Neuroscience Final year 1

Focus on disorders, ADHD, ASD, substance abuse, depressive disorders, anxiety disorders, and PTSD

What type of disorder is ADHD classified as by the DSM5?

It’s considered a developmental disorder (A disorder initially present in children).

What is an essential feature of ADHD?

A persistent pattern of inattention and hyperactivity-impulsivity that is shown clinically to interfere with functioning or development significantly.

Can ADHD remain evident in adulthood

Yes

ADHD Subtypes

Inattentive type, hyperactive-impulsive type, and combined type.

How long must symptoms have occurred and what’s the typical age it’s onset in?

Symptoms must have occurred over the past 6 months.

The age of onset children is typically less that 12 years old.

Inattentive Type. Symptoms

• Often distracted by extraneous stimuli (in older adolescents and adults, this includes unrelated thoughts).

• Issues staying focused on tasks or activities. Examples include lectures, conversations or long readings

• Don’t seem to listen when spoken to directly.

• Difficulty following instructions. Shown by not completing schoolwork, chores, or job

• Difficulty organizing tasks and work. Shown by poor time management, being disorganized, and missing deadlines.

• Avoiding disliked tasks that require sustained mental effort like preparing reports and completing forms.

• Often losing things

• Not paying attention to details and make careless mistakes

• Forgets daily tasks

6 needed for diagnosis

Hyperactive/Impulsive type

• Fidgeting, tapping hands or feet, or squirming in a seat.

• Inability to remain seated

• Running and climbing where it’s inappropriate

• Inability to quietly play or do leisure activities.

• Often “on the go.”

• Talking too much

• Blurting out an answer before the question is finished. Or finishing other people’s sentences

• Interrupting or intruding on others. Doing things or participating with people without permission

• Difficulty waiting for their turn.

6 needed for diagnosis

Combined type

Combination of at least six symptoms from inattentive and 6 symptoms from hyperactive/impulsive type.

What are key features of ADHD

• Manifestations of the disorder must appear in multiple settings

• Context matters, knowing there it was assessed may affect judgement. Be aware that other factors could seem like ADHD. Prevalence different by country. Close supervision minimizes the signs.

• Issues associated with ADHD create problems in the child’s life.

• ADHD is not an intellectual disorder

• Mild delays in language motor, and social developments are common

Prevalence of ADHD

7.2-7..2% Prevalence or around 7.6%

There’s a 3:1 Male to female ratio of getting it

Adult ADHD is around 2.5% prevalence

These statistics are for North America since prevalence varies by country

Causes of ADHD

• Possibly up to 80% genetic

• Mutations in the D4 receptor. Therefore, there’s a failure of dopamine reuptake.

• Environmental factors can cause epigenetic changes

What are environmental risks to cause ADHD?

• Children with a mutation in the dopamine reuptake transporter (DAT1) are more likely to develop ADHD if their mother smokes during pregnancy.

• Perinatal hypoxia (oxygen deprivation around birth)

Go, No-Go Task

• Concept of rewarding kid for responding when they should

• There are two types of errors:

  • Omission error: not responding when they should

  • Commission error: responding when they shouldn’t

• ADHD kids make both types of errors where as neurotypicals only make omission errors

Iowa Gambling Task

• Has 4 sets of cards. 2 are low risk while 2 are higher risk. 2 in each have higher reward and 2 have a higher penalty

• ADHD kids tend to pick the high risk deck.

• Neurotypicals tend to pick the low risk deck

Behavior in kids with ADHD

• ADHD kids tend to require more reward. Hence an ADHD person will want to chase it due to not getting it.

• reduced inhibition compared to others and hence increase in impulsivity

• Hyperfocus

Dual Pathway model suggests

Possible dysfunctions with executive function in the frontal lobe and the reward function, which is controlled by mesocorticolimbic dopamine.

Regions of brain associated with ADHD

Alerting system: Frontal cortex, parietal cortex, and thalamus

On lateral surface: dorsolateral prefrontal cortex (DLPFC), parietal cortex, ventrolateral prefrontal cortex (VLPFC).

In Medial wall: Dorsal anterior midcingulate cortex (daMCC/daCC*), Striatum caudate & putamen, cerebellum.

Frontostriatal Circuit: ventral anterior cingulate cortex, dorsal anterior cingulate cortex. Both activate nucleus accumbens (helps understand emotions and releases dopamine). caudate nucleus, putamen, amygdala, cerebellum. Last 2 are abnormities.

ADHD comorbidities

% of ADHD population

only ADHD 31%

Oppositional defiant disorder 40%

Conduct disorder 14%

Anxiety disorder 345

Tic disorder 11%

Mood disorder 4%

Genetically comorbid with Autism

ADHD treatments

• Methylphenidate: an amphetamine that helps ADHD people focus

• Behavioral Treatments

• Electrical treatments: add magnets to the skull to activate electrical activity in the brain. Ultrasonic sound can target regions such as the cingulate cortex

Why do amphetamines work

They block dopamine transporter so it builds up in the synapse

What type of disorder is Autism Spectrum Disorder?

It is a developmental disorder that begins in early childhood and lasts permanently.

It is a spectrum disorder since there’s a range of symptoms which vary from individuals. currently there’s a 1-3 grading scheme

When does autism first appear?

It’s first recognized in the second year of life.

Usually there’s normal development for the first 12 months, then a decline in function

Three major areas of difficulty in autism

• Impaired communication

• Impaired social interaction

• restricted behavior, interests, and activities

Possible key features for autistics

• They don’t communicate in the way they’re supposed to

• Difficulties with eye contact, hence leading to social impairment

• Narrow focus leads to hyperfocus on one thing

• Ritualistic behavior

• Echolalia: Repeating the same thing over and over once heard.

• Staccato speech

• odd combination of verbal abilities

• over literal understanding of language

Apgar score

• Is a series of tests done after birth

• There are 5 autistics characteristics. for each characteristics, the score goes down.

• It’s easier to tell after a year.

Theory of Mind

The ability to attribute mental states to others and understand that others are separate selves with their own point of view and feelings

Allegedly low functioning ASD kids don’t have theory of the mind

Autism and emotions

Autistics tend not to be able to understand emotions so they will observe other emotions to understand them.

It’s possible for autistic people to feel emotions but have difficult expressing them.

Ritualistic behavior of autistics

Stimming: allegedly pointless behavior related to sensory stimulation

Preference for status quo so things remain the same

Prevalence of ASD

Different prevalence globally.

4:1 male to female ratio

Suggested reasons for difference in males and females developing autism

ASD biology is related to male development

ASD could manifest differently in females

Is ASD genetically related

Yes. There’s a high concordance rate for monozygotic twins (31%-90%)

There’s a 0-5% concordance rate for dizygotic twins

There are a lot of genetic complexities between ASD-related conditions as there’s many genes involved

Environmental factors that cause ASD

Maternal diet: Influences the microbiome

Folic acid status

Maternal smoking

Maternal infection: relates to immune activation

Low maternal education level: Correlation with poverty

Exposure to air pollutants: Impacts immune system development since maternal immune system is altered

Poor socioeconomic status

Advanced maternal and paternal age

Likely a combination of factors.

Microbiome and ASD

Gut microbiota itself is the microorganisms, bacteria, viruses, protozoa, and fungi present in the gastrointestinal tract.

Gut-Brain Axis: When microbiome influences brain functions.

Gastrointestinal disturbances are common with those having ASD, so there might be comorbidities.

Mouse models of ASD

Show that maternal immune activation results in impaired social communication and stereotyped behaviors. Disturbed gastral intestine and immune functions also related

Brain of those with ASD

Grows faster, resulting in too many connections with dendrites

increased microglia activation and elevated proinflammatory cytokines

Neurobiology in autistics

Autism viewed as a condition resulting from overall brain reorganization during early development.

This is due to acceleration brain development in early life.

There are morphological abnormalities at the microstructural level.

Simon Baron-Cohen autism theory

Believed that excessive testosterone activation during early development leads to autism.

Prenatal testosterone relation with ASD

It influences:

Ability to make appraisals related to other people limited. Referred to as “mind-reading.”

Amount of eye contact made

Mirror neurons

Neurons that activate when observing a person preforms a certain action

They’re found in various parts of the cortex and the insula. This is related to social cognition and are related to understanding the action.

They play a role in empathy

Mirror neuron relation to autism

Was found that deficits in autism are related to those controlled by mirror neurons.

There’s reduced activity in the frontal mirror neuron system.

It is corelated with the severity of the disorder.

Autism Treatment

Applied Behaviour Analysis (ABA): Rewards for microbehaviors considered better until a manageable point is achieved.

Reward

It refers to stimuli that are desirable and positive and can affect behaviour.

Reward system discovery

Discovered by Olds and Milner in 1954 by intracranial self-stimulation (ICSS). It involved a rat fitted with an electrode on his brain. The connects to a stimulator controlled by a lever so the rat could self-stimulate. This caused rat to neglect needs. It’s similar to human addiction.

Reward circuit official name

mesocorticolimbic dopamine system or reward system.

Location of the reward circuit and anatomy

In midbrain, specifically called ventral tegmental area (VTA).

Neurons project axons in the limbic system

What is the key neurotransmitter for the reward system

dopamine

Parts of the mesocorticolimbic dopamine system

Ventral tegmental area (VTA): contains neurons producing dopamine and projects to these parts: hippocampus, nucleus accumbens, and prefrontal cortex

What’s the difference between addictive drugs and naturally occurring rewards

Addictive drugs lead to supraphysiological dopamine which is a much larger amount of dopamine than naturally occurring rewards.

Where do addictive drugs release dopamine

nucleus accumbens

What does dopamine in the nucleus accumbens do + what other parts do

Gives a teaching signal related to expectation and experience. Then with the prefrontal cortex and hippocampus there can be reward and learning a need to go after it again

Official addiction definition

syndrome where there’s a loss of control over reward-seeking behaviour.

Symptoms of substance use disorder

Need to 2 out of 11 to be diagnosed:

• Using in spite of adverse consequences

• Preoccupation with obtaining the drug

• Significant time used to attempt obtaining drug

• Craving

• Use results in failure to fulfill major role obligations

• Tolerance (more drug needed for same effect).

• Withdrawal

Withdrawal

Corticotropic releasing hormone (CRH) is involved in anxiety and processing depression and promotes unpleasant emotions. This creates withdrawal symptoms:

• Muscle aches

• cramps

• anxiety attacks

• sweating

• nausea

• convulsions

• death

Due to compensatory adaptations attempting to restore homeostasis so there’s an imbalance from quitting.

Salience

A process when a recovering addict understands the drug is harmful but still seeks it out.

Factors to make people more prone to addiction

Stressful events: it can make someone more likely to use drugs to block effects of it

Lack of a mature brain: increased impulsivity. This is result of high dopamine but low seratonin.

Adverse childhood experiences: increase risk of disorder in general

Adverse Child experiences Scale

Meant to assess negative childhood experiences. It is in form of a questionnaire.

This is important since it’s linked to: risky health behaviors, chronic health conditions, increased mental health disorders, and increased morbidity and mortality.

Do all drugs act on the same neurotransmitter

False, they each produce unique effects for that drug

Cannabis

Is an antinausea agent and can create relaxation at low doses. Higher doses results in a paranoia and creates schizophrenia-like symptoms.

It’s from cannabis sativa and cannabis indica plant

Most common is delta-9-tetrahydrocannabinol (THC). It’s responsible for psychoactive response

Has 80-100 components

Cannabis adminsitration

Inhalation: 50% enters lungs. Reaches brain in 30 seconds and peaks around 30-40 minutes while lasting 3-4 hours. subjective state for 12 hours.

Vaping: peaks after 10 minutes.

Cannabis is distributed everywhere and stays in fatty tissue

Oral: Absorbed from gut. requires and hour and peaks at 2-3 hours. Larger doses for same effect as inhaled.

Psychological effects of cannabis

Cognitive: Decreased attention, concentration, learning. Short-term memory impaired.

Behavioral: Reduced movement and increased talkativeness

Perceptual: decreased visual, pain, and time perception

Subjective: different stages

Mood swings or anxiety at high doses. results in psychotic symptoms

Effects influenced by surroundings.

Endogenous cannabinoid system or endocannabinoid system

It’s activates during stress in attempt to regulate.

Endogenous ligands are anandamide (AEA) and 2-arachinonoyllgglycerol (2-AG)

Main receptors are CB1 for brain and CB2 for immune system.

THC and Anandamide binds to CB1

2-AG and CBD bind to both

How endocannabinoids work

CB1 receptors are located presynaptically on axon terminals

anandamide and 2-AG are retrograde messengers and carry information in opposite directions.

There’s the synthesis and release in response to depolarization of the postsynaptic cell.

How THC works

It mimics the shape and anandamide and uses the same mechanisms. It then binds to the CB1 receptor pre-synaptically to inhibit further neurotransmitters.

This results in euphoric feelings due to increase in dopamine.

Regions of brain

Cerebral cortex: cognition hence impacted

Hypothalamus: results in increased appetite

Medulla: reduced nausea since functions reduced

Cerebellum: motor control impacted

Spinal cord: impacts pain

Basal Ganglia: movement

Cannabis side effects

Can cause psychosis after frequent high use of THC

Increased depression risk after frequent high use of THC

What is schizophrenia classified as

a psychotic disorder. It is also a neurodevelopmental disorder with same networks as autism

What are schizophrenia myths

• They’re violent and dangerous

• They have multiple personalities

• They see things that aren’t there. Their hallucinations are mostly auditory.

Schizophrenia characteristics

Positive symptoms: Symptoms beyond normally occurring experiences.

Negative symptoms: Deficient compared to normal behaviour

Cognitive symptoms: Affect cogitation and are characterized by erratic changes in speech, motor behaviour, and emotions.

DSM-5 diagnostic criteria

Must have one of:

• Delusions

• Hallucinations

• Disorganized speech

Can have:

• Grossly disorganized or catatonic behaviour

• Negative symptoms: diminished emotion, avolition, limited thought/speech, emotional and social withdrawal, and apathy

Needs at least two symptoms. They must be long-lasting

Development of shcizophrenia

Usually diagnosed in late adolescence or early adulthood. There is a lag of 1-2 years between initial symptoms and diagnosis.

For 85% of people, full schizophrenia is preceded by a prodromal stage lasting 1-2 years where subdued symptoms start appearing such as:

• magical thinking

• minor illusions

• ideas of reference

development and prognosis in schizophrenia

Around 78% of people being treated go through a pattern of relapse and recovery

prognosis in schizophrenia is poorer that most other disorders, however recovery is likely given: good social adjustment prior to onset of schizophrenia, low negative symptoms, and good social support for patients.

symptoms decrease with age.

Schizophrenia in males versus females

Males experience schizophrenia more severely than females.

Women can develop it in their early 30s rather than in late adolescence

Schizophrenia stages

Premorbid: around 6,7, or 8. There’s mild motor, cognitive, and social impairments. Is similar to autism.

Prodromal: in adolescence. Unusual psychotic-like behaviours. It’s like mini schizophrenia but not strong enough for diagnosis.

Onset/deterioration: Early adulthood. positive, negative, cognitive, and mood symptoms. Example is magic thinking

Chronic/residual: Around 30s. Positive, negative, and cognitive symptoms

Etiology of schizophrenia

Inheritance is very typical for genetics.

Monozygotic twins have almost 50% risk. dizygotic is half of that.

perinatal factors that increase risk of schizophrenia

Influenza during pregnancy increases risk of schizophrenia by 500%

Bacteria or viruses during pregnancy also increase risk. This is due to increase in body temperature

Stressors during pregnancy.

Pregnancy and deliverery complications

prenatal nutrition (example, Dutch hunger winter where malnutrition caused change in insulin and schizophrenia development).

Brain of schizophrenic

Enlarged ventricles caused other parts of the brain to be compressed

Reduced hippocampus due to degradation. neurons disorganized in this region

dendric loss causes shrinkage

dendrite connections in schizophrenics

reduced dendritic spine density in prefrontal cortex.

Due to dendritic connections increasing exponentially until it stops and the process reverses.

Treatment for schizophrenia

No real cure.

Chlorpromazine: originally and anesthetic but was shown to work with psychotic patients. Issue is it caused lack of awareness

Other antipsychotics used. They don’t produce too much sedation. They enable patients to resume normal life.

Referred to as neuroleptics

How do antipsychotics work:

Affect dopamine by blocking the D2 and D4 receptors

Posistron Emission Tomography (PET)

An imaging technology that detect changes in blood flow by measuring uptake of compounds like oxygen and glucose.

This is done by injecting radioactive molecules into blood steam.

It’s useful to analyse neuron metabolic activity.

basal ganglia and schizophrenia

D2 receptors are disturbed. Specifically in the straitum

Cause of positive symptoms in schizophrenia

Excessive stimulation of D2 receptors in the striatum

What receptor is understimulated in schizophrenia and what’s the condition called

D1 receptors in the prefrontal cortex.

Condition is called hypofrontality. It causes struggles with planning, problem solving, and high-level reasoning

Not dopamine thing related to schizophrenia

Reduced glutamate activated, resulting in cognitive and negative symptoms

Lack of balance from Gaba results in disorganized thinking and behaviour.

Excess glutamate causes abnormal synaptic pruning.

What is a mood disorder

When general emotional sate is inconsistent with circumstances and impacts your ability to function

Major Depression Disorder

Most common mood disorder. There’s a consistent feeling of sadness and hopelessness or anhedonia (lack of pleasure in things they used to enjoy). This must be daily

Major Depression Disorder Symptoms

Must have one of:

• Depressed mood most of the day, nearly everyday by subjective report or observations made by others

• Significantly diminished interest or pleasure in all or nearly all activities for most of the day, nearly everyday.

Can have:

• Significant weight loss or weight gain unintentionally. or decrease or increase in appetite nearly every day

• Insomnia or hypersomnia nearly every day

• Psychomotor agitation or retardation nearly every day.

• Fatigue or loss of energy nearly every day

• Feeling worthless or excessive or inappropriate guilt nearly every day

• Diminished ability to think or concentrate, or indecisiveness nearly every day

• Reoccurring thoughts about death, recurrent suicidal ideation without plan, or suicide attempt or plan for suicide.

Needs 5 or more total

Major Depression Disorder Subtypes

Typical: Eats less, weight loss, sleep less, motor retardation

Atypical: Eats more, weight gain, sleeps more, psychomotor agititation

Sex Differences in depression potential causes

Women could be twice as likely to have depression due to social discrimination or due to estrogen influencing cortisol.

Greater estrogen makes people more reactive to environmental stimuli. Lack of oxytocin prevents people from feeling effect of events

Dysthymia

A low grade by chronic type of depression.

This form tends to go unnoticed

It can be characterized by lower functioning and reduced friends. It is harder to treat.

Double dysthymia

When dysthymia progresses to be major depression. At this point, treatment can be done to return to a dysthymic state.

Helplessness notion for depression

Developed by Richard Solomon after electrocuting dogs and finding that dogs unable to stop be electrocution seemed to be helpless even after the experiment. As a result, there was diminish behaviour.

Theory developed: After uncontrolled events, people can call into a depressive state.

Issue: Based on animal behaviour, not human behaviour.

Hopelessness theory for depression

Developed by Beck that having a bad world view can lead to a depressive state. This could result from having negative past experiences, therefore causing people to believe present and future with also be negative

Cognitive Behavioural Therapy (CBT)

Treatment developed using the hopelessness theory. It is a type of therapy designed to modify a person’s world view by eliminating judgement and promoting focus on the present.

Melancholia

A severe type of depression.

Was found that they have high cortisol in their system. So this developed theory that either stress promotes depression or cortisol promotes depression

Genetic link to depression

First degree relatives are 2-3 times at greater risk of developing depression.

Concordance rate with monozygotic twins is 45.6%

Concordance rate between dizygotic twins is 20.2%

Monoamine hypothesis for depression

Thought depression resulted from a defficient in monoamine (neurotransmitters with an amine group connected to an aromatic ring) signaling.

This causes a limited release of neurotransmitters and deficit in ability to clear neurotransmitters from the synapse. Plus limited receptors to bind to.

Serotonin

Its circuits form one of the ascending forebrain systems.

It plays a role in sleep, sexual behaviour, eating, and mood/cognition..

Is derived from 5-hroxytrptophan (5-HT)

Uncontrollable shift of stressors, role in depression

Makes people vulnerable to a depressive-like state. This could be due to allostatic overload.

MAO inhibitors

MAO is an enzyme that breaks down serotonin. It was found that inhibiting it can treat depression