Basis Neurobiologi

Gangguan Mood
Oleh:
Dr. H. Jaya Mualimin,
SpKJ,Mkes.

WHAT CAUSE GANGGUAN MOOD?

The cause of bipolar disorder is not entirely known
Genetic, neuro-chemical and environmental
factors probably interact at many levels to play a
role in the onset and progression of bipolar
disorder
The current thinking is that this is a predominantly
biological disorder that occurs in a specific part of
the brain and is due to a malfunction of the
neurotransmitters (chemical messengers in the
brain)
As a biological disorder, it may lie dormant and be
activated spontaneously or it may be triggered by
stressors in life

Tumbuh-Kembang Otak
Gopnick et. al. (1999)hipotesis jaringan
kabel telepon
350 gr

1000 gr

2500
sinap/neur
on

15000
sinap/neur
on

1200-1400 gr
100 Milyar
neuron
Sinap ???

Neuron dan koneksi sinaptik

Hebb Rules
Impuls dari
neuron lain

Transmisi
Impuls
saraf

Pembebasan
zat hantar saraf

The New Born Brain 2002, p 208

Mekanisme-mekanisme neuroplastisitas

Prunning
Apoptosis
Sprouting
Collateral sprouting
Heterotypic
Homotypic
Seeman P. Brain development. Am J Psych
1999;156(2):168

Pathopsikologis Neuron
stressStressors(psychological, hormonal,
medication)

Ganggua
n mental

Genes
Multiple
susceptibility
alleles each of
small effect;
BDNF, Bcl-2,
diacylglycerolkina
seeta

Epigenetics
Gene and Protein
Expression,
e.g., BDNF levels
reduced during
depression,
mania,
Oxidative stress

Cells:
Multiple
glialand
neuronal
abnormalities;
mitochondrial
dysfunction

Systems:
Abnormal function and
information processing
In multiple, interacting
circuitsBipolarDisorder
s

Behavior:
Complex
interactions
affecting
emotional,
psychomotor,
cognitive,
visceromotor
function

Neurotropik Sebagai Patofisiologi Defisit Kognitif pada GB

 First messenger:

Hipotesis

Deficiency monoamin neurotransmitter

Serotonine (5-HT)-Norepinephrine (NE)-Dopamine (DA)
Glutamate-GABA
Ion channel: Na+; Ca2+

Celluler level:
neural survival >< apoptosis and mitochondrial dysfunction
BDNF (Brain-Derived Neurotrophic Factor) Bcl2 (B-cell Lymphoma)
NAA (N-Acetyl Aspartate)
myo-inositol

Neuroimmune:
cytokines (Interleukin, Tumor Necroting Factor,
Interferon)

Neurohormonal:
cortisol-estrogen-tyroid

Brain Areas that Regulate Mood

FC: Frontal cortex (esp.

prefrontal and cingulate)
-cognitive function, attention
HP: Ventral Hippocampus
-cognitive function, memory
NAc: Nucleus
Accumbens(ventral striatum)
-reward and aversion
Amy: Amygdala-mediates
responses to emotional
stimuli
HYP: Hypothalamus regulates
sleep, appetite, energy, sex
VTA: Ventral TegmentalArea
-Sends
dopaminergicprojections to
other areas
DR: Dorsal Raphenuclei -send
serotonergicinput to other
areas
LC: Locus Coeruleus-sends
noradrenergic input to other
areas.

Perubahan Struktur Otak

pada GB
Pelebaran ventrikel lateral atau
ventricular/brain ratios (VBRs) (1)
Ventrikel lateral pada Lk >> Wt
Volume lobus temporal medial
pada GB vs kontrol, ditemukan pula
pada keadaan eutim (2)
Rata-rata VBR
meningkatsecarabermaknasetelah3
1.AndreasenNC. dkk. Am J Psychiatry 1990; 147: 893tahun (3)
9002.
2.Olson SC, dkk. BiolPsychiatry 1990; 27: 59A-60A3.
3.Vita A, dkk. SchozophrRes 1988; 1: 165-166

Patofisiologi Defisit Kognitif pada GB

Peranan BDNF pada Perubahan Neuron

Defisit Kognitif Penanda Sifat GB

Defisit kognitif terlihat pada stadium

awal penyakit (1)
Terdapat pada keluarga kandung yang
tidak GB tetapi mempunyai persamaan
kerentanan genetik (2)
Penanda endofenotipik kerentanan
genetik
Eutimik tanpa obat vs dengan
obatperforma kognitifnya tidak berbeda
(3)

Besar kemungkinan defisit

kognitifpenanda sifat GB1
1. AlbusM, dkk. ActaPsychiatrScand. 1996; 94: 87-932.
2. ZallaT, dkk. PsyciatryRes. 2004;121: 207-217
3. 3.GoswamiU, dkk. J Psychopharmacol. 2002; 16: 456

DefisitKognitifpadaDepresiBipolar VS Unipolar

Fungsi
eksekutif

Memori

Faktor Neurotropik pada GB

BDNF, NGF, dan FNF
Di hipokampus dan korteks serebri
Hipokampus berperanan penting
dalam mood dan memori
Volume berkurang pada depresi
Penting dalam kelangsungan hidup
GABA, DA, NE, dan Serotonin
BDNF
mengaturmooddankognitifpadaGB

terimakasih