel that she had made a mistake in marrying him. Mes) she has also been having difficulties at work She i assigned the most menial tasks atthe firm Pecans Been sient importance spore: She sis that she frequently does # is required, an aA iat is given her, never does more en ae tndmever demonstrates any assertiveness her protesonne, 2 that she will never go very sary nection oy acusese des not have the right "em - otmoney cee tes does her husband, yet she dreams band inohes eee Powe Her soil with her his aoe Seater coupes, The man in te ihe women yg ie of her husband. She i. sul ath he peo oe interesting and urimpres better offthan cae tne Seem 10 lke her are prob Under the bur Ei , marriage, ee of her dissatisfaction with Nef uninterested) ey on Ner Social life, feeling tired 2 fe" she now enters treatment for " thi ti tie me. (Spitzer eta, 2002, pp. sie)1 i ; | | Sous of death or suc, Major Depressive Disorder The disgnostic criteria for major depressive disorder esquire that the person exhibit more symptoms than are ssquired for dysthymia and that the symptoms be more sistent (not interwoven with periods of normal rood). To receive a diagnosis of major depressive disoe- éezaperson must be in a major depressive episode (initial or single, or recurrent). An affected person must experi- ace either markedly depressed moods or marked loss of intrest in pleasurable activities most of every day, nearly every day, for at least 2 consecutive weeks. In addition to ‘Saving one or both of these symptoms, the person must. caperience at least three or four additional symptoms daring the same period (for a total of at least five symp- toms), as detailed in the DSM-IV-TR table, Criteria for Major Depressive Episode. These symptoms include cog- aitive symptoms (such as feelings of worthlessness or gilt, and thoughts of suicide), behavioral symptoms (uch as fatigue, or physical agitation), and physical symptoms (such as changes in appetite and sleep pat- terns). Itshould be noted that few if any depressions—includ- ingmilder ones—occur in the absence of significant ans ty (¢g,, Akiskal, 1997; Merikangus et al., 2003; Mineka al, 1998). Indeed, there is a high degree of overlap seen measures of depressive and anxious symptoms in ‘eseports and in clinician ratings. At the diagnostic le thee are very high levels of comorbidity between moo ‘8d anxiety disorders. As discussed later in this chapter (ee Developments in Thinking 7.2 on p. 250), the issues Ssttounding the co-occurrence of depression and anxiety, ‘hich have received a great deal of attention in recent years, “every complex. The following account illustrates a f major depressive disorder. moderately severe Connie Connie, a 33-year-old homemaker and mother of a 4-year- old son, Robert, is referred ...to a psychiatric outpatient rogram because ... she has been depressed and unable to concentrate ever since she separated from her hus- band 3 months previously. Connie left her husband, Don- ald, after a 5-year marriage. Violent arguments between them, during which Connie was beaten by her husband, hhad occurred for the last 4 years oftheir marriage, begin: when she became pregnant with Robert. There were daily arguments during which Donald hit her hard enough to leave bruises on her face and arms. Before her marriage... she was close to her parents {and} had many friends whom she also saw regularly... Inhigh school she had been a popular cheerleader and a ‘good student, ... She had no personal history of depres- sion and there was no family history of ... mental illness. During the first year of marriage, Donald became increasingly irritable and critical of Connie. He began to request that Connie stop calling and seeing her friends after work, and refused to allow them or his in-laws to visit their apartment... Despite her misgivings about Donald's behavior toward her, Connie decided to become preg- nant. During the seventh month of the pregnancy... Donald began complaining [and] began hitting her with his fists. She left him and went to live with her parents for a week. He expressed remorse....and...Connie returned to her apartment. No further violence occurred until after Robert's birth. At that time, Donald began using cocaine every weekend and often became violent when he was high. In the 3 months since she left Donald, Connie has become increasingly depressed. Her appetite has been poor and she has lost 10 pounds. She cries alot and often Wakes up at 5:00 Am. and is unable to get back to (continued)CHAP TEN 7 Mor tvanders and Suiile Connie pale and thin... the speaks slowly, i Her depressed mood and lack of enerBy. She. ‘/6 thal her only pleasure 1 In belng wth er son She ‘able to Lake care of him phystcally, but feels gully because her preoccupation with hier own bad feelings prevents Her {fom belng able to play with him, She now has no contacts ‘other than ith ho parents anderson he fols woth les dnd blames hereel for her marital problems say that if she had been a better wile, maybe Donald would have been able (0 give up the cocalne,. (adapted fromm Spl et al 300 9p, 414-43) Note that Connie’ case nicely illustrates that perso With major depresive disnrder shows not only mod tymptoms of sade hut alo a variety of symptoms that tre mote severe than in milder forms of depression, Cone tle shows vars cognitive dlstonthons, including feeling ‘worthless and yuity. She complains ofa ack of energy anid inability 1 play with her child, Her biological eymptoms ippetite and twill friends ko occurs commonly with depression, i part becaue the person is unmotivated to eck contact, Connie's cave aleo nicely ilusrates the mull pplecompler Interacting factors that may be involved in the tology of depression, Althouglt Connie did not have « personal or a family history of depression, the experiences from 5 years ofa very difficult mariage with a violent and abusive husband were suliclent to finally precipitate her major depression, DEPRESSION THROUGHOUT THE LIFECYCLE Altho he onset of unipolar mood disorder mut often oc during, late adolewence up to middle wut reactions may begin at any tine fron eatlycikdhoend to Cold age, Depression was once thought not to vceur jn dhildhood, hut more recent revearch hae found snajor depressions in presdolewent children, and iti etinated ‘that about 2.0 4 percent of chuol-age children mect the criteria for sone form of unipolar diorder, with perhaps fanother 2 percent exhibiting chaonic mild depression (see Garber 6 Horawits, 2002), ven infants may experience » form of depression (commun knnwn as unaclitie depres ‘on or despait) if they ate separated for a prolonged period from thelr attachient figure (usually thelr mother, Havaloy, 1973, 19805 Speer eta, 1), “rhe incidence of depression vies sharply during a Jewence-# period of great tunnel for many people, Sneed, ane review estimated that approximately 15 020 percent of adolescents experience nisior depresive dlsor- der at some point ducting their wdotesrnt years (Lewine “sohin 6 Vaan, 2002), nnd the wveraye ayy onset for ws been decreas solescenn depresion has Dee surg pare Mea thevineon eta 1993 Speier ea, Pa ‘ perind that gx differences jy hk fs during this tlie p rye (Wankin& Abram, 4 depression first emerne mn, ay qed ce, 20: Nolen Hore Gig jn esearch 71 on p. 244) the jor depressive divorder in adgte eimat at eat hough youn. aduliond when yu duals sow small but siicant psychoses jpe rare in many donna, including helt Occupation their interpersonal relationships, and ther general gyi." Uf life (eqhe Vewinsohn, Hobe, et aly 2003), Seg! Chapter 1) ve occurrence of major Aepresion cantina, Interlife,Ahough the I-year prevalence of major dep, inlay ven ple we se uner adults (Kessler etal 2003), major depression pyar als are stil considered majong Hic heath problenm today (Beekman, Deeg, etal, 2 Moree, esearch suggests hat rates of depression ag, plyically ill residents of nursing homes or residential ae facltes are substantially higher than among older adel, living at home (see Powers et al 2002). Unfortu, depression in ater life can be difficult wo diagnose becase many of the symptoms averlap with those of veveral ma ical nese anu dementia (Alexopoulos eta, 200) att is very important to try and diagnose it elibly breve depression in later life has many adverse consequences 8 person's health, including doubling the vsk of dah io people who have had a heart attack or stoke (Suk et a, 2002) (wee Chapter 10), (ee Developmen ter effects of 3 SPECIFIERS FOR Majon DEPRESSION Some ink uals who meet the basic criteria for diagnosis of major depreion an have adiional patterns of symptoms features that are important to note when making dig” sisbecause they have implications for understanding = ahout the course of the disorder and/or its most effect treatment, They: different patterns of symptoms off tures are called specifiers in DSM-1V-TR. One such spe fier is major depressiveepivode with melancholic featur Thi designation sapped wen, in dition to meld the criteria for major depression a patient either bas interest or pleasure in almost all activities ar does not 4 10 usually pleasurable stimuli or desired events. In #4 tion, the patient must experience at least three of the Sing early moringamaenings (2) depression srs in the maming, (3) marked payhomotr = tomato, spicata appetite a 2 (5) inapproprinte on excesive gui, and (6) 6 ited ‘ is qualitatively different from the sadnes tlenced during a nonmelancholic depression. This subtype of depression nasa wih a higher Joading than other forms of depression (Kendler, 7"} atc ymptoms, characterized by loss of contac ay and dslsions (Ge bei) or hllcintions sits? erEELION) ay sometimes accompany Srptoms of major depression. In such cares eh, srg the diagnosis that is noted is neve settee episode with psychotic features 0, drresiions oF hallucinations present ar ent-—that is they seem in some sense “appro ne aris depression because the conten ier oe, sch a8 themes of personal inadequacy cu fred punishment, death, and disease. For example, $etutisional idea that one’s internal organs have totally forted—an idea sometimes held. by severly ed people—ties in with the mood ofa despondiont Feelings of worthlessness and guilt areakeo carne apart of the clinical picture (Ohayon &e Shatrberg Sha). Psychtically depressed individuals are likely tne a pooret long-term prognosis than nonpsychotie Spresives (Coryell, 1997), and any recurrent episodes salikelyto be characterized by psychotic syreptome ing et al, 2004). Treatment generally involves an (psychotic medication as well as an antidepressant In Ferre cass, psychotic depression occurs in the context Mpospartum depression (Miller, 2002), where mothers {uy Hl their babies because of the hallucinations or {sions they have ‘Athird important specifier is used when the individ- aul shows “atypical fentures” Major depressive episode with aypical features includes a pattern of symptoms Guacerized by mood reactvitys that is, the person's ‘ood brightens in response to potential positive evens. In tition, the person must shove two or more of the follow ificant weight gain or increase (sleeping too much), {leaden paralysis (heavy feelings in arms or legs), and (#)along-standing pattern of being acutcly sensitive to re major edinarily, fe mood- int fie noe weight, excessive gt symptoms: wei Characteristic Symptoms ‘Three of the following: Early morning awakening, depression worse in the ‘morning, marked psychomotor agitation or retardation, loss of appetite or qualitatively different depressed mood. Delusions or hallucinations (usually mood-congruent); feelings of guilt and ‘worthlessness common. “Mood reactvity—brightens to positive events; 190 ofthe four following 1 gain or increase in appetite, hypersomnia, leaden paralysis, being acutely sensitive t Atleast two or more episodes in past2years that have ocurred at the sme ime (usually fall or winter), and full remission at the same time (usually spring) other nonseasonal episodes in same 2-year period. ie Unipolar Mood Dieanders nber of imerpersonal rejection. & disproportionate number if individuals who have atypical features are fernabes, have an earlier-than-average age of onset and who are more likely to show suicidal thoughts (Matra, Revicki Davidson, & Stewart, 2003). This is also an important specifier because there are indications that individuals th atypical features may preferentially respond to a dif- ferent class of antidepressants—the monoamine oxidave inhibitors—than do most other depressed individuals, See ‘Table 7.1 fora summary of the major specifiers. Although not recognized as an official specifier itis not uncommon that major depression may coexist with dysthymia in some people, a condition given the designa- tion double depression (Holand & Keller, 2002; Keller, Hirschfeld, & Hanks, 1997). People with double depression are moderately depressed on a chronic basis (meeting, symptom criteria for dysthymia) but undergo increaved problems from time to time, during which they also mest ria for a major depressive episode. Among, clinical ‘samples of people with dysthymia, the experience of dou- ble depression appears to be common, although it may be much less common in people with dysthymic disorder who never seek treatment (Axiskal, 1997). For example, one clinical sample of nearly 100 individuals with early onset dysthymia (onset before age 21) were followed for 5 years, during which time 77 percent experienced at least tone major depressive episode (see also Keller et al, 1997; Klein et al, 2000). Although nearly all individuals with double depression appear to recover from their major depressive episodes (at least for a while), recurrence is ‘common (Boland & Keller, 2002; Klein etal. 2000). DEPRESSION AS A RECURRENT DISORDER When a diagnosis of major depressive disorder is made, itis usually also specified whether this is a first and therefore single terpersonal rejection. ~ aCHAPTER 7 Mond Disonlersand Suicide (initial) episode or a recurrent episode (preceded by one or more previous episodes). This reflects the fact that depressive episodes are usualy tive-lim= iteds according to DSM-IV-TR, the average dura tion of an untreated episode is about 6 months. In 2 large untreated sample of depressed women, cer tain predictors pointed to a longer time to spon! Reous remission of symptoms: having financial iffculties, severe stressful life events, and high ‘genetic risk (Kendler, Walters, & Kessler, 1997). In some cases major depression does not remit for ‘over 2 years, in which case chronic ‘major depres- sive disorder is diagnosed, Although most depressive episodes remit (which is not said to occur until symptoms have Femitted for at east 2 months), depressive episodes ‘usually recur at some future point. In recent years, Fecurrence has been distinguished from relapse, ‘where the latter term refers to the return ‘of symp- toms within a fairly short period of time and prob- ably reflects the fact that the underlying episode of depression has not yet run its course (Boland & toe iil rte lites or thos n he see empha mre eto eR scsonl eft day rich dpesson ccs rina nthe llard winter months ndten remit in the spring or sumer months. Keller, 2002; Frank eta, 1991), Relapse may com- monly occur, for example, when pharmacotherapy is terminated prematurely after symptoms have remitted but before the underlying episode is really over (Hollon tal, 2002a, 2002b; 2008). The proportion of patients who will exhibit a recur- rence of major depression is very high (about 80 percent, according to Judd, 1997), although the time period before a recurrence occurs is highly variable. In one very large national study of over 400 patients across 5 sites followed for more than a decade, 25 to 40 percent had a recurrence within 2 years, 60 percent within 5 years, 75 percent within 10 years, and 87 percent within 15 years (Boland & Keller, 2002; Keller & Boland, 1998). There is also evidence that the probability of recurrence increases with the number of prior episodes. The traditional view was that between episodes, per- son suffering from a recurrent major mood disorder is ‘essentially normal. However, as more research data on the course of depression became available (e.g, Coryell & Winokur, 1992; Judd et al, 1998), it became clear this is frequently not the case. For example, in a large 5-site study with over 400 patients, Judd et al, (1998) found that even patients experiencing their first episode at the time the study began showed no symptoms at all during only 54 percent of weeks during a 12-year follow-up period, rela- tive to only 37 percent showing no symptoms among those experiencing a second or later episode at the start of the study. Moreover, people with some residual symptoms, and/or with significant psychosocial impairment, follow- jing an episode are even more likely to have recurrences than’ those whose symptoms remit completely (Judd, Paulus, Zeller, eta, 1999; Solomon et al, 2004). SEASONAL AFFECTIVE DISORDER Some people who experience recurrent depressive episodes show a seasonal pattern commonly known as seasonal affective disorder, ‘To meet DSM-IV-TR criteria for recurrent major depres sion with a seasonal pattern, the person must have hat least two episodes of depression in the past 2 years occut+ ring at the same time of the year (most common; fallor winter) and full remission must also have occured atthe same time of the year (most commonly, the sprin addition, the person cannot have had other, nons depressive episodes in the same 2-year period, and most of the person's lifetime depressive episodes must have been of the seasonal variety. Prevalence rates suggest that winter seasonal affective disorder is more common in people living at higher latitudes (northern climates) and in younger people. > What are the major features that differentiate dysthymic disorder and major depressive disorder? _| > What are three common specifiers of major depressive disorder? > Distinguish between “recurrence” and “relapse,”causal FAcTORs IN ‘x]POLAR Moop pisORDERS _paderag the development of unipolar mood disor persion bee feed onthe pole roles of bo. So sod sociocultural factors. Although Sie cen Bas eal Been Tied separate at koe gee sock! be to undentand how thes fer factors are interrelated, in onder to 3 ppopnchosocal model, soiogical Causal Factors pus beg bees known that a variety of diseases and drugs EBE= mood keading somtimes to depresion and Boo daton or even bypomania Indeed, this idea ‘Shes w Hippocrates. who hypothesized that depres. BB ssaassed by an cxcess of “black hile" in the system spose As we will discuss, in the past half-century szempting to establish a biological bass for Sree cecrdess have considered a wide range of factors. ¢ GexETKC INFLUENCES Farsi studies have shown that Sipsuence of mood disorders is approximately three Sather emong blood relatives of persons with clini- Sspesed unipolar depression than in the popula- z= = ie (eg. Sullivan, Neale, & Kendler, 2000; "ele Scineider, & McGuifin, 2002). More importantly, tere: i mudies, which can provide much more con- — netic influences on 2 disorder, also, =e. “contribution to unipolar \ ‘twin: Sollivan et al (2000) did a quantitative review — Ftestin studies (the tral numberof tins sud ‘= sazorer 21,000) and found that monozygotic co-twins ¢apei with unipolar major depression ase about tice, Bdywadevelop majordepressionas ( 7.) —W2-/. seEzpticco-twins Averagingacross | 7 ‘eral of these studies, this review ‘sags that about 31 to 42 percent “fe variance in lability to major ‘ration was due to genetic influ- ‘adoption method Canal Factors in Unipolar Mot Disorders tion studies on mood disorders published thus far, the most adequate one (Wender etal, 1986) found that wnipe~ lar depression nccttied about seven-timesmore offen in EBs iwesof-the severely depressed adoptees than in the biological relatives of control adoptees (Wal- lace et a 2002; Wender etal, 1986). Taken together, the results from family, twin, and adoption studies make a steongcase for amoderategenctis sal patterns of-unipolar major, ution as for bipolar disorder (Farmer Eley. Met lace etal, 2002), However, the evidence for a genetic con= tribution is much less consistent for milder but chronic forms of unipolar depression such as dysthymia, with some studies finding no evidence of genetic contributions (Roth & Mountjoy, 1997; Wallace et al, 2002), Finally attempts tg identify specifi genes that may be responsible for these genetic luences have not yt been success although there are some promising leads (Plomin et aly 2001; Wallace et al, 2002). gene involved in the trans toni, which is one ofthe key neurotransmitters involved in depression, There are two different kinds of versions or alleles involwed—the short allele (5) and the tong allele (Dy and people have two short alleles (5s), two long alleles (12), oF onc of each (sl). Prior work with animals had suggested that having ssalleles might predispose to depression rela~ tive to having alleles, but human work on this iste had provided mixed results. In 2003, Caspi, Sugden, Mofit, and colleagues published a landmark study in which they tested for the possibilty ofa gene-environn involving this erotonin-transporter gene (see Chapter 3). ‘They used 847 people in New Zealand who had been fol- lowed fom birth until 26 years of age, at which time the researchers assessed diagnoses of major depression in the past year, and the occurrence of stressful life events in the previous 5 years. Their results were very Hiking: fadviduals who possesed the ssalleles Were twice as likely to develop lepression following four ér more stress- ful life events in the past 5 years as those Who possessed the Ilalleles and had four interaction ‘=e The estimate was even higher for ‘bac serere, recurrent depressions. ‘Scubly however, the same review con- ued that even more variance in the ‘SSiey to major depression is due to ‘ interact with other disturbed hormonal and nexroptrs logical patterns and biological ripthms (2. Gaiow Nemeroff, 2003).An interesting new focus of some o> Fewearch is on understanding how interactocs <= these different neurobiological stems ax EOE resilience in the face of major stress (a very comico Gipitant for depreuion}, which in num may bee Fo why only a suet of people undersoing mice depression (Southwick et al 2005).MAUTIES OF HORMONAL REGULAT: hormonal causes or correlates of some for rater i ss a 10044 aly 2002). The tnajority of attention has bec, jon the ypothalamic-pituitary-adrenal (HPA) aie ‘p particular on the hormone which is 2% gel bythe outermost portion ofthe adrenal glands aig regulated through 9 complex feedback loop (ace we! in Chapter 3 68 Howland & Thase, 1990). As Fie yedin Chapters 3,5,and 6 the human stress response Sociated with clevated activity of the HDA axis, which ly controlled by horepinephrine and serotonin. The n of stress or threat can lead to norepinephrine re : ity inthe hypothalamus, causing the release of conte Sossamon CRE fo thel poe Srvbich in turn triggers release of adrenocorticatrophie pomane (ACTH) from the pituitary. The ACTH then typ= JAllrtravels through the blood to the adrenal cortex of the.» ‘areal gands where etal is released. Blood plasiita els of cortisol are known to be elevated in som to 40 ~ Fit of severely depressed hospitalized patients (Thase al, 2002). Sustained elevations in cortisol can result from increased CRH activation (for example, during sus- no8! i isp ‘Causal Factors in Unipolar Mood Disorders tained stress or threat), increased secretion of ACTH, oF the failure of feedback mechanisms. See Figure 7.2. ‘One line of evidence that implicates the failure of feedback mechanisms in some depressed patients comes from robust findings that in about 45 percent of seriously depressed patients, a potent suppressor of plasma cortisol in normal individuals, dexamethasone, either fails entirely to suppress cortisol or fails to sustain its suppression (Thase et al., 2002). This means that the HPA axis is not ‘operating properly in these “dexamethasone nonsuppres- sors” It was initially thought that DST nonsuppressor Patients constituted a distinct subgroup of people with severe or melancholic depression (Holsboer, 1992). How- ever, subsequent research showed that several other groups of psychiatric patients, such as those with panic disorder, also exhibit high rates of nonsuppression. This suggests that nonsuppression may merely be a nonspecific indica- tor of generalized mental distress. Recent findings have revealed that depressed patients with elevated cortisol also tend to show memory impair- ‘ments and problems with abstract thinking and complex problem solving (Belanoff et al., 2001). Some of these cognitive problems may be related to other findings showing that prolonged elevations in cortisol such as seen in moderate to severe depression result in cell death in the Patient with Major Depression Other regulatory factors Normal Subject Other regulatory FIGURE 7.2 Response to Stress in a Normal Subject and a Patient with Major Depressive Disorder In normal subjects and in patients with ‘major depression, periods of stress are ‘typically associated with increased levels of both cortisol and carticotropin- releasing factor. Corticotropin-releasing {actor stimulates the production of corticotropin, which in turn stimulates the production of cortisol. Cortsal Inhibits the release of corticotropin from the pituitary and the release of - Whatis the role of stressful life events in inipolar depression, and what kinds of datheses have been proposed to interact vith them? > Descibe the following theories of depression: Beck's cognitive theory, the helplessness and ss theories, and interpersonal \BIPOLAR DISORDERS ‘plr disorders are distinguished from unipolar disorders ‘nthe presence of manic or hypomanic symptoms. A pet- ‘a who experiences a manic episode has a markedly cle~ ‘ed, cuphoric,and expansive mood, often interrupted by fis outbursts of intense irritability oF even ve> particularly when others refuse to go along with bipolar Disorders person's wishes and schemes. These extreme ‘moods must persis for at least a week for this diagnosis 10 bbe made, In addition, three or more additional symptoms must occur inthe same time period. There must ako be significant impairment of occupational ancl social func sind. hospitalization is often necessary during manic episodes. In milder forms, st 10 a diagnosis of hypon experiences abnormally elev ‘mood for at least 4 days. In addi at least three other symptoms simi mania but to a lesser degree (cf inflated self-esteem, decreased need for sleep lights of ideas, pressured speech, etc.) Although the symptoms listed are the same for manic and hypomanic episodes, there is much less impairment in social and occupational functioning in hypomania, and hospitalization is not required. 1 kinds of symptoms can lead nic episode, in which a person rated, expansive, of irritable n,the person must have lar to those involved in Cyclothymic Disorder It has tong been recognized that some people ae subject to cyclic mood changes les severe than the mood SSvngs see in bipolar disorder These are the symptoms Of the disorder known as eyeothymic disorder. In DSM-iv-TR, eyclothymia is defined asa less serious ver~ Sion of major bipolar disorder, minus certain extreme Symptom and payehotie features, such as delusions, and aimee the marked ‘impairment caused. by fallblown tmanie or major depresive episodes. Inthe depressed phase of eyclothymic disordes a per- sons mood iusjsted an he o sh experiencesa dstinet loss of interest or pleasure in customary activities and pas- times n aio the person may show other symptoms Aah as Tow energy, feelings of inadequacy, socal with- tawal and » pessimistic, brooding atitude. Essential the symptoms are similar to those in someone with dys- thymfa except without the duration criterion Symptoms of the hypomanic phase of cyclothymia arecatentally the opposite of the symptoms of d)sthymia. Inthis phase ofthe disorder, the person may become espe Gilly creative and productive because of increased phy Gal and mental energy. There may be significant pes treween episodes in which the person vith eyelothyi functions ina elatively adaptive manner. For a diagnosis (feyelothymia, there mast beat least a 2-year span during sihigh there are numerous periods with hypomanic and depressed symptoms (1 year for adolescents and. ch deen) and the symptoms must cause clinlly significant istres or Impairment in functioning (although not as Severe ain bipolar disorder). (Sethe DSM-IV-TR table, Giteria for Cyelothymic Divorder) Because individuals with epelothymia ate a increased tisk of later developing full-biown bipolar disorder (eg Akiskal & Pinto, 1999), DSM-IV-TR recommend that they be treated “The following case illustrates cylothymia. 1253