Lecture 25

Question 1

Autistic Disorder Basics

Answer 1

Autistic spectrum disorder describes a wide range of developmental disorders that are characterized by troubles with social interaction and communication, and by restricted and repetitive behavior.

The incidence of autism is around 1% of population

In many cases there are clear cognitive impairments, intellectual disability, or reduced imaginative ability, but this is not always the case

Parents usually notice signs during the first two or three years of their child’s life. Social impairments are often the first symptoms to emerge.

Some infants with autistic disorder do not seem to care whether they are held. Some arch their backs when picked up, as if they do not want to be held.

No attachment. This does form but slowly and later in the day.

Question 2

Autism causes

Answer 2

Like intellectual disability, autism encompasses a large set of disorders with diverse underlying causes.

It is associated with a combination of genetic and environmental factors that affect early brain development).

Estimates of the heritability of autism are around 70%, but as high as 90% for autism spectrum disorder.

Many cases have been linked to spontaneous rare gene mutations that have severe effects. These include chromosomal abnormalities involving deletions, duplications or inversions of genetic material.

Other cases are associated with multigene interactions across common gene variants.

Some cases have been linked to maternal viral infections during pregnancy

Question 3

Autism and language

Answer 3

Many people with autism have abnormal or even nonexistent language. About a third to a half of individuals with autism do not develop enough natural speech to meet their daily communication needs.

They may echo what is said to them or they may refer to themselves as others do—in second or third person

People with autism generally have atypical interests and behaviors

They may show stereotyped movements, such as flapping their hand back and forth or rocking back and forth. They may exhibit compulsive or ritualistic behaviour.

Question 4

Mild forms of autism

Answer 4

Mild forms of autistic spectrum disorder often do not include a delay in language development or the presence of important cognitive deficits

Mild forms of autism (often called Asperger’s syndrome) mostly just involve deficient or absent social interactions and repetitive and stereotyped behaviors along with obsessional interest in narrow subjects

Question 5

Autism incedence

Answer 5

Incidence of autistic disorder is around 1% of population

Disorder is four times more common in males than in females

If only cases of autism with intellectual disability are considered, the ratio falls to 2:1 (males:females)

If only cases of high-functioning autism are considered (those with average or above-average intelligence and reasonably good communicative ability), the ratio rises to approximately 7:1 (males:females)

Question 6

Autism XX XY

Answer 6

Within species, the heterogametic sex shows slightly more variability on all kinds of traits (from morphology to academic performance).

More common in men

Question 7

Brain activity in autism

Answer 7

There often appears to be significant abnormalities in the development of the brains of autistic children
Kids who develop autism tend to have a slightly small brain at birth, but it grows abnormally fast and by 2–3 years of age is often about 10% larger than a normal brain

Following this early spurt, growth of the autistic brain slows down, and by adolescence it is only about 1–2 percent larger than normal.

Hypotheses for the cellular and molecular bases of early brain overgrowth include the following:
Altered neuronal migration during early gestation
Abnormal formation of synapses and dendritic spines
Overconnectivity in key brain regions
Unbalanced excitatory–inhibitory neural networks

Question 8

FFA activity in autism

Answer 8

fMRI studies on people with autism have revealed marked abnormalities in brain activity. For example, there is little or no activity in fusiform face area of autistic adults looking at pictures of human faces.

As autistic kids are not interested in face, dont look at it and so do not develop activity in the FFA

Question 9

Autism treatment

Answer 9

The main goals when treating children with autism are to lessen the impact of the associated deficits and family distress, and to increase quality of life and functional independence.

Intensive, sustained special education programs and behavior therapy early in life can help children acquire self-care, communication, and life skills, and often improve functioning and decrease symptom severity and maladaptive behaviors.

Group homes can be created with 5 autistic people and a career for the times they need help.

Medications generally do not address the core symptoms, but often help reduce the irritability, inattention, and repetitive behaviors. All kinds of medications may be tried, including:
anticonvulsants (↑ GABA receptor activity)
antidepressants (↑ serotonin receptor activity)
antipsychotics (↓ dopamine receptor activity)
stimulants (↑ dopamine receptor activity)

Essentially you try different drugs until a combo works. No particular rationale.

Question 10

Substance abuse basics

Answer 10

Drug addiction is an extremely serious debilitating disorder. The big players are alcohol, opiates, cocaine and meth, nicotine, barbiturates and benzos.

Problems with alcohol abuse: 
automobile accidents 
fetal alcohol syndrome
cirrhosis of the liver
Korsakoff's syndrome
increased rate of heart disease
increased rate of intracerebral hemorrhage
pancreatitis, diabetes, etc., etc.

Question 11

Genes and addiction

Answer 11

Epidemiological studies estimate that genetic factors account for 40–60% of the risk factors for alcoholism.

Alcohol consumption is not distributed equally across the population; in the United States, 10 percent of the people drink 50 percent of the alcohol

Many twin studies and adoption studies confirm that the primary reason for this disparity is genetic

Question 12

Reinforcement and drug use

Answer 12

Drugs that lead to dependency must first reinforce people’s behavior

If, in a particular situation, a behavior is regularly followed by reinforcement that behavior will become more frequent in that situation

It is contextual, people can not smoke on flights because they have not had their behaviour on flights reinforced. They wont crave anything until they land. Does NOT drive they are not addicted.

Question 13

What is addiction

Answer 13

Effectiveness of a reinforcing stimulus is greatest if it occurs immediately after a response occurs

If reinforcing stimulus is delayed, it becomes considerably less effective

The consequences of the actions teach us whether to repeat that action, and events that follow a response by more than a few minutes were probably not caused by that response

The speed by which the brain perceives reinforcement is thought to explain the relative addictive potential of different drugs, such as heroin versus morphine

Heroin addicts faster as reinforcement is faster. Takes ages for alcohol to become an addiction as your brain must unconsciously associate the reward to the behaviour even if you already do consciously.

Question 14

Neural mechanisms of addiciton

Answer 14

All reinforcers, natural (food, water, sex) or otherwise, seem to cause the release of dopamine in the striatum, particularly in the nucleus accumbens

All addictive drugs rapidly increase dopamine levels in the nucleus accumbens.
Dopamine release in the nucleus accumbens in not as simple as it sounds, however. Aversive stimuli can also trigger release of dopamine here, and some areas of the nucleus accumbens promote avoidance behaviors. So, it’s complicated.

Question 15

Tolerance

Answer 15

Fact that increasingly large doses of drugs must be taken to achieve a particular effect

Caused by compensatory mechanisms that oppose the effect of the drug. Not all addictive drugs produce tolerance and withdrawal.

Question 16

Withdrawal symptoms

Answer 16

Appearance of symptoms opposite to those produced by drug when the drug is suddenly no longer taken

Caused by presence of compensatory mechanisms (that relate to drug tolerance)

Question 17

Negative reinforcement

Answer 17

Removal or reduction of an aversive stimulus that is contingent on a particular response, with an attendant increase in the frequency of that response

Question 18

Downregulating opioid system

Answer 18

Some rehabs will put people under and flush their system with strong antagonists. Opiod system reacts well and downregulates. Problem is, they just go back on drugs straight after.

Question 19

Drug use and the PFC

Answer 19

People with a history of drug use show the same deficits on tasks that involved the PFC as do people with damage to this region.  Addicts also show structural abnormalities in the PFC. 
When addicts (who are not currently high) perform tasks that normally activate the prefrontal cortex, their medial prefrontal cortex is less activated than that of healthy control subjects, and they perform more poorly on the tasks 

In cocaine addicts, the more cocaine they took, the less brain activity in their PFC

Without coke, less activity cos downregulated by coke

Question 20

Naltrexone

Answer 20

A somewhat long-acting, slow onset opioid receptor antagonist that is prescribed to alcoholics and opiate addicts.

It reduces the high produced by opiates (because the opiates can’t bind to the receptor), but it also tends to reduce drug, alcohol, and food cravings in certain people

Question 21

Naloxone

Narcan

Answer 21

Extremely rapid (and short lived) opioid receptor antagonist that reverses the effects of an opiate overdose.

During an opiate overdose, people can lose consciousness and stop breathing. An injection of naloxone immediately reverses these effects and will actually put addicts into withdrawal.

Question 22

Methadone maintenance

Answer 22

Potent opiate, similar to morphine or heroin but it has a slow onset and offset.

Methadone maintenance programs administer the drug to their patients in the form of a liquid, which they must drink in the presence of the personnel supervising this procedure

Similar maintenance treatments are used with nicotine addiction (nicotine patches, gum, vaping, etc.)

Question 23

Buprenorphine

Answer 23

Buprenorphine is a high affinity partial agonist for the  opiate receptor. It blocks the effects of other opiates, but itself only produces only a weak opiate effect

It is a relatively new treatment for opiate addiction. It is commonly mixed a little naloxone (an opiate receptor antagonist) to reduce the potential for abuse.

Most common treatment now

Question 24

Varenicline

Answer 24

Approved for therapeutic use to treat nicotine addiction

Serves as partial agonist for nicotinic receptor, just as buprenorphine serves as a partial agonist for -opioid receptor

Question 25

Cocaine vaccine

Answer 25

Compounds have been developed that cause the person’s own immune system to create antibodies against a drug, like cocaine.

When antibodies bind to the drug, it can no longer cross the blood brain barrier.

This approach is being explored for cocaine, heroin, meth, and nicotine.

Question 26

DBS and TMS

Addiction treatment

Answer 26

Researchers have tried DBS (deep brain stimulation) in many areas of the brain, including the basal ganglia and PFC.

TMS (transcranial magnetic stimulation) of the PFC is also currently being tested.

Question 27

ADHD basics

Answer 27

ADHD is a mental disorder characterized by problems paying attention, hyperactivity, or difficulty controlling (inhibiting) behavior in an age-appropriate manner.

More than 5% of children in North America are now being treated for ADHD. The symptoms generally appear before a person is 12 years old, are present for more than six months, and cause problems in school, home, or elsewhere.

ADHD is usually first discovered in the classroom, where children are expected to sit quietly and pay attention to teacher or work steadily on project

Prevalence rates vary widely across different communities, with a range of 1 to 10% of children. Diagnosis is can be difficult because symptoms are not well defined. Boys are diagnosed three times more often than girls.

ADHD is often associated with aggression, conduct disorder, learning disabilities, depression, anxiety, and low self-esteem

Question 28

ADHD symptoms

Answer 28

In general, children with ADHD often show reckless and impetuous behavior, act without reflecting, let interfering activities intrude into ongoing tasks, and have difficulty withholding a response

Symptoms of inattention include such things as “often had difficulty sustaining attention in work tasks or play activities” or “is often easily distracted by extraneous stimuli”

The condition can be difficult to distinguish from hyperactivity, inattention, and impulsivity that are still within the range of normative behaviors. Many children with ADHD have a good attention span for tasks they find interesting.

IMPORTANT

Question 29

ADHD causes and treatments

Answer 29

The causes of ADHD include environmental and genetic factors. Estimated heritability of ADHD ranges from 75 to 91%. Certain cases are related to previous infection of or trauma to the brain.

Drug and alcohol use and infections during pregnancy are associated with an increase risk for the child, as is low birth weight.

Treatment
Management of ADHD typically involves counseling and medications, often stimulants that raise dopamine levels by blocking or reversing the dopamine reuptake transporter (e.g., Ritalin and Adderall). Antidepressants may also be helpful.

Question 30

OCD basics

Answer 30

OCD (about 2% of population) is characterized by
repeatedly having certain thoughts (“obsessions”) and
a need to repeatedly check things or repeatedly perform certain routines (“rituals“ or “compulsions”)
to an extent that it causes distress & impairs general functioning.

There are a variety of symptoms, but they often get clustered into 4 groups: symmetry, cleaning, hoarding, and forbidden thoughts.

The “forbidden thoughts” cluster is associated with intrusive and distressing thoughts of a violent, religious, or sexual nature, whereas the “cleaning” cluster is associated with germs, bodily fluids, and contamination.

Question 31

OCD and intrusive thoughts over lifespan

Answer 31

The compulsive behaviours are driven by intrusive thoughts, and they often involve obsessive hand washing, cleaning, counting, or checking on things (e.g., to see if a door is locked). Some people have difficulty throwing things out.
The compulsions are often performed to seek relief from obsession-related anxiety, driven by a fear that something bad will happen if the ritualistic behaviour is not done properly or a belief that life cannot proceed as normal while the imbalance remains.
Most adults with OCD realize that their behaviors do not make sense, they understand that their notions do not correspond with reality; however, they feel that they must act as though their notions are correct, and they are typically unable to control their obsessions or compulsions for more than a short period of time.

Question 32

OCD causes and incidence

Answer 32

Incidence of OCD is about 2 percent
It most commonly begins in young adulthood (before 25)
The cause of OCD is a combination of genetic and environmental factors. Genetic factors account for ~50% of the variability.
Environmental risk factors include a history of child abuse or other adverse events. Some cases have been documented following infections.

Question 33

OCD treatment

Answer 33

Treatment
Treatment always involves counseling, often a version of cognitive behavioral therapy (CBT) known as exposure and response prevention, which involves increasing exposure to what causes the problems while not allowing the repetitive behavior to occur.

Treatment sometimes includes antidepressants such as selective serotonin reuptake inhibitors (SSRIs)

Without treatment, the condition often lasts decades.

Question 34

Neural mechanisms of OCD

Post brain damage OCD

Answer 34

Sometimes OCD symptoms appear after brain damage, particularly to basal ganglia, cingulate gyrus, or prefrontal cortex
Several functional imaging studies have found evidence of increased activity in the frontal lobes and striatum in patients with OCD
Treatment for severe cases can include a brain lesion, specifically a cingulotomy, which is the cutting of a fiber bundle between PFC and anterior cingulate.

Deep brain stimulation within basal ganglia areas is an active area of research.