PATOGENESIS DEPRESI

• nerve cell BRAIN + NEUROTRANSMITTERS

connections • Amygdala • Dopamin
• nerve cell growth • Thalamus • Serotonin
• the functioning of • Hippocampus • Epinefrin
nerve circuits
GE

MEDICAL PROBLEMS : GENETIC :

• Hypo/Hyperthyroid • Serotonin-transporter gene
DEPRESSION
(5-HTT)
• CRHR1
• G1463A
• Familial

STRESSFUL LIFE EVENTS :

• Hormonal – HPA Axis
MEDICATIONS
• Early losses
• Trauma
Brain + Neurotransmitters
• The amygdala - The amygdala is part of the limbic system, a group of
structures deep in the brain that’s associated with emotions such as
anger, pleasure, sorrow, fear, and sexual arousal. Activity in the
amygdala is higher when a person is sad or clinically depressed. This
increased activity continues even after recovery from depression.
• Thalamus - Some research suggests that bipolar disorder may result
from problems in the thalamus, which helps link sensory input to
pleasant and unpleasant feelings.
• Hippocampus - The hippocampus is smaller in some depressed
people, and research suggests that ongoing exposure to stress
hormone impairs the growth of nerve cells in this part of the brain.
• Neurotransmitter - dalam bagian otak tersebut juga turut berperan
dalam Patogenesis Depresi : Brain cells usually produce levels of
neurotransmitters that keep senses, learning, movements, and moods
perking along. But in some people who are severely depressed or
manic, the complex systems that accomplish this go awry. For
example, receptors may be oversensitive or insensitive to a specific
neurotransmitter, causing their response to its release to be excessive
or inadequate. Or a message might be weakened if the originating cell
pumps out too little of a neurotransmitter or if an overly efficient
reuptake mops up too much before the molecules have the chance to
bind to the receptors on other neurons. Any of these system faults
Neurotransmitters
• Dopamin is essential to movement. It also influences motivation and
plays a role in how a person perceives reality. Problems in dopamine
transmission have been associated with psychosis, a severe form of
distorted thinking characterized by hallucinations or delusions.
• Serotonin : helps regulate sleep, appetite, and mood and inhibits
pain. Research supports the idea that some depressed people have
reduced serotonin transmission. Low levels of a serotonin byproduct
have been linked to a higher risk for suicide.
• Epinefrin/Norepinephrine : constricts blood vessels, raising blood
pressure. It may trigger anxiety and be involved in some types of
depression.
Genetic
• Masih belum banyak diketahui peran masing-masing gen dalam
patogenesis depresi
• a particular variant in a serotonin-transporter gene (5-HTT) were more likely to
become depressed in response to stress. The gene comes in “short” (less efficient)
and “long” (more efficient) versions. No combination of short or long variants leads
directly to depression, but short versions of the gene put people at a distinct
disadvantage if they experience stressful life events.
• researchers studied a gene that influences a person’s reaction to childhood abuse.
This gene (CRHR1) provides the code for one of the stress hormones —
corticotrophin-releasing hormone or CRH (see “How stress affects the body”). For
this study, published in Archives of General Psychiatry, researchers interviewed 621
adults and tested their DNA. Among people who suffered childhood abuse, those
with the relatively protective versions of the CRHR1 gene had half the symptoms of
depression as participants without this genetic variation. This study not only added
to knowledge about protective genes, but also lent further credence to the theory
that stress hormones play an important role in depression.
• G1463A. People with this atypical DNA sequence are more likely to have
major depression than those who don’t.
• It is well known that depression and bipolar disorder run in families.
A person who has a first-degree relative who suffered major depression has an
increase in risk for the condition of 1.5% to 3% over normal.
Stressful Life Events
• nearly everyone encounters stressful life events: the death of a loved one, the
loss of a job, an illness, or a relationship spiraling downward. Some must cope
with the early loss of a parent, violence, or sexual abuse. While not everyone who
faces these stresses develops a mood disorder — in fact, most do not — stress
plays an important role in depression.
• Stress has its own physiological consequences. It triggers a chain of chemical
reactions and responses in the body. If the stress is short-lived, the body usually
returns to normal. But when stress is chronic or the system gets stuck in
overdrive, changes in the body and brain can be long-lasting.
• Stress can be defined as an automatic physical response to any stimulus that
requires you to adjust to change. Every real or perceived threat to your body
triggers a cascade of stress hormones that produces physiological changes. We all
know the sensations: your heart pounds, muscles tense, breathing quickens, and
beads of sweat appear. This is known as the stress response.
• Hipotalamus  corticotropin-releasing hormone (CRH), which has the job of rousing
your body. Hormones are complex chemicals that carry messages to organs or groups of
cells throughout the body and trigger certain responses. CRH follows a pathway to your
pituitary gland, where it stimulates the secretion of adrenocorticotropic hormone
(ACTH), which pulses into your bloodstream. When ACTH reaches your adrenal glands, it
prompts the release of cortisol.
• The boost in cortisol readies your body to fight or flee. Your heart beats faster — up to
five times as quickly as normal — and your blood pressure rises. Your breath quickens as
your body takes in extra oxygen. Sharpened senses, such as sight and hearing, make you
more alert.
• CRH also affects the cerebral cortex, part of the amygdala, and the brainstem. It is
thought to play a major role in coordinating your thoughts and behaviors, emotional
reactions, and involuntary responses. Working along a variety of neural pathways, it
influences the concentration of neurotransmitters throughout the brain. Disturbances in
hormonal systems, therefore, may well affect neurotransmitters, and vice versa.
Early losses
• Certain events can have lasting physical, as well as emotional, consequences.
Researchers have found that early losses and emotional trauma may leave
individuals more vulnerable to depression later in life. death of a parent or the
withdrawal of a loved one’s affection, may resonate throughout life, eventually
expressing themselves as depression
• The British psychiatrist John Bowlby focused on early losses in a number of
landmark studies of monkeys. When he separated young monkeys from their
mothers, the monkeys passed through predictable stages of a separation
response. Their furious outbursts trailed off into despair, followed by apathetic
detachment. Meanwhile, the levels of their stress hormones rose. Later
investigators extended this research. One study found that the CRH system and
HPA axis got stuck in overdrive in adult rodents that had been separated from
their mothers too early in life. This held true whether or not the rats were
purposely put under stress. Interestingly, antidepressants and electroconvulsive
therapy relieve the symptoms of animals distressed by such separations.
Trauma
• The role of trauma. Traumas may also be indelibly etched on the psyche. A
small but intriguing study in the Journal of the American Medical
Association showed that women who were abused physically or sexually as
children had more extreme stress responses than women who had not
been abused. The women had higher levels of the stress hormones ACTH
and cortisol, and their hearts beat faster when they performed stressful
tasks, such as working out mathematical equations or speaking in front of
an audience.
• early trauma causes subtle changes in brain function that account for
symptoms of depression and anxiety. The key brain regions involved in the
stress response may be altered at the chemical or cellular level. Changes
might include fluctuations in the concentration of neurotransmitters or
damage to nerve cells. However, further investigation is needed to clarify
the relationship between the brain, psychological trauma, and depression.
Medical Problem
• medical illnesses or medications may be at the root of up to 10% to 15% of
all depressions.
• thyroid hormone (hyperthyroidism) can trigger manic symptoms. On the
other hand, hypothyroidism, a condition in which your body produces too
little thyroid hormone, often leads to exhaustion and depression.

• Heart disease has also been linked to depression, with up to half of heart
attack survivors reporting feeling blue and many having significant
depression. Depression can spell trouble for heart patients: it’s been linked
with slower recovery, future cardiovascular trouble, and a higher risk of
dying within about six months. Although doctors have hesitated to give
heart patients older depression medications called tricyclic antidepressants
because of their impact on heart rhythms, selective serotonin reuptake
inhibitors seem safe for people with heart conditions.
Others medical problem
• degenerative neurological conditions, such as multiple sclerosis,
Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease
• stroke
• some nutritional deficiencies, such as a lack of vitamin B12
• other endocrine disorders, such as problems with the parathyroid or
adrenal glands that cause them to produce too little or too much of
particular hormones
• certain immune system diseases, such as lupus
• some viruses and other infections, such as mononucleosis, hepatitis, and
HIV
• cancer
• erectile dysfunction in men.
Table 1: Medications that may cause depression
Antimicrobials, antibiotics, antifungals, and antivirals
acyclovir (Zovirax); alpha-interferons; cycloserine (Seromycin); ethambutol (Myambutol); levofloxacin (Levaquin);
metronidazole (Flagyl); streptomycin; sulfonamides (AVC, Sultrin, Trysul); tetracycline

Heart and blood pressure drugs

beta blockers such as propranolol (Inderal), metoprolol (Lopressor, Toprol XL), atenolol (Tenormin); calcium-
channel blockers such as verapamil (Calan, Isoptin, Verelan) and nifedipine (Adalat CC, Procardia XL); digoxin
(Digitek, Lanoxicaps, Lanoxin); disopyramide (Norpace); methyldopa (Aldomet)

Hormones
anabolic steroids; danazol (Danocrine); glucocorticoids such as prednisone and adrenocorticotropic hormone;
estrogens (e.g., Premarin, Prempro); oral contraceptives (birth control pills)

Tranquilizers, insomnia aids, and sedatives

barbiturates such as phenobarbital (Solfoton) and secobarbital (Seconal); benzodiazepines such as diazepam
(Valium) and clonazepam (Klonopin)
Miscellaneous
acetazolamide (Diamox); antacids such as cimetidine (Tagamet) and ranitidine (Zantac); antiseizure drugs;
baclofen (Lioresal); cancer drugs such as asparaginase (Elspar); cyclosporine (Neoral, Sandimmune); disulfiram
(Antabuse); isotretinoin (Accutane); levodopa or L-dopa (Larodopa); metoclopramide (Octamide, Reglan); narcotic
pain medications (e.g., codeine, Percodan, Demerol, morphine); withdrawal from cocaine or amphetamines
• Mood dan Afek
kesedihan, berkurangnya reaksi terhadap hal-hal menyenangkan atau tak
menyenangkan, rasa hampa, apati, cemas, tegang, iritabel, marah
• Pikiran – Kognisi
konsentrasi berkurang, sulit membuat keputusan, kurang percaya diri, rasa
bersalah, tak berdaya, keinginan mati, ide-ide bunuh diri
• Aktivitas Psikomotor
retardasi (melambatnya gerakan-gerakan tubuh, penurunan ekspresi wajah,
berkurangnya komunikasi,) agitasi (gelisah, tak bisa diam, hiperaktivitas, tak
bertujuan dan tak terkendali)
• Somatik
perubahan fungsi dasar (insomnia, hipersomnia, peningkatan/penurunan
nafsu makan, penurunan libido), penurunan vitalitas (letih, kehilangan semangat),
sensasi tubuh (pegal, nyeri, rasa tertekan, kedinginan, tungkai berat) dan gejala-
gejala viseral (keluhan-keluhan saluran cerna dan kardiovaskular