I.

OVERVIEW

Depression (also known as major depression, major depressive disorder, or clinical depression) is
a common but serious mood disorder. It causes severe symptoms that affect how a person feels,
thinks, and handles daily activities, such as sleeping, eating, or working.

To be diagnosed with depression, the symptoms must be present for at least 2 weeks.

There are different types of depression, some of which develop due to specific circumstances.

 Major depression includes symptoms of depressed mood or loss of interest, most of the
time for at least 2 weeks, that interfere with daily activities.
 Persistent depressive disorder (also called dysthymia or dysthymic disorder) consists of
less severe symptoms of depression that last much longer, usually for at least 2 years.
 Perinatal depression is depression that occurs during pregnancy or after childbirth.
Depression that begins during pregnancy is prenatal depression, and depression that
begins after the baby is born is postpartum depression.
 Seasonal affective disorder is depression that comes and goes with the seasons, with
symptoms typically starting in the late fall or early winter and going away during the
spring and summer.
 Depression with symptoms of psychosis is a severe form of depression in which a
person experiences psychosis symptoms, such as delusions (disturbing, false fixed
beliefs) or hallucinations (hearing or seeing things others do not hear or see).

People with bipolar disorder (formerly called manic depression or manic-depressive illness)
also experience depressive episodes, during which they feel sad, indifferent, or hopeless,
combined with a very low activity level. But a person with bipolar disorder also experiences
manic (or less severe hypomanic) episodes, or unusually elevated moods, in which they might
feel very happy, irritable, or “up,” with a marked increase in activity level.

Other depressive disorders found in the Diagnostic and Statistical Manual of Mental Disorders,
Fifth Edition (DSM-5-TR) include disruptive mood dysregulation disorder (diagnosed in
children and adolescents) and premenstrual dysphoric disorder (that affects women around the
time of their period).

Who gets depression?

Depression can affect people of all ages, races, ethnicities, and genders.

Women are diagnosed with depression more often than men, but men can also be depressed.
Because men may be less likely to recognize, talk about, and seek help for their feelings or
emotional problems, they are at greater risk of their depression symptoms being undiagnosed or
undertreated.

Studies also show higher rates of depression and an increased risk for the disorder among
members of the LGBTQI+ community.

What are the signs and symptoms of depression?

If you have been experiencing some of the following signs and symptoms, most of the day,
nearly every day, for at least 2 weeks, you may have depression:

 Persistent sad, anxious, or “empty” mood

 Feelings of hopelessness or pessimism
 Feelings of irritability, frustration, or restlessness
 Feelings of guilt, worthlessness, or helplessness
 Loss of interest or pleasure in hobbies and activities
 Fatigue, lack of energy, or feeling slowed down
 Difficulty concentrating, remembering, or making decisions
  Difficulty sleeping, waking too early in the morning, or oversleeping
 Changes in appetite or unplanned weight changes
 Physical aches or pains, headaches, cramps, or digestive problems without a clear
physical cause that do not go away with treatment
 Thoughts of death or suicide or suicide attempts

Not everyone who is depressed experiences all these symptoms. Some people experience only a
few symptoms, while others experience many. Symptoms associated with depression interfere
with day-to-day functioning and cause significant distress for the person experiencing them.

Depression can also involve other changes in mood or behavior that include:

 Increased anger or irritability

 Feeling restless or on edge
 Becoming withdrawn, negative, or detached
 Increased engagement in high-risk activities
 Greater impulsivity
 Increased use of alcohol or drugs
 Isolating from family and friends
 Inability to meet the responsibilities of work and family or ignoring other important roles
 Problems with sexual desire and performance

Depression can look different in men and women. Although people of all genders can feel
depressed, how they express those symptoms and the behaviors they use to cope with them may
differ. For example, men (as well as women) may show symptoms other than sadness, instead
seeming angry or irritable. And although increased use of alcohol or drugs can be a sign of
depression in anyone, men are more likely to use these substances as a coping strategy.

In some cases, mental health symptoms appear as physical problems (for example, a racing heart,
tightened chest, ongoing headaches, or digestive issues). Men are often more likely to see a
health care provider about these physical symptoms than their emotional ones.

Because depression tends to make people think more negatively about themselves and the world,
some people may also have thoughts of suicide or self-harm.

Several persistent symptoms, in addition to low mood, are required for a diagnosis of depression,
but people with only a few symptoms may benefit from treatment. The severity and frequency of
symptoms and how long they last will vary depending on the person, the illness, and the stage of
the illness.

If you experience signs or symptoms of depression and they persist or do not go away, talk to a
health care provider. If you see signs or symptoms of depression in someone you know,
encourage them to seek help from a mental health professional.

What are the risk factors for depression?

Depression is one of the most common mental disorders in the United States. Research suggests
that genetic, biological, environmental, and psychological factors play a role in depression.

Risk factors for depression can include:

 Personal or family history of depression

 Major negative life changes, trauma, or stress

Depression can happen at any age, but it often begins in adulthood. Depression is now
recognized as occurring in children and adolescents, although children may express more
irritability or anxiety than sadness. Many chronic mood and anxiety disorders in adults begin as
high levels of anxiety in childhood.

Depression, especially in midlife or older age, can co-occur with other serious medical illnesses,
such as diabetes, cancer, heart disease, chronic pain, and Parkinson’s disease. These conditions
are often worse when depression is present, and research suggests that people with depression
and other medical illnesses tend to have more severe symptoms of both illnesses. The Centers for
Disease Control and Prevention (CDC) has also recognized that having certain mental disorders,
including depression and schizophrenia, can make people more likely to get severely ill from
COVID-19.

Sometimes a physical health problem, such as thyroid disease, or medications taken for an illness
cause side effects that contribute to depression. A health care provider experienced in treating
these complicated illnesses can help determine the best treatment strategy.

How is depression treated?

Depression, even the most severe cases, can be treated. The earlier treatment begins, the more
effective it is. Depression is usually treated with psychotherapy, medication, or a combination of
the two.

Some people experience treatment-resistant depression, which occurs when a person does not get
better after trying at least two antidepressant medications. If treatments like psychotherapy and
medication do not reduce depressive symptoms or the need for rapid relief from symptoms is
urgent, brain stimulation therapy may be an option to explore.

Quick tip: No two people are affected the same way by depression, and there is no "one-size-
fits-all" treatment. Finding the treatment that works best for you may take trial and error.

Psychotherapies

Several types of psychotherapy (also called talk therapy or counseling) can help people with
depression by teaching them new ways of thinking and behaving and helping them change habits
that contribute to depression. Evidence-based approaches to treating depression include
cognitive-behavioral therapy (CBT) and interpersonal therapy (IPT). Learn more
about psychotherapy.

The growth of telehealth for mental health services, which offers an alternative to in-person
therapy, has made it easier and more convenient for people to access care in some cases. For
people who may have been hesitant to look for mental health care in the past, virtual mental
health care might be an easier option.

Medications

Antidepressants are medications commonly used to treat depression. They work by changing
how the brain produces or uses certain chemicals involved in mood or stress. You may need to
try several different antidepressants before finding the one that improves your symptoms and has
manageable side effects. A medication that has helped you or a close family member in the past
will often be considered first.

Antidepressants take time—usually 4–8 weeks—to work, and problems with sleep, appetite, and
concentration often improve before mood lifts. It is important to give a medication a chance to
work before deciding whether it’s right for you. Learn more about mental health medications.

New medications, such as intranasal esketamine, can have rapidly acting antidepressant effects,
especially for people with treatment-resistant depression. Esketamine is a medication approved
by the U.S. Food and Drug Administration (FDA) for treatment-resistant depression. Delivered
as a nasal spray in a doctor’s office, clinic, or hospital, it acts rapidly, typically within a couple of
hours, to relieve depression symptoms. People who use esketamine will usually continue taking
an oral antidepressant to maintain the improvement in their symptoms.

Another option for treatment-resistant depression is to take an antidepressant alongside a

different type of medication that may make it more effective, such as an antipsychotic or
anticonvulsant medication. Further research is needed to identify the role of these newer
medications in routine practice.

If you begin taking an antidepressant, do not stop taking it without talking to a health care
provider. Sometimes people taking antidepressants feel better and stop taking the medications
on their own, and their depression symptoms return. When you and a health care provider have
decided it is time to stop a medication, usually after a course of 9–12 months, the provider will
help you slowly and safely decrease your dose. Abruptly stopping a medication can cause
withdrawal symptoms.

Note: In some cases, children, teenagers, and young adults under 25 years may experience an
increase in suicidal thoughts or behavior when taking antidepressants, especially in the first few
weeks after starting or when the dose is changed. The FDA advises that patients of all ages
taking antidepressants be watched closely, especially during the first few weeks of treatment.

If you are considering taking an antidepressant and are pregnant, planning to become pregnant,
or breastfeeding, talk to a health care provider about any health risks to you or your unborn or
nursing child and how to weigh those risks against the benefits of available treatment options.

To find the latest information about antidepressants, talk to a health care provider and visit
the FDA website .

Brain stimulation therapies

If psychotherapy and medication do not reduce symptoms of depression, brain stimulation

therapy may be an option to explore. There are now several types of brain stimulation therapy,
some of which have been authorized by the FDA to treat depression. Other brain stimulation
therapies are experimental and still being investigated for mental disorders like depression.

Although brain stimulation therapies are less frequently used than psychotherapy and
medication, they can play an important role in treating mental disorders in people who do not
respond to other treatments. These therapies are used for most mental disorders only after
psychotherapy and medication have been tried and usually continue to be used alongside these
treatments.

Brain stimulation therapies act by activating or inhibiting the brain with electricity. The
electricity is given directly through electrodes implanted in the brain or indirectly through
electrodes placed on the scalp. The electricity can also be induced by applying magnetic fields to
the head.

The brain stimulation therapies with the largest bodies of evidence include:

 Electroconvulsive therapy (ECT)

 Repetitive transcranial magnetic stimulation (rTMS)
 Vagus nerve stimulation (VNS)
 Magnetic seizure therapy (MST)
 Deep brain stimulation (DBS)

ECT and rTMS are the most widely used brain stimulation therapies, with ECT having the
longest history of use. The other therapies are newer and, in some cases, still considered
experimental. Other brain stimulation therapies may also hold promise for treating specific
mental disorders.

ECT, rTMS, and VNS have authorization from the FDA to treat severe, treatment-resistant
depression. They can be effective for people who have not been able to feel better with other
treatments; people for whom medications cannot be used safely; and in severe cases where a
rapid response is needed, such as when a person is catatonic, suicidal, or malnourished.

Additional types of brain stimulation therapy are being investigated for treating depression and
other mental disorders. Talk to a health care provider and make sure you understand the potential
benefits and risks before undergoing brain stimulation therapy. Learn more about these brain
stimulation therapies.

Natural products

The FDA has not approved any natural products for treating depression. Although research is
ongoing and findings are inconsistent, some people use natural products, including vitamin D
and the herbal dietary supplement St. John’s wort, for depression. However, these products can
come with risks. For instance, dietary supplements and natural products can limit the
effectiveness of some medications or interact in dangerous or even life-threatening ways with
them.

Do not use vitamin D, St. John’s wort, or other dietary supplements or natural products without
talking to a health care provider. Rigorous studies must be conducted to test whether these and
other natural products are safe and effective.

Daily morning light therapy is a common treatment choice for people with seasonal affective
disorder (SAD). Light therapy devices are much brighter than ordinary indoor lighting and
considered safe, except for people with certain eye diseases or taking medications that increase
sensitivity to sunlight. As with all interventions for depression, evaluation, treatment, and follow-
up by a health care provider are strongly recommended. Research into the potential role of light
therapy in treating non-seasonal depression is ongoing.

How can I find help for depression?

A primary care provider is a good place to start if you’re looking for help. They can refer you to
a qualified mental health professional, such as a psychologist, psychiatrist, or clinical social
worker, who can help you figure out next steps. Find tips for talking with a health care provider
about your mental health.

You can learn more about getting help on the NIMH website. You can also learn about finding
support and locating mental health services in your area on the Substance Abuse and Mental
Health Services Administration (SAMHSA) website.

Once you enter treatment, you should gradually start to feel better. Here are some other things
you can do outside of treatment that may help you or a loved one feel better:

 Try to get physical activity. Just 30 minutes a day of walking can boost your mood.
 Try to maintain a regular bedtime and wake-up time.
 Eat regular, healthy meals.
 Break up large tasks into small ones; do what you can as you can. Decide what must get
done and what can wait.
 Try to connect with people. Talk with people you trust about how you are feeling.
 Delay making important decisions, such as getting married or divorced, or changing jobs
until you feel better. Discuss decisions with people who know you well.
 Avoid using alcohol, nicotine, or drugs, including medications not prescribed for you.

How can I find a clinical trial for depression?

Clinical trials are research studies that look at new ways to prevent, detect, or treat diseases and
conditions, including depression. The goal of a clinical trial is to determine if a new test or
treatment works and is safe. Although people may benefit from being part of a clinical trial, they
should know that the primary purpose is to gain new scientific knowledge so that others can be
better helped in the future.

Researchers at NIMH and around the country conduct many studies with people with and
without depression. We have new and better treatment options today because of what clinical
trials have uncovered. Talk to a health care provider about clinical trials, their benefits and risks,
and whether one is right for you.

To learn more or find a study, visit:

 Clinical Trials – Information for Participants: Information about clinical trials, why
people might take part in a clinical trial, and what people might experience during a
clinical trial
 Clinicaltrials.gov: Current Studies on Depression : List of clinical trials funded by the
National Institutes of Health (NIH) being conducted across the country
 Join a Study: Depression—Adults: List of studies currently recruiting adults with
depression being conducted on the NIH campus in Bethesda, MD
 Join a Study: Depression—Children: List of studies currently recruiting children with
depression being conducted on the NIH campus in Bethesda, MD
  Join a Study: Perimenopause-Related Mood Disorders: List of studies on
perimenopause-related mood disorders being conducted on the NIH campus in Bethesda,
MD
 Join a Study: Postpartum Depression: List of studies on postpartum depression being
conducted on the NIH campus in Bethesda, MD

Where can I learn more about depression?

Free brochures and shareable resources

 Chronic Illness and Mental Health: Recognizing and Treating Depression: This
brochure provides information about depression for people living with chronic illnesses,
including children and adolescents. It discusses signs and symptoms, risk factors, and
treatment options.
 Depression: This brochure provides information about depression, including different
types of depression, signs and symptoms, how it is diagnosed, treatment options, and how
to find help for yourself or a loved one.
 Depression in Women: 4 Things to Know: This fact sheet provides information about
depression in women, including signs and symptoms, types of depression unique to
women, and how to get help.
 Perinatal Depression: This brochure provides information about perinatal depression,
including how it differs from “baby blues,” causes, signs and symptoms, treatment
options, and how to find help for yourself or a loved one.
 Seasonal Affective Disorder: This fact sheet provides information about seasonal
affective disorder, including signs and symptoms, how it is diagnosed, causes, and
treatment options.
 Seasonal Affective Disorder (SAD): More Than the Winter Blues: This infographic
provides information about how to recognize the symptoms of SAD and what to do to get
help.
 Teen Depression: More Than Just Moodiness: This fact sheet is for teens and young
adults and provides information about how to recognize the symptoms of depression and
what to do to get help.
 Digital Shareables on Depression: These digital resources, including graphics and
messages, can be used to spread the word about depression and help promote depression
awareness and education in your community.

Federal resources

 Depression (MedlinePlus - also en español )

 Moms’ Mental Health Matters: Depression and Anxiety Around Pregnancy (Eunice
Kennedy Shriver National Institute of Child Health and Human Development)

Research and statistics

 Journal Articles : This webpage provides articles and abstracts on depression from
MEDLINE/PubMed (National Library of Medicine).
 Statistics: Major Depression: This webpage provides the statistics currently available on
the prevalence and treatment of depression among people in the United States.

Multimedia

 Depression Mental Health Minute: Take a mental health minute to watch this video on
depression.
 NIMH Experts Discuss the Menopause Transition and Depression: Learn about the
signs and symptoms, treatments, and latest research on depression during menopause.
 NIMH Expert Discusses Seasonal Affective Disorder: Learn about the signs and
symptoms, treatments, and latest research on seasonal affective disorder.
 Discover NIMH: Personalized and Targeted Brain Stimulation Therapies: Watch this
video describing repetitive transcranial magnetic stimulation and electroconvulsive
therapy for treatment-resistant depression. Brain stimulation therapies can be effective
treatments for people with depression and other mental disorders. NIMH supports studies
 exploring how to make brain stimulation therapies more personalized while reducing side
effects.
 Discover NIMH: Drug Discovery and Development: One of the most exciting
breakthroughs from research funded by NIMH is the development of a fast-acting
medication for treatment-resistant depression based on ketamine. This video shares the
story of how ketamine infusions meaningfully changed the life of a participant in an
NIMH clinical trial.
 Mental Health Matters Podcast: Depression: The Case for Ketamine: Dr. Carlos
Zarate Jr. discusses esketamine—the medication he helped discover—for treatment-
resistant depression. The podcast covers the history behind the development of
esketamine, how it can help with depression, and what the future holds for this innovative
line of clinical research.

II. ANATOMY AND PHYSIOLOGY

Anatomy of the Brain

Overview

The brain is an amazing three-pound organ that controls all functions of the body, interprets
information from the outside world, and embodies the essence of the mind and soul. Intelligence,
creativity, emotion, and memory are a few of the many things governed by the brain. Protected
within the skull, the brain is composed of the cerebrum, cerebellum, and brainstem.

The brain receives information through our five senses: sight, smell, touch, taste, and hearing -
often many at one time. It assembles the messages in a way that has meaning for us, and can
store that information in our memory. The brain controls our thoughts, memory and speech,
movement of the arms and legs, and the function of many organs within our body.

The central nervous system (CNS) is composed of the brain and spinal cord. The peripheral
nervous system (PNS) is composed of spinal nerves that branch from the spinal cord and cranial
nerves that branch from the brain.
Brain

The brain is composed of the cerebrum, cerebellum, and brainstem (Fig. 1).

Figure 1. The brain has three main parts: the cerebrum, cerebellum and brainstem.
Cerebrum: is the largest part of the brain and is composed of right and left hemispheres. It
performs higher functions like interpreting touch, vision and hearing, as well as speech,
reasoning, emotions, learning, and fine control of movement.

Cerebellum: is located under the cerebrum. Its function is to coordinate muscle movements,
maintain posture, and balance.

Brainstem: acts as a relay center connecting the cerebrum and cerebellum to the spinal cord. It
performs many automatic functions such as breathing, heart rate, body temperature, wake and
sleep cycles, digestion, sneezing, coughing, vomiting, and swallowing.
Right brain – left brain

The cerebrum is divided into two halves: the right and left hemispheres (Fig. 2) They are joined
by a bundle of fibers called the corpus callosum that transmits messages from one side to the
other. Each hemisphere controls the opposite side of the body. If a stroke occurs on the right side
of the brain, your left arm or leg may be weak or paralyzed.

Not all functions of the hemispheres are shared. In general, the left hemisphere controls speech,
comprehension, arithmetic, and writing. The right hemisphere controls creativity, spatial ability,
artistic, and musical skills. The left hemisphere is dominant in hand use and language in about
92% of people.

Figure 2. The cerebrum is divided into left and right hemispheres. The two sides are connected
by the nerve fibers corpus callosum.
Lobes of the brain

The cerebral hemispheres have distinct fissures, which divide the brain into lobes. Each
hemisphere has 4 lobes: frontal, temporal, parietal, and occipital (Fig. 3). Each lobe may be
divided, once again, into areas that serve very specific functions. It’s important to understand
that each lobe of the brain does not function alone. There are very complex relationships between
the lobes of the brain and between the right and left hemispheres.
Figure 3. The cerebrum is divided into four lobes: frontal, parietal, occipital and temporal.
Frontal lobe

 Personality, behavior, emotions

 Judgment, planning, problem solving

 Speech: speaking and writing (Broca’s area)

 Body movement (motor strip)

 Intelligence, concentration, self awareness

Parietal lobe

 Interprets language, words

 Sense of touch, pain, temperature (sensory strip)

 Interprets signals from vision, hearing, motor, sensory and memory

 Spatial and visual perception

Occipital lobe

 Interprets vision (color, light, movement)

Temporal lobe

 Understanding language (Wernicke’s area)

 Memory

 Hearing

 Sequencing and organization

Language

In general, the left hemisphere of the brain is responsible for language and speech and is called
the "dominant" hemisphere. The right hemisphere plays a large part in interpreting visual
information and spatial processing. In about one third of people who are left-handed, speech
function may be located on the right side of the brain. Left-handed people may need special
testing to determine if their speech center is on the left or right side prior to any surgery in that
area.

Aphasia is a disturbance of language affecting speech production, comprehension, reading or

writing, due to brain injury – most commonly from stroke or trauma. The type of aphasia
depends on the brain area damaged.

Broca’s area: lies in the left frontal lobe (Fig 3). If this area is damaged, one may have difficulty
moving the tongue or facial muscles to produce the sounds of speech. The person can still read
and understand spoken language but has difficulty in speaking and writing (i.e. forming letters
and words, doesn't write within lines) – called Broca's aphasia.

Wernicke's area: lies in the left temporal lobe (Fig 3). Damage to this area causes Wernicke's
aphasia. The individual may speak in long sentences that have no meaning, add unnecessary
words, and even create new words. They can make speech sounds, however they have difficulty
understanding speech and are therefore unaware of their mistakes.
Cortex

The surface of the cerebrum is called the cortex. It has a folded appearance with hills and
valleys. The cortex contains 16 billion neurons (the cerebellum has 70 billion = 86 billion total)
that are arranged in specific layers. The nerve cell bodies color the cortex grey-brown giving it
its name – gray matter (Fig. 4). Beneath the cortex are long nerve fibers (axons) that connect
brain areas to each other — called white matter.

Figure 4. The cortex contains neurons (grey matter), which are interconnected to other brain
areas by axons (white matter). The cortex has a folded appearance. A fold is called a gyrus and
the valley between is a sulcus.

The folding of the cortex increases the brain’s surface area allowing more neurons to fit inside
the skull and enabling higher functions. Each fold is called a gyrus, and each groove between
folds is called a sulcus. There are names for the folds and grooves that help define specific brain
regions.
Deep structures

Pathways called white matter tracts connect areas of the cortex to each other. Messages can
travel from one gyrus to another, from one lobe to another, from one side of the brain to the
other, and to structures deep in the brain (Fig. 5).
Figure 5. Coronal cross-section showing the basal ganglia.

Hypothalamus: is located in the floor of the third ventricle and is the master control of the
autonomic system. It plays a role in controlling behaviors such as hunger, thirst, sleep, and
sexual response. It also regulates body temperature, blood pressure, emotions, and secretion of
hormones.

Pituitary gland: lies in a small pocket of bone at the skull base called the sella turcica. The
pituitary gland is connected to the hypothalamus of the brain by the pituitary stalk. Known as the
“master gland,” it controls other endocrine glands in the body. It secretes hormones that control
sexual development, promote bone and muscle growth, and respond to stress.

Pineal gland: is located behind the third ventricle. It helps regulate the body’s internal clock and
circadian rhythms by secreting melatonin. It has some role in sexual development.

Thalamus: serves as a relay station for almost all information that comes and goes to the cortex.
It plays a role in pain sensation, attention, alertness and memory.

Basal ganglia: includes the caudate, putamen and globus pallidus. These nuclei work with the
cerebellum to coordinate fine motions, such as fingertip movements.

Limbic system: is the center of our emotions, learning, and memory. Included in this system are
the cingulate gyri, hypothalamus, amygdala (emotional reactions) and hippocampus (memory).
Memory

Memory is a complex process that includes three phases: encoding (deciding what information is
important), storing, and recalling. Different areas of the brain are involved in different types of
memory (Fig. 6). Your brain has to pay attention and rehearse in order for an event to move from
short-term to long-term memory – called encoding.
Figure 6. Structures of the limbic system involved in memory formation. The prefrontal cortex
holds recent events briefly in short-term memory. The hippocampus is responsible for encoding
long-term memory.

 Short-term memory, also called working memory, occurs in the prefrontal cortex. It
stores information for about one minute and its capacity is limited to about 7 items.
For example, it enables you to dial a phone number someone just told you. It also
intervenes during reading, to memorize the sentence you have just read, so that the
next one makes sense.

 Long-term memory is processed in the hippocampus of the temporal lobe and is

activated when you want to memorize something for a longer time. This memory has
unlimited content and duration capacity. It contains personal memories as well as
facts and figures.

 Skill memory is processed in the cerebellum, which relays information to the basal
ganglia. It stores automatic learned memories like tying a shoe, playing an
instrument, or riding a bike.
Ventricles and cerebrospinal fluid

The brain has hollow fluid-filled cavities called ventricles (Fig. 7). Inside the ventricles is a
ribbon-like structure called the choroid plexus that makes clear colorless cerebrospinal fluid
(CSF). CSF flows within and around the brain and spinal cord to help cushion it from injury.
This circulating fluid is constantly being absorbed and replenished.
Figure 7. CSF is produced inside the ventricles deep within the brain. CSF fluid circulates inside
the brain and spinal cord and then outside to the subarachnoid space. Common sites of
obstruction: 1) foramen of Monro, 2) aqueduct of Sylvius, and 3) obex.

There are two ventricles deep within the cerebral hemispheres called the lateral ventricles. They
both connect with the third ventricle through a separate opening called the foramen of Monro.
The third ventricle connects with the fourth ventricle through a long narrow tube called the
aqueduct of Sylvius. From the fourth ventricle, CSF flows into the subarachnoid space where it
bathes and cushions the brain. CSF is recycled (or absorbed) by special structures in the superior
sagittal sinus called arachnoid villi.

A balance is maintained between the amount of CSF that is absorbed and the amount that is
produced. A disruption or blockage in the system can cause a build up of CSF, which can cause
enlargement of the ventricles (hydrocephalus) or cause a collection of fluid in the spinal cord
(syringomyelia).
Skull

The purpose of the bony skull is to protect the brain from injury. The skull is formed from 8
bones that fuse together along suture lines. These bones include the frontal, parietal (2), temporal
(2), sphenoid, occipital and ethmoid (Fig. 8). The face is formed from 14 paired bones including
the maxilla, zygoma, nasal, palatine, lacrimal, inferior nasal conchae, mandible, and vomer.
Figure 8. The brain is protected inside the skull. The skull is formed from eight bones.

Inside the skull are three distinct areas: anterior fossa, middle fossa, and posterior fossa (Fig. 9).
Doctors sometimes refer to a tumor’s location by these terms, e.g., middle fossa meningioma.

Figure 9. A view of the cranial nerves at the base of the skull with the brain removed. Cranial
nerves originate from the brainstem, exit the skull through holes called foramina, and travel to
the parts of the body they innervate. The brainstem exits the skull through the foramen magnum.
The base of the skull is divided into 3 regions: anterior, middle and posterior fossae.
Similar to cables coming out the back of a computer, all the arteries, veins and nerves exit the
base of the skull through holes, called foramina. The big hole in the middle (foramen magnum) is
where the spinal cord exits.
Cranial nerves

The brain communicates with the body through the spinal cord and twelve pairs of cranial nerves
(Fig. 9). Ten of the twelve pairs of cranial nerves that control hearing, eye movement, facial
sensations, taste, swallowing and movement of the face, neck, shoulder and tongue muscles
originate in the brainstem. The cranial nerves for smell and vision originate in the cerebrum.

The Roman numeral, name, and main function of the twelve cranial nerves:

Number Name Function

I olfactory smell

II optic sight

III oculomotor moves eye, pupil

IV trochlear moves eye

V trigeminal face sensation

VI abducens moves eye

VII facial moves face, salivate

VIII vestibulocochlear hearing, balance

IX glossopharyngeal taste, swallow

X vagus heart rate, digestion

XI accessory moves head

XII hypoglossal moves tongue

Meninges

The brain and spinal cord are covered and protected by three layers of tissue called meninges.
From the outermost layer inward they are: the dura mater, arachnoid mater, and pia mater.

Dura mater: is a strong, thick membrane that closely lines the inside of the skull; its two layers,
the periosteal and meningeal dura, are fused and separate only to form venous sinuses. The dura
creates little folds or compartments. There are two special dural folds, the falx and the tentorium.
The falx separates the right and left hemispheres of the brain and the tentorium separates the
cerebrum from the cerebellum.

Arachnoid mater: is a thin, web-like membrane that covers the entire brain. The arachnoid is
made of elastic tissue. The space between the dura and arachnoid membranes is called the
subdural space.

Pia mater: hugs the surface of the brain following its folds and grooves. The pia mater has many
blood vessels that reach deep into the brain. The space between the arachnoid and pia is called
the subarachnoid space. It is here where the cerebrospinal fluid bathes and cushions the brain.
Blood supply
Blood is carried to the brain by two paired arteries, the internal carotid arteries and the vertebral
arteries (Fig. 10). The internal carotid arteries supply most of the cerebrum.

Figure 10. The common carotid artery courses up the neck and divides into the internal and
external carotid arteries. The brain’s anterior circulation is fed by the internal carotid arteries
(ICA) and the posterior circulation is fed by the vertebral arteries (VA). The two systems connect
at the Circle of Willis (green circle).

The vertebral arteries supply the cerebellum, brainstem, and the underside of the cerebrum. After
passing through the skull, the right and left vertebral arteries join together to form the basilar
artery. The basilar artery and the internal carotid arteries “communicate” with each other at the
base of the brain called the Circle of Willis (Fig. 11). The communication between the internal
carotid and vertebral-basilar systems is an important safety feature of the brain. If one of the
major vessels becomes blocked, it is possible for collateral blood flow to come across the Circle
of Willis and prevent brain damage.
Figure 11. Top view of the Circle of Willis. The internal carotid and vertebral-basilar systems are
joined by the anterior communicating (Acom) and posterior communicating (Pcom) arteries.

The venous circulation of the brain is very different from that of the rest of the body. Usually
arteries and veins run together as they supply and drain specific areas of the body. So one would
think there would be a pair of vertebral veins and internal carotid veins. However, this is not the
case in the brain. The major vein collectors are integrated into the dura to form venous sinuses —
not to be confused with the air sinuses in the face and nasal region. The venous sinuses collect
the blood from the brain and pass it to the internal jugular veins. The superior and inferior
sagittal sinuses drain the cerebrum, the cavernous sinuses drains the anterior skull base. All
sinuses eventually drain to the sigmoid sinuses, which exit the skull and form the jugular veins.
These two jugular veins are essentially the only drainage of the brain.
Cells of the brain

The brain is made up of two types of cells: nerve cells (neurons) and glia cells.
Nerve cells

There are many sizes and shapes of neurons, but all consist of a cell body, dendrites and an axon.
The neuron conveys information through electrical and chemical signals. Try to picture electrical
wiring in your home. An electrical circuit is made up of numerous wires connected in such a way
that when a light switch is turned on, a light bulb will beam. A neuron that is excited will
transmit its energy to neurons within its vicinity.

Neurons transmit their energy, or “talk”, to each other across a tiny gap called a synapse (Fig.
12). A neuron has many arms called dendrites, which act like antennae picking up messages
from other nerve cells. These messages are passed to the cell body, which determines if the
message should be passed along. Important messages are passed to the end of the axon where
sacs containing neurotransmitters open into the synapse. The neurotransmitter molecules cross
the synapse and fit into special receptors on the receiving nerve cell, which stimulates that cell to
pass on the message.
Figure 12. Nerve cells consist of a cell body, dendrites and axon. Neurons communicate with
each other by exchanging neurotransmitters across a tiny gap called a synapse.

Glia cells

Glia (Greek word meaning glue) are the cells of the brain that provide neurons with nourishment,
protection, and structural support. There are about 10 to 50 times more glia than nerve cells and
are the most common type of cells involved in brain tumors.

 Astroglia or astrocytes are the caretakers — they regulate the blood brain barrier,
allowing nutrients and molecules to interact with neurons. They control homeostasis,
neuronal defense and repair, scar formation, and also affect electrical impulses.

 Oligodendroglia cells create a fatty substance called myelin that insulates axons –
allowing electrical messages to travel faster.

 Ependymal cells line the ventricles and secrete cerebrospinal fluid (CSF).

 Microglia are the brain’s immune cells, protecting it from invaders and cleaning up
debris. They also prune synapses.
 III. PATHOPHYSIOLOGY

Non-Modifiable Factors: Modifiable Factors:

 Age  History of Abuse

 Gender  Lack of Social
Unknown Etiology
 Genetics Factor Support
 Biochemical Factor  Major Life Events
 Family History of  Substance Abuse
Mental Illness

MONOAMINE HYPOTHESIS NEUROTROPHIC HYPOTHESIS NEUROENDOCRINE HYPOTHESIS

Deficiency in 5-HT, NE, and DA Low BNDF responsible for loss of mono Dysregulation in HPA=increased CFR
aminergic neurons Dysregulation in HPT=Thyroid
Hormone Deficiency
Hippocampus lose its ability to inhibit
CRF release by Hypothalamus  Elevated CFR
 5-HT, NE, DA Decreased
Increased released of Corticosteroids  Cortisol Level Decreased
 Decreased feedback
inhibition from
 Andhedonia hippocampus
 Anergia
 Insomnia/Hypersomnia
 Poor Cognition/Concentration
 Depressed Mood
 Psychomotor Agitation
 Recurrent thoughts of Death or Suicide

Depression

PSYCHOTHERAPY AND IF NOT TREATED AND MANAGED

PHARMACOTHERAPY
POOR PROGNOSIS
GOOD PROGNOSIS