Neurological and Psychiatric Disorders
College 1 - ADHD
Russel A. Barkley - deficit in behavioral inhibition (tekort gedragsremming)
- Working memory
- Self-regulation of emotions
- Internalization of speech
- Reconstitution (behavioral analysis)
Edmund Sonuga-Barke - multiple developmental pathways (neurobiological + enviromental)
ADHD = persistent, pervasive extremely hyperactive, impulsive and inattentive
(onoplettend). Different terminology and concepts. Validity of a diagnosis is still under
discussion because there are a lot of subtypes and comorbidity.
DSM-5: inattention and hyperactivity-impulsivity
Prevalence
6% school children > 40% persistence into adulthood > 30% ADHD alone (other comorbid).
No objective diagnosis. It's a subjective judgement from multiple informants.
- observations usually not very useful -> first meetings x clear symptoms
Also a lot of comorbidity: ODD or OD, depression and anxiety disorders, learning diabilities,
language and speech problems.
‘Typical’ child with ADHD:
- Boy
- Around 10 years old
- Hyperactive and impulsive
- Easily distracted
- Problems at school and home
- Not many friends
numerous factors influence the diagnosis: comorbidity,
gender, age etc. A lot more boys suffer from ADHD,
usually more than double.
Another thing is brain development: late maturation of the frontal cortex. The frontal
cortex had been linked to symptoms of ADHD. Childeren with ADHD often show slower
development in these regions, which may explain difficulties with attention regulation and
impulse control.
Genetic risk factors: ADHD clusters in families (Brother/sister at 3-5 times higher risk).
70-80% hereditary. There are multiple genes that contribute to the disorder. Also in linkage
study they discoverd multiple chromosol loctions, although little consistency and small effect.
Research for causes
,Lower dopamine transporter (DAT) availibility in ADHD. So there is reduced presence or
function of DAT in the brain. DAT are responsible for reabsorbing dopamine from the synaps.
These are crucial for attention and behavior regulation.
Neuroimaging (fMRI) measures oxygen consumption by neurons, which indicate activity.
Abnormalities in brain regions can be identified through this technique.
Brain volume differences occur between ADHD patients and controls, mostly in the caudate
and cerebellar regions. These are involved in motor control, attention and impulsive
regulation. ADHD reduces brain volume.
Altered functional connectivity in ADHD brain. Some connections in the brain are
increased and some are decreased. This leads to dysfunctional communication.
In drug abuse, large amounts of dopamine are released, reinforcing behaviour. Over time,
the brain becomes less sensual to natural rewards, increasing dependens of the drug.
Treatment
Stimulans > target is 5-HTT, DAT, NET
1. methylphenidate - inhibitor (mostly used)
2. dexamphetamine - inhibitor
Non-Stimulans > target is NET (1) and α2 adrenoceptor (2+3)
1. atomoxetine - inhibitor
2. Guanfacine - agonist
3. Clonidine - agonist
Methylphenidate: blocks the reuptake of dopamine and noradrenaline (no reabsorbtion).
leads to improved attention, focus, and impulse control.
Atomoxetine: Selectively inhibits the noradrenaline reuptake transporter (NET), increasing
the level of noradrenaline. Better concentration, communication and memory etc.
Side effects
- stimulans > decreased appetite, insomnia, tachycardia (hoge hartslag), nausea
- atomoxetine > nausea, vertigo (hoogtevrees)
Methylfenidaat had a much slower effect than cocaine which makes it less likely to be
abused compared to drugs like cocaine.
Methylphenidate improves the respone inhibition in children with ADHD. Measured by the
Stop-Signal Reaction Time (SSRT) task. They have a faster SSRT.
College 2 - preclinical addiction
Part 1: General introduction
1. Definitions of drugs, drug use, and addiction
2. Explanation of clinical addiction, impact on the brain
3. Description of addiction cycle and relevant brain regions
Why?: the intake of natural or synthetic substances for their psychoeffective properties is a
behaviour widely represented in humans (history)
,A large number of recreational activities (non-drug!) strongly alter the brain activity. Drug
use is another form of recreational activity where brain activity is modified through specific
pharmacological compounds.
Drugs cause a lot of deaths. That is why it is a problem.
Neurobiology of reward (neurons)
When dopamine is produced it is shipped down the axon and released in the synapse it
binds to dopamine receptors. It gives a sign of ‘reward’ or pleasure. Drugs influence the
reward system by acting on neurons in the Ventral Tegmental Area (VTA) and Nucleus
Accumbens (NAc). They affect the release of dopamine, enhancing a feeling of pleasure.
Neurobiology of reward (brain)
Dopamine is critical not only for reward but also for learning, motivation, and goal-directed
behavior. It suggests that endogenous opioids (naturally occurring brain chemicals) also
play a key role in this reward circuit, especially in areas like the VTA, NAc, and amygdala.
Addiction = a chronic psychatric disorder on the brain (brain disease). Addictive substances
cause structural changes in the organization of the brain. Addiction behanvior is largely
maintained by progressive and persistent neuroadaptations, caused by repeated drug use.
Clincal term for addiction is substance use disorder (SUD). The diagnosis has evolved:
1. Pharmacology-related
2. Psychology-related
DSM 5 criteria
, Severty of SUD
- Mild: presence of 2-3 symptoms
- Moderate: presence of 4-5 symptoms
- Severe: presence of 6 or more symptoms
Risk of addiction is not the same for all drugs
Questions
- Why does an addict spend 90% of their time thinking, searching for/ scoring the drug? >
Addiction rewires the brain’s reward system (dopamine pathways). Drug = reward.
- Why is the behavioral repertoire of an addict restricted to just these aspects at the expense
of other activities? > Drugs hack the brain's natural reward system. The brain becomes
less sensitive to normal rewards, and only drugs produce a significant feeling of satisfaction.
- Why can one not just stop taking drugs? > Addiction changes the brain’s structure and
function. Without the drug, the addict feels dysphoric or incapable of experiencing pleasure.
- Why does one relapse even after months/years of abstinence? > The brain retains "drug
memories"/ triggers. Environments, people, stress activate memories, causing craving.
Neurobiological theories of addiction:
● Opponent-process theory (Koob): Addiction shifts from seeking positive drug
rewards to using drugs to avoid negative emotions.
● Incentive-sensitization theory (Robinson & Berridge): Addiction arises from
heightened desire for the drug and related cues.
● Aberrant learning theory (Redish): Excessive dopamine reinforces drug-related
behaviors, leading to pathological learning.
● Habit theory (Everitt & Robbins): Drug habits become dominant, overriding
goal-directed control.
The addiction cycle
● Binge/ intoxication: consuming an intoxicating substance
and experiencing its rewarding/ pleasant effect.
● Withdrawal/ negative affect: experiencing a negative
emotional state in the absance of the sunstance.
● Preoccupation/ anticipation: seeking substances again
after a period of abstinence.
Binge/ intoxication
Rewarding effects: the basal ganglia (nucleus accumbens), ventral tegmental area
(dopamine), naturally occurring opioids, driven by positive reinforcement.
Repeated drug use leads to compulsive substance seeking by strengthening habit formation
in the dorsal striatum. These reward and habit neuralcircuits explain how environmental
cues trigger intense cravings, reinforcing addictive behaviors.
