Neurobiology of psychiatric disorders summary
Content
Les 1: intro ............................................................................................................................................. 2
Signs of mental illness ......................................................................................................................... 2
From signs to diagnosis ...................................................................................................................... 3
Neurobiology and psychiatry: a multilevel approach ......................................................................... 5
Les 2: Developmental dyslexia and dyscalculia .................................................................................. 6
Introduction neurodevelopmental disorders ....................................................................................... 6
Reading, phonology and dyslexia ....................................................................................................... 6
Arithmetic, numerosity and dyscalculia .............................................................................................. 9
Les 3: Imaging ......................................................................................................................................11
PET ....................................................................................................................................................11
MRI ....................................................................................................................................................11
Les 4: Anatomy of the limbic system ................................................................................................. 14
Function of the hippocampal formation............................................................................................ 15
Function of the amygdaloid body...................................................................................................... 15
Function of the limbic basal ganglia loop ........................................................................................ 16
Les 4: ASD ............................................................................................................................................ 16
Introduction ASD............................................................................................................................... 16
Neurocognitive theories .................................................................................................................... 17
Social cognition theories ................................................................................................................... 19
Les 5: Psychiatric genetics Autism ..................................................................................................... 21
Defining the phenotype ..................................................................................................................... 21
Genetic architecture of neuropsychiatric disease ............................................................................. 22
Complex disease model in clinical genetics ...................................................................................... 22
Genetic causes, susceptibility variant, liability................................................................................. 23
Les 5: Psychiatric genetics Schizophrenia ......................................................................................... 23
Searching for genes ........................................................................................................................... 23
Genes for schizophrenia and bipolar disorder .................................................................................. 24
What do we learn from GWAS studies............................................................................................... 24
Les 6: Neurobiology of psychosis (schizophrenia) ............................................................................ 24
Diagnosis and phenomenology ......................................................................................................... 24
Genetics............................................................................................................................................. 25
Neurobiology ..................................................................................................................................... 25
Les 7: Animal models in psychiatric disorders ................................................................................. 26
1
, Short overview of tests ...................................................................................................................... 28
Les 8: Neuropsychology and neurobiology of emotions ................................................................... 29
Basic emotion vs constructed emotion .............................................................................................. 30
Amygdala and emotion...................................................................................................................... 30
Insula and emotion ............................................................................................................................ 31
OFC and emotion .............................................................................................................................. 31
ACC and emotion .............................................................................................................................. 31
Cross-categorical findings ................................................................................................................ 31
Les 9: Depression ................................................................................................................................. 31
Neurobiology of major depressive disorder (MDD) ......................................................................... 32
Epigenetics & depression .................................................................................................................. 33
Les 10: Neurobiology of anxiety and its disorders............................................................................ 34
Anxiety............................................................................................................................................... 34
Anxiety disorders and OCD .............................................................................................................. 36
Les 1: intro
Signs of mental illness
Psychiatric disorders are characterised by disturbances in one or more mental functions:
• Cognitive: reasoning, rationality and perception
o Consciousness
o Concentration, attention
o Memory: short term, long term, orientation (in time, space, persons)
o Cognition
o Cognitive distortions: rational thinking but biased towards negative thoughts
o Delusions: unrealistic convictions of persecution, hidden meanings, megalomania
(delusion of grandeur)
▪ Can happen in severe depression and is then coloured by the depression
▪ Delerium tremors specific for alcohol withdrawal
o Perception
o Hallucinations
▪ Visual hallucinations are always sign of brain problem/dysfunction for which
a cause can be identified
▪ Auditory hallucinations are typical of schizophrenia
o Obsessive thoughts: OCD
▪ Difference between obsessive and delusions is that the person with obsessive
thoughts knows the thought is absurd but get anxious when they do not do it
• Affective: emotion
o Mood changes (in the pathological range)
▪ Maladjusted emotions
2
, ▪ Seen in borderline patients (mood instability) often paired with
automutulation
o Anhedonia
▪ Typical sign of major depression
▪ Anticipatory vs consummatory
o Anxiety
▪ Panic
▪ Phobia
▪ Social anxiety
o Anger, irritability
• Conative: motivation and behaviour
o Hyperactivity
o Apathy
o Aggressive behaviour
o Substance abuse / addiction
o Eating disorders
o Impulsive behaviour
o Compulsive behaviour
o Sexually inappropriate behaviour
o Loss of decorum
• (Somatic: body function)
o Panic attack
o Sleeping disturbance
o Eating disturbance
o Motor dysfunction e.g. catatonia
o Diurnal rhythm disturbances
o Difficulties with urine/faeces elimination
o Sexual dysfunction
o Fatigue
o Pain
However, none of these dysfunctions alone indicate one disorder.
From signs to diagnosis
Diagnosis makes a distinction between what is normal and what is pathological. It is an essential part
of doctor-patient interaction but also between professionals. There are several categories for diagnosis:
• Etiology (cause)
• Course
• Treatment
• Prognosis
The current classification system for psychiatric disorders is the DSM-5. This classification is based
on clinical symptoms rather than e.g. blood tests. In order for something to be diagnosed as a disease it
needs to lead to impairment or distress.
• Core symptoms
• Complementary symptoms
• # Symptoms
3
, • Duration
• Functional impairment/distress
Diagnosis is a polythetic system which allows for flexibility since not all e.g. depressed individuals
show the exact same symptoms. However, the same disease can thus have different neurobiological
pathologies and therefore a combination of symptoms and neurobiology is important. In the end,
psychiatric disorder diagnoses are clinical constructs.
A DSM diagnosis does not describe:
• A real entity in the outside world (“reification”)
• The etiology of the disorder
• The brain dysfunctions associated with the disorder
• The life history behind the disorder
• The significance of the disorder for the patients or for the family and wider context
The major DSM-5 categories are:
• Neurodevelopmental disorders
o Highly genetic
▪ Twin studies to determine genetic susceptibility
o Autism and ADHD most common
o Intellectual disability: Down syndrome and Fragile X syndrome
• Schizophrenia spectrum and other psychotic disorders
o Schizophrenia
▪ Decline in cognitive functions that are progressive
▪ Develop at early age (20’s)
o Delusional disorders
▪ Develop at later age (50’s)
• Bipolar and related disorders
o Mood instability
o Highly genetic
• Depressive disorders
o Major depressive disorder
o Persistent depressive disorder
o Premenstrual dysphoric disorder
• Anxiety disorder
o Key feature is anxiety
o Least genetic disorder
o Least neurobiologically studied beside panic disorder
• OCD and related disorders
o Key feature is obsessive thoughts and/or compulsive behaviour
o OCD and body dysmorphic disorder
• Trauma and stress related disorders
o Psychopathology as a consequence of traumatic life events
o PTSD
• Feeding and eating disorders
o Key feature is eating behaviour
o Anorexia nervosa
4
Content
Les 1: intro ............................................................................................................................................. 2
Signs of mental illness ......................................................................................................................... 2
From signs to diagnosis ...................................................................................................................... 3
Neurobiology and psychiatry: a multilevel approach ......................................................................... 5
Les 2: Developmental dyslexia and dyscalculia .................................................................................. 6
Introduction neurodevelopmental disorders ....................................................................................... 6
Reading, phonology and dyslexia ....................................................................................................... 6
Arithmetic, numerosity and dyscalculia .............................................................................................. 9
Les 3: Imaging ......................................................................................................................................11
PET ....................................................................................................................................................11
MRI ....................................................................................................................................................11
Les 4: Anatomy of the limbic system ................................................................................................. 14
Function of the hippocampal formation............................................................................................ 15
Function of the amygdaloid body...................................................................................................... 15
Function of the limbic basal ganglia loop ........................................................................................ 16
Les 4: ASD ............................................................................................................................................ 16
Introduction ASD............................................................................................................................... 16
Neurocognitive theories .................................................................................................................... 17
Social cognition theories ................................................................................................................... 19
Les 5: Psychiatric genetics Autism ..................................................................................................... 21
Defining the phenotype ..................................................................................................................... 21
Genetic architecture of neuropsychiatric disease ............................................................................. 22
Complex disease model in clinical genetics ...................................................................................... 22
Genetic causes, susceptibility variant, liability................................................................................. 23
Les 5: Psychiatric genetics Schizophrenia ......................................................................................... 23
Searching for genes ........................................................................................................................... 23
Genes for schizophrenia and bipolar disorder .................................................................................. 24
What do we learn from GWAS studies............................................................................................... 24
Les 6: Neurobiology of psychosis (schizophrenia) ............................................................................ 24
Diagnosis and phenomenology ......................................................................................................... 24
Genetics............................................................................................................................................. 25
Neurobiology ..................................................................................................................................... 25
Les 7: Animal models in psychiatric disorders ................................................................................. 26
1
, Short overview of tests ...................................................................................................................... 28
Les 8: Neuropsychology and neurobiology of emotions ................................................................... 29
Basic emotion vs constructed emotion .............................................................................................. 30
Amygdala and emotion...................................................................................................................... 30
Insula and emotion ............................................................................................................................ 31
OFC and emotion .............................................................................................................................. 31
ACC and emotion .............................................................................................................................. 31
Cross-categorical findings ................................................................................................................ 31
Les 9: Depression ................................................................................................................................. 31
Neurobiology of major depressive disorder (MDD) ......................................................................... 32
Epigenetics & depression .................................................................................................................. 33
Les 10: Neurobiology of anxiety and its disorders............................................................................ 34
Anxiety............................................................................................................................................... 34
Anxiety disorders and OCD .............................................................................................................. 36
Les 1: intro
Signs of mental illness
Psychiatric disorders are characterised by disturbances in one or more mental functions:
• Cognitive: reasoning, rationality and perception
o Consciousness
o Concentration, attention
o Memory: short term, long term, orientation (in time, space, persons)
o Cognition
o Cognitive distortions: rational thinking but biased towards negative thoughts
o Delusions: unrealistic convictions of persecution, hidden meanings, megalomania
(delusion of grandeur)
▪ Can happen in severe depression and is then coloured by the depression
▪ Delerium tremors specific for alcohol withdrawal
o Perception
o Hallucinations
▪ Visual hallucinations are always sign of brain problem/dysfunction for which
a cause can be identified
▪ Auditory hallucinations are typical of schizophrenia
o Obsessive thoughts: OCD
▪ Difference between obsessive and delusions is that the person with obsessive
thoughts knows the thought is absurd but get anxious when they do not do it
• Affective: emotion
o Mood changes (in the pathological range)
▪ Maladjusted emotions
2
, ▪ Seen in borderline patients (mood instability) often paired with
automutulation
o Anhedonia
▪ Typical sign of major depression
▪ Anticipatory vs consummatory
o Anxiety
▪ Panic
▪ Phobia
▪ Social anxiety
o Anger, irritability
• Conative: motivation and behaviour
o Hyperactivity
o Apathy
o Aggressive behaviour
o Substance abuse / addiction
o Eating disorders
o Impulsive behaviour
o Compulsive behaviour
o Sexually inappropriate behaviour
o Loss of decorum
• (Somatic: body function)
o Panic attack
o Sleeping disturbance
o Eating disturbance
o Motor dysfunction e.g. catatonia
o Diurnal rhythm disturbances
o Difficulties with urine/faeces elimination
o Sexual dysfunction
o Fatigue
o Pain
However, none of these dysfunctions alone indicate one disorder.
From signs to diagnosis
Diagnosis makes a distinction between what is normal and what is pathological. It is an essential part
of doctor-patient interaction but also between professionals. There are several categories for diagnosis:
• Etiology (cause)
• Course
• Treatment
• Prognosis
The current classification system for psychiatric disorders is the DSM-5. This classification is based
on clinical symptoms rather than e.g. blood tests. In order for something to be diagnosed as a disease it
needs to lead to impairment or distress.
• Core symptoms
• Complementary symptoms
• # Symptoms
3
, • Duration
• Functional impairment/distress
Diagnosis is a polythetic system which allows for flexibility since not all e.g. depressed individuals
show the exact same symptoms. However, the same disease can thus have different neurobiological
pathologies and therefore a combination of symptoms and neurobiology is important. In the end,
psychiatric disorder diagnoses are clinical constructs.
A DSM diagnosis does not describe:
• A real entity in the outside world (“reification”)
• The etiology of the disorder
• The brain dysfunctions associated with the disorder
• The life history behind the disorder
• The significance of the disorder for the patients or for the family and wider context
The major DSM-5 categories are:
• Neurodevelopmental disorders
o Highly genetic
▪ Twin studies to determine genetic susceptibility
o Autism and ADHD most common
o Intellectual disability: Down syndrome and Fragile X syndrome
• Schizophrenia spectrum and other psychotic disorders
o Schizophrenia
▪ Decline in cognitive functions that are progressive
▪ Develop at early age (20’s)
o Delusional disorders
▪ Develop at later age (50’s)
• Bipolar and related disorders
o Mood instability
o Highly genetic
• Depressive disorders
o Major depressive disorder
o Persistent depressive disorder
o Premenstrual dysphoric disorder
• Anxiety disorder
o Key feature is anxiety
o Least genetic disorder
o Least neurobiologically studied beside panic disorder
• OCD and related disorders
o Key feature is obsessive thoughts and/or compulsive behaviour
o OCD and body dysmorphic disorder
• Trauma and stress related disorders
o Psychopathology as a consequence of traumatic life events
o PTSD
• Feeding and eating disorders
o Key feature is eating behaviour
o Anorexia nervosa
4
