Jefferson Journal of Psychiatry

Volume 9 | Issue 2 Article 8

June 1991

Psychiatric Manifestation of Vitamin B-12

Deficiency: An Update
David Metzler, M.S., M.D.
University of Kentucky, Lexington, Kentucky

William H. Miller, M.D.

University of Kentucky, Lexington, Kentucky

C. Stephen Edwards, M.D.

University of Kentucky, Lexington, Kentucky

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Recommended Citation
Metzler, M.S., M.D., David; Miller, M.D., William H.; and Edwards, M.D., C. Stephen (1991) "Psychiatric Manifestation of Vitamin
B-12 Deficiency: An Update," Jefferson Journal of Psychiatry: Vol. 9 : Iss. 2 , Article 8.
DOI: https://doi.org/10.29046/JJP.009.2.005
Available at: https://jdc.jefferson.edu/jeffjpsychiatry/vol9/iss2/8

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 Psychiatric Manifestations of Vitamin B-12
Deficiency: An Update
David Me tzler, M.S., M.D.
William H . Miller, M.D.
C. Stephen Edwards, M.D.

Abstract

Psychiatric manifestations ofoitamin B-12 deficiency are reuieuiedfrom 1986 to the present.
Specific clinical entities reviewed include depression, organic psychosis , obsessive-compulsive
disorder, childhood manifestations and dementia. We recommend that consideration be given to
B-12 deficiency as an etiological fa ctor in some cases qf depression, organic psychosis, certain
childhood disorders and dementia. Routine screening ofpeople overage 65 is addressed.

Vita m in B-12 (Co ba la m in) d eficien cy may be as high as 5% in populat ions over
age 50 a nd up to 10% in pati ent s over age 65 ( I). Th e d eficie ncy can result from
inad equ at e int ak e (e .g., ch ro nic unbalan ced di et, breast -fed ba bies of vegan moth-
ers), impaired a bso rpt ion (e.g., gas t ric lesion s, perniciou s anemia, gast rectomy, small
bowe l di sease), vit amin B-12 degr ad at ion (e .g., nit ro us oxide anesthesia) , increased
re q uire me n t (e .g., pan cr eatic insu fficien cy, hype rthyroidism), or can be multifacto-
ria l (e .g., ch ro nic a lcoho lism) ( 1-3) . Si nce t he firs t rep ort of psychiatric sequelae by
Add ison in 1868 (4), a number of th e m anifesta tion s of t his defi ciency hav e been
record ed.
H ect or a nd Burton reviewed th e lit erature up to 1986 (5) and cited the following
di agn oses, or sym p to ms, with a n e tiology of B-12 deficie ncy: 20 pat ie nt s prese n ted
with d elirium; 24 with d epression ; 14 with psych osis; 65 wit h slow cerebration,
co nfus ion, or mem ory loss; 4 with irrit ability or person ality cha nge; 15 with hallucina-
ti on s or delusions; 4 with schizophre nia or paraphreni a ; 3 with mania; a nd 3 wit h
d em entia. Recen tly, Lind enbaum e t al (6) found a number of psychi atric m an ifesta-
tions of cobala m in d eficiency in th e 40 pati ents whom th ey st ud ied . They found 15
patient s who exhibite d combinations of th e followin g sym pto ms : 13 wit h memory
loss; 3 with disorientation; I with obtund ation; 2 with d epression ; I wit h irrit a bility; 2
with hallucinations; I with agit ation; 2 with mark ed person ality cha nge ; and I with
abnorm al behavior.
Th e following discussion will review th e recent lit e rat u re of psychiat ric sequelae
as soc ia te d with vitamin B- 12 deficien cy. The focus will be on th e specific clinical
e n tities of d epression , orga nic psych osis, obsessive-co m pulsive disorder, chi ldhood
m ani fest ations a nd d em entia with resp ect to B-12 deficien cy.
43
 J EFFERSO N J O UR 'AL OF PSYCHIATRY

DEPRESSION

In th eir lett er to th e ed ito r, Levitt and Joffe (7) exa m ine d B-12 an d folat e levels
in unm edi cat ed pati ent s with well-defin ed major depression to det ermine th e associ-
ation between psychotic depression and serum levels of B-12 a nd folat e. Of 53
pati ents that th ey saw, five (9%) had psychotic d epression a nd 48 (9 1%) had major
depression a lone. In those with psychotic depression, th e a u t ho rs found a statist ically
signifi cant d ecr ease for B-12 level s, but not for folat e. Th ey posed t he q uesti on of
wh ether or not lower B-12 predi sp oses to the d evelopm ent of psych o tic symptoms
during a depressive e pisode. In a no t he r st udy (8) of 44 co nsecut ive unm edi cat ed
ou t pa t ie n ts with a m aj or d epressive di sord er, th ey no te d a low B- 12 level was
associat ed with a n ea rly age of onset for maj or d epression . Levitt an d Joffe postu lat ed
that pati ents might be more susce p tible to d epression wh en B-12 d eficie ncy begins at
an early a ge.
H eap and Mumford (9) report ed a case of what wa s th ou ght to be post-pa rt urn
depression, bu t wa s lat er discovered to be folat e and B-12 d eficien cy ca used by ch ronic
gia rd ias is. The depressive symptoms were acc o m pa nied by malaise, leth argy, neg lect
a t hom e, and visual hallu cinations. Th e pati ent resp onded to th e replacem ent of
vitamin B-12 a nd folat e.

ORG ANIC PSYCHOSIS

Phillips and Kah an er (10) report ed a pati ent with a paran oid psych osis without
a ny cha nge in cog nit io n who pr esent ed with B-12 d eficien cy. Th is 89-year-old pa t ient
had becom e paranoid nin e months prior to hospitalization a nd began to wit hdraw
and s tay at home. She was placed in a long-t erm care facility a fte r havin g a " no rmal "
or ganic work-up. Th e paranoia incr eased with sym pto ms of ag ita t ion, rapid speech ,
tangentiality, and a slightly e leva te d mo od. The di a gn osis was fe lt to be a del usio na l
disorde r o r bipolar di sorder, manic typ e, with psychoti c fea t u res . T welve months
lat er aft er a n acut e myoca rdi al infarcti on , her B-12 level was fou nd to be low. Aft er a
few days of B- 12 replacem ent th erap y, a cha nge was not ed in her paran oia and sho rt ly
th ereaft er she re su me d a ll her norm al ac t ivit ies .
Lass en a nd Ewald (II) report ed a 64-year-old wom an wh o prese n t ed in a
psychotic st at e with clouded consciousne ss, loss of orie n ta t io n to pe rson , place , and
time, anxi ety, restlessn ess, incoh erent speech, a nd rapidly fluctu at ing delu sions of
pers ecution. Despit e successful treatm ent of her hyperthyroidism th e pa ti e n t re-
mained psychotic. Two weeks lat er, her seru m B-12 level was found to be low.
Replacem ent th erap y wa s initiat ed a nd th e psych osis di sappeared .

CHILDHOO D DISORDERS

G arewal et al (12) studi ed 23 patients with infantile tre mor syndrom e. These
patients a ll pr esent ed with tremors , pallor, skin pigm ent ation , regression of mil e-
s tones, a nd a subnorm al d evelopm ent al qu oti ent. These patient s res po nd ed to B-12
PSYCHI ATRI C MANIFESTATI O NS OF VITAMIN B-12 DEFICIEN CY: AN UPDATE 45

replaceme n t th e rapy. Int crcstingly, th e aut ho rs com me n te d " t hc initial mcnt al

regression a nd persist en ce of me n ta l ret ardation in ch ild re n with infantile trcmor
syndro me co uld well be du e to a deficie n t supply of vitamin B-12 to th c nerv ous
sys te m during th c cruc ia l growing period ." Sa do witz et at ( 13) described a case of a
vita m in B-12 d eficient in fant who pr esent ed wit h decreased appctit e, lethar gy,
irrit ability, listlessn ess, diminish ed a bility to suc k a nd swa llow and loss of previously
a t ta ine d m ilest on es, Th e patient res ponde d within two days aft er B-12 repl acem ent
th erap y was sta rte d. Ca rt lidge a nd Cu rnoc k ( 14) d escribed a pati ent with Down's
synd ro me who had becom e Ictha rgic, anorexic, ir rit abl e, and withdrawn . Th e pati ent
a lso responded to vit amin B-12 th erapy.

O BSESSIVE-CO MPU LSIVE DISORDER

In th c onl y rc cent article reviewin g B-12 Icvel a nd obsess ive-co mpu lsive d isord er
(OCD), H crm esh e t al (15) reviewed 30 pati ents. Six (20%) of th e 30 pa tie n ts had
abnorm all y low Icvcls of vit amin B-12. This was st ati sti cally sign ifican t when com-
pared to co nt rol grou ps. No repl acem ent th erapy was mention ed .

DEMENTIA

It is es ti mate d th at 10% of peopl e ove r 65, 20% ove r 75, an d 30% over 85 have
som e va rie ty of dementia ( 16). H ector a nd Burton (5) focus ed on B-12 deficien cy a nd
it s relation to th e d evelopm ent of d e m entia, Thcy foun d t h rcc cases of d cm cntia
which could bc a t t ri bu te d to vitam in B-12 d eficien cy. T hey concluded t ha t obtaining a
vita m in B-12 level in searc h ing for th c e tiology of dcm c nti a was unjustifi ed.
Rawlin son a nd Ea gles ( 17) stud ied 50 d em en ted patients with diagnoses of
Alzh eim er-type d em enti a a nd m ult i-infarc t demc nt ia . They found no sta tistica lly
sign ifica n t diffe ren ces in t hc two groups with res pect to vitami n B- 12 and folat e
levels. They divided th e pat ient s int o th ose who lived wit h som eone or those who lived
a lone. Th e gro up th at lived al on e had sta tist ica lly signi fican t lowe r B-12 Icvels. From
thi s, th ey concl ude d, " .. . vit amin B-12 deficien cy is mu ch more likely to be a rcsult ,
rather th an a ca use of dcm cnting illn ess."
In ot he r studies, Abalan a nd Dclil c ( 18) found low se rum B-12 leve ls in four
patient s with pr e-senil e dem entia , a ll of whom did not resp ond to re placem e nt
th erapy. Karnaze and C arm el (19) found low B-12 levels in 29% of t he ir prim ary
d em enti a pati ents a nd in non e of th eir second ary d em entia pati c nt s. T hey could not
d et ermine if th e dem entia ca use d th c deficien cy, if th c d eficien cy ca used t he
d em entia, or if th erc was a com mo n pr ed isp ositi on for th e d evelop me n t of both
di sord ers. Rcn voize ct al. (20 ) st udie d 150 dem ent ed pa ti ent s an d found 22 cases of
vita m in B-12 deficien cy, H e not ed th at two of th e seve n reversibl e cas es responded to
B-12 repl acem en t. Ka ssircr a nd Kop elman (2 1) desc ribe d t hc cas e of a 62-ycar-old
m an who had pr esent ed with a four- to six-mo nt h hist ory of prog ressive cha nges in
m ent al status associa te d with cmo tional la bility, ga it dist urbance and visual impair-
m cnt. They en te rtaine d th e di agn osis of Alzh eim e r's disease and bcgan to exc lude a ll
46 J EFFERSO N J O URNAL OF PSYCHIATRY

ot he r reversibl e ca uses of d em entia . They discovered a low serum B-12 level with out
hemat ological m anifest ations. With vita m in B-12 repl acem ent t he rapy th e pati ent 's
ment al stat us was normal in two mon t hs, a nd he cou ld walk wit hou t help, follow ed by
improvem ent in his emo tional lability a nd hi s visua l ac u ity. Finall y, Wieland (22)
st ud ied a co m m u nity of86 elde rly pat ient s a nd found 5 resid en ts with low se r u m B- 12
despi te bein g non- anemic. One of th ese pati ents ca rried t he diagnosis of dem entia.
Dram atic clin ica l im prove me n t was not ed in this patient with B-12 t herapy.

DISC USSION

The evide nce th at B-12 deficien cy is as socia te d with d epression, organic psych o-
sis a nd th e aforem entioned ch ild hoo d manifest ation s lends cre de nce to conside ra tion
of obtaining B-12 levels in pati ent s who pr esent with th ese problems. Eva ns et at (23),
a fte r having two pati ents with organi c psychosis respond to B-12 th erapy, stat ed t hat
" . . . psychiatric m anifest ations may be th e first sym pto ms of vita m in B- 12 defici en cy
a nd thus a n te d a te an emia a nd spina l co rd disease. " Becau se of t his, they recom -
m end ed conside ra tion of B-12 deficien cy a nd se ru m B-12 de ter mi nations in all
pati ent s with orga nic psychiatric sym pto ms . H ect or a nd Burton (5) , who stat ed th a t
obta ining a se r um B-12level in dem ent ed pati en ts wa s unjust ified , a lso sta te d th at a
B-12 level was cur re n tly part of th e work -up if th e re was a de lirium associat ed with
th e dem entia. Ar guabl y, in pat ient s ove r 65 wit h d ep ression or a psychotic di stur-
ba nce, a se r um B-12 level sho uld becom e a standa rd la borat ory procedure.
This review found four cases of de m entia t hat were reversib le wit h vitamin B- 12
t he ra py. A mu ch higher number of dem ent ed pati ent s had B- 12 defici en cy, but
repl acem ent th erapy did no t have any effec t on th e reversal of th eir dem entia. It
sho uld also be m ention ed th a t long-t erm follow-u p of th e four reve rs ible cases was
not add ressed in th ese st ud ies . Larson a nd Reifle r (24), along wit h Karnaze and
Car me l ( 19), point ed ou t t ha t without ad equat e follow-u p, it wou ld be difficult to
d et e rmine wh ether or not t he B-12 deficien cy ca use d th e demen tia or vice-versa.
It is difficult to disagr ee with H ect or a nd Burt on (5), who sta ted, " . .. those who
co nte nd that vit amin B-12 deficien cy ca uses d em entia face th e inerti a of an impres-
sive am ount of clini cal work th at fail s to support that associa tion ." T o do so, one mu st
take th e view that B-12 deficien cy ca uses dem entia by a slow pr ocess which becom es
irreversible aft er a ce rtain stage in this process is rea ch ed.
Thompson and Fr eedm an (16) di scuss suc h a th eo ry based on a model present ed
by H erbert and H erzlich , wh o tri ed to expla in B-12 deficien cy a nd it s effec ts on th e
brain a nd th e nervou s syste m. They prop osed four stages of B-12 d eficien cy: nega tive
B-12 bal an ce, B-12 d epl eti on , B-12-d eficient eryt h ro po ies is a nd B-12 defi cie ncy
a ne m ia . Only during th e final s tage does th e patient becom e anem ic a nd develop an
eleva te d MCV. Thompson a nd Fr eedm an felt t ha t th e most import ant q ues tion was
a t wh at stage myelin dam age occu r re d. It see ms th ere is sign ifica nt doubt still
re mai ning a bout th e associa tion bet ween B-12 d eficien cy a nd dem e nt ia. Sin ce th e
ti m e of irreversibl e myel in dam age is not kn own , it wou ld make sense to try to
PSYCHIATRI C MANIFESTATI ONS OF VITAMIN B-12 DEFICI ENCY: AN UPDAT E -17

pr event this from happening, possibl y pr eventing a dem enti a th at would be irrevers-
ible once it was discovered .
It is impossibl e to estimate th e in cid en ce of vita m in B-12 d eficie ncy wit h resp ect
to it s associa tion with th e afore me nt ione d illn esses. No nethe less , it ma kes intuitive
se nse to co ns ide r vit amin B-12 deficien cy in th e norm al work-up for any of th e clinical
e n tities m entioned in this review. A more import ant q uestion may lie in the
pr evention of th ese illn esses by scree ning peopl e over age 65 on routine physical
exa m s. A vitamin B-12 level cos ts a ppro xim a te ly $20.00. If 10% of th ose over 65 will
develop vitamin B-12 d eficien cy ( I), th en thi s subse t of th e popul ation is at risk to
develop th e a fore me ntione d clinical en tities. Conside ring th at a pa tie nt with dem en-
ti a will incur th ou sands of dollars in m edi cal bill s, expe rie nce loss of quality of life a nd
s t ress family m embers by th e a mo u n t of ca re required , screeni ng t he population ove r
age 65 a ppears to be cos t effec tive.

CO NC LUSIO N

A review of the psychiatric mani fest ati on s associa te d wit h B-12 deficien cy has
been di scu ssed. T aking into acco un t th e ava ila ble d at a , it is advocated that consid er-
a tion be given to B-12 deficien cy as a n etiolog ica l fact or in som e cases of depressi on ,
orga nic psych osis in ad ults, a nd ce r ta in child hoo d disord ers. Also, screening of
individuals on routin e physi cal exa m at a ge 65 for B-12 deficien cy was advoca ted as a
measure to pr event organic psychoses, depression a nd dementi a (r eve rs ible a nd
irreversibl e) from d eveloping.

ACKNOWLEDGEMENT S

The authors would like to ac knowledge th e technical assis tance of Tag H eist er,
University of Kentucky Departm ent of Psychi at ry librari an ; and Vi rgi nia Lynn Gift
a nd Debbie H oward , Universit y of Kentucky Dep a rtment of Psychi at ry wor d proc es-
so rs.

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