ADHD PATHOPHYSIOLOGY

Question 1

1. What is ADHD?

Answer 1

ADHD stands for Attention-Deficit/Hyperactivity Disorder, a condition characterized by symptoms of inattention, hyperactivity, and impulsivity.

Question 2

2. Is ADHD influenced by genes?

Answer 2

Yes, ADHD is highly heritable (74%), suggesting a strong genetic component.

Question 3

3. How is ADHD related to genes?

Answer 3

ADHD is polygenic, meaning it arises from the combination of many gene variants, each with a small effect.

Question 4

4. Which neurotransmitter pathways are involved in ADHD?

Answer 4

Dopamine pathways (DAT, DRD4, DRD5, TAAR1, MAOA, COMT, DBH), serotonin pathways (SERT, 5HT1B, TPH2), and noradrenaline pathway (ADRA2A) are implicated in ADHD.

Question 5

5. What role does the locus coeruleus (LC) play in ADHD?

Answer 5

The LC-noradrenergic system, which provides a major source of noradrenaline (NA) in the brain, is involved in ADHD. NA release affects concentration and attention.

Question 6

6. How is the LC-noradrenergic system modulated?

Answer 6

Inputs from prefrontal cortex (PFC) neurons modulate the activity of LC neurons, impacting NA release.

Question 7

7. What brain regions are affected in ADHD?

Answer 7

ADHD is associated with reduced volume in the prefrontal cortex (PFC) and posterior parietal cortex (PPC).

Question 8

8. What functions are controlled by the PFC?

Answer 8

The PFC is responsible for executive functions, such as planning, decision making, short-term memory, personality expression, controlling social behavior, speech, and language.

Question 9

9. What functions are controlled by the PPC?

Answer 9

The PPC is involved in planned movements, spatial reasoning, and attention.

Question 10

10. What is the attentional network?
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Answer 10

The attentional network comprises pathways between the PFC and PPC and is responsible for processes like response inhibition, vigilance, working memory, and planning

Question 11

11. What is the fronto-striatal network?

Answer 11

The fronto-striatal network connects the PFC, striatum, and ventral tegmental area (VTA). It plays a role in hyperactivity and impulsivity.

Question 12

12. What is the executive function network?

Answer 12

The executive function network is involved in higher-level cognitive processes and is associated with the PFC.

Question 13

13. What is the fronto-cerebellar network?

Answer 13

The fronto-cerebellar network connects the PFC and the cerebellum and is implicated in ADHD symptoms.

Question 14

14. What is the reward network?

Answer 14

The reward network involves pathways between the PFC, striatum, and VTA. ADHD individuals may have difficulties focusing on long-term rewards and exhibit impulsive behavior for short-term rewards.

Question 15

15. How do imbalances in brain circuits affect ADHD symptoms?

Answer 15

Imbalances in different brain circuits can enhance or suppress attention, activity, and impulsivity, leading to changes in behavior associated with ADHD.

Question 16

16. What are the key deficits in ADHD?

Answer 16

ADHD is characterized by deficits in response inhibition, vigilance, working memory, planning, and the ability to focus on long-term rewards.

Question 17

17. Is the environmental factor significant in ADHD?

Answer 17

Gene-environment interplay (G × E) is recognized to contribute to psychopathology, including ADHD. However, causal environmental risk factors for ADHD are not well understood.

Question 18

18. How does dopamine affect ADHD symptoms?

Answer 18

Dopamine dysregulation in the mesocorticolimbic pathway, which connects the ventral tegmental area (VTA) with the PFC and ventral striatum, is associated with hyperactivity and impulsivity in ADHD.

Question 19

19. How does noradrenaline affect ADHD symptoms?

Answer 19

Deficits in noradrenaline due to modulation of PFC neurons contribute to inattention in ADHD.