Affective Disorder Flashcards
What is affective disorders?
disorders of emotions and mood (also ‘mood disorders’)
Example of affective disorder
depression, anxiety disorder, bipolar disorder
Criteria for depression or mania
Duration is important
Depression = depressed mood, > 2 weeks
Mania = abnormally elevated mood, > 1 week
Diagnostic criteria
In Europe: ICD10
Distinguish key/main symptoms and associated symptoms
How can depression be diagnosed according to ICD10
Severity (# of symptoms) Mild (4) Moderate (5-6) Severe (>= 7) • without psychotic symptoms • with psychotic symptoms
Key symptoms of depression on ICD 10
persistent sadness or low mood
loss of interest or pleasure
fatigue or low energy
Psychotic symptoms
Illusions (false beliefs) and hallucinations
Somatic symptoms of depression
Headaches, Vertigo
Back pain
Breathing problems e.g. right chest
Cardiac symptoms e.g. palpitations
Gastrointestinal symptoms e.g. nausea, abdominal pain
Gynecological problems e.g. menstrual irregularities, pain
Course of illness
- single episode
- recurrent
- chroinic
Issue of “healing”
- Impairment/ disability persists often beyond the depressive episode
- 50% of major depressive episodes remit within 3 months
- Severe and co-morbid depression average duration: 7.6 months
- The longer the episode, the lower the probability of remission
Depression in EU
25% (9% at all time)
Disability adjusted life years
(measure of disease burden)
Number of years lost due to illness, disability or early death
Depression may be number one in future
Depression and gender
more women
Components of bipolar disorder
Mania
Depression/ Irritability
Psychotic symptoms
Cognitive impairment/thought disorders
Logorrhea
Example of mania where one talks a lot
Mania and psychotic symptoms
High comorbidity but not necessity, it is possible to be maniac without psychotic symptoms
Scale of bipolar
Severe depression depression baseline hypomania (no disruption of social relationships and no psychotic symptoms) mania
Subtypes of bipolar
Cyclothymic personality (not yet a disease but mood shift within the extreme of normal range) Cyclothymia... mood range from hypomania to depression Bipolar 1... mania and severe depression Bipolar 2... range within hypomania and severe depression Unipolar mania... range within normal and mania
Extreme of bipolar
Rapid cycling with no normal state in between mania and severe depression
Prevalence of bipolar disorder
low (-1%)
Bipolar and gender
equal ratio for male and female
High genetic influence
Recurrent unipolar depression and depression
For twin study, 50% and 80% respectively
Influence of inducing depression
genes, early childhood, neuroendocrine factors, neuroanatomy, stressful life events
The more episodes of depression you have
more likely you will have additional episodes regardless of the number of stressful life events
5HT gene and depression
5-HTTLPR encodes for promoter region SLC6A4
Short-allele… less 5HT transporter (for reuptake) associated with neuroticism
Long-allele… more 5HT transporter leading to better response to SSRI
Paradox: Lack of 5HT leads to depression, but then how is s-allele w/less reuptake (more 5HT) leads to neurotocism?
Gene-environment interaction
- L-allele work as a protective measure against depression
- Age of stressful events may matter
- s-group have more sensitive amygdala
Two potential NT involved in depression
5HT and NE (SSRI and SNRI)
Anatomical key player in depression
limbic system (cingulate cortex, hippocampus, amygdala and medial part of prefrontal cortex)
Anatomically how is brain changed by depression?
- Less serotonin production
- decreased prefrontal cortex volume and activity
- decreased activity of subgenual anterior cingulate cortex (sgACC, Cg25)
- increased sensitivity of amygdala especially to negative emotion
- lack of sensitivity in ventral striatum
In the old days, neuroendocrine factors were thought as depression
HPA axis dysregulation
Treatment
- Prozac (antidepressants may not be beneficial for mild syptoms)
- psychotherapy
- CBT (faster result than psychotherapy)
- ElectroConvult Therapy
- Transcranial Magnetic Stimulation
- light therapy
Drugs for depression
• Selective serotonine reuptake inhibitors (SSRI)
e.g., Fluoxetine (Prozac), Sertraline, Paroxetine, Citalopram
•Noradrenaline reuptake inhibitors (NRI)
e.g., Reboxetine, Bupropione (+ dopaminergic)
• Serotonin-Noradrenaline reuptake inhibitors (SNRI)
e.g., Venlafaxine, Mirtazapine, Duloxetine
• Tri- or tetracyclic antidepressants (TZA); side efffects
e.g., Amitripyline, Doxepine, Imipramine
• Monoamine-oxidase (MAO) inhibitors
e.g., Tranylcypromine
Non-serotonin/NE related drugs (fast)
• Ketamine (NMDA-receptor antagonist)
What is potential mechanism on action of SSRI?
Not the amount of NT available but rather the sensitivity of receptor seems to influence the clinical effect; decrease in sensitivity increase the positive clinical effect
Issue of antidepressants
It seems to be only effective (experimental vs placebo comparison) for severe depressive patients
Drug treatment for bipolar
• Mania: - Lithium - Valproate - Second generation antipsychotics (e.g., Quetiapine, Olanzapine, Risperidone) •Depression: - Quetiapine - Antidepressant + Mood stabilizer (e.g., SSRI + Lithium) • Maintenance: - Lithium - Valproate - Second generation antipsychotics
What is anxiety?
- Basal behavior necessary for the survival of the individual
- Appearance in men and animals. Animal models available
- Dysregulation leads to anxiety disorder
Example of anxiety disorders on DSM/ICD
- Generalized anxiety disorder
- Panic disorder
- Agoraphobia
- Social Phobia
- Simple Phobia
- Posttraumatic stress disorder
Clinical features of generalised anxiety disorder
A. Excessive anxiety and worry (apprehensive expectation), occurring more days than not for at least 6 months, about a number of events or activities
B. The person find it difficult to control the worry
C. Three (or more) of the following symptoms (with at least some symptoms present for more days than not)
(1) restlessness or feeling keyed up or on edge
(2) being easily fatigued
(3) difficulty concentrating or mind going blank
(4) irritability
(5) muscle tension
(6) sleep disturbances
D. Significant interference with the person’s functioning
E. Exclude substance effects, general medical conditions and other psychiatric disorders
What is a panic attack
Discrete episode of intense fear or dicomfort, in which four (or more) of the following symptoms developed abruptly and reached a peak within 10 minutes: palpitations trembling or shaking shortness of breath chest pain or discomfort nausea fear of dying paresthesias sweating Fear of losing control shortness of breath derealization/depersonalization vertigo chills or hot flushes
Frequency: 10-30 % of the general population
Risk marker for psychiatric disorders and risk factor for panic disorder
PANIC DISORDER
- Recurrent and unexpected panic attacks
- At least one of the attacks has been followed by 1 month (or more) of the following:
a) persistent concern about having additional attacks
b) worry about the implications of the attack or its consequences (e.g. loosing control, having a heart attack, „going crazy“)
c) significant change in behavior related to the attack
AGORAPHOBIA
（病的な）外出嫌い
- Anxiety about being in places or situations from which escape might be difficult (or embarrasing) or in which help may not be available
- Avoidance of the situations
Neuroanatomy of panic disorder
Panic attack: reticular formation
Fear: Amygdala
Agoraphobia: preforntal cortex
SOCIAL PHOBIA
A. Marked and persistent fear of one or more social or performance situations in which the person is exposed to unfamiliar people or to possible scrutiny by others.
The individual fears that he or she will act in a way (or show anxiety symptoms) that will be humiliating or embarrassing
B. Exposure to the situation provokes an anxiety response
C. The person recognizes that the fear is excessive/unreasonable
D. The feared social or performance situations are avoided
E. Significant interference with the person’s functioning
F. Exclude substance effects, general medical conditions and other psychiatric disorders
Generalized: if the fears include most social situations
(also consider the additional diagnosis of avoidant personality disorder)
SPECIFIC PHOBIA
A. Marked, persistent, excessive or unreasonable fear cued by the presence or anticipation of a specifc object or situation
B. Exposure provokes an anxiety response
C. The person recognizes that the fear is excessive/unreasonable
D. The phobic situation is avoided
E. Significant interference with the person’s functioning
F. Exclude other psychiatric disorders
Specific type: Animal type, Natural environment type (heights, storm, water), Blood-injection-injury type, Situational type (planes, elevators, enclosed places), Other type: situations that may lead to choking, vomiting, or contracting an illness
POSTTRAUMATIC STRESS DISORDER
A. Traumatic event that involved actual or threatened death or serious injury, or a threat to the physical integrity of self or others. The person’s response involved intense fear, helplessness, or horror.
B. The traumatic event is persistently reexperienced
C. Persistent avoidance and numbing
D. Persistent symptoms of increased arousal
E. Duration (symptoms in B, C and D) is more than 1 month
F. Significant interference with the person’s functioning
Acute: duration of symptoms is less than 3 months
Chronic: duration of symptoms is more than 3 months
With delayed onset: onset more than 6 months after the stressor
LIFETIME-PREVALENCE OF ANXIETY DISORDERS
Panic Disorder 3.2-3.6 Agoraphobia 2.1-10.9 Social Phobia 11.3-16.0 Simple Phobia 4.5-11.3 Generalized Anxiety Disorder 1.9-31.1 Posttraumatic Stress Disorder 7.8 *Lifetime-comorbidity increase to 10-40% if a patient already has one
TREATMENT OF ANXIETY DISORDERS
-Effective and well tolerated treatment available: Psychotherapy Cognitive Behavioral Therapy Pharmacotherapy Antidepressants (SSRI) (Avoid benzodiazepines and neuroleptics) -Individual treatment planning -Because the trend to become chronic and to be a risk factor for other psychiatric disorders (depression, substance disorder)
Need for
Early treatment
Maintenance treatment in selected patients
NEW ANTIDEPRESSANTS IN THE TREATMENT OF ANXIETY DISORDERS
Venlafaxine: effective in GAD, panic disorder and social phobia
Duloxetine: effective in GAD
Treatment for simple phobia
Behavioral Treatment (exposure) Paroxetine (20 mg/die)
What are the trends of treatment
Learning and plasticity New drug targets: NMDA and GABAA receptor subtypes Neuropeptides and HPA system Atrial Natriuretic Peptide (ANP) PTSD: HPA system and hippocampal atrophy
NMDA receptor drugs
Used for fear extinction
D-Cycloserine: partial agonist; facilitates exposure therapy
HA-966: antagonist
at the strychnine-insensitive glycine-recognition site of the NMDA receptor complex
POSSIBLE TARGETS FOR ANXIOLYTICS
- Receptor subtypes: GABA, 5HT, NMDA
- Neuropeptides: NK-1-Antagonist, CRH-R1-Antagonist, ANP-R-Agonist, CCK-4-Antagonist
- Modulation of Neuroactive steroids
- Second messenger systems and growth factors
What are neuropeptides/ Peptide hormones
- Detectable in the CNS
- Modulate neurotransmission
- CNS-activity independent of peripheral effects
examples: Corticotropin releasing hormon (CRH) Cholecystokinine (CCK-4) Neuropeptide Y (NPY) Atrial natriuretic peptide (ANP)
ATRIAL NATRIURETIC PEPTIDE (ANP)
• Peripheral release after atrial stretching
• Controls fluid regulation and hormonal secretion
• Neuromodulator
• Increased release during lactate-induced panic attacks (Possible reason for the lack of HPA activation
and Inhibits the sympathetic activity of the heart)
• Inhibits the HPA system (ACTH, prolactin, cortisol)
• Anxiolytic activity?
Animal Models of ANxiety (MAN)
Induced by elevated plus maze
What are current “effective” treatment to treat anxiety?
Effective treatment is available (CBT, AD) with new drug targets and treatment approaches have been generated
Anxiety and HPA axis
Hypoactivity of the HPA system and hippocampal atrophy may be a vulnerability factor for PTSD
