Psychopharmacology is the study of how drugs affect mood, perception,

thinking or behavior. Drugs that achieve these effects by acting in the

nervous system are called psychoactive drugs. The term
psychopharmacology encompasses two large fields: psychology and
pharmacology. Thus, psychopharmacology attempts to relate the actions and
effects of drugs to psychological processes.

Drug is an administered substance that alters physiological functioning.

Instrumental drug use consists of using a drug to address a specific purpose.
For example, one may take an antidepressant drug such as Prozac for the
purpose of reducing depression. Furthermore, most adults consume
caffeinated beverages such as coffee to make them wake up in the morning,
another socially acceptable purpose. These drugs are often called therapeutic
drugs. Recreational drug use refers to using a drug entirely to experience its
effects. For example, drinking alcohol purely to experience its intoxicating
effects. Or using cough syrups to achieve mind-altering effects such as
euphoria or hallucinations.

Virtually any drug that changes the way you feel does this by altering how
neurons communicate with each other. Neurons (more than 100 billion in your
nervous system) communicate with each other by releasing a chemical
(neurotransmitter) across a tiny space between two neurons (the synapse).
When the neurotransmitter crosses the synapse, it binds to a postsynaptic
receptor (protein) on the receiving neuron and the message may then be
transmitted onward. Obviously, neurotransmission is far more complicated
than this – links at the end of this module can provide some useful
background if you want more detail – but the first step is understanding that
virtually all psychoactive drugs interfere with or alter how neurons
communicate with each other.

There are many neurotransmitters. Some of the most important in terms of

psychopharmacological treatment and drugs of abuse are outlined in Table 1.
The neurons that release these neurotransmitters, for the most part, are
localized within specific circuits of the brain that mediate these behaviors.
Psychoactive drugs can either increase activity at the synapse (these are
called agonists) or reduce activity at the synapse (antagonists). Different
drugs do this by different mechanisms, and some examples of agonists and
antagonists are presented in Table 2. For each example, the drug’s trade
name, which is the name of the drug provided by the drug company, and
generic name (in parentheses) are provided.
Table 1

Table 2 provides examples of drugs and their primary mechanism of action, but it is very
important to realize that drugs also have effects on other neurotransmitters. This contributes to
the kinds of side effects that are observed when someone takes a particular drug. The reality is
that no drugs currently available work only exactly where we would like in the brain or only on a
specific neurotransmitter. In many cases, individuals are sometimes prescribed one
psychotropic drug but then may also have to take additional drugs to reduce the side effects
caused by the initial drug. Sometimes individuals stop taking medication because the side
effects can be so profound.
Table 2

Pharmacokinetics: What Is It – Why Is It Important?

While this section may sound more like pharmacology, it is important to realize how important
pharmacokinetics can be when considering psychoactive drugs. Pharmacokinetics refers to
how the body handles a drug that we take. As mentioned earlier, psychoactive drugs exert their
effects on behavior by altering neuronal communication in the brain, and the majority of drugs
reach the brain by traveling in the blood. The acronym ADME is often used with A standing for
absorption (how the drug gets into the blood), Distribution (how the drug gets to the organ of
interest – in this module, that is the brain), Metabolism (how the drug is broken down so it no
longer exerts its psychoactive effects), and Excretion (how the drug leaves the body). We will
talk about a couple of these to show their importance for considering psychoactive drugs.

Drug Administration

There are many ways to take drugs, and these routes of drug administration can have a
significant impact on how quickly that drug reaches brain. The most common route of
administration is oral administration, which is relatively slow and – perhaps surprisingly – often
the most variable and complex route of administration. Drugs enter the stomach and then get
absorbed by the blood supply and capillaries that line the small intestine. The rate of absorption
can be affected by a variety of factors including the quantity and the type of food in the
stomach (e.g., fats vs. proteins). This is why the medicine label for some drugs (like antibiotics)
may specifically state foods that you should or should NOT consume within an hour of taking
the drug because they can affect the rate of absorption. Two of the most rapid routes of
administration include inhalation (i.e., smoking or gaseous anesthesia) and intravenous (IV) in
which the drug is injected directly into the vein and hence the blood supply. Both of these
routes of administration can get the drug to brain in less than 10 seconds. IV administration
also has the distinction of being the most dangerous because if there is an adverse drug
reaction, there is very little time to administer any antidote, as in the case of an IV heroin
overdose.

Why might how quickly a drug gets to the brain be important? If a drug activates the reward
circuits in the brain AND it reaches the brain very quickly, the drug has a high risk for abuse
and addiction. Psychostimulants like amphetamine or cocaine are examples of drugs that have
high risk for abuse because they are agonists at DA neurons involved in reward AND because
these drugs exist in forms that can be either smoked or injected intravenously. Some argue that
cigarette smoking is one of the hardest addictions to quit, and although part of the reason for
this may be that smoking gets the nicotine into the brain very quickly (and indirectly acts on DA
neurons), it is a more complicated story. For drugs that reach the brain very quickly, not only is
the drug very addictive, but so are the cues associated with the drug (see Rohsenow, Niaura,
Childress, Abrams, & Monti, 1990). For a crack user, this could be the pipe that they use to
smoke the drug. For a cigarette smoker, however, it could be something as normal as finishing
dinner or waking up in the morning (if that is when the smoker usually has a cigarette). For both
the crack user and the cigarette smoker, the cues associated with the drug may actually cause
craving that is alleviated by (you guessed it) – lighting a cigarette or using crack (i.e., relapse).
This is one of the reasons individuals that enroll in drug treatment programs, especially out-of-
town programs, are at significant risk of relapse if they later find themselves in proximity to old
haunts, friends, etc. But this is much more difficult for a cigarette smoker. How can someone
avoid eating? Or avoid waking up in the morning, etc. These examples help you begin to
understand how important the route of administration can be for psychoactive drugs.

Drug Metabolism

Metabolism involves the breakdown of psychoactive drugs, and this occurs primarily in the
liver. The liver produces enzymes (proteins that speed up a chemical reaction), and these
enzymes help catalyze a chemical reaction that breaks down psychoactive drugs. Enzymes
exist in “families,” and many psychoactive drugs are broken down by the same family of
enzymes, the cytochrome P450 superfamily. There is not a unique enzyme for each drug;
rather, certain enzymes can break down a wide variety of drugs. Tolerance to the effects of
many drugs can occur with repeated exposure; that is, the drug produces less of an effect over
time, so more of the drug is needed to get the same effect. This is particularly true for sedative
drugs like alcohol or opiate-based painkillers. Metabolic tolerance is one kind of tolerance and it
takes place in the liver. Some drugs (like alcohol) cause enzyme induction – an increase in the
enzymes produced by the liver. For example, chronic drinking results in alcohol being broken
down more quickly, so the alcoholic needs to drink more to get the same effect – of course,
until so much alcohol is consumed that it damages the liver (alcohol can cause fatty liver or
cirrhosis).

Recent Issues Related to Psychotropic Drugs and Metabolism

Grapefruit Juice and Metabolism

Certain types of food in the stomach can alter the rate of drug absorption, and other foods can
also alter the rate of drug metabolism. The most well known is grapefruit juice. Grapefruit juice
suppresses cytochrome P450 enzymes in the liver, and these liver enzymes normally break
down a large variety of drugs (including some of the psychotropic drugs). If the enzymes are
suppressed, drug levels can build up to potentially toxic levels. In this case, the effects can
persist for extended periods of time after the consumption of grapefruit juice. As of 2013, there
are at least 85 drugs shown to adversely interact with grapefruit juice (Bailey, Dresser, &
Arnold, 2013). Some psychotropic drugs that are likely to interact with grapefruit juice include
carbamazepine (Tegretol), prescribed for bipolar disorder; diazepam (Valium), used to treat
anxiety, alcohol withdrawal, and muscle spasms; and fluvoxamine (Luvox), used to treat
obsessive compulsive disorder and depression. A link at the end of this module gives the latest
list of drugs reported to have this unusual interaction.

Individualized Therapy, Metabolic Differences, and Potential Prescribing Approaches for the
Future

Mental illnesses contribute to more disability in western countries than all other illnesses
including cancer and heart disease. Depression alone is predicted to be the second largest
contributor to disease burden by 2020 (World Health Organization, 2004). The numbers of
people affected by mental health issues are pretty astonishing, with estimates that 25% of
adults experience a mental health issue in any given year, and this affects not only the
individual but their friends and family. One in 17 adults experiences a serious mental illness
(Kessler, Chiu, Demler, & Walters, 2005). Newer antidepressants are probably the most
frequently prescribed drugs for treating mental health issues, although there is no “magic bullet”
for treating depression or other conditions. Pharmacotherapy with psychological therapy may
be the most beneficial treatment approach for many psychiatric conditions, but there are still
many unanswered questions. For example, why does one antidepressant help one individual
yet have no effect for another? Antidepressants can take 4 to 6 weeks to start improving
depressive symptoms, and we don’t really understand why. Many people do not respond to the
first antidepressant prescribed and may have to try different drugs before finding something
that works for them. Other people just do not improve with antidepressants (Ioannidis, 2008).
As we better understand why individuals differ, the easier and more rapidly we will be able to
help people in distress.

One area that has received interest recently has to do with an individualized treatment
approach. We now know that there are genetic differences in some of the cytochrome P450
enzymes and their ability to break down drugs. The general population falls into the following 4
categories: 1) ultra-extensive metabolizers break down certain drugs (like some of the current
antidepressants) very, very quickly, 2) extensive metabolizers are also able to break down
drugs fairly quickly, 3) intermediate metabolizers break down drugs more slowly than either of
the two above groups, and finally 4) poor metabolizers break down drugs much more slowly
than all of the other groups. Now consider someone receiving a prescription for an
antidepressant – what would the consequences be if they were either an ultra-extensive
metabolizer or a poor metabolizer? The ultra-extensive metabolizer would be given
antidepressants and told it will probably take 4 to 6 weeks to begin working (this is true), but
they metabolize the medication so quickly that it will never be effective for them. In contrast, the
poor metabolizer given the same daily dose of the same antidepressant may build up such high
levels in their blood (because they are not breaking the drug down), that they will have a wide
range of side effects and feel really badly – also not a positive outcome. What if – instead –
prior to prescribing an antidepressant, the doctor could take a blood sample and determine
which type of metabolizer a patient actually was? They could then make a much more informed
decision about the best dose to prescribe. There are new genetic tests now available to better
individualize treatment in just this way. A blood sample can determine (at least for some drugs)
which category an individual fits into, but we need data to determine if this actually is effective
for treating depression or other mental illnesses (Zhou, 2009). Currently, this genetic test is
expensive and not many health insurance plans cover this screen, but this may be an important
component in the future of psychopharmacology.

Other Controversial Issues

Juveniles and Psychopharmacology

A recent Centers for Disease Control (CDC) report has suggested that as many as 1 in 5
children between the ages of 5 and 17 may have some type of mental disorder (e.g., ADHD,
autism, anxiety, depression) (CDC, 2013). The incidence of bipolar disorder in children and
adolescents has also increased 40 times in the past decade (Moreno, Laje, Blanco, Jiang,
Schmidt, & Olfson, 2007), and it is now estimated that 1 in 88 children have been diagnosed
with an autism spectrum disorder (CDC, 2011). Why has there been such an increase in these
numbers? There is no single answer to this important question. Some believe that greater
public awareness has contributed to increased teacher and parent referrals. Others argue that
the increase stems from changes in criterion currently used for diagnosing. Still others suggest
environmental factors, either prenatally or postnatally, have contributed to this upsurge.

We do not have an answer, but the question does bring up an additional controversy related to
how we should treat this population of children and adolescents. Many psychotropic drugs used
for treating psychiatric disorders have been tested in adults, but few have been tested for
safety or efficacy with children or adolescents. The most well-established psychotropics
prescribed for children and adolescents are the psychostimulant drugs used for treating
attention deficit hyperactivity disorder (ADHD), and there are clinical data on how effective
these drugs are. However, we know far less about the safety and efficacy in young populations
of the drugs typically prescribed for treating anxiety, depression, or other psychiatric disorders.
The young brain continues to mature until probably well after age 20, so some scientists are
concerned that drugs that alter neuronal activity in the developing brain could have significant
consequences. There is an obvious need for clinical trials in children and adolescents to test
the safety and effectiveness of many of these drugs, which also brings up a variety of ethical
questions about who decides what children and adolescents will participate in these clinical
trials, who can give consent, who receives reimbursements, etc.

The Elderly and Psychopharmacology

Another population that has not typically been included in clinical trials to determine the safety
or effectiveness of psychotropic drugs is the elderly. Currently, there is very little high-quality
evidence to guide prescribing for older people – clinical trials often exclude people with multiple
comorbidities (other diseases, conditions, etc.), which are typical for elderly populations (see
Hilmer and Gnjidict, 2008; Pollock, Forsyth, & Bies, 2008). This is a serious issue because the
elderly consume a disproportionate number of the prescription meds prescribed. The term
polypharmacy refers to the use of multiple drugs, which is very common in elderly populations
in the United States. As our population ages, some estimate that the proportion of people 65 or
older will reach 20% of the U.S. population by 2030, with this group consuming 40% of the
prescribed medications. As shown in Table 3 (from Schwartz and Abernethy, 2008), it is quite
clear why the typical clinical trial that looks at the safety and effectiveness of psychotropic
drugs can be problematic if we try to interpret these results for an elderly population.

Example: Depression Symptoms: Depressedmood,neurovegetativesymptoms,anhedonia,

Screening: SIGECAPS Clinician-administered: HamiltonDepressionScale Pt-completed:

BeckDepression Inventory ,

Differential: MajorDepressiveDisorder ,Dysthymia,BipolarDepression, Depression

duetoGeneralMedicalCondition,Drug intoxication/withdrawal,Demoralization,

Treatment: Psychotherapy: Interpersonal,Cognitive, Somatictherapy: Medications(SSRI,SNRI,

TCA,MAOI,etc) Phototherapy ,ECT ,DBS,VNS

Effectiveness: ModeratetoHigh
Risks: Sideeffects (sexual,weightgain,etc.) ‘Switching’intomania;suicide;stigmatization

A brain =1012 neurons

Each neuron connects to 7000 other neurons

Total number of neural connections in the brain: 10,000,000,000,000,000
 The Effects of Stress on Your Body

You’re sitting in traffic, late for an important meeting, watching the minutes tick away. Your
hypothalamus, a tiny control tower in your brain, decides to send out the order: Send in the
stress hormones! These stress hormones are the same ones that trigger your body’s “fight or
flight” response. Your heart races, your breath quickens, and your muscles ready for action.
This response was designed to protect your body in an emergency by preparing you to react
quickly. But when the stress response keeps firing, day after day, it could put your health at
serious risk.

Stress is a natural physical and mental reaction to life experiences. Everyone expresses stress
from time to time. Anything from everyday responsibilities like work and family to serious life
events such as a new diagnosis, war, or the death of a loved one can trigger stress. For
immediate, short-term situations, stress can be beneficial to your health. It can help you cope
with potentially serious situations. Your body responds to stress by releasing hormones that
increase your heart and breathing rates and ready your muscles to respond.

Yet if your stress response doesn’t stop firing, and these stress levels stay elevated far longer
than is necessary for survival, it can take a toll on your health. Chronic stress can cause a
variety of symptoms and affect your overall well-being. Symptoms of chronic stress include:

 irritability
 anxiety
 depression
 headaches
 insomnia

Central nervous and endocrine systems

Your central nervous system (CNS) is in charge of your “fight or flight” response. In your brain,
the hypothalamus gets the ball rolling, telling your adrenal glands to release the stress
hormones adrenaline and cortisol. These hormones rev up your heartbeat and send blood
rushing to the areas that need it most in an emergency, such as your muscles, heart, and other
important organs.

When the perceived fear is gone, the hypothalamus should tell all systems to go back to
normal. If the CNS fails to return to normal, or if the stressor doesn’t go away, the response will
continue.
Types of Learning Disabilities
Learning disabilities are neurologically-based processing problems. These processing
problems can interfere with learning basic skills such as reading, writing and/or math. They
can also interfere with higher level skills such as organization, time planning, abstract
reasoning, long or short term memory and attention. It is important to realize that learning
disabilities can affect an individual’s life beyond academics and can impact relationships with
family, friends and in the workplace.

Since difficulties with reading, writing and/or math are recognizable problems during the school
years, the signs and symptoms of learning disabilities are most often diagnosed during that
time. However, some individuals do not receive an evaluation until they are in post-secondary
education or adults in the workforce. Other individuals with learning disabilities may never
receive an evaluation and go through life, never knowing why they have difficulties with
academics and why they may be having problems in their jobs or in relationships with family
and friends.

Learning disabilities should not be confused with learning problems which are primarily the
result of visual, hearing, or motor handicaps; of intellectual disability; of emotional disturbance;
or of environmental, cultural or economic disadvantages.

Generally speaking, people with learning disabilities are of average or above average
intelligence. There often appears to be a gap between the individual’s potential and actual
achievement. This is why learning disabilities are referred to as “hidden disabilities”: the person
looks perfectly “normal” and seems to be a very bright and intelligent person, yet may be
unable to demonstrate the skill level expected from someone of a similar age.

A learning disability cannot be cured or fixed; it is a lifelong challenge. However, with

appropriate support and intervention, people with learning disabilities can achieve success in
school, at work, in relationships, and in the community.

Specific Learning Disabilities

Auditory Processing Disorder (APD)

Also known as Central Auditory Processing Disorder, this is a condition that adversely affects
how sound that travels unimpeded through the ear is processed or interpreted by the brain.
Individuals with APD do not recognize subtle differences between sounds in words, even when
the sounds are loud and clear enough to be heard. They can also find it difficult to tell where
sounds are coming from, to make sense of the order of sounds, or to block out competing
background noises.
 Dyscalculia
A specific learning disability that affects a person’s ability to understand numbers and learn
math facts. Individuals with this type of LD may also have poor comprehension of math
symbols, may struggle with memorizing and organizing numbers, have difficulty telling time, or
have trouble with counting.

Dysgraphia
A specific learning disability that affects a person’s handwriting ability and fine motor skills.
Problems may include illegible handwriting, inconsistent spacing, poor spatial planning on
paper, poor spelling, and difficulty composing writing as well as thinking and writing at the same
time.

Dyslexia
A specific learning disability that affects reading and related language-based processing skills.
The severity can differ in each individual but can affect reading fluency, decoding, reading
comprehension, recall, writing, spelling, and sometimes speech and can exist along with other
related disorders. Dyslexia is sometimes referred to as a Language-Based Learning Disability.

Language Processing Disorder

A specific type of Auditory Processing Disorder (APD) in which there is difficulty attaching
meaning to sound groups that form words, sentences and stories. While an APD affects the
interpretation of all sounds coming into the brain, a Language Processing Disorder (LPD)
relates only to the processing of language. LPD can affect expressive language and/or
receptive language.

Non-Verbal Learning Disabilities

A disorder which is usually characterized by a significant discrepancy between higher verbal
skills and weaker motor, visual-spatial and social skills. Typically, an individual with NLD (or
NVLD) has trouble interpreting nonverbal cues like facial expressions or body language, and
may have poor coordination.

Visual Perceptual/Visual Motor Deficit

A disorder that affects the understanding of information that a person sees, or the ability to
draw or copy. A characteristic seen in people with learning disabilities such as Dysgraphia or
Non-verbal LD, it can result in missing subtle differences in shapes or printed letters, losing
place frequently, struggles with cutting, holding pencil too tightly, or poor eye/hand
coordination.

Learn more about Visual Perceptual/Visual Motor Deficit

Related Disorders

ADHD
A disorder that includes difficulty staying focused and paying attention, difficulty controlling
behavior and hyperactivity. Although ADHD is not considered a learning disability, research
indicates that from 30-50 percent of children with ADHD also have a specific learning disability,
and that the two conditions can interact to make learning extremely challenging.

Dyspraxia
A disorder that is characterized by difficulty in muscle control, which causes problems with
movement and coordination, language and speech, and can affect learning. Although not a
learning disability, dyspraxia often exists along with dyslexia, dyscalculia or ADHD.

Executive Functioning
An inefficiency in the cognitive management systems of the brain that affects a variety of
neuropsychological processes such as planning, organization, strategizing, paying attention to
and remembering details, and managing time and space. Although not a learning disability,
different patterns of weakness in executive functioning are almost always seen in the learning
profiles of individuals who have specific learning disabilities or ADHD.

Neurological disorders are medically defined as disorders that affect the brain as well as the
nerves found throughout the human body and the spinal cord. These three parts of the body
work together and are referred to as the central nervous system that control everything in the
body. Neurology is the medical science that deals with the nervous system and disorders that
affect it.

A neurological disorder is defined as any disorder of the body nervous system. Structural,
biochemical or electrical abnormalities in the brain, spinal cord or other nerves can result in a
range of symptoms. Examples of symptoms include paralysis, muscle weakness, poor
coordination, loss of sensation, seizures, confusion, pain and altered levels of consciousness.
The specific causes of neurological problems vary, but can include genetic disorders,
congenital abnormalities or disorders, infections, lifestyle or environmental health problems
including malnutrition, and brain injury, spinal cord injury or nerve injury.
There are many recognized neurological disorders, some relatively common, but many rare.
They may be assessed by neurological examination, and studied and treated within the
specialties of neurology and clinical neuropsychology. Mental disorders, on the other hand, are
 "psychiatric illnesses" or diseases which appear primarily as abnormalities of thought, feeling or
behavior, producing either distress or impairment of function.
Conditions that are classed as mental disorders, or learning disabilities and forms of Intellectual
disability, are not themselves usually dealt with as neurological disorders.
Neurological disorders can be categorized according to the primary location affected, the
primary type of dysfunction involved, or the primary type of cause. The broadest division is
between central nervous system disorders and peripheral nervous system disorders.
Neurological disorders can affect an entire neurological pathway or a single neuron. Even a
small disturbance to a neuron's structural pathway can result in dysfunction.
According to the University of California, San Francisco, there are more than 600 neurological
disorders that strike millions of Americans each year. These diseases and disorders inflict great
pain and suffering on millions of patients and their families, and cost the U.S. economy billions
of dollars annually.
Social Security approves disability benefits for serious cases of epilepsy, cerebral palsy,
Parkinson's disease, multiple sclerosis, ALS, and other nerve-based diseases.

Statistics: Neurological Disorders (August 3, 2018)

 Nearly 1 in 6 of world's population suffer from neurological disorders (UN)

 More than 50 million people have epilepsy worldwide.
 The prevalence of migraine is more than 10% worldwide.
 The US National Institute for Neurological Disorders and Stroke (NINDS) estimated in a 2006
report that about 50,000 new cases of Parkinson's disease are diagnosed in the US each year,
and the total number of cases in the US is at least 500,000.
 Despite the fact that highly effective, low-cost treatments are available, as many as nine out of
10 people suffering from epilepsy in Africa go untreated.
 Many brain disorders are chronic and incurable conditions whose disabling effects may
continue for years or even decades.
 In its 2012 annual report, the Alzheimer's Association (AA) estimates that 5.4 million people in
the US have Alzheimer's disease (AD). By 2050, the AA estimates that between 11 million and
16 million Americans will have the disease, with one new case appearing every 33 seconds.
 As the global population ages, the impact of neurological disorders will be felt both in
developed and developing countries, reaching a significant proportion in countries with a
growing percentage of the population over 65 years.
 In Europe it has been estimated that 35% of all disease burden is attributable to brain disorders
(Olesen & Leonardi 2003).
 The US National Institute of Mental Health (NIMH) estimates that about 1 in 4 American adults
suffer from a diagnosable mental disorder in any given year, with nearly 6% suffering serious
disabilities as a result.
 Approximately 6.2 million people die because of stroke each year.
 Alzheimer's disease is the most common cause of dementia and may contribute to 60 to 70%
of cases.
 It is estimated that there are globally 35.6 million people with dementia with 7.7 million new
cases every year.
 The World Health Organization reports that various types of neurological disorders affect
millions of people around the world, including 24 million that suffer from Alzheimer's disease
and 326 million who experience migraines

Issues in the Ethics in Using Animal Research

1. To discover possible causes of potential treatments of learning disabilities and mental
disorders
2. To use tissue culture or computers instead of animals
3. To focus on actual, potential benefits to human health
4. Sometimes, not accurate results if animals are used
5. Consider differences in human and animal physiological structures
6. Consider cultural setting

Significance of studying physiological psychology:

1. To identify parts of the nervous system related to illnesses
2. To allow new technology to diagnose and treat these illnesses

Is Physiological Psychology a natural science or a social science?

1. Consider the disciplines it falls under: natural science-biology. Neurology, physiology
Social science – cognitive psychology,
experimental psychology
2. Consider social issues: natural science – technology, environment
Social science – ethics, culture

Benefits of technology in studying physiology psychology:

1. Facilitation of diagnosis and treatments
2. Accurate results

Future careers in physiological psychology:

1. Biological psychologists
2. Neurosurgeons