Biochemical Profile of Depressed Adolescents

Biochemical Profile of Depressed Adolescents AMAN U. KHAN. M.O . Abstract . Eighty-four adolescents between the ages of 13 and 17 were investigated with the help of dexamethasone suppression test (DST ). thyrotropin releasing hormone stim ulation test (T RH I. and 24· hour urin ary co nten t of J-methoxy-a hydr cxy-pheneth ylene glycol (MHPG) . This grou p included 33 depressed (majo r dep ression) ami 5 1 nond eprcsscd adolescent s who were hospitalized in a psychiatri c inpat ien t unit. DST was found to he a highl y sensitive and fairly specific test (69.9% of the depressed group was DST positive. whereas R2% of the nondcpressed group was DST negative). TR H stimulation test and urinary MII PG tests did not show significan t sensitivit y or specificity for major depress...ion . Thi rty-three percent of the major depression and 17.6% of the nondepressed group showed blunted response on TR H stimula tion test. Similarly. 56.6% of the major dep ression group and 41 % of the nondepresscd group had MHPG values beyond the normal range . J. Amer. Acad. Child Adol. Psychiat.. 1987. 26. 6:873-878. Key Words: major depression. dexamethasone depression test. urinary MHPG . TR H test.

Th e suhjcc t of ado lescent de pression has been shro uded in co nt roversy becau se of the supposed difficulti es in un ravelling the problem of "adolescent turmoil ." Whereas so me authori ties contend that adolescen t depression is an identifiable diagnostic entity similar to that seen in ad ults (Carlson and Strober. 1979). others argue t hat extra po lation of adu lt depressive phenom enology to young persons is highly fallible (G laser. 1967). Several epide mio logical studies indica te that tran sien t symptoms of depression appea r to be q uite co mmon in ado lescents a nd probably reflect their stage of developme nt. Prevalence of persistent sympto ms of depression a ppears to be quite close to reported ligures for adults. however. Schoenbach et a\. ( 1983) measured dep ressive sympto ms in 624 young adolescents (ages 12 to 15) on the Center for Epidemio logic Studies Depressio n Sca le. Reports of depressive sympto ms wit hout regard to durati on were quite frequ ent in ado lescents. ran ging from 18% to 76% in white boys. 34% to 76% in white an d black girls. a nd 14% to 85% in black boys. Prevalence of persiste nt sympto ms ranged I % to 15% in male adolescents and 2% to 13% in fema le ado lescents. howeve r. Onl y a few studies of hospital ized adolescen ts have investigated bioch emi cal a nd electro physiological paramete rs of depression . such as dexam ethason e supp ression test (DST). thyrotropin-releasing hormone stim ulatio n test (T R H). urinary 3-methoxy-4 hydrcxyph encthylcnc glycol (MHPG ). and po lysorn nography. In a chan review stud y of 100 hosp italized adolescents who were adm inistered DST. Crumley et al. (1982) found that 42 of the adolescents were OST positive. Six of the 42 ado lescents had no evide nce of depression a nd were false pos itive ( 14.2%); however. Extein et a\. ( 1982) found that 8 of 15 hospitalized depressed adolescents were OST positi ve. whereas o nly I o r 12 nond eprcsscd co ntro l subjects was OST positive. Hsu et a\. (1983) . found 9 of 14 hospitalized de pressed ado lescents and 15% of the co ntro l subjects to be OST positi ve. Robbins and Alessi (1985) reported 5 of 18 hospitalized suicidal ado lescents with major depressio n to be DST positive. These studies ind icate tha t positi ve results of DST are quite variabl e in ho spitalized

depre ssed adolescents. ranging from 30% to 65%. False positives also tend to be higher in this gro up than those report ed in adu lt popu lations (Carro ll et ul., 1981). Thi s variability. in part . reflects dilliculties in clinical diagno sis of de pressio n in ado lescents. Most studies of TRH tests have been don e in de pressed ad ults. and no info rmat ion has yet been available on any large sam ple of depressed adolescents. Loosen an d Prange ( 1982) summarized 41 studies of917 depressed patient s who were subjected to the TRII test. Five studies in volving 36 pat ient s were negat ive. Positive results varied from 20% to 77%. Kirstein et a\. ( 1982) tested 25 pati en ts (aged 19 to 7 1 years). Ten of 13 un ipolar depressed pat ient s a nd 2 of 12 bipo lar pati ent s showed blunted respon se to the TRII test. Sternbach et a\. ( 1985) tested 12 un ipo lar and 10 bip olar pat ients. Th ree or 12 unipolar (all men) showed a blunted respon se to the TRII test. but non e of the bipolars was positive. Blunted respon ses to the TRH test. in the abse nce of usual endocri ne ex plana tions. have been report ed in 5% of the normal subjects (Anderson et a\. 197 1). The importance of the T RII test in distinguishing gro ups of depressed pati ents remain s co ntro versial beca use some investigators believe that only a min orit y of patients with uni polar depression show a blunted respon se (Hollister et al., 1976; Loosen et al.. 1977; Prange et al., 1977; Takahashi et al., 1974)_ whereas oth er investigato rs mai ntain that TRH tests ma y be useful in co nfirming the diagno sis of major depression (Gol d et al., I980 b). Th e TRH test is influenced by several factors that may produce variable result s. For example. TRH-induced th yroidstimulating hormone (TS H) respon se is redu ced with increasing age (Snyder a nd Utiger. 1972); being ma le (Noel et al ., 1974); acute sta rvation (Ca rlson et al., 1977); chro nic rena l failure (Czernie how et al.. 1976 ); Klin efelter' s syndro me (Ozawa a nd Shish iba, 1975); repetit ive ad ministratio n of TRH (Staub et al., 1978); administrati on of so matos tatin, neur orcnsin, dopamine (Spau lding ct al.. 1972); thyroid hor mo ne and glucoco rticoids (Otsuk i et al., 1973). Blunted response is a lso observed in anorexia nervosa (Go ld et al., 1980a ) and alcoh olism (Loosen et al., 1979). Another source of variation amo ng TRH studies is the crite ria for positive results (blunted respon se) used by different studies, Definition of blunting has varied from a max imal change in TSH less than 2.5 UIU/ ml to 7.0 U IU/ ml (Gol d et al., 1981; Sch ildkraut. 1965). Obviously. the definit ion of blunting will influ ence the freq uency of positive result s.

Received Ma}' 4, 1987; revised June 29, 1987; accepted Jllly 16, / 98 7.

Dr. Khan is Profe.'i.m r and Chief Division ofChild and Adolescent Psychiatry. Southern Illinois University School of Medicine. P.O. Box 3926. Springfield, IL 62708......here reprints ma.1' be requested. 089O-8567/8 7/2606-1>873$02.00/0 ©1987 by the American Academy of Chi ld and Adolescent Psychiat ry. R73

874

KII AN

A great deal o f resear ch in th e affective di so rders has bee n moti vated by the advance me nt of monoam ine hypothesis. which p rop osed that the affecti ve disord ers are caused by fun ction al cha nges in the central mon oam in e ncurut ran smitters, T his hypothesis has found support in the pha rmacological usc o f reserpine. tr icyclic a ntide pressants. and mo noa m ine oxidase in hibitors. which affect ca techo lam ines and indolami ncs. However. measurem ent of ca techo lam ine precurso r tyro sine. the ca tccho Jami nes (do pa mine and norepinephrin e). and th eir me tabolites horn ovanillic acid (H VA). van illylmandelic acid . an d MHPG in th e hlood . urine. a nd spina l fluid or dep ressed pa tients have prod uced inco nsiste nt results. Bim odal d istri bution of th e urinary excretio n of M HPG appears to be a co nsisten t find ing in a group of de pressed patien ts (Berger and Barchas, 1977). however . Seve ra l investigators ha ve suggested that th ere a re at least two gro ups of dep ressed patien ts who ca n be sepa rated neuroch emi call y (Maas, 1975; Sch ildkraut et al., 1981 ). On e or th ese grou ps appears to have an abno rm ality in noradren ergic system as suggested by decreased levels of urina ry MHPG . Forty to sixty pe rce nt of urinary MIIPG o riginates in th e central nerv ou s system fro m the metabolism or cen tra l norepinephrine (Maas et ul.. 1979). Seve ral inv estigat ors have attempted to rep licat e th e findin g of decr eased uri nary MHPG excretion in depressed ad o lescents (Cytryn et a l., 1974; McKnew and Cy try n, 1979). Inco nsisten t findi ngs a nd possible group hetero geneity based o n differen ces in diagnostic cri ter ia. however . have led to th e co nclusio n that furt her in vestigat ion is nece ssary before a de fin ite stat em ent uhu ut noradrenergic fun ctioning in depressed children a nd adolescent s ca n he mad e (Low e and Cohe n, 1983). To our know ledge. ado lescent depression has not heen stu d ied with multiple bio logical tests to determine sensitivity and spec ificity. Th is study was designed to inve stigate three o f the biolo gica l markers that have been shown to be o f some sign ifica nce in depression . Hypothalamic-p ituitary-adren al axis d ysfun ction. norep inephrine metabolism were invcstigated with th e help or DST. TRII . and urin a ry co nte nt or MHPG. Method

Subject s A total of 106 ad olescents, ad mi tted to an in pati ent psych iatric unit during a peri od o f I I m onths. were assessed for parti cipati on in thi s study. Fifteen ad olescents refused to participate, Seven others were excl uded because of th e medi cal exclusio n c riteria for DST and TRH tests (Ca rro ll et al.. 1981; Loosen and Pran ge. 1982 ). such as pregnan cy. severe weight loss. d iabetes. acute withdrawal from alcoh ol. use of m ed ication s suc h as ben zod iazepines. neurolepti cs, lith ium. and birth co ntrol pills. The rem ain ing 84 subjects wh o part icipated in the study incl ud ed 37 boys and 47 girls between thc ages or 13 and 17 (X. 16 .17; S.D .. 1.4). Th e nonpart icip ants included 10 boys a nd 12 girls bet ween the ages of 14 o r 17 (X. 16.2; S.D .. 1.2). Th e dia gno stic categories of th e nonparticipants included conduct disord ers ( 13 subjects ). substance abuse disorders (3). o rgan ic brain synd ro mes (2). att ent io n deficit d isorder wit h hype ractivit y (I). major depression (J) . S0 I11 3 toform disorder ( 1). and bor derli ne perso nality disord er (I).

This group was fairl y simi lar to th e pa rtic ipa nt grou p. with the exce ption o f a higher pro portio n of co nd uct di sord er dia gnoses in thi s gro up (59 % versus 26%). Diagnostic categories of the participan ts are listed in Ta ble I . No ne of th e parti cipants was ta king an y medi cation at th e time of ad mission or du rin g th e first 2-wcek pe riod of evalua tio n.

Clinical Evaluation Diagnosis was based on informa tion derived fro m exte nsive famil y and indi vidu al intervie ws. collatera l information from schoo l and co m m unity age ncies if invol ved. an d ward obscrvation of the ado lesce nt by the hospit al sta ll. Spec ific qu estions were as ked in se mistruc tured inte rviews to elicit in format ion a bout th e signs a nd sym ptoms incl uded in th e DSMIII criteria o f dia gnosis of majo r depression and o ther di sorders. T he interviews were co nducted by child psychiatry fellows and th e att ending psychi atri st. Su bjective assessme nt of dep ressio n was mad e wit h th e help of Beck's depression inventory. which was filled o ut by eac h ado lescen t at th e tim e of ad m ission. Hamilton 's Depression Scale was used to rat e th e seve rity of depression . Initial sco res o n Beck' s and Ham ilton's scales are listed in Table I. The scores o n Beck 's inventory are speciall y not eworthy. About o ne third o f the adol escents with major depression scored less than 15. ind icating an abse nce or presen ce of mi ld depression . This situation. however. changed 2 wee ks later when a seco nd assessmcnt on Beck's inventory revea led sco res that were co nsistent wit h moderate to severe deprcssion . Final dia gno sis was made in a m ultidisciplin ary teac hi ng co nfere nce. held by the end of 2 weeks of hospitali zatio n. DSM-III diagno stic criteria were used for mak ing th e diagno sis in all cases. The pat ient s were gro uped on the basis o f primary dia gno sis. Th e seco nda ry diagnoses of co nd uct di so rders. schizo id d isord er. o ppositiona l disorder. etc. were quite co m m o n. Ho wever. maj or depression . if present. was always th e prima ry diagnosis. irres pective of other seco ndary di agnoses. The ad olescents with co nd uct disorders and substa nce ab use disord ers were carefully evalu ated to rule o ut majo r depression . A seco ndary diag nos is of conduct di sord er was given to 12 of th e ad olescents with major depression (36 %). T he seco ndary d iagnoses in primary co nd uct d isorde r gro up included schizoid disorder (3 suhjccts) and dys thrnic disorder (4 su bjec ts), Fou r or five subjects in primary atte ntio n deficit gro up had co nd uct disorde r as seco ndary d iagnosis. Prim ary substa nce ab use di sorder gro up co ntai ned seco ndary d iagnoses of dys thy mic disorder (3 su bjec ts) a nd schizoid diso rde r (2 subjects). Axes 1\ and III were give n no d iagnoses. excep t in two cases whe re bron chial asth ma was listed o n Axis III.

Neuroendocrinological 1'eJI.'i T hese tests included th yrot ro pin-releasing horm one stim ulation . dexamethasone supp ressio n. a nd 24-ho ur urinary MIIPG . These tests were d un e du rin g the first 10 da ys o r hospitali zat ion . The TRH test was done first. DST I da y later . and MHPG 3 da ys afte r DST tests to avoid influencing th c tests o n each other.

TR II Test Arter an overnight fast. 500 ~g of synthetic TRH (p ro tireline) was given intravenously over 30 seconds. and fou r blood

BIOCH EMICAL PROFIL E

or

sampl es were taken at baseline. 15-min. 3D-mi n. and 60-min interval s after the injecti on. The baselin e blood sampl e was tested for levels of TSH. Tot. and T J uptake. The other three sampl es were tested for levels ofTSH . Th e greatest increm ent in TSH from baseline (max ~ TSH ) was used to assess TSH response. TSH levels were measured with radioirnmun oassays (Abbo tt Laboratorie s Kit , HTSII RIABEAD).

DST One milligram of dexamethasone was given ora lly at I 1:00 Blood sam ples for cortiso l were d rawn th e next day at 4:00 P.M. and 11:00 P.M. Co rtisol values over 5 pg/m l in any of the samples were co nsidered abno rmal (fai lure to suppress or DST positive). P.M.

Urinary Jllll'G A 24-hr urine collection was obtained in a standardized mann er by the nursing staff abo ut a week or more after ad missio n. Samples of low volume «500 mlj24 hr ) were discarded. Sodium mctabi sulfite. 0.5 g was added to each urine sample as a preservative for MHP G. and the samples were refrigerated immediately after vo iding. The samples were frozen and were later tested for MHPG by electro n-capture gas-liquid chromatography according to the method of Dekirmenjian and Maas (1970). Thirty-nin e of the subj ects completed a 24-hr urine co llectio n; the rest of the samples were discarded as the y were incomplete because of lack of patients' coo peration with the procedure . All the tests were carried o ut by one lahoratory. Results

There was no significant difference between the 22 nonparticipant s and the 84 participant s with regard to age and sex . Th e nonparticipant group, however, includ ed a greater proTA 8U: I.

87 5

DEPR ESSED ADOLESCENTS

portion of adolescents with co nd uct disorders than the participant gro up. Tabl e I shows the dem ographi c data o n all experimen tal subjects, which are grouped into seven diagno stic categories. Th e first six group s are categorized on the basis of primary diagno ses (DSM-III criteria). The seventh gro up is heterogenous and contains o ne o r two ado lesce nts from several diagnostic catego ries such as so mato form disorder, separation anxiet y disorder, o veranxious disorder. and schizo id disorder. One-way analysis of variance of the data indicated that there was no significant difference amo ng the groups with regard to the ages of the subjects. The group with major depression co ntained a significantly higher num ber of female subjects (78.8%), and the atte ntion deficit a nd substancc ab use gro ups co ntained a signi ficantly higher num ber of male subjects. Th e sco res o f Beck's Depression Invent ory we re significantly higher in the group with major de pressio n than the ot her gro ups ( P < 0.005). T he result s of DST, TRH stim ulatio n test, and 24- hr urinary content of MHPG a re presented in Ta ble 2. DST was co nsidered positi ve when o ne or both cort isol values were abo ve 5 pg/DL. Th e criterio n for TRII positive test was established at a maximal increase in serum TSH abo ve baseline (max~TSII) to be equal or less than 7.0 U IU/ ml. No rmal values of MHPG were set by the laborato ry (International Clinical Laboratories) at 1.1027 to 1.647 mg/24 hours for fema le subjects and at 1.164 to 2.2 16 mg/ 24 hours fo r ma le subjec ts. Any values abov e o r below these ranges were co nsidered abnormal and, possibly, indicative of depression . Several of the diagnostic groups that co ntained onl y on e or zero subjects with positive test results were co mbined for statistical analysis. The data were co mpared in two ways. First. the major depression group was co m pared with the rest of the six groups co mbined. Chi-square anal ysis o f these data (Table 3) indicated that the majo r depression group was

Demographic DOlO. Scores on Beck 's lnvrntnrv, and Hamilton Depression Scale 011 J'ariolls Diugnostu:Grollp,\"

Diagnostic Categories

Major depression Conduct disorders Dysthymic disorder Adjustment disorders Substance abusedisorders Attention deficit disorders Otherdiagnoses T ARI.E 2.

Beck's Inventory Scores

Sex

Age

No. of Patients

33 22 6 6 7 5 5

Hamilton's Scores

Mean

S.D .

Male

Female

Mean

S.D .

Mean

S.D .

15.09 14.70 15.0

0.04 1.57 0.8t 1.06 lAO 0 .75 1.36

7 13 I 3 5 5 3

26 9

17.36 8.00

22.15

6.56

5

12.00

3 2 0 2

9.00 11.00 6.00 8.00

10.73 4.1 5 4.H9 3.62 4.63 3.64

15.2 15A 13.8 14.6

4.82

Results (% Positive} 0/ DST, TRJJ-7i.'.{I. and 24 -JJour Urina ry .\lHPG in J'arious Diagnostic Groups

Diagnostic Categories Major depression Conduct disorders Dysthymic disorder Adjustment disorders Substance abuse disorders Attention deficit disorders Other diagnoses

No. of Patients 33 22 6 6 7 5 5

DST (% Positive)

69.7 13.6 16.7 0.0 14.3 20.0 40.0

24-Hour Urinary MHPG (% of Samples)

TRlf Test (% Positive) 33.0 22.7 0.0 16.7 42.9 0 .0 0 .0

» Expected

< Expected

Normal Val ues

12.0 13.6 16.7 0.0 28.6 20.0 20.0

39.4 4.6 16.7 16.7 28.6 20.0 40.0

48.5 81.8 66.6 83.3 42.8 60.0 40.0

876

KHAN

significantly different from the rest of the groups with regard to DST (P < 0.000 1). T here was, however, no significa nt difference between these two groups with regard to TRH stimulation test and 24-hr urinarycontent of MHPG. In a second analysis, the seven groups were combined into three groups (majo r depression, dysth ymic disorde r, and the rest of the five groups combined into a nonaffectivc disorder group). Chi-square ana lysis of th ese data Crable 4) indicated that the depression gro up co ntained a significantly higher number of ado lescents with DST positive than the other

groups. There was no significant difference among the three groups with regard to th e TR H test and MHPG levels. S ensitivity and Specificitv ofthe TeJlS Sensitivity of a test ma y be defined stati stically as the proportion of positive results in the presence of disease. Similarly, specificity of a test ma y be de fined as the proporti on of negative results in the absence of disease. Chi-square analysis of the data fro m depressed and nondepressed patients indicated that the DST test is Quite sensitive and fairly specific (69 .9% of the depressed gro up was positive, whereas 82% of the nondeprcsscd group was negative). These 3. Comparison a/Majo r Depression Group With Other Diagnostic Groups Combined {Chi-square Analysis)

T ABU:

Major Dep ression

Tests

(N ~

Other D iagnoses (N~ 5 1)

33)

DST -positive DST-negative

23 10

8

T RH-positive T RH-negative

II

9

22

42

43 P = 0.000 I

N5" MHPG Normal values Greater than expected Less than expected

19

11 4 t4

10

17

NS e

NS. no nsignificant results. T ABLE 4 .

Comparison ofThree Diagnostic Groups Wlth Chi-square Analysis

Major Tests

Depression (N ~

33)

Dysthymic Noneffective Disorder Disorders (N ~

6)

DST-pos itive DST-ncgative

23 10

1 5

TRH -positive T RH-negative

II

/' = 0.0236 o

MJlPG No rmal values Greater than expected Less than expected " NS. no nsignificant results.

22

11 4

14

6

45)

(N -

7

38 P

~

0.000 1 9 36

NS·

NS

3 1 1

16 9 16

NS

NS

results were highly significant (P ~ 0.000 I ). T RH stimulation test and 24-hr urinary MHPG did not show significant sensitivity or specificity for depression. however. In the depressed group, all three tests (DST, TRH, MHPG) were positive in six patient s (20.6 %), a nd DST and MHPG were positi ve in 12 patient s (42.4%). T R H and MHPG were positive in six patients (20.6%). In the nondepressed group, none of the patients had all thr ee tests positive; two tests (DST a nd MHPG ) were positive in four patients ( 10%). None had both DST and T RH or MHPG a nd T R H positive. Furt her analysis of the patients in both gro ups that had completed all th ree tests (DST, TR H, a nd MHPG ), indicated that the depressed group had an average of 1.63 tests positive, whereas the nond epressed group had 0.89 tests positive. T his difference was significant ( P = 0.0007). Discussion

The proportion of adolescents with major depression in our po pulation (33%) is comparable with the findings of several studies of hospitalized adolescents (H udgen s, 1974; Kin g and Pillman, 1969). A diagnosis of depression is generally difficult in most ado lescents at the time of admission . Most adolescents do not want to be hospitalized, even after serious suicidal atte mpts . Th ey den y or hide their depressed feelings for fear of prolonging their hospitalization. The diagnosis of depression is further complicated by the presence of conduct problems such as aggressive activities, running away. stealing. and defiant behavior. which are frequently present in these adolescents. Thirty-six percent of our depressed adolescents carried a secondary diagnosis of conduct disorder, which is consistent with several previous reports(Marriage et al.• 1986). It ta kes at least a week or 10 da ys befo re man y of these adolescents accept the support from milieu staff and begin to recognize and/or admit to their depression. Observations of these adolescents in the hospital with regard to their interests. peer interactions, sleeping and eating habits. level of energy. and verbalizations are most helpful in making diagnosis of depression. DST was positive in 69.9% of depressed ado lescents. Thi s figure is comparable with several studies of DST in depressed hospitalized adolescents (lIsu et al., 1983; Robbi ns a nd Alessi, 1985). False positive DST in our group was 18%, which is also eompa rahle with results repo rted by other studies (Crumley et al., 1982; Hsu et al., 1983). False positive DST has been reported in various medical conditions such as Cushing's disease, uncon trolled diabetes, temporal lobe epilepsy, major physical illness. pregnancy. acute withdrawal from alcohol. anorexia ncrvosa, severe weight loss, and use of medications (such as phenytoin sodium. barbi turate, and meprobamate). Our selection criteria excluded adolescents with the above medical conditions. None of our patients were diagnosed as anorexic. The weight loss from depression was generally minima l (5 to 10 po unds). In fact, the adolescents with majo r depression tended to gain some weight rather than lose it. Although one third of the depressed adolescents showed a blunted response to TRH test. this finding was not significant when compared with the results of the nondcpressed group (which showed blunted respon se in 17%). T he factors co ntributing to low sensitivity ofTRH stimulation test in adolescents

BIOCH EMICAL PROFILE OF DEPRESSED AIXl I.ESCENTS

are unclear. It appears that the criteria for blunted respon se suggested by Gold et al. ( 1980b) ma y be 100 stringent for diagnosing adolescent depression. Mo re studies of normal popu latio ns are necessary to clarify the normal ran ge of TSH response to TRH sti mu latio n test among adolescen ts. Studies of ur inary M HPG have led 10 the hypothesis that depres sion ca n be biochemically an d pha rmacologica lly divided into at least two types (Schildkraut et al., 1978). One type is characterized by smaller amounts of urinary MHPG and a favorable response to imipramine o r desipramine . Th e other type has large qu antities of urinary MIIPG a nd a favorabl e response to amitriptyline. The pat ients with low levels of urinary MHPG ma y have decreased norepinephrine activity in the central nervous system . Our da ta indi cate that urinary co ntent of MHPG beyond the normal range is not specific to depression but appears to be prese nt across all diagno stic categories in adolescents. Davis et aI., (1981) , in a study of 42 adu lt depressed pati ents. reported that both cortisol elevati on and TSH blunting were assoc iated with low urinary MHPG excretion . In our study, o nly 47% of the depressed pati ents with positive DST a nd 55% of the depressed pati ents with blunted TS II respo nse had low MHPG excretio n, Biochemical studies of the brain a nd their relati on ship to mental disord ers have led to an extensive search for labo rato ry markers that ca n be used in th e dia gnosis and predi ction of treatment of these disorders. More than a dozen laboratory tests, mostly pro posed for affective disord ers, have found so me clin ical applicabi lity in psychiatry (Gre den , 1985). Sensitivity and specificity of th ese tests remain low. however. It is possible that with better classificati on of psychiat ric disorders and more stringent criteria for selectio n of pat ients, these tests may becom e more useful in psychiatry . At present. DST appea rs to be a sensitive laboratory aid in the diagnosis of major depression. Various parameters a nd normal values of the TRH stim ulatio n test appear to be less well defined for the adol escent populatio n. A grea t deal of normal data are required before this test may beco me helpful in diagnosing adolescent depression . Low or high excretio n of MHPG in urin e docs not appear specific for depression and ma y be fou nd acros s oth er diagno stic categories in adolescents. References Anderson. M. S., Bowers, C. J., Kasun. A. J. ct al. (19 71), Synthetic TRH. a potent stimulation of th yro tropin in man. New Engl. J. Med.. 285 :1279- 1283. Berger, P. A. & Barch as, J . D. (19 77). Biochemical Hypothesis oj Affecth'e Disorders in Psychopharm acology ' From Theory /0 Practice, ed . J. D. Rarcha.., P. A. Berger. R. D. Ctcranctlo. & G . R. Elliot. New Yor k: Oxfo rd Universi ty Press, pp . 15 1- 173. Ca rlson, G. A. & Strober. M. (11J 79). Affective d isorders in ado lesce nce: issues in misd iagno sis. J . Clin. Psychiat.. 39:63- 66. Ca rlson, I I. E.. Krenick. E. J.• C hopra . J. J. ct a l. ( 1977), Alterations in basal and TRH -st imu lated serum levels of th yrotrop in. pro lactin , and th yroid horm on es in starved obese men . J. Clin. Endocrin.

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