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CLASS NOTES
17 Jan 2025
Fear
Research with humans
 Emotional memory-damage to the amygdala interferers with effects of emotions on
memory
 When people encounter events that produce a strong emotional response, they are more
likely to remember these events. Cahill et al (1995) studied a patient with bilateral
degeneration of amygdala
 I another study researchers questioned patients with Alzheimer’s disease who had
witnesses the devastating earthquake that struck Kobe Japan, in 1995
 They found that memory of this frightening event was inversely correlated with amygdala
damage. The more a patient’s amygdala was degenerated, the less likely it was the patient
remembered the earthquake
Flashbulb memory?
Aggression
 Aggressive behavior can consist of actual attacks or they may simply involve threat
behaviors which consist of postures or gestures that warn the adversary to leave or it will
become the target of an attack
 The threatened animal might show defensive behaviors-threat behaviors or an actual
attack against the animal that is threatening it-or it might show submissive behaviors-
behaviors that indicate that it accept defeat and will not challenge the other animal.
 Predation involves a member of one species attacking a member of another species,
usually for food. While engaged in attacking a member of the same species or defending
itself against the attack, an animal appears to be extremely aroused and excited, and
the activity of the sympathetic branch of its autonomic nervous system is high.
 Neural network-they found that aggressive attack and predation can be elicited by
stimulation of different parts of the periaqueductal gray matter (PAG).
 In addition, the hypothalamus and amygdala influence attack and predation behaviors
through excitatory and inhibitory connections with the PAG.
 These principal regions of the amygdala and two regions of the hypothalamus affect
defensive rage and predation, both of which appear to be organized by PAG.
 Role of serotonin-a group of researchers has studied the relationship between
serotonergic activity and aggressiveness in a free ranging colony of rhesus monkeys
 They assessed serotonergic activity by capturing the monkeys, removing a sample of CSF
and analyzing it for 5-HIAA, a metabolite of serotonin (5-HT). when 5-HT is released,
most of the neurotransmitter is taken back into the terminal buttons by means of reuptake,
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but some escapes and is broken down to 5-HIAA, which finds its way into CSF. High
levels of 5-HIAA in the CSF indicate increased serotonergic activity.
 It appears that serotonin does not simply inhibit aggression, rather it exerts a controlling
influence on risky behavior, which includes aggression.

Research with humans

 Socialization
 Role of hereditary-early experiences can certainly impact development of aggressive
behavior, but studies have shown hereditary plays a significant role,
 Viding studied a group of same sex twins at the ages of 7 years and 9 years and found a
higher correlation between monozygotic twins than dizygotic twins on measures of
antisocial behavior and levels of callous, unemotional behavior, which indicates a genetic
component in development of these traits.
 Role of serotonin-studies have found that serotonergic neurons plays an inhibitory role in
human aggression
 Reduces serotonin release indicated by low levels of 5-HIAA in the CSF is associated
with aggressive and other forms of antisocial behavior inclosing assault, arson, murder
and child abuse
 More recent studies have reported a very weak inverse relationship between serotonin
and aggression, suggesting that more research is needed.

20 Jan 2025
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Facial expression of emotions-innate response

 Charles Darwin (1872/1965) suggested that human expressions of emotion have evolved
from similar expressions in other animals. He said that emotional expressions are innate,
unlearned responses consisting of a complex set of movements, principally of the facial
muscles.
 Classic research by Ekman and his colleagues (Ekman and Friesen, 1971; Ekman, 1980)
tends to confirm Darwin’s hypothesis that facial expression of emotion uses an innate,
species-typical repertoire of movements of facial muscles.
 A study by Sauter et al., (2010) reached similar conclusions. The investigators carried out
a vocal version of the study by Ekman and Friesen. They presented European English-
speakers and natives of isolated northern Namibian villages with recordings of sounds of
nonverbal vocalizations to situations that would be expected to produce the emotions of
anger, disgust, fear, sadness, surprise, or amusement. The participants were told a story
and then heard two different vocalizations (sighs, groans, laughs, and so on).
Neural basis of communication of emotions-recognition
 Thin slice assessment-brief-10 sec-assess what emotions a person is experiencing through
tone, face, efficacy questioned but qualifies individual will be able to detect in short span
 Recognition of another person’s facial expression of emotions is generally automatic,
rapid, and accurate.
 Tracy and Robbins (2008) found that observers quickly recognized brief expressions of a
variety of emotions. If they were given more time to think about the expression they had
seen, the participants showed very little improvement.
 Rapid assessments are sometimes called “thin slice” judgments by researchers. Thin slice
assessments of situations and behaviors with emotional content (such as deception or
communication) have been found to be as accurate when exposure to content is less than
30 seconds, as when it is 300 seconds.
 Additional time to assess emotional content does not lead to greater accuracy.
Laterality of emotional recognition
 Left hemisphere-language and logical reasoning
 Right-emotions
 Many studies have found that the right hemisphere plays a more important role than the
left hemisphere in comprehension of emotion.
 Bowers et al., (1991) found that patients with right hemisphere damage had difficulty
producing or describing mental images of facial expressions of emotions.
 The investigators found that comprehension of emotion from word meaning increased
the activity of the prefrontal cortex bilaterally, the left hemisphere more than the right.
Comprehension of emotion from tone of voice increased the activity of only the right
prefrontal cortex.
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 Heilman et al., (1983) recorded a particularly interesting case of a man with a disorder
called pure word deafness, caused by damage to the left temporal cortex
 Pure word deafness-read and write efficiently, but understanding or comprehending
spoken language is difficult, so perceive as unrelated noise.
Role of amygdala and PFC
 The amygdala plays a special role in emotional responses. It plays a role in emotional
recognition as well.
 Several studies have found that lesions of the amygdala (the result of degenerative
diseases or surgery for severe seizure disorders) impair a person’s ability to recognize
facial expressions of emotion, especially expressions of fear
 Several studies suggest that the amygdala receives visual information that we use to
recognize facial expressions of emotion directly from the thalamus and not from the
visual association cortex.
 Adolphs (2002) notes that the amygdala receives visual input from two sources:
subcortical and cortical. The subcortical input (from the superior colliculus and the
pulvinar, a large nucleus in the posterior thalamus) appears to provide the most important
information for this task.
 In fact, some people with blindness caused by damage to the visual cortex can recognize
facial expressions of emotion even though they have no conscious awareness of looking
at a person’s face, a phenomenon known as affective blindsight.
 Krolak-Salmon et al. (2004) recorded electrical potentials from the amygdala and visual
association cortex through electrodes that had been implanted in people who were being
evaluated for neurosurgery to alleviate a seizure disorder. They presented the people with
photographs of faces showing neutral expressions or expressions of fear, happiness, or
disgust. They found that fearful faces produced the largest response and that the
amygdala showed activity before the visual cortex did
Role of imitation in recognition of emotional expressions-the mirror neuron system
 Adolphs et al., (2000) discovered a possible link between somatosensation and emotional
recognition. They found that the most severe damage to this ability was caused by
damage to the somatosensory cortex of the right hemisphere.
 They suggest that, when we see a facial expression of an emotion, we unconsciously
imagine ourselves making that expression. Often, we do more than imagine making the
expressions—we actually imitate what we see

Perceiving disgust
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 Several studies have found that damage to the insular cortex and basal ganglia impair
people’s ability to recognize facial expressions of a very specific emotion: disgust
 In addition, a functional-imaging study by Wicker et al., (2003) found that both smelling
a disgusting odor and seeing a face of a person showing an expression of disgust activate
the insular cortex
 A functional-imaging study by Thielscher and Pessoa (2007) asked participants to press
one of two levers to indicate whether the facial expression they saw was one of disgust or
fear. The expressions varied in intensity, and one of them was actually neutral, indicating
neither disgust nor fear. Nevertheless, the participants were asked to press one of the
levers on every trial, indicating disgust or fear. When the participants saw faces
expressing disgust, the insular cortex and part of the basal ganglia were activated.
Neural basis of communication-expression
 Facial expressions of emotion are automatic and involuntary
 The observation that emotion is followed by facial expression is confirmed by two
neurological disorders with complementary symptoms.
 The first, volitional facial paresis, is caused by damage to the face region of the
primary motor cortex or to the fibers connecting this region with the motor nucleus of
the facial nerve, which controls the muscles responsible for movement of the facial
muscles. The interesting thing about volitional facial paresis is that a patient cannot
voluntarily move the facial muscles but will express a genuine emotion with those
muscles
 In contrast, emotional facial paresis is caused by damage to the insular region of the
pre frontal cortex, to the white matter of the frontal lobe, or to parts of the thalamus.
This system joins the system responsible for voluntary movements of the facial
muscles in the medulla or caudal pons. People with this disorder can move their face
muscles voluntarily but do not express emotions on the affected side of the face.
 These two syndromes clearly indicate that different brain mechanisms are responsible for
voluntary movements of the facial muscles and automatic, involuntary expression of
emotions involving the same muscles.
22 Jan 2025
Thirst
 Refers to sensation that people say when they have been dehydrated
 Approximately two-thirds of the body’s water is contained in the intracellular fluid, the
fluid portion of the cytoplasm of cells.
 The rest is extracellular fluid, which includes the intravascular fluid (the blood plasma),
the cerebrospinal fluid, and the interstitial fluid (fluid that bathes our cells).
 The volume of two of the fluid compartments of the body must be kept within precise
limits: the intracellular fluid and the intravascular fluid (EXTRACELLULAR F).
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 A loss of intracellular water deprives cells of the ability to perform many chemical
reactions, and a gain of water can cause their membranes to rupture.
 The volume of intravascular fluid must be closely regulated because of the mechanics of
the operation of the heart. If the blood volume falls too low, the heart can no longer pump
the blood effectively; if the volume is not restored, heart failure will result. This condition
is called hypovolemia.
Types of thirst
 Osmometric and volumetric thirst
 O refers to an increase in osmotic pressure on intracellular fluid when the cell is
dehydrated
 v measuring the volume of blood plasma
Osmometric thirst
 occurs when the solute concentration of the interstitial fluid increases. Solutes are
substances, such as salts, dissolved in a solution.
 An increase in interstitial solute concentration draws water out of the cells, and they
shrink in volume.
 Osmosis-movement of water through a semipermeable membrane from a region of low
solute concentration to one of high solute concentration
 Water moves by concentration gradient
 interstitial cell or fluid-outside thing bathing the other cells, concentration outside-draw
water from cell
 Verney suggested that these detectors, which he called osmoreceptors are neurons whose
firing rate is affected by their level of hydration.
 That is, if the interstitial fluid surrounding them became more concentrated, they lose
water through osmosis. The shrinkage causes them to alter their firing rate, which sends
signals to other parts of the brain.
Why do we feel thirsty after a salty meal
 The salt is absorbed from the digestive system into the blood plasma.
 The salt concentration of the blood draws water from the interstitial fluid, which in
turn causes water to leave the cells and causes osmometric thirst.
Exam-identify specific type of thirst, define the process, neural mechanisms involved
Volumetric thirst-osmoreceptors, median preoptic nucleus
 Volumetric thirst occurs when the volume of the blood plasma—the intravascular volume
— decreases.
 Loss of blood (hypovolemia) is the most obvious cause of pure volumetric thirst.
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 hypovolemia involves a loss of sodium as well as water (that is, the sodium that was
contained in the fluid that was lost), volumetric thirst leads to a salt appetite.
 Hypovolemic shock-emergency condition in which severe blood and fluid loss make the
heart unable to pump enough blood to the body. Can stop organ to stop working.
o Caused due to loss of 20 or more percent of blood in body-cuts or injuries,
bleeding from injuries, internal bleeding
o Excessive diarrhea, sweating, burns vomiting
o Symptoms- rapid heart rate, anxiety, low urine output, chest pain, shallow
breathing, blue lips and ginger nails.

27 JAN 2025
 Interstitial fluid
 Intravascular CSF
 Balance between intravascular and interstitial fluid
 Osmoreceptors-neurons involves in osmometric thirst
Who detects the loss of fluid in blood plasma?
 Detector cells in the heart and kidneys contribute to monitoring blood volume and
inducing volumetric thirst when intravascular fluid is low.
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 Cells in the kidneys detect decreases in blood flow. In response to low blood volume,
the kidneys are responsible for the presence of the hormone angiotensin following a
cascade of biochemical events. Angiotensin initiates drinking and a salt appetite,
causes the kidneys to conserve water and salt, and increases blood pressure.
o Cells in kidneys detect decreased in blood flow-activate the hormones
angiotensin-angiotensin initiates drinking and a salt appetite-causes kidneys to
con serve water and salt-increasers blood flow
 Therefore, reduced blood flow to the kidneys causes water and salt to be retained,
encourages the animal to find and ingest water and salt and allows the organism to
compensate for reduced blood volume until fluid balance can be restored.
 A second set of receptors for volumetric thirst is located in the atria of the heart.
 These baroreceptor cells (in the heart) are stretch sensitive and detect when blood
volume in the heart falls.
 A reduction in blood flow to the heart increases drinking- severing the nerves to the atrial
baroreceptors decreases drinking,
 This demonstrates the important role of these receptor cells
Median preoptic nucleus
Neural mechanisms of thirst
Thirst-brain mechanisms
 the osmoreceptors that initiate drinking are located in the OVLT and SFO of the lamina
terminalis.
 Lamina terminals contains 2 specialized circumventricular organs-
o Organum vasculosum of lamina terminalis (OVLT) and
o Subfornical organ (SFO)
 The signal for volumetric thirst is provided by angiotensin. Because this peptide does
not cross the blood–brain barrier, it cannot directly affect neurons in the brain except for
those located outside the blood–brain barrier, such as the OVLT and SFO. In fact,
research indicates that the SFO is the site at which blood angiotensin acts to produce
thirst.
 LT in the 3rd ventricle and extending to intraventricular forum.
28 Jan 2025
 In a functional-imaging study by Egan et al., (2003), the investigators administered
intravenous injections of a salty solution to human volunteers while their brains were
being scanned.
 The researchers observed strong activation of several brain regions, including the lamina
terminalis and the anterior cingulate cortex.
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 When the participants were permitted to drink water, they did so and almost immediately
report that their thirst had been satisfied.
 Simultaneously, the activity in the anterior cingulate cortex returned to base line values.
However, the activity in the lamina terminalis remained high.
 These results suggest that the activity of the anterior cingulate cortex reflected the
participants’ thirst, which was immediately relieved by a drink of water.
 In contrast, the continued activity in the lamina terminalis reflected the fact that the
blood plasma still contained a high concentration of solutes. After all, it takes
around 20 minutes for a drink of water to be absorbed into the general circulation.
Anterior cingulate cortex or gyrus in medial frontal lobe, around limbic system and all-front
of cingulate gyrus, near limbic system
Subfornical organ (SFO)-volumetric sensation, osmoreceptors also present
 very low doses of angiotensin injected directly into the SFO caused drinking
 destruction of the SFO or injection of a drug that blocks angiotensin receptors abolished
the drinking
 Neurons in the SFO send their axons to another part of the lamina terminalis: the median
preoptic nucleus, a fiber bundle that connects the amygdala and anterior temporal lobe
Damaged-we will not be aware of thirst-so not drinking-adipsia
Median preoptic nucleus
 It is present in lamina terminals seen to play a role in fluid regulation in humans
 McIver et al., (1991) reported that brain damage that includes this region can cause
adipsia—lack of drinking.
 The patients report no sensation of thirst even after they are given an injection of
hypertonic saline. To survive, they must deliberately drink water at regular intervals each
day, even though they feel no need to do so.
video-do u know how u r thirsty? (1.47)
Case study-type of thirst?
Less hydrated and more dehydrated-which type of thirst?
Then neural mechanisms will change depending which thirst it is.
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30 Jan 2024
Hunger
 To stay alive, our cells must be supplied with fuel and oxygen.
 Fuel comes from the digestive tract, and its presence there is a result of eating.
 But the digestive tract is sometimes empty; in fact, most of us wake up in the morning in
that condition.
 So there has to be a reservoir that stores nutrients to keep the cells of the body nourished
when the gut is empty.
 Indeed, there are two reservoirs: one short-term and the other long-term.
 The short-term reservoir stores carbohydrates, and the long-term reservoir stores fats.
 Beta cells and alpha cells in pancreas
The short-term reservoir-stores glycogen which is converted to glucose for energy
 The short-term reservoir sustains our fuel needs for several hours between meals.
 It is located in the cells of the liver and the muscles
 It is filled with a complex, insoluble carbohydrate called glycogen (livers converts to
glucose for functioning)
Focusing on liver cells
 Cells in the liver convert glucose (a simple, soluble carbohydrate) into glycogen and
store the glycogen.
 They are stimulated to do so by the presence of insulin (beta cells), a peptide hormone
produced by the pancreas.
 Thus, when glucose and insulin are present in the blood, some of the glucose is used as a
fuel, and some of it is stored as glycogen. (insulin’s job)
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 Later, when all of the food has been absorbed from the digestive tract, the level of
glucose in the blood begins to fall.
 The fall in glucose is detected by cells in the pancreas and in the brain.
 The pancreas responds by stopping its secretion of insulin and starting to secrete a
different peptide hormone: glucagon-alpha cells. (increase glucose)
 The effect of glucagon is opposite that of insulin: It stimulates the conversion of
glycogen (stored in the liver) into glucose.
 When excess glucose is available, the liver soaks up excess glucose and stores it as
glycogen
 when plenty of glucose is available, and it releases glucose from its reservoir when the
digestive tract becomes empty and the level of glucose in the blood begins to fall
3 Feb 2025
Video-hormone control of hunger-3.36
Hypothalamus responsible for hunger
Full
high glucose, insulin in release
High energy
High lipid, leptin release-satiety signal
Leptin levels rarely change as it is based on adipose tissue
Hungry
low glucose
Low energy
Low lipid
Empty stomach-growl-ghrelin present -urge to eat
Tell hypothalamus-motivate to find food
Role of hypothalamus
 The carbohydrate (glycogen) reservoir in the liver is reserved primarily for the
central nervous system (CNS).
 When you wake in the morning, your brain is being fed by your liver, which is in the
process of converting glycogen to glucose and releasing it into the blood.
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 The glucose reaches the CNS, where it is absorbed and metabolized by the neurons
and the glia. This process can continue for a few hours, until all of the carbohydrate
reservoir in the liver is used up.
 Usually, we eat some food before this reservoir gets depleted, which permits us to refill it.
But if we do not eat, the CNS (and the rest of the body) must start living on the
products of the long-term reservoir.
Long-term reservoir
 long-term reservoir consists of adipose tissue (fat tissue). This reservoir is filled with
fats or, more precisely, with triglycerides.
 Triglycerides are complex molecules that contain glycerol (a soluble carbohydrate, also
called glycerin) combined with three fatty acids (stearic acid, oleic acid, and palmitic
acid).
 Adipose tissue is found beneath the skin and in various locations in the abdominal
cavity.
 It consists of cells that are capable of absorbing nutrients from the blood, converting
them to triglycerides, and storing them.
 The size of the fat cells is determined by the amounts of triglycerides that these cells
contain.
 The long-term fat reservoir is what keeps us alive when we are fasting.
 As we begin to use the contents of our short-term carbohydrate reservoir, fat cells start
converting triglycerides into fuels that the cells can use and releasing these fuels into
the bloodstream.
 When we wake up in the morning with an empty digestive trat, our CNS is living on
glucose released by the liver. (till we hv compounds, short-term)
 The other cells of the body are living on fatty acids
Signals to start a meal
 An empty stomach and upper intestine provide an important endocrine signal to the
brain that it is time to start thinking about finding something to eat.
 Ghrelin is a potent stimulator of food intake, and it even stimulates thoughts about food.
 A peptide hormone called ghrelin is released from the gastrointestinal system when
individuals are in the fasting phase and the digestive system is empty
 Ghrelin then binds to receptors in the hypothalamus (lateral-hunger related so) to
help stimulate eating behavior.
 Fasting-increased secretion of ghrelin-feeling hungry
 Possible cause of overeating is chronic elevation in blood level of ghrelin.
 Other causes of hunger
 Gluco-deprivation-a fall in blood level (a condition known as hypoglycemia) is a potent
stimulus for hunger
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o Detector cells are present in the brain

 Lipo-deprivation-depriving cells of lipids
o Detector cells are present in liver

Signals to stop a meal

 Satiety-feeling of fullness
 Satiety-signals that stop a meal
 Short-term satiety-signals to stop a single meal
 Long-term s-signals arise in adipose tissue, control the intake of calories by modulating
the sensitivity of brain mechanisms to the hunger and satiety signals
Before eating-ghrelin increases by gastrointestinal cells, signal to brain, leptin
After eating-satiety-leptin increases by adipose cells

10 Feb 2025
Brain mechanisms of hunger
Hypothalamus
Lateral area:
 Role on hunger
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 After the lateral hypothalamus was destroyed, animals stopped eating or drinking.
Electrical stimulation of the same region would produce eating, drinking, or both
behaviors.
Ventromedial area:
 Role in satiety
 lesions of the ventromedial hypothalamus produced over eating that led to obesity,
whereas electrical stimulation suppressed eating.
Neurotransmitters related to hunger
neuropeptide Y:
Neuropeptide Y:
 A NT secreted by neurons found in the arcuate nucleus, located in the hypothalamus.
 They carry signals from the brain stem selecting glucodeprivation and liver-
lipodeprivation to the hypothalamus
 Infusion of neuropeptide Y into the hypothalamus produces ravenous, almost frantic
eating,
 In response, hypothalamus produces melanin-concentrating hormone (MCH) and orexin
Role of peptides produced by the neurons in the hypothalamus:
 Melanin-concentrating hormone (MCH) and orexin
 Referred to as orexigens which is appetite inducing chemicals
 Produced by neurons in the lateral hypothalamus
 Stimulate hunger and decrease metabolic rate-increasing and preserving body’s energy
store
 Orexin may also play a role in relationship between eating and sleeping
o Yamanaka et al., (2003) suggest that the decreased activity seen in orexin-
secreting neurons after feeding may contribute to the sleepiness that is often felt
after a meal.
Compounds stimulated by orexigens
Agouti-related protein (AGRP)
 An orexinergic peptide
 Acts together with neuropeptide Y to promote hunger
 Infusion of a very small amount of this peptide into the third ventricle produces an
increase in food intake.

Endocannabinoids
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 Stimulated by Marijuana-increased production of orexigens-increased appetite

Dopamine
 Ghrelin activates dopaminergic (DA) neurons in the ventral tegmental area (VTA)
Brain mechanism of satiety
 Ventromedial hypothalamus is an important satiety regulator
 The anorexigens or appetite-suppressing peptides, function as signals with effects in
the ventromedial hypothalamus.
 Leptin
o Hormone secreted by adipose tissue, suppresses eating and raises the animal’s
metabolic rate
o Activation of leptin receptors on NPY/AGRP-secreting hormones on the arcuate
nucleus-inhibitory effect-decreases production of NPY and AGRP-increases
fullness or reduces appetite
 The arcuate nucleus contains another system of neurons that secrete 2 peptide
anorexigens.
o CART-cocaine and amphetamine regulated transcript
o Alpha-melanocyte stimulating hormone-alpha-MSH-released by CART
 Leptin (excitatory so does this) activates CART/alpha-MSH when then inhibit MCH
(melanin concentrating hormone) and orexin neurons in the lateral hypothalamus and
present their stimulatory.
 Ghrelin and orexin also inhibits CART/alpha-MSH neurons, which decreases the
anorexic effect of these 2 peptides.

Pro-opiomelanocortin (POMO)-neuron when activated, they secrete alpha-MSH

14 Feb 2025
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Obesity
 One way of assessing body weight and health risks associated with being under or
overweight is to calculate a body mass index (BMI) score.
 The formula to calculate a BMI score is: weight (kg) / [height (m)]2 or weight (lb.) /
[height (in.)]2 multiplied by 703.
 BMI scores are categorized in four basic categories.

Possible causes
 Genetic: Genetic differences—and their effects on development of the endocrine system
and brain mechanisms that control food intake and metabolism—appear to be
responsible for the majority of cases of extreme obesity
 Environmental: Body weight is the result of the difference between two factors:
calories consumed and energy expended. In modern industrialized societies,
inexpensive, convenient, good-tasting, high calorie food is readily available, which
promotes an increase in intake.
 As Bray et al., (2004) point out, consuming high-fructose corn syrup, found in many
prepared foods, including soft drinks, fruit drinks, processed foods, and baked goods,
may contribute to obesity. Fructose, unlike glucose, does not stimulate insulin secretion
or enhance leptin production, so this form of sugar is less likely to activate the brain’s
satiety mechanisms.
 The transition to college life is often associated with changes in eating and physical
activity patterns.

25 Feb 2025
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Physical activity factors:

 Changes in people’s expenditure of energy
 We expend energy in two basic ways: through physical activity and through the
production of heat.
 Body’s ability to generate heat as a part of metabolism-thermogenesis
 “non-exercise activity thermogenesis,” or NEAT-an increase in involuntary activity:
muscle tone, postural changes, and fidgeting.
o The amount of fat tissue that a person gained was inversely related to his or her
level of NEAT.
Genetic factors
 heredity appears to affect people’s metabolic efficiency. However, until recently,
variations in only two genes were found to cause obesity in humans: the gene for the
MC4 receptor and the FTO gene (fat mass and obesity related gene), which codes for
an enzyme that acts in hypothalamic regions related to energy balance, such as the
PVN, and the arcuate nucleus.
 People differ in this form of efficiency.
o Thrifty phenotypes-Those with an efficient metabolism have calories left over to
deposit in the long-term nutrient reservoir, and these calories accumulate in the
form of increased adipose tissue.
o Spendthrift phenotype-people with an inefficient metabolism can eat large meals
without getting fat.
 A fuel- efficient automobile is desirable, but a fuel-efficient body runs the risk of
becoming obese—at least in an environment where food is cheap and plentiful.
 Perhaps individual differences in metabolic efficiency reflect the nature of the
environment experienced by their ancestors. Perhaps people whose ancestors lived in
regions where food was scarce or subject to periods of famine are more likely to have
inherited efficient metabolisms.
 Leptin
o So far, researchers have found several cases of familial obesity caused by the
absence of leptin produced by mutations of genes responsible for production of
leptin or the leptin receptor. Treatment of people who are leptin-deficient with
injections of leptin has dramatic effects on body weight.
3 March 2025
Eating disorders
 Anorexia-2 types-binge eating and purging
 BMI differentiation in anorexia and binge-eating disorder
 Cases study-identify types of disorder and biological factors
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 DSM-5 groups several related diagnoses together in the category feeing and eating
disorders
 Eating disorders include AN, BN, BED
 Each of these disorders include extreme changes in eating behavior
 Persistent pattern of eating behavior that impairs physical health or psychological health
 The DSM does not consider obesity a mental illness at this time due to research
implicating genetic, physiological, behavioral and environmental contributing factors.

Anorexia nervosa
 Literally mean lack of appetite
 2 sub-divisions-eat little and exercise vigorously
 Binge eating or purging type-eat in binges followed by induced vomiting, laxatives,
excessive exercise or diuretics
 More in females
 Comin in thin figure professionals-ballet, cheerleader, figure skating, models
Bulimia nervosa
 Word bulimia comes from Greek “bous” which means ox and limos that is hunger. It is
meant to denote a hunger of such proportions that the person could eat an ox
 An eating disorder which is characterized by recurrent binge eating, followed by
compensatory behaviors such as vomiting, use of laxatives, enemas, diuretics
BED
 Defined as excessive food intake within a 2-hour period accompanied by a sense of lack
of control
 Ppl with this disorder suffer emotional distress over their binge eating
 19

Possible causes

 Brain changes -Some reports indicate the presence of enlarged ventricles and widened
sulci in the brains of patients with anorexia, which indicate shrinkage of brain tissue.
(Fig 12.27)
 Ventricles enlarge, brain tissue reduces
 Genetic factors-primarily from twin studies, that hereditary factors play an important role
in the development of anorexia nervosa. the incidence of anorexia nervosa is higher in
girls who were born prematurely or who sustained birth trauma during complicated
deliveries, which suggests that biological factors independent of heredity may play a role.
 Dietary factors- some individuals go on a diet to bring their body weight closer to what
they perceive as ideal. Once they get set on their course and begin losing weight,
physiological and endocrinological changes bring about the symptoms of starvation and
the vicious cycle begins.
 Hormonal changes- Another possible cause could be the changes in hormones that
accompany puberty.
 Role of NPY, role of glucocorticoids, thyroid, growth hormone, genotypes
Treatment
 CBT, pharmacological treatment
 Alternative therapies
 Success rates for most eating disorder treatments are low, however some alternate
therapies have shown higher success rates
 Bergh, Södersten, and their colleagues have devised a novel and apparently effective
treatment protocol for anorexia. The patients are taught to eat faster by placing a plate of
food on an electronic scale attached to a computer that displays the time course of their
 20

actual and ideal intake. After the meal the patients are kept in a warm room, which
reduces their anxiety and their activity level.
10 March 2025
Sexual development
 Reproductive behaviors constitute an important category of social behaviors, because
without them, most species would not survive
 These behaviors which include courting, mating, parental behavior and most forms of
aggressive behaviors are most striking categories of sexually dimorphic behaviors,
behaviors that differ in males n females
 Hormones that are present both before and after birth play a very special role in
development and control of sexually dimorphic behaviors as well as sexual orientation
Differences
 The term “sex” typically refers to the genetic or physiological characteristics of males
and females,
 while the term “gender” typically refers to the socially-influenced identity, role, and/or
behavior of an individual.
Sexual maturation
 The primary sex characteristics are influenced by organizational effects of hormones
and include the gonads, internal sex organs, and external genitalia. These structures are
present at birth.
 The secondary sex characteristics, such as enlarged breasts and widened hips or a beard
and deep voice, are influenced by the activational effects of hormones and do not appear
until puberty.
 At puberty the gonads are stimulated to produce their hormones, and these hormones
cause the person to mature sexually.
 The onset of puberty occurs when cells in the hypothalamus secrete gonadotropin-
releasing hormones (GnRH), which stimulate the production and release of two
gonadotropic hormones by the anterior pituitary gland.
 The two gonadotropic hormones are follicle stimulating hormone (FSH) and
luteinizing hormone (LH), named for the effects they produce in a female.
 However, the same hormones are produced in males, where they stimulate the testes to
produce sperms and to secrete testosterone.
 These gonadotropic hormones are ultimately responsible for sexual maturation
 Negative feedback loop-present for cortisol, progesterone, works for specific or
general?, working-HPA axis, HPT axis, T3, T4, thyroxine, difference in terms of atoms-3
and 4
 Adrenal gland-adrenal medulla internal or external?
 21

 3 major categories of hormones-glucocorticoids,

 Releasing factor hormones, inhibiting hormones

Human sexual behavior

 Human sexual behavior, like that of other mammals, is influenced by activational
effects of gonadal hormones
o ACTIVATIONAL EFFECTS OF SEX HORMONES IN WOMEN
 Testosterone has an activational effect on sexual behavior of men
 Women do not require to estradiol or progesterone to experience
sexual interest or to engage in sexual behavior
 Studies with women suggest that variations in levels of ovarian
hormones across menstrual cycle affect sexual interest but that
other factors such as (sexual initiation with partners or terminating
pregnancy) can also affect sexual behaviors
 The presence of androgens may facilitate effect of estradiol on
women’s sexual interest
Neural control of sexual behaviors in males
 Sexual reflexes such as sexual posturing, erection and ejaculation are organized in
spinal cord
 LSt cells a group of neurons in the lumbar region of the rat spinal cord, play a crucial
role in triggering an ejaculation
 Brain mechanisms have excitatory and inhibitory control of circuits responsible for
erection and ejaculation
 22

 Stimulating medial preoptic area produces copulatory behavior destroying it

permanently abolishes behavior
 Destruction of sexually dimorphic nucleus-part of MPA, in laboratory animals
impairs mating behavior
 Ejaculation in men is accompanied by increased behavior in brain’s reinforcement
mechanisms several thalamic nuclei, lateral putamen, and cerebellum
In females
 Most important forebrain region for female sexual behavior is the ventromedial
nucleus of the hypothalamus-VMH. Its destruction abolishes copulatory behavior
and its stimulation facilitates this behavior
 Both estradiol and progesterone exert their facilitating effects on female sexual
behavior in this region and studies have confirmed existence of progesterone
receptors there
 Steroid sensitive neurons of VMH send axons to the PAG of the midbrain, these
neurons through their connections with the medullary reticular formation, control
the particular responses that constitute female sexual behavior
 Orgasm in women is accompanied by increased activity in the PAG.
Sexual orientation
 Constitutes stable sexual attraction towards the opposite sex-heterosexuality, same
sex-homosexuality or both sexes-bisexuality, or showing no interest in individuals of
either sex-asexuality after maturity
 Factors that determine sexual orientation of individuals
o Development of specific brain structures
o Fraternal birth order
o Heritability-confirmed through twin studies
o Organizational and activational effect of hormones

Activational and Organizational Effects of Hormones

 It appears that sexual orientation is not strongly related to variations in the levels of sex
hormones during adulthood, ruling out a role for activational effects of sex hormone
exposure.
 Many studies have examined the levels of testosterone in gay and heterosexual men and
found no differences between these groups. Similarly, most studies have found no
difference in sex hormones between groups of women who are heterosexual and those
who are not.
 men and women who are treated with sex hormones for medical reasons do not change
their sexual orientation, further suggesting that exposure to hormones in adulthood is not
a factor in the development of sexual orientation
 23

 not due to levels of hormones, it is due to certain predisposition factors, prenatal factors
12 March 2025
role of androgens
 The secretion of androgens begins prenatally
 Prenatal androgens can affect humans social behavior and sexual behavior as well as
anatomy
 In a disorder known as congenital adrenal hyperplasia (CaH), the adrenal glands
secrete abnormal amounts of androgens, the syndrome causes prenatal masculinization.
 Boys born with CAH develop typically; the extra androgen does not seem to have
significant effects.
 However, a girl with CAH will be born with an enlarged clitoris, and her labia may be
partly fused together. (The scrotum and labia develop from the same tissue in the fetus
Treatment
 Once the syndrome has been identified, the person will be given a synthetic hormone that
suppresses the excessive secretion of androgens.
 If masculinization of the genitals is pronounced, surgery is sometimes performed to
correct them.
Further effects
 As a group, approximately one third of females with CAH describe themselves as
bisexual or homosexual
 A plausible explanation for the increased incidence of lesbian or bisexual sexual
orientation of women with CAH is that the androgens affect development of the brain.
Androgen sensitivity syndrome
 genetic males develop female external genitalia, but internally retain the testes and do not
develop a uterus or fallopian tubes.
 If an individual with this syndrome is raised as a girl, the testes are typically removed
because they often become cancerous;
 if testes are removed, the body will mature into that of a woman at the time of puberty
through the effects of the small amounts of estradiol produced in the body.
 At adulthood the individual will function sexually as a woman, although surgical
lengthening of the vagina may be necessary.
 Individuals with this syndrome report average sex drives, including normal frequency of
orgasm in intercourse and are often, though not always, attracted to male partners
 No uterus,
Cloacal Exstrophy
 24

 people’s sexual identity and sexual orientation are strongly influenced by biological
factors and cannot easily be changed by the way a child is raised (environmental factors
 A developmental abnormality known as cloacal exstrophy results in the birth of an
intersex individual who is genetically male with fully developed testes but urogenital
abnormalities, often including the lack of a penis
 Individuals with cloacal exstrophy are often sexually attracted to females
 In the past, many genetically male individuals born with this condition were raised as
females, primarily because it is relatively easy to surgically construct a vagina that can
function in intercourse but very difficult to construct a functioning penis.
 However, studies have shown that approximately 50 percent of intersex individuals with
cloacal exstrophy later expressed dissatisfaction with their surgical gender assignment
and began living as men, often undergoing gender-change procedures
17 March 2025
Sexually dimorphic brain
 The human brain is a sexually dimorphic organ
 the sexual dimorphism of the human brain is a result of differential exposure to
androgens prenatally and during early postnatal life.
 Sexual dimorphism in the human brain could also be a result of differences in the social
environments of males and females
 Several postmortem studies have examined the brains of gay and heterosexual men and
women. So far, these studies have found differences in the size of three different
subregions of the brain:
o the suprachiasmatic nucleus (SCN),
o a sexually dimorphic nucleus of the hypothalamus-regulating sexual behavior
o and the anterior commissure-a fiber bundle that interconnects parts of left and
right temporal lobes
 We cannot necessarily conclude that any of the brain regions mentioned are directly
involved in people’s sexual orientation (or gender identity). It is also possible that
differences may lie elsewhere in the brain, in some regions as yet unexplored by
researchers. However, the observation that differences in brain structure are related to
sexual orientation and gender identity suggests that biological factors including exposure
to prenatal hormones have an effect on both sexual orientation and gender identity
Role of Prenatal Environment in Sexual Orientation
 Studies by Blanchard (2001) and by Bogaert (2006) found that gay men tend to have
more older brothers— but not more older sisters or younger brothers or sisters.
 When mothers are exposed to several male fetuses, their immune system may become
sensitized to proteins that only males possess (such as Y-linked proteins).
 25

 As a result, the response of the mother’s immune system may affect the prenatal brain
development of sexually dimorphic structures of later male fetuses.
Heredity and Sexual Orientation
 Twin studies take advantage of the fact that identical twins have identical genes, whereas
the genetic similarity between fraternal twins is, on the average, 50 percent.
 Bailey and Pillard (1991) found that the concordance rate for non-heterosexual sexual
orientation among twin brothers was 52 percent for identical twins and only 22 percent
for fraternal twins—a difference of 30 percent. Other studies have shown differences of
up to 60 percent, suggesting that a genetic component plays a role in sexual orientation in
males.
 Genetic factors also appear to affect female sexual orientation. Bailey et al., (1993) found
that the concordance of female monozygotic twins for non-heterosexual sexual
orientation was 48 percent, while that of dizygotic twins was 16 percent.

Stress and health

 Stress can be defined as a state of worry or mental tension caused by a difficult situation.
Stress is a natural human response that prompts us to address challenges and threats in
our lives (WHO, 2023).
 Once the situation is over, our physiological conditions get back to normal. When the
situation continues to persist, it affects our physiology.
 Harmful effects produced not by the stimuli themselves but by our reactions to them-
stress response
 The physiological responses that accompany negative reactions, prepare us for flight or
fight response, coined by Walter Cannon leading to a state of arousal.
 Once the situation is over, our physiological conditions get back to normal
 When the situation continues to persist, it affects our physiology
Physiology of stress
 Emotions include
 26

o Behavioral response
o endocrine response and
o autonomic response
 Endocrine and autonomic response can have adverse effects on health
Exam-could be asked to create a situation and then write

 Inhibitory signals from hypothalamus-anterior pituitary-ACTH-adrenal gland-

glutocorticoids or epinephrine or norepinephrine from adrenal medulla
 Hypothalamus-CRH-anterior pituitary-ACTH-adrenal cortex-release
glutocorticoids
 Adrenal medulla release epinephrine and non-epi, which will have sympathetic
and parasympathetic response
 2 pathways of stress physiology-
 SYMPATHETIC ADRENAL-MEDULLARY SYSTEM
o Controls release of catecholamine stress hormones (epinephrine and non-
epinephrine)
o Stressful stimulus or environment-hypothalamus and SNS activation-
adrenal medulla releases epinephrine and norepinephrine
o Catecholamine hormones-rapid activation of SNS
o Epinephrine affects glucose metabolism
o Epinephrine plus norepinephrine=increases blood flow to
muscles=including in heart outputs=including in BP
o Norepinephrine-stress hormone and a NT
 27

o Some of the behavioral and physiological responses produced by aversive

stimuli appear to be mediated by noradrenergic neurons (neurons whose
primary NT is norepinephrine).
o For example, micro dialysis studies have found that stressful situations
increase the release of norepinephrine in the hypothalamus, frontal cortex,
and lateral basal forebrain
o destruction of the noradrenergic axons that ascend from the brain stem to
the forebrain prevented the rise in blood pressure that is normally
produced by social isolation stress.
o The stress-induced release of norepinephrine in the brain is controlled
by a pathway from the central nucleus of the amygdala to the locus
coeruleus, the nucleus of the brain stem that contains norepinephrine-
secreting neurons
o Norepinephrine-sustain attention and arousal in the situation
o Epinephrine-flight and fight for the situation
o Up and down of both

 HYPOTHALAMIC PITUITARY ADRENAL AXIS-feedback mechanisms

also
 Inhibitory signals from hypothalamus-anterior pituitary-ACTH-adrenal gland-
glutocorticoids or epinephrine or norepinephrine from adrenal medulla
 Hypothalamus-CRH-anterior pituitary-ACTH-adrenal cortex-release
glutocorticoids
o The other stress-related hormone is cortisol, a steroid secreted by the
adrenal cortex.
o Cortisol is called a glucocorticoid because it has profound effects on
glucose metabolism
 28

o glucocorticoids help to break down protein and convert it to glucose, help

to make fats available for energy, increase blood flow, and stimulate
behavioral responsiveness, presumably by affecting the brain.
o The release of glucocorticoid is controlled by the activity of the
hypothalamic pituitary adrenal axis (HPA axis).
19 March 2025
o The secretion of glucocorticoids is controlled by neurons in the
paraventricular nucleus of the hypothalamus (PVN)
o The neurons of the PVN secrete a peptide called corticotropin releasing
hormone (CRH), which stimulates the anterior pituitary gland to secrete
adrenocorticotropic hormone (ACTH).
o CRH (also called CRF, or corticotropin-releasing factor) is also secreted
within the brain, where it serves as a neuromodulator/neurotransmitter,
especially in regions of the limbic system that are involved in emotional
responses, such as the periaqueductal gray matter, the locus coeruleus,
and the central nucleus of the amygdala
Health Effects of Long-Term Stress
 Chronic or repeated stressful situations have found evidence of ill health.
 concentration camps, who were subjected to long-term stress, have had
generally poorer health later in life than other people of the same age
 Hans Selye suggested that most of the harmful effects of stress were produced by
the prolonged secretion of glucocorticoids
 These effects include increased blood pressure, damage to muscle tissue, steroid
diabetes, infertility, inhibition of growth, inhibition of the inflammatory
responses, and suppression of the immune system.
Effects of Stress on the Brain
 Research with animals has shown that long-term exposure to glucocorticoids destroys
neurons located in the CA1 field of the hippocampal formation. (Implication of LTP )
 The hormones appear to destroy the neurons by decreasing the entry of glucose and
decreasing the reuptake of glutamate.
 Research on rats-investigators found that this short-term stress affected the
functioning of the animals’ hippocampi.
 The stressed rats’ ability to learn a spatial task was impaired, and primed-burst
potentiation (a form of long-term potentiation) was impaired in hippocampal slices taken
from stressed rats
 29

 Apkarian et al. (2004b) found that each year of severe chronic back pain resulted
in the loss of 1.3 cm3 of gray matter in the cerebral cortex, with the greatest
reductions seen in the dorsolateral prefrontal cortex.
21 Marh 2025
 Prenatal stress

o Brunson et al. (2005) confirmed that stress early in life can cause the
deterioration of normal hippocampal functions later in life.
o Salm et al. (2004) found that mild prenatal stress can affect brain
development and produce changes that last the animal’s lifetime.
o the investigators observed impaired performance in the Morris water maze
and deficient development of long-term potentiation in the hippocampus.
They also found dendritic atrophy in the hippocampus, which might have
accounted for the impaired spatial learning and synaptic plasticity
 Resilience

o Fac tors such as the presence of various protective hormones (such as

testosterone, neuropeptide Y, and a hormone called DHEA that mediates
negative effects of excess cortisol) and controlled exposure to stress-related
stimuli can promote resilience in the event of stress.
 30

Psychoneuroimmunology
o the stress response can impair the functions of the immune system, which
protects us from assault by viruses, microbes, fungi, and other types of
parasites. Study of the interactions between the immune system and behavior
(mediated by the nervous system) is called psychoneuroimmunology.
o Immune system
o The immune system derives from white blood cells that develop in the
bone marrow and in the thymus gland
o Two types of specific immune reaction occur when the body is
invaded by foreign organisms, including bacteria, fungi, and viruses:
chemically mediated and cell-mediated reactions.
o Chemically mediated immune reactions involve antibodies.
Infectious microorganisms have unique proteins on their surfaces,
called antigens.
o These proteins serve as the invaders’ calling cards, identifying them
to the immune system. Through exposure to the microorganisms, the
immune system learns to recognize these proteins. The result of this
learning is the development of special lines of cells that produce
specific (antibodies)-proteins that recognize antigens and help to
kill the invading microorganisms
o Bone marrow produces different types of WBC cells-b cells, t cells,
monocytes, neutrophil
o Thymus specificizes in producing t cells-adaptive immunity
o When pathogen is detected-releases cytokines-Proliferation of WBC-
releases t cells-attacks pathogens directly
o Chemical mediated-b cells-antibodies-release proteins
o 2 specific immunity reactions-cell mediated and chemically mediated
(antibodies)-proteins that recognize antigens and help to kill the
invading microorganisms
o Cell mediated-release cytokines-proliferate WBC-attacks pathogen
directly
o Glucocorticoids-suppress specific immune response by interfering
with the message conveyed by the cytokines
 31

PTSD
o MRI studies have found evidence of hippocampal damage in veterans with combat
related posttraumatic stress disorder
o the volume of the hippocampal formation was reduced by over 20 percent, and the loss
was proportional to the amount of combat exposure the veteran had experienced
o Gilbertson et al. (2002) suggests that at least part of the reduction in hippocampal volume
seen in people with PTSD may predate the exposure to stress. In other words, a smaller
hippocampus may be a predisposing factor in the acquisition of PTSD. Gilbertson et al.,
studied 40 pairs of monozygotic twins in which only one member went to Vietnam and
experienced combat during the Vietnam War. Almost half of the men who experienced
combat developed PTSD. As expected, the hippocampal volumes of these men were
smaller than those of the men who did not develop PTSD after their combat experience.
o amygdala is responsible for emotional reactions in people with PTSD and that the
prefrontal cortex plays a role in these reactions in people without PTSD by inhibiting the
activity of the amygdala (Rauch et al., 2006).
 32

25 March 2025
Unit-3
 Schizophrenia
 Substance use disorders
 Major affective disorders
 Anxiety disorders
 Case-identify disorder, write biological factors
Anxiety disorder
 Anxiety disorders are characterized by unrealistic, unfounded fear and anxiety.
 anxiety disorders are the most common psychiatric disorders
types
 GAD
 PD
 Agoraphobia
 SAD
 33

Possible causes
 Don’t know exact causes. Combination of many.
 Gene-environment interaction
 Heritability-Family studies and twin studies indicate that panic disorder, generalized
anxiety disorder, and social anxiety disorder all have a hereditary component. Genetic
investigations indicate that variations in the gene that encodes production of the BDNF
protein may play a role in anxiety disorders. Brain drive neurotropic factor-regulate
neural survival, synaptic plasticity and neurogenesis-crucial aspects for emotional
regulation (amygdala)
 Chronic stress reduces BNDF, decreased BNDF-heightened fear
 BNDF-amygdala, increased fear to stimuli
 No structural changes, only increased activity 4 anxiety
 Environment- experiencing trauma might trigger an anxiety disorder, especially
someone who has inherited the higher risk
 Atrophy-major affective disorder, not in anxiety disorders
Brain changes
 Amygdala, cingulate, prefrontal and insular cortexes are involved in AD
 Amygdala plays an important role in tempering fear and anxiety. Patients with anxiety
disorders have been found to show heightened amygdala response to anxiety cues
 34

 PET studies shows that panic attack is associated with decreased activity in right
orbitofrontal cortex and anterior cingulate cortex, increased activity in amygdala,
(OFC and ACC functions are higher order functioning, emotional regulation-positive or
negative and decision-making-evaluation, decreased activity of these, increased fear)
 Phan et al. (2005) found that people with social anxiety disorder showed increases in
the activation of the amygdala when they looked at pictures of faces with angry,
disgusted, or fearful expressions. In addition, the activation of the amygdala was
positively correlated with the severity of the people’s symptoms.
 Monk et al. (2008) found that adolescents with generalized anxiety disorder showed
increased activation of the amygdala and decreased activation of the ventrolateral
prefrontal cortex while looking at angry faces.
 Stein et al. (2007) found that college students with a high level of anxiety (but without a
diagnosis of one of the anxiety disorders) showed increased activation of the amygdala
and the insular cortex, both of which correlated positively with students’ anxiety
measures.
 Amygdala symptoms maybe due to disrupted modulation with the central nervous
system. Low serotonin system activity and elevated noradrenergic system are responsible
for its development
2 April 2025
Major affective disorders
 Possible causes
 Heritability-close relatives of people who suffer from affective disorders r 10 times more
likely to develop these disorders than are people without afflicted relatives.
 Concordance rate for monozygotic twins was 69 percent however for di twins was only
13 percent
 RORA gene, involved in control of circadian rhythms, had the strongest association with
the occurrence of major depressive disorder.
 Evidence suggested that another gene, GRM8, which codes for the production of a
metabotropic glutamate receptor, may also be involved.
 McGrath et al. (2009) found that RORB, another circadian gene, was associated with
rapid cycling bipolar disorder seen in children.
 Glutamate-ionotropic and metabotropic receptors
 Changes in glutamate-metabotropic
Role of frontal lobe
 frontal cortex plays a critical role in development of depression. In particular, they
hypothesize that the subgenual ACC serves as an important focal point in a network of
brain regions that are involved in the regulation of mood and a decrease in the activity of
this region is consistently seen after successful antidepressant treatment.
 35

 neuroimaging studies of depressed patients is hyperactivity of this region, along with

decreased activity in other regions of the frontal cortex, including the dorsolateral PFC,
the ventrolateral PFC, the ventromedial PFC, and the orbitofrontal cortex (Mayberg,
2009).
 Studies have shown that a variety of successful antidepressant treatments reliably
decrease the activity of the subgenual ACC and, usually, increase the activity of other
regions of the frontal cortex
Monoamine hypothesis
 Underlying pathophysiologic basis of depression is a depletion in the levels of serotonin,
norepinephrine and or dopamine in CNS
 Most investigators have focused their research efforts on 2 monoamine norepinephrine
and serotonin
 Studies shows that tryptophan depletion is the precursor of 5-HT, or serotonin ha little or
not effect on the mood of healthy people but it does lower the mood of people with a
personal poor family history of affective disorders. Thus, there appears to be
physiological differences in the brains of vulnerable people
 Also, SSRIs and SNRIs increase level of 5HT or norepinephrine in the brain very rapidly,
the drugs do not relieve the symptoms of depression until they have taken for several
weeks and monoaminergic neurons have adapted to the presence of increased NT.
 Suggesting that something other than a simple increase in monoaminergic activity is
responsible for the normalization of mood.
 Mant investigators believe that the increased extracellular levels of monoamines
produced by administration of antidepressants drugs begins a chain of events that
eventually produce changes in the began that re ultimately responsible for antidepressant
effect
 Exact nature of this chain of events is still unknown.
 Good one as of now.
Role of 5HT transporter
 Several studies have accumulated evidence that implicates the serotonin transporter in
depression. A portion of the gene—the promoter region—for the 5-HT transporter (5-
HTT) comes in two forms, short and long.
 A longitudinal study by Caspi et al. (2003) followed 847 people over a period of more
than 20 years, starting at three years of age, and recorded the occurrence of stressful
events in their lives, including abuse during childhood, romantic disasters, bereavements,
illnesses, and job crises.
 The investigators found that the probability of major depression and suicidality increased
with the number of stressful life events the people had experienced.
 36

 Moreover, the increase was much greater for people with one or two copies of the short
alleles for the 5-HTT promoter. This study showed evidence of an interaction between
environment and genetics
7 April 2025
 Several meta-analyses of the studies investigating a possible role of 5HTT promoter in
depression have concluded that, although some studies have found positive effects when
the results of all published studies are combined no significant effects emerged
 Until further research shows otherwise it appears that a role of 5HTT promoter in
depression is unproven.
Role of neurogenesis
 all the evidence about human neurogenesis has been by extrapolation from studies with
laboratory animals.
 Several studies with laboratory animals have shown that stress inhibits adult neurogenesis
and increases vulnerability to depression
Role of circadian rhythms
 90 percent of ppl with an episode of depression report changes in their patterns of sleep-
sleep is shallow, fragmented, sleep-wave sleep is reduced and stage 1 is increased, rem
sleep occurs earlier a higher proportion of REM periods in first half of night and usually
have difficulty initiating and maintaining a good night’s sleep
 Case studies-diagnostic criteria, symptoms and then bio
Substance abuse
 Rates of substance abuse, in general are higher among men, however some research
suggests that rates of prescription drug abuse maybe similar among amn and women
 Abuse of prescription painkillers increased over 25 percent in the five years between
2005 and 2010
 Substance use disorders are characterized by impaired control over the use of substance-
such as taking increasing amounts of the drug, a desire to reduce the amount of the drug
used or unsuccessful attempts to cut back, large amounts of time spent obtaining the drug,
drug craving, failure to meet educational, occupational, or family obligations, continued
use even after experiencing interpersonal problems related to use of drug, failure to stop
using despite problems related to use, experiencing tolerance and withdrawal
Positive reinforcement
 refers to the effect that certain stimuli have on the behaviors that preceded them. If, in a
particular situation, a behavior is regularly followed by an appetitive stimulus (one that
 37

the organism will tend to approach), then that behavior will become more frequent in that
situation
 Most drugs of abuse have reinforcing effects. (There is one exception—hallucinogens).
That is, their effects include activation of the reinforcement mechanism. This activation
strengthens the response that was just made
 Dopamine pathway, mesolimbic pathway, reward pathway
 Particularly, if the drug was taken by a fast-acting route such as injection or inhalation,
the last response will be the act of taking the drug, so that response will be reinforced.
This form of reinforcement is powerful and immediate and works with a wide variety of
species.
 Snorting, smoking, or injecting a drug automatically increases the abuse potential of the
drug compared to using a slower route of administration, such as taking a drug orally,
because more of the drug enters the brain more rapidly and activates the reinforcement
pathway more strongly
 Role in substance abuse
o The effectiveness of a reinforcing stimulus is greatest if it occurs immediately
after a response. If the reinforcing stimulus is delayed, it becomes consider ably
less effective.
o many individuals who use drugs recreationally prefer heroin to morphine not
because heroin has a different effect, but because it has a more rapid effect. In
fact, heroin is converted to morphine as soon as it reaches the brain. But because
heroin is more lipid soluble, it passes through the blood–brain barrier more
rapidly, and its effects on the brain are felt sooner than those of morphine
 neural mechanisms
o the release of dopamine appears to be a necessary (but not sufficient) condition
for positive reinforcement to take place.
o Role of mesolimbic pathway
 Drugs that are abused— including amphetamine, cocaine, opiates,
nicotine, alcohol, PCP, and cannabis—trigger the release of dopamine in
the nucleus accumbens (NAC), as measured by microdialysis. Different
drugs stimulate the release of dopamine in different ways.
 process of substance abuse begins in the mesolimbic dopaminergic system
and then produces long-term changes in other brain regions that receive
input from these neurons.
 The first changes appear to take place in the ventral tegmental area (VTA)
 single administration of a variety of commonly abused drugs (including
cocaine, amphetamine, morphine, alcohol, and nicotine) increased the
strength of excitatory synapses on dopaminergic neurons in the VTA in
mice. This change appears to result from insertion of additional AMPA
receptors into the postsynaptic membrane of the DA. This process,
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normally mediated by glutamatergic NMDA receptors, is the neural basis

of many forms of learning.
 A single injection of a reinforcing drug produces synaptic strengthening in
the VTA that lasts for about five days. If an animal receives cocaine for
about two weeks, the changes in the VTA persist.
o Role of striatum
 As a result of the changes in the VTA, increased activation is seen in a
variety of regions that receive dopaminergic input from the VTA,
including the ventral striatum, which includes the NAC, and the dorsal
striatum, which includes the caudate nucleus and putamen.
 Synaptic changes that are responsible for the compulsive behaviors that
characterize substance abuse occur only after continued use of a drug. The
most important of these changes appears to occur in the dorsal striatum
 At first, the person using the drug experiences the pleasurable effects of
the drug, reinforcing the behaviors that cause the drug to be delivered to
the brain
 Eventually, these behaviors become habitual, and the impulse to perform
them becomes difficult to resist. The early reinforcing effects that take
place in the ventral striatum (namely, in the NAC) encourage drug-
taking behavior, but the changes that make the behaviors become
habitual involve the dorsal striatum.
 Studies with monkeys performing a response reinforced by infusion of
cocaine over a long period of time show a prgression of neural changes,
beginning in the ventral striatum (in the NAC) and continuing upward
to the dorsal stria tum as the behavior becomes more automatic and
habitual
o Connections Between Mesolimbic Pathway and Striatum
 neural changes responsible for chronic drug use follow a dorsally
cascading set of reciprocal connections between the striatum and the
ventral tegmental area.
 neurons in the ventral NAC project to the VTA, which sends dopaminergic
projections back to a more dorsal region of the NAC, and so on. This
back-and-forth communication continues, connecting increasingly dorsal
regions of the striatum, all the way up to the caudate nucleus and putamen.
 the control of compulsive drug-taking behavior is established by
interactions between the ventral and dorsal striatum that are mediated by
dopaminergic connections between these regions and the VTA.
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