Lithium Responsive Manic‐like Symptoms in Two Individuals With Autism and Mental Retardation

CASE REPORT Lithium Respon sive Manic-like Symptoms in Two Individuals With Autism and Mental Retardation RO NALD STEING ARD . M.D..

A ND

JO SEPII BIED ERM AN. M .D.

A bst ract. Thi s report describes the d iagnosis. co urse. and pharmacological treatment of two patients. ages 7 and 20. with infantile autism and mental retardation. who developed acute episodes of mani c-like sym pto ms. Diagno stic and treatment co nsiderations in indiv iduals with autism who develop these type of sym ptoms are discussed . J . Amer. Acad. Child Adol. Psychiat.• 1987. 26.6:932-935. Key Words : autism, lithi um, mania. mental retardat ion.

Infantile autism is a severe psychopa thological disorder of mixed etiology. It is classified in the DSM-III as a pervasive develop mental disorder man ifested by severe di fficulties in social relationship s. gross deficit s or peculiariti es in language developmen t. a nd unusual respo nses to env iro nmental stim uli. Infant ile autism is frequen tly associated with men tal retarda tio n. Altho ugh several studies ha ve documented the cooccurren ce of affecti ve illness in the ment ally retarde d populati on (Rivinus and Harmatz, 1979: Sovner and Hurl ey. 1983). little atte ntio n has been paid in the litera ture to the manifesta tion and treatment of affective disorders in indiv iduals with a utism . To our knowledge . there is only one report in the literature of two cases of children with autis m ma nifesting a major affective disorder. Thi s paper reports on the diagnosis and treatm ent of two ind ividu als with infan tile autism who deve loped concurrent sympto ms suggestive of bipola r disord er. manic type.

typic behaviors. and inappropriate use of toys. Because of the cluster of symp tom s characterized by gross deviance in social. linguistic. and cognitive deve lop me nt. in the context of normal motor developm ent his co nd ition was suggestive of the diagnosis of infantile autism . Tim was referred to a special ed ucatio n program a nd referred 10 one of us (1. B.) for psychia tric follow-up and pare ntal counseling. Fam ily history W3.'i negative for developmental disorders but positive for lithium-responsive man ic-depressive disorder in his mat ernal aunt. From the initial diagnosis at age 2. he received inte nsive psycho-ed ucational interve ntions a nd made adeq uate progress. Du ring semia nn ual follow-up he conti nued to manifest stereotypic beha viors. pervasive impairment in social skills. lack of eye contact, absence of a socia l smile. and marked inhibition . Speech progressed slowly but was mainl y echolalic. Beha vior was erratic with significan t hyperact ivity. Mood was labile. Affect was genera lly inappropriate but primari ly inhibited . He was not aggressive. destructi ve. or bizarre . At age 6. withou t clear precipit ants. Ti m's behavior ac utely and drastically chan ged. He started manifesting sudde n and uncharacteristic agita tion. He developed initial a nd terminal inso mnia. His mood drastically cha nged from generally inhibited to appearing unusually happy most of t he tim e. He lau ghed frequ entl y. loudl y. and ina ppropriately. His atti tude toward strangers also cha nged from marked inhibition a nd withdrawal to fearlessness a nd outgoingness. He becam e more aggressive and self-abusive. From being a generally cooperative child he became a serious management pro blem for parent s a nd teachers. His symptoms inte nsified over the next several weeks a nd parent s reques ted he be reevaluated. At th e time of reevaluat ion he was noted to ha ve an elated affect with frank and uncharacteristic bursts of laughter. an uncharacteristica lly friendly a nd outgoing atti tude toward the examiner (J . B.). and intense psycho motor agitation. T he symptom atic picture of a n ac ute an d sudde n change in mood a nd behavior in this mod erately retard ed. non verbal auti stic child with a positive famil y histo ry of mani c-depressive disord er was suggestive ofa mani c episode. Be was treated initially for several weeks with th ioridazine in doses of up to 200 mg/day with minimal results. Th e persistent and escalating clinical picture of mani c-like symptoms prompted us to add lith ium carbonate to the neurol ept ic. Lithium treatment was closely monitored by plasma level determinations of up to 1.0 meq / L. With the co mb ination of lith ium ca rbo nat e and the antipsychotic. the clin ical pict ure stabi lized within 2 weeks. H is agitation . inso mnia. expa nsive affect. inappropria te behavior.

Case Report s

Patient J Ti m. a 9-year. IO-m on th-old white hoy. is the oldest of two siblings born to midd le-class parents and the product of an unco mplicated pregna ncy and de livery. Motor milestones were mildl y dela yed . In the second year. he was noted to be markedl y unr espon sive, failed to parti cipate in social games of toddlcrhood. rarely smiled respo nsively. and was difficult to hold. His pare nts became concerned when he failed to develo p language. The parents sought a deve lopmental evaluation that revealed age app ropriat e motor skills. norm al audi ological evalu ation . but gross delay in language and adaptive skills. Tim was responding erratically to sounds. had difficulti es adju sting to minor cha nges in his enviro nment. was unabl e to participate in a ny type of social interactio n, and lacked social smile. He had lim ited respon siveness to his parents and other famil y mem bers. had poo r eye co ntac t. gross deficits in language developm ent . repet itive and stereo-

Rrceivrd Ju ly 14. 1986: revised Feb. / 6. 198 7; accepted Feb. 13. / 98 7. From fhl' Pediatric Psychophurmacologv Unit, ..ICC 615. MW .mchus ctts General tt osnnal: Boston ,\fA 02 114, Reprint requests to Dr. Stringard. This work " 'as supported in parr hy the Chartunski Foundation (J. B.). We thank Debra Knee fo r assistance. 089O-8567/87/2606-0932S02 .00/0 1987 by the American Academ y of C hild and Ado lescent Psychiatry. 932

MANIC-LIKE SYMPTOMS IN

AUTIS ~I

self-abusive behavio r. a nd aggressive outbursts disap peared . He beca me ca lmer a nd beha viorally more appropriate. He continued to he closely followed ove r the past 4 years at monthl y intervals. and he has been maintain ed o n 200 mg of thioridazi ne a nd 1.200 mg ofJithium carbonate with excellent recovery and stab ility. During th is follow-up time. mild downward fluctuations in the level of lithium or reduction of the dose of thioridaz ine produced rapid deterioration wit h the eme rgence of the origi na l man ic-like symptomatology. T im never developed de pressive symptoms. He has progressed at schoo l, a nd intrafamilial functi oning has im pro ved.

Patient 2 Ja mes. a 24-yea r-old ma n. is the product of a full-term , unco mplica ted pregna ncy a nd delivery. He is the you ngest of four siblings from middle-class parents. Both parents are social workers. Du ring his first year of life, his parents not ed lack of eye con tact. lack of a social sm ile. no start ling response. and no relatedn ess to his ca retakers. His motor develop ment was within norma l limit s. but his social, linguistic. and cognit ive developm ent were grossly defective. He failed to develo p speech. Psychological testing placed the level of cogn itive development in the moderately retarded range. He had pcculiar responses to noises a nd engaged in stereotypic behaviors. Since early childhood he also manifested severe behavio ral disturba nces includi ng head banging and aggressive outbu rsts. He had difficulty sleeping a nd requ ired almost consta nt supe rvision. Famil y histo ry was negati ve fo r developmental a nd psychiatri c disorders. Initial developmental. medical. a nd psych iat ric evaluations during the first and seco nd years of life produ ced a variety of diagno stic considerations. includ ing men tal reta rda tion . childhood schizo phrenia. and "sym biot ic psychosis." Because of the severit y of his symptom s he was trea ted almost conti nuously from ages 6 to 19 years with a varie ty of a ntipsycho tic medicat ion s- at times with extremely high do ses (in excess of lg/ day of chlorproma zine a nd 90 rug/day of haloperido l) with minimal success. He was placed in multiple schools a nd residential setti ngs and had multiple psychia tric hospitalizati on s. Since latency. variou s care givers noted a seaso nal pattern of fall and spring episodes of behavioral deteriorations. Duri ng these episodes. Ja mes wou ld become ac utely agita ted . restless. and wou ld evidence an increase in the nu mbe r of aggressive outbursts. self-ahusive behavior. and head- ban ging. Although he was a poor sleeper. during these episod es he would not sleep at a ll. Th e episodes lasted for several months a nd remitted spo ntaneou sly. At age 20. he was referr ed 10 the Psycho pharm acology Unit of the Massachu setts Ge neral Hospital at the time of o ne of these episodes and was seen in cons ulta tio n by o ne of the a uthors (J . B.). At the lime. he was taki ng 600 mg of chlorpromazine eac h da y. He had to be acco mpan ied by several staffme mbers fro m his residential sett ing to help restrai n him . He was unmanageable. requiring co nsta nt supervis ion and restraining to a void severe head banging. On exam ina tion he was noted to be acutely agitat ed. and he man ifested a predomina ntly expa nsive affect that was descri bed as uncha racteristic and a depa rt ure fro m his usua lly in hibited mood. The developmen ta l history, the developmental course. and the cluster of sympto ms were co mpatible with the diag nosis of infantil e

AND MENTAl. RHARDATION

933

autism wit h mod erate men tal retardation. In addition to his deve lop menta l diso rder. he appeared to have a superimposed episodic major psychiat ric distu rban ce, Th e seaso nal qu alit y and the cluster of man ic-like symptoms of insomnia. agitation . intrusiveness. un usua l and excessive smiling and laughter. a nd expansive affect were suggestive of a manic episode. Based o n this diagnosis. lithium carbo nate was added to his treat me nt in slowly increasing dose s aimed at attaining therape utic plasma levels. T he clinical picture stabilized within 3 weeks afte r the int rodu ct ion of lithium ca rbonate. Since the n he has continued to he followed monthl y over the past 4 years. He has heen maint ained on lithium carbonate at plasma levels of 1.0 10 1.2 meq / L an d chlorpromazi ne 800 mg/day . Att empts to lower the dose of either d rug has resulted in a rapid emerge nce of tile manic-like symptoms. Since the introduction of co m bined lithium neuroleptic treatment. the behavioral cycles have been aborted. For the first time in 20 years. his pa ren ts reported tha t Ja mes slept through the night. T he d readed fall months norm alized. and Jam es req uired less supervisio n. His parent s could take him to public places suc h as restauran ts and recrea tiona l places for the first tim e in his life. Over the past 4 years. he has had only one brief fall episode of sym ptoms breakthrough with self-abusive bchavior. which required a slight increment in the dose of lithium. Thi s episode remitted after only a few days of increased do se of his medications. Over the years. his speech has improved. as has his level of relatedness and socialization. Excerpted from a lette r to J. R. from Jam es's mother. with her permi ssion : "For years o ur son . Jam es. was able to experience only spo radic periods of sleep duri ng the night. which necessitated either his father or myself to stay with him duri ng the night. ... As Jam es became olde r and bigger his severe. physical aggressive outbursts created very seriou s problems regarding my abilit y to handle him alone. His self-ah usive behavio r reached a poi nt where his head bangi ng a nd bit ing of his wrists and a rms requ ired continuous holdi ng by his fath er a nd broth er. the o nly mem bers of the fa m ily stro ng eno ugh to hold him . At this point. whe n Jam es was 18. he moved from a day prog ram to a residential program ," (James was subseq uently disc harged ho me after allegedly assaulti ng a teacher at the school : this occurred just before his arrival for treatmen t at o ur clinic .) "With the exception of o ne very brief. less intense episode with self-abusive behavior. approxi ma tely 3 years ago. James has been magnificentl y stabilized on lithium ca rbo nate and thora zine .... James retires at 9:00 P.M. and sleeps to 7:00 A .M. . .. . Jam es is a happy individual who smiles a lot, has good eye co ntac t. and seems so content with him self a nd others . li e shows affectio n a nd allows affecti on to be shown to him . . . . Were it not for the pharmacological trea tment. Jam es would not ha ve been afforded the opportu nity to live a normal. hap py life with those who love him dea rly and in his own co mmunity." Discussion T he pat ients discussed arc characterized by severa l co mmon features. Bot h had a diagnosis of infa ntile a utism associa ted with men ta l retardation. Bot h had limited verbal skills. were cared for by thei r families . and were receiving inte nsive psycho-ed ucat ional in terve ntio ns. Bo th had a n ac ute o nset of

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STE INGA RD AND

un characteristic. susta ined. severe psychiatri c sym pto ms witho ut clear precipitants. charac terized by unusual and seve re mood cha nges of expa nsive-dy sphoric qu ality. assoc iated with psychomotor agita tion. inso mn ia. aggressive o utb ursts. and in the case of James. very severe sclf-ah usc. Both were severe ly ill and. if not co ntro lled. wou ld have necessitat ed inpat ient tre atm ent. T he sym pto ma tic picture that th ese pa tients dev eloped is co m pa tible with several diagnos tic co nsideratio ns. First. th is co uld be part o f th e pe rvasive de velopmental di sor der syndrome itself. because behav ioral diffi cult ies, aggressive outbursts. and self-abuse a re co m mo nly encou ntered in developme nta lly delayed individu als. The ac ute ness and un characte ristic nature of th e sym ptoms suggested a superi mposed major psych iat ric d isorder. however. Second. the sym ptoma tic picture co uld represen t an ac ute psychotic episode. Th ese pati en ts. however . d id not have obvio us psychotic sym pto ms such as bizarre be haviors or hall uci na tio ns. T hird. thi s co uld rep resent a n agita ted affective or sch izoaffec tivc di sorder. Thi s diagno stic hypothesis is sup ported by th e develo pme nt of an acute a nd severe agitat ed state. Th is state is associated with man ic-like sympto ms suc h as an un cha racteristic and pers istent cha nge in mood and behavior of severed weeks d ura tion. Sym ptoms incl ude increased activi ty. decreased sleep. a nd increased involvement in unusual activities such as approachi ng a nd tou ch ing strangers. as well as selfabusive behaviors. suggestive of a m ani c episode. It is importa nt to stress th at beca use o f th e limited verbal skills. other man ic sym pto ms suc h as pressured speech and night of ideas co uld not be asce rtained. Despi te th ese lim itation s. it is notewort hy th at both patients me t DSM-1l1 criteria for a ma nic episode. Fu rther ev ide nce for this diagnostic con sideratio n was suggested in James by the longitudi nal co urse of episodic seaso na l decompcnsations and . in Tim. by a positive famil y histo ry for lith ium-responsive mani c-dep ressive diso rde r in an au nt. These pa tients failed to respo nd to high doses of phe nothiazin es whe n prescribed alone. but the y respo nded whe n treatment with lithium ca rbo na te at adequate plasma levels was added. The lack of respo nse to high doses of a ntipsychotics is consisten t with our diagnostic hypothesis. because antipsychotic thera py is known to be highly effecti ve in controlling behavioral disturba nces in developmentally disordered pa tient s (Bied erm an and Jcllinck. 1984 ; Wi nsbe rg and Yepes. 1( 78). However , it was ineffecti ve in co ntrolling th e sym ptoms of these pat ients. suggesting that these were not just sym pto ms of a non specific agitated state. Positive respon se to lithi um carbo nate treat ment. however. is not in itself diagnos tic of a ma nic episode. because positive responses to lith iu m have been reported in a variety of neuropsychiat ric disorders in ad ults and child ren (Jefferson et al.. 1986). In th ese cases. the decisio n to use lithi um ca rbo nat e followed diagnostic co nsideratio n and not th e othe r way aro und . Even if th ese pat ient s had not responded to lit hium , we wo uld have pursued other pharmaco logical strategies used in th e treat ment of bipola r patient s. mani c. such as treat ment with carba mezap ine. In fact . lack of response to lithium in manicdep ressive pati ent s docs no t im ply m isdiagnosis. because about 30 % of mani c-d epress ive patients do not respo nd to lith ium carbo na te.

RI ED I:R.~tA N

Bot h pa tients ma nifested o nly ma nic-like symptoms wit hout d ep ressive sym pto ms. Thi s is a n u nu sual but pla usible form o f bipolar disord er a nd docs not necessa rily preclude this d iagnosis, becau se th ese pat ient s cou ld still devel op depre ssive bouts in th e futu re. The two pati ent s had a chro nic co urse of their di sord er necessitat ing chronic pha rmacotherapy. A chronic course of an affective d isorder is not un usual. It is estimated th at in about 20 % of patients wit h major a ffective d isord ers. the course is chronic (DS M-III). During the extended follow-up pe riod , these pati en ts required co mbined antipsychoti c-lithium treatment. Attempts to reduce either the lith iu m o r the ant ipsych otic result ed in th e rapi d recurren ce of the initi a l sympto ms . Th e need for co mbi ned neu rolepti c-lithiu m treatm ent is not unusual. because this treatmen t approach is widely used in psychop ha rmacologica l practice in the management of bipola r pat ien ts (Rifkin and Siris . 1983). Moreo ver. it has been shown that co mb ined lithium-ant ipsych ot ic treat ment is superior to an tipsych oti c treatment alo ne in exci ted schizoaffcctive a nd manic pat ients (Bied erman et al., 1979 ). O ne o f the reported pati ents was a prepu bertal ch ild. Alth ou gh the exis tence of mani c-depressive illness in prep ube rta l child ren is still co ntroversial. its validity has been gain ing increasing recog nition. Case repo rts of man ic symptoms in you ng child ren ha ve been reported (Feinstein and Wolpert 1973; Pozn a nski et al., 1984: Weinberg and Bru m back. 1976). We recent ly reported o n th e presence of hipolar d isorder. mani c. in nonretardcd child ren with atte ntion deficit di sord er using criterio n-based struct u red interviews and blind rate rs (Biederma n et aJ.. 1987). A sim ilar diagnostic controversy applies to the diagnosis of bipo lar disorder, ma nic type. in developmentally de layed individuals with limited verbal skills . Sovn er and Hurley (1983) stresse d th at both bipolar and no nbipola r major affective di so rders can be observed in me ntally retarded pa tien ts. includi ng th ose wit h impairment in the severe or p rofound ran ge of retard ati on . eve n when language developme nt is impaired or abse nt. In th ose pati en ts. th ese investigators recom mended th at th e d iagnosis of th e affective illness ca n be supported by o bservation of behavior and funct ioni ng over time and in vario us sett ings. In reviewi ng the English language literat ure over the past 10 years. we were only ab le to find onc other reported case of a simi la r clinical experience in autistic individ ua ls (Ko rno to and Hir ata . 1984 ). R ivin us a nd lI armat z ( 1979) reported th e cases of five nonautistic mentally retarded pati ents with bipolar disord er who also respo nded to lith iu m ca rbo na te. In tha t repo rt. two patient s also had a posi tive fami ly h istory of an affective disorder. These researchers suggest that th e dia gnosis of mania in the retarded can best be made by compari ng th e patien t's normal be havior with that whic h he o r she exhibits d uri ng periods of un stable mood. Int rusiveness. assa ultivcncss, de stru cti veness. and self-abuse also suggest ma nia whe n co m pa red with baseline. C hanges in eating and sleeping patt ern s. usuall y. decreased appe tite and sleep. ca n also he obse rved du ring th e man ic ep isode in retar ded pa tien ts. Szyma nski and Biederm an (1984) reported th at difficu lties with the diagnosis of affective d isorders in retarded persons stem fro m the misconception that retarded people do not suITer from affec tive di sorders. a nd th at th e clin ical pres-

MANIC-LIKE SYMPTOMS IN AUTISM AND ME NTAL RETARDATION

entation is d ifferent from that encou ntered in the nonrctard ed popul ation . They comme nted that in making the diagnosis of affective illness in reta rded person s with poor verballan gua ge and co nce ptual abilities. th e clinician can not expect the patient to verhalize affect ive changes; therefore. maj or d iagnostic im porta nce is assum ed by beha viora l sym pto ms. An effective tre atment strategy follows an effective diagno stic assessment. It is the diagnostic assessmen t tha t sho uld guide the treating clin ician in choos ing an appropria te treat mcnt modality for the affected pati ent. Thi s was the case in o ur patients. Th e d iagnost ic con siderat ion ora bipolar d isorder. mani c-type in these two au tistic ind ividuals was a n im po rta nt clinica l hypothesis. For these patients. it mean t a choice of treatment that had a major im pact in their lives. In both cases. the y not o nly returned to prem orbid levels of functi oning. but their improved funct ion ing allowed them to achieve an im pro ved psycho social status by mak in g substa ntial progress in language a nd ada ptive skills. The two cases presented in this report. like those reported by K orn ot o and Hirata (1984). illustrate the need for careful diagnost ic assessmen t in ind ivid uals with pervas ive development al disorders. Th ese reports raise the co nside ration th at the presen ce of infantile autism in a patient d ocs not preclude the presenc e of another psychiatric disorder. The dia gno sis of a manic epi sode can be suspected when a major change in functioning from the patient's baselin e is observed characterized by the acute emergence of chang es in sleep. appetite. predominant aff ect, and behavior in the absen ce of dear psychosocia l precip ita nts. If ma nic-like sym ptoms arc present. consideratio n sho uld be given to the dia gnosis of bipol ar disorde r. manic. If a manic episod e is suspected. a trial of lithium a lo ne or in combination with a ntipsychotics is reco m mended. If lithiu m treatment is in effecti ve or .associatcd with significa nt adv erse effects. co nsideratio n sho uld be given

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to alternative treatment approac hes for th is di sorder. such as ca rbamezapine and va lproic acid . References Biederm a n. J.• Lern er. Y. & Belmaker. II . ( 1979). Co mb ination o f lithium ca rbo nate and haloperid ol in schizo-a ffective di sorder. A rch. Gen. Psvch iat.• 36:327-333. - - Jellinek, M. S. (1984 ). Psychopharmacology in ch ildren, 1\'e\'o' Eng. 1. Med..• 3 10:968-972. - - Munir. K.. Knee. D . et al. ( 1987). High rate of'a ffective disorders in probands with att ention deficit di sord er and in their rela tives: a co ntrolled famil y study . Amer. J. Psychiat.. 144:330 - 333. Feinstein. S. C. & Wolpert. E. ( 1973), Ju venile ma nic-depressive illness: clin ical and therape utic co nsiderations. T his Journal. 12:123. Jefferson , J . W.• G reist. J. H .. Acke rma n. D . L. & Ca rro ll. J. A. ( 1986). Lithium En cycl opedia fo r Cli nical Practice. Washin gton. D.C.: American Psychiatric Press. Komoto. J. & Hirata. J. ( 1984). In fantile a ut ism and affective diso rder.1. A UI. Develpm. Dis.• 14:81-84 . Poznanski. E. 0 .. Israel. M. C. & G rossman, J. ( 1984). Hypom a nia in a four -year-old. This Journ al. 23: 105- 110. Rifkin , A. & Siris. S. G . ( 1983), Drug treatment of man ia. In: Schizophrenia and Affective Disorders: Biologv and Tr eatment, ed . A. Rifkin . Boston . Mass.: Wright. PSG Inc. pp. 79- 116. Rivinus. T. & Il annatz. J. S, (1979). Diagno sis and lithium treatment of affective disorder in the retarded: five case stud ies. Anwr. J. Psychiat ., 136:551 - 554 . Sovncr. R. & Hurl ey. A. ( 1983). Do the ment all y retarded suffer fro m affective illness'! Arch. Gen. Ps whiut.• 40:6 1-6 7. Szymanski . L S. & Biederrnan . u. ( 1984). Dep ression a nd anorex ia nervosa of person s with Do w n synd ro me. A mer. J. M ent. l h~r. . 89:246-25 1. Weinberg. W. & Bru m back. R. (1976). Man ia in childhoo d: case stud ies and litera ture review. A m ('r, 1. Dis. Child., 130:380. Win sbcrg. B. G . & Yepes. L. E. ( 197X). Antipsychot ics (majo r tran quilizers. neu rolcptics). In: Pediatric Psvchopharmucoiogv: 111(' UsC! of Beha vior ,\ / od l/ i'itlK Drugs in Children, cd . J. S. Werr y. New York: Brunncr/M azcl, pp. 234-274.