Vitamin B6 and vitamin B1 status in acute psychosis

Vol 4, No 2, April-June, 1995 _{B Vitanins assesstr,enl t23}

vitamin

86 and

vitamin

Bl status

in

Acute psychosis

Jos Utama*, Hera G. Tamara**, Drupadi

Dillon***,

Evi Setiadi

****,

Wilmar Musram

****

Abstrak

Pada pertengahan abad ke-20 konsep biopsikiatri sebagai dasar penyakir jiwa mulai dikenbangkan. Telah ditenwkan beberapa zat kimia seperti LSD (lysergic acid

diethylan

dapat

nenintbullan

psitosrs.

IjlD

dan serotonin (5HT) nenpury-ai struktur

ya

hasil penguraian

se

_inyai

sifa

_yang

aupuh. Diketahuipulabahwasintesisserotonindannorepinefrin(NE)nutlaknenerlukanpiridol<satfogùtlfipl,bentukaktifvinntin

86, _{sebagai kofaktor' Hingga sekarang kepastian nengenai perubahan SHT dan NE pada pendirnàp.ritosis nnsih belunt dapat} disimpulkan. Tuiuan penelitian kani ialah untuk uengetahui perubahan status vitatnin 86 dan vitanûn BI penderita dengan berbagai tingkat kegowatan keadaan psil<osrs. .I/osil senentara nenuniukkan bahwa sraus vitantin 86 langsung beihubungan deigan keadaan psikosis sedangkan status vitanùn Bl tidak

Abstract

In the nidst of our _{century, the biological concepl} of the pathogenesis of ntental illness was launched. Several agents were discovered that nûnûc the sy,,tpton$ of nental disease like I,J,D (tysergii acid diethylanûde) and reserpine. _{It v,asfound that Ij,D and}

serotonin (5HT) were structurally similar and that the brealcdown products of 5HT had potent halluiinogenic properties.

It was also

known that the ss:nsl16it of 5HT and norepinephrine (NE) were pyridoxatphisphate (Pip), the active _{fttrtn of-vitàtnin} 86, dependent.

However,

definitiv

_{resent still}

inc

_{I of our srudy}

is to lookfor

chan

_{the diferent}

s

_prelintinary

findings show

that

_{dependent while vitantin}

Bï

_{stutus is not.}

Key words : acute ps),chosis, _{serotonin, norepinephrine, vitatnin 86 and vitauin}

Bl

_status.

INTRODUCTION

In the midst of our century, several relatively effective

and

selective drugs

for

the

management

of

schizophrenia and manic-depressive patients were

in-troduced. This

condition stimulated the biological

concept of the pathogenesis of mental illness. In addi-tion, other agents were discovered that mimic some

of

the _{symptoms of mental illnesses. These include} lyser-gic acid diethylamide (LSD) which induces hallucina-tions and altered emotional states and antihypertensive

agents, such as reserpine, which can cause depression.

At

the same time,

it

was noted that serotonin (5-hydroxytryptamine, 5HT) and LSD were structurally similar and that breakdown products of 5HT, such as

dimethyltryptamine, had potent hallucinogenic

properties.'

These observations _{led to} speculations that a deficiency of amine neurotransmitters (NT) in

the central nervous system (CNS) might be causative

of depression or that an excess could result in mania. Further, since antipsychotic agents antagonize the ac-tions of dopamine (DA) as a NT in the forebrain, it was

Departnent of Neurology, I ndo nes i a, J akarta, _{I nd} o nesi a.

'-..

124

Utann et al

proposed that there may be a state of functional over-activity of DA in the limbic system or cerebral cortex in schizophrenia or mania.

Until the mid 1960s the only known NTs were a handful of biogenic amines. In the late 1960s the role

of

amino acids, such as gamma aminobutyric acid (GABA), glycine and glutamate, as NTs became ap-parent. The decade of 1960 witnessed the appreciation

of

peptides as

NTs.

Although peptides represent the most diverse group of transmitters, yet the amino acids are the most abundant

NTs. GABA,

the most

in-hibitory NT,

accounts

for

25-40%

of

synapses, depending on the brain region.

During early development, a rapid and massive death occurs among the postmitotic neurons whose axons have reached and connected

with

their target territory. 2'3 Th" ability of neurons to survive through this developmental death period has been hypothesized

to

depend on target-derived neuronotrophic factors, which taken up

by

the axonal terminals and used to stimulate

life

supporting cell activities. The concept of a nerve growth factor (NGF) was born, and in the 1960s its existence and general properties were estab-lished by Levy-Montalcini et al.

ap

The discovery

of

NGF has been a milestone

in

modern neurobiology. We know now that NGF is critical for the survival

of

certain neurons as well as

for

the outgrowth

of

their neurites and that

it

also stimulates the synthesis

of

transmitter producing enzymes. Glial cells surround -and greatly outnumber - neurons in both the peripheral nervous system (PNS)

-

(satellite and Schwann cells)

and

the

CNS

(astroglia,

oligodendroglia

and microglia). Certain roles of glial cells have long been recognized eg, electrical insulation (myelin), histologi-cal organization (radial glia, glial lining) and

monitor-ing

of

extracellular

fluid

composition (blood -brain -barrier). The discovery

of

very close anabolic and metabolic interrelations prompted Hyden et

al,6

to propose the concept cf a glia-neuron functional unit.

Further analyses have revealed the ability of glial cells

to

produce and release neuronotrophic agents, like pyruvate, and their ability to respond to neuronal signals,T'8

It

is also known, that the B vitamins

espe-cially

the vitamins Bl, E}6,

Bl2

and

folic

acid are essential cofactors

for

the normal activities

of

cell neurons

and

their

axons,

including

regenerative processes.

A

deficiency

of

vitamin

B

complex may result

in

disturbances

of

function

of

both the PNS (nerve conduction velocity) and CNS (higher cortical

functions) as

well

as the

synthesis

of

NTs

like serotonin and GABA.

In

spite

of

much work, definitive findings con-cerning the 5HT and NE alterations in psychotics are

Ned J Indones

at present still inconclusive. The key problem has been the absence of good methods for examining localized NT and functional changes, However, as the synthesis of 5HT and NE is vitarnin 86 dependent, estimation

of

vitamin 86 and vitamin

Bl

status in the diverse stages

of

psychosis could provide us more information.We hypothetize that, metabolic and nutrient requirements in acute psychotics

will

be higher than under normal conditions, consequently vitamin

86

and vitamin B1 status

will

fluctuate according to the acuteness of the illness. The objective of this study is to look for altera-tions between the vitamin 86 and vitamin B1 status and the stage of psychosis of the patients.

METIIODS

The material consisted of 27 acute psychotic patients, 16 males and 11 females, ages between l7-60 years.

All

cases were new inpatients, admitted for at least one month

in

the State Mental Hospital

of

Bogor, West Java,

with

pure mental illnesses. The examination consisted

of

general physical diagnostics, clinical néurological and mental assessment, routine blood and vitamin 86 and vitamin

Bl

status. The examinations had been done twice, prior to the treatment, directly at the tinre of adnrittance and secondly, after one month of hospital treatment. Standard psychotic medications

were chlorpromazine,

diazepam, carbamazepine parenterally and

orally,

besides phenobarbital and trihexyphenydil tablets for epileptic insults and parkin-sonism.

The vitamin

Bl

status was expiessed

in

the thiamine-pyrophosphate _{(TPP) effect which is} deter-mined by the method

of

Schouten, a modification

of

the Dreyfus test.e

Vitamin

86

status

is

determined

by

the

ery-throcyte aminotransferase (EAT) activity test and ex-pressed in the coefficient of EAT activation (CA) l0).

In previous studies a TPP effect < _{27 % and} a CA < 1.40 were found fora normal vitamin

Bl

and vitamin 86 status, respectively.g't0 Th" TPP value greater than 277o and that

of

CA

greater than 1.40 indicate the deficiency

in

vitamin

Bl

and

86

respectively. The t-test was used

to

compare the TPP and

CA

values before and after treatment.

RESULTS

Vol 4, No 2, April-June, 1995

assessment revealed schizophrenia

oses including one epileptic and th.ree

cases,

all

were

in

an acute anxiety

were normal before and after treatment.

status

patients (77.8%) (Figure

l).

A

secon

the same patients, one month

later,

al vitamin -86

.tut*

_for

all but

one

patient

_{re 2), with a slight}

improve-ment

of

the

status

for

2 patients (7.4%)

(Figure

3),

_{he vitamin}

86

_status

of

_the

patients

_{D) and}

after on

sD),

t

?'3:

0.0005)

of the

patients _{prior to treatment}

(%

_{Tpp effect}

=

_37.11

t

31.07) (x

t

one month of treatment (%

TPP

effect

_{72) (x}

t SD),

_{rhe difference}

is just

signi

_p < 0.05).

DISCUSSION

tenance, the normal

tbe nervous system.

lowances

(RDA)

fo

periodically revised by the Dietary Allowances Com_ mittee

of

the Food and Nutrition

Board.

These al_

t levels sufficiently high to cover the

I healthy individuals in their age and

vels are set high because the exact

allowance,

will

not nec

but the

risk

of

becomi

intake

is

_{less than the}

mended.

B Vitarttitts assessiltent 125

rncrease( tissue tequirûme,ntt

for

_vitamins

nny

cause a _{nutdtiona\ delïcïency to deve\op, despite the}

ingestion

ofa

diet that had previously been adequate.

For example, requirements for some vitamins mày be

altered by the use of certain antivitamin drugs, such as the interference _{wirh the utilization}

of

folic

_{acid by} trimethoprim.

ll

Dir"ur".

_{associated with an increased}

metabolic rate, such _{as hyperthyroidism and condi_}

tions accompanied

by

_fever

or

_{tissue wasting, also} increase the bodys requirements

for

vitamins.

_The

impact

of disease

on requirements

for

_{nutrients may} vary according to its phase and intensity. The need for therapy

with

_{vitamins may change ihroughout the}

course

of

the illness and _{eventually, cure should be}

associated with a _{tapering down of the vitamin therapy.}

The

induction

of

convulsive

seizures

_by

pyridoxine deficiency may be the result of a lowered concentration of

GABA.

Glutamate decarboxylase, a pyridoxal phosphate requiring enzyme, catalyses the

synthesis of this inhibitory CNS _{neurotransmitter. In} addition, pyridoxine deficiency leads to decreased con_

centrations

of

the

neurotransmitters

NE

and

serotonin.l2 The dramatic improvement of the vitamin 86 status, the rapid _{shifting lrom a deficient state to an} almost normal condition, indicates a direct connection between the vitamin 86 status of the patients and the course of the disease.

As PLP is an essential _{cofactor for the synthesis}

of serotonin and NE, a fluctuation

in

the vitamin 86

status may result in similar changes

in

serotonin and

NE

levels. An increase

or decrease

in

the serotonin

and NE levels of _{psychotic patients is dependent both}

upon the vitamin 86 status and the phaseànd intensity of the mental process. _{An acute psychotic patient re_}

quires a higher amount of nutrients and subsequently

will

have a low vitamin

86 status,

resulting

in

lower

levels of serotonin and NE. On the other

haù,

chronic

and stable psychotics

will

_{require less nutrients.}

Thus an adequate vitamin B6 status together with an average normal diet

will

produce _{normal to high} normal serotonin and NE levels in these patients. Al_

though some preliminary findings are supporting these

conclusions, yet because

of

_{the limiteâ material, an}

evaluation

of

_{more patients over}

a

_{longer period}

of

time together with a more extensive study-would be the answer,

We conclude that the vitamin

86

status

of

the

patierrts.is fluctuating paradoxically

to

the stage

of

psychosis. _{The higher the state of mental disintegra_} tion the lower the _{vitamin 86} status of the patients.

No dramatic change is found

in

the vitamin 81

7

t26 Utann et al _{Ned J Indottes}

I

Before treatment

E

Aftertreatment

[image:4.595.63.554.70.382.2] [image:4.595.61.554.394.712.2]

Vit.

86

Vit.

81

Vit. B6+Vit. 81 status

Figure

l.

Histogratn of the psychotic patientsu,ithlowvit. BI,vit. 86 and aconrbined lowvit. Bl and 86statusbeforeand

afier treattnent.

NORMAL STATUS

-f-After treatrirent

--l--Before treatment

12 8 9 lO11 '121314 15 161718 192021 22324252627

Patlent Number

Figure 2. Vit 86 sraus of rhe psychotic patie,ils otr rulnittance aatd afier one uonrh of hospitalizatiott

o

J G o

lD .E E lE -Ë

3

-9

Ë

3 o

c

.9

(g CL

o

s

o

L

o

G

.E o

o

tr .9_o

oo

Vol 4, No 2, April-June, 1995

1

2

3 4

5

6 7 I I

1011 1213141516.t7.t8 1920212?2324252627 [image:5.595.52.549.38.421.2]

Patient Number

Figure 3. Vit 81 status of the psychotic patients on adtnittance and after one nrcnth of hosl italizatiott

REFBRENCES

1. Carlsson A. Early psychopharmacology and the rise in

modern brain research, I Psychopharmacol 1990;4:120-6. 2. Cumingham TJ. Naturally occurring neuron death and its

regulation by developing neural pathways. Int Rev Cytol 1982;74:163-86.

3. Hamburger

V.

Oppenheim

RN.

Naturally occurring neuronal death in vertebrates. Neurosci Comrnent 1982;l: 39-55.

4. Levi-Montalcini

R.

Developmental neurobiology and the natural history of nerve growth factor. Annu Rev Neurosci

1982;5:341-61.

5. Levi-Montalcini R. Angeletti

PU.

Nerve growth factor. Physiol Rev 1 968 _;48 :534-69.

6. Hyden H. RNA in brain cells. In: _{Quarton GC. Melnechuk}

T. Schmitt FO. editors. New York: Rockefeller Univ press

1967;248-66.

B Vitanins assessilrcnt r27

{-Aftertreatrnent

--l--Before treatment

NORMAL STATUS

7. Selak I. Skaper SD, Varon S. Pyruvate participation in the

low molecular weight trophic activity for CNS neurons in glia-conditioned media. f Neurosci 1986;5:23-8.

8. Varon S. Skaper SD. Facci L. Rudge

I.

Manthorpe M.

Trophic and metabolic couplings between astroglia and

neurons. In: Althaus H. Seifert W. editors. Glial-Neuronal Communications in Development and Regeneration. New

York: Springer 198 6;49 l-504.

9. _{Setiadi E, Musram W, Hamopidjari D,} Djalil H. Efek Tpp

(tiaminpirofosfat) dan konsumsi

vit

B1 sekelompok mahasiswa. Maj Kedok Indon l99l;41,645-8.

10. Musram W. Penetapan status vitamin

86

dengan uji

aminotransferase eritrosit. Maj Kedok Indon 1994; 44,

154-7.

I

l.

Roe DA, Drug interference with the assessment of nutrition-al status. Clin I-ab Med 1981;l:647-64.

12. Dakshinamurti K. B vitantins and nervous system function,

In:

Wurtman RJ. Wurtrnan IL editors. Nutrition and the