Case 9- depression Flashcards
Amino acid neurotransmitters
1) Acetylcholine (excitatory or inhibitory)
2) Glutamate (excitatory)
3) GABA (inhibitory)
Biogenic amines neurotransmitters
1) Dopamine (excitatory via D1 receptors and inhibitory via D2 receptors)
2) Norepinephrine (excitatory)- hormone and neurotransmitter
3) Epinephrine (excitatory)
4) Serotonin (excitatory or inhibitory)
Neuropeptides neurotransmitters
1) Substance P (excitatory)
2) Opioids (inhibitory)
Catecholamines
A subtype of the biogenic amines containing Dopamine, Norepinephrine and Epinephrine
Indoleamine
A subtype of the biogenic amines. Includes Serotonin and Imedazoleamine
The neurotransmitters linked to depression
Histamine, serotonine, dopamine and norepinephrine
Movement of Serotonin in the brain
Serotonin originates in the raphe nuclei within the brainstem. The axon then moves to the Cerebellum and up to the middle of the brain in the striatum and through the rest of the brain in the cortex.
Serotoninergic pathway
How Serotonin moves through the brain. Goes through the Cerebellum, Cerebral cortex, Hippocampus and the Striatum. The striatum is in the centre of the brain.
What does Serotonin control
Serotonin controls the arousal/sleep wake cycle. It is implicated in mood and behaviours. Linked to appetitive emotions (drive to do things) and emotions.
The three Dopaminergic pathway
Mesolimbic, Mesocorticol and Nigrostriatal
The Mesolimbic dopamine pathway
Start= Ventral tegmental area (VTA)
Finish= Limbic system- nucleus accumbens, hippocampus, amygdala
Reward pathway so can lead to addiction
The Mesocortical dopamine pathway
Start= Ventral tegmental area (VTA)
Finish= Cortex (mostly frontal aspect)
Involved in mood control, can cause depression
The Nigrostriatal dopamine pathway
Start= Substantia Nigra
Finish= Striatum- caudate and putamen nuclei of the basal ganglia
Involved in movement and control, when damaged it causes Parkinson’s disease
Neurotransmitter
A chemical that is specifically released at synapses to communicate between neurones.
Norepinephrine (neurotransmitter)
Used as a neurotransmitter for the Cerebellum, Cerebral cortex, Thalamus and limbic system. The cell bodies originate from the locus ceruleus. It influences arousal/wakefulness. It is implicated in mood and behaviour like appetitive (the desire to do something) and sexual behaviour
Monoamine theory of depression
The main biological theory of the cause of depression. States that depression is due to a reduction in the levels and/or effectiveness of the monoamines (biogenic amines, catacholamines). The main neurotransmitters involved are serotonin, dopamine and Noradrenaline
Arguments in support of the monoamine theory of depression
Tricyclic antidepressants (TCA’s)
Monoamine oxidase inhibitors (MAOI’s)
Reserpine
Arguments in support of the monoamine theory of depression- TCA’s
A drug which treats depression by inhibiting 5-HT (serotoninin) and NA (noradrenaline) reuptakes. This increases neurotransmitter levels in the synapse
Arguments in support of the monoamine theory of depression- MAOI’s
An antidepressant that inhibits the action of Monoamine, which is an enzyme that breaks down neurotransmitters. Increases concentration of 5-HT and NA.
Arguments in support of the monoamine theory of depression- Reserpine
Reserpine is a drug that treats high blood pressure by reducing 5-HT and NA. In patients taking this drug there is a sudden increase in the suicide rate
Arguments against the monoamine theory of depression
- TCAs and MAOIs take time to work. If the problem was simply low levels of neurotransmitters then the effect of these drugs increasing neurotransmitter levels should happen within minutes.
- Cocaine increases the levels of these monoamines in the brain but is not an antidepressant.
- Limited evidence of lowered 5-HT/NA levels or their metabolites in the blood/ CSF/ urine/ brain of people with depression.
- 1/3 of depressed patients do not respond to usual antidepressant drugs.
Triggers for mental disorders
- Stress can lead to depression/anxiety by affecting 5-HT function. Stress can also affect neurogenesis (making new neurons) and neuromorphology (repairing neurons and changing their function).
- Genetics- some people have a genetic predisposition, there is a high concordance in monozygotic twins.
The link between Stress and the Hypothalamic-pituitary-adrenal axis
When you are stressed the Amygdala releases CRH causing the Hypothalamus to release more CRH which acts on the pituitary gland. The anterior pituitary gland releases ACTH into the blood stream. ACTH acts on the adrenal gland to release cortisol, the stress hormone. You get a negative feedback so it’s a short term response. This pathway also feedbacks on the Hippocampus and the Prefrontal cortex, so that you remember the stressful situation.
Where are the cortisol (Glucocorticoid) receptors located in the brain?
In the Hippocampus, pre-frontal cortex, amygdala and hypothalamus.
How chronic stress can alter neuronal morphology
There is continual activation of the Hypothalamix-piuitary-adrenal pathway and release of cortisol. In the Hippocampus long term stress can induce structural changes like a decrease in dendrites and pyramidal cells, this causes a decrease in memory. In the prefrontal cortex you also get a decrease in dendritic cells and Pyramidal cells this can lower your attention and affect emotions. In the Amygdala there is an increase in branching (arborisation), it becomes more activated and there is increased anxiety.
Stress and BDNF levels
The chemical called ‘Brain derived neurotrophic factor (BDNF)’ increases neurogenesis and synaptic formation (helps repair damage due to chronic stress) through increased gene expression. Stress and high levels of cortisol act to reduce BDNF levels so neurons begin to break down. Especially in the Hippocampus and subventricular zones
Cortisol and serotonin
In depression patients tend to have high circulating levels of cortisol. Cortisol may have an effect on the function of 5-HT receptors and serotonergic transmission. Serotonergic activity is important for neurogenesis and control of BDNF levels. Cortisol effects the levels of 5-HT neurons and their receptors in the Hippocampus decreasing BDNF levels
Main 5-HT receptor altered in chronic stress
5-HT1a. There is increased somatodendritic 5-HT1a function in depression.
Lowering 5-HT in healthy subjects
If you lower 5-HT in healthy subjects there is little or no effect on mood. There are effects on cognition as there is increased response times to happy and neutral (but not sad) targets when you increase 5-HT. There is impaired recall to positive and neutral targets but increased attention to negative items/memories when you decrease 5-HT levels.
Antidepressants and chronic stress
Antidepressants increases Serotonin levels, this increases BDNF levels counteracting the effects of chronic stress. This increases Neurogenesis and Neurorepair.
Genetic and environmental influences on depression
Its genes plus environment. Genetic influences can effect our response to stress, there is a gene related to the 5-HT system. The gene is called 5-HTT and is a serotonin transporter, it reuptakes serotonin back into the cell after it has been released as a neurotransmitter.
Evidence that genes play a role in depression
- In a 5-HTT polymorphism, serotonin is more quickly taken back into the cells. This means you are more likely to get depression as the 5-HT is in your synapses for less time.
- There is another 5-HT transporter which is activated more in the Amygdala, so serotonin is removed more quickly there. This is linked to stress.
Environmental effects on depression
The loss of a parent in childhood leads to an increased level of depression as an adult as it leads to changes in the HPA axis function, releasing more cortisol. Infants and children react more to cortisol so traumatic effects when younger are more likely to cause depression.
Vulnerability and Resilience- depression
Vulnerability and resilience play a role in depression. Resilience to stress depends on the 5-HT system maintaining a positive emotional bias. Vulnerability is mediated by genetic risk factors and/or early life adversity (leading to higher cortisol response and hence impaired 5-HT neurotransmitters.
How resilience changes in depression
In depression there are abnormalities in postsynaptic 5-HT1A receptors which can impair resilience.
• There is increased Somatodendritic 5-HT1A function in depression.
• There is decreased Postsynaptic 5-HT1A number and function in depression.
DSM-5 terminology
One episode= Major Depressive episode (MDE)
More then one episode= Major Depressive disorder (MDD)
ICD-11 terminology
One episode= Single episode depressive disorder
More then one episode= Recurrent Depressive disorder
What can be associated with depression
There may be a prominent pattern of associated symptoms. Anxiety is very common. Often it is ‘generalised anxiety (disorder),’ ‘panic (disorders)’ or ‘obsessive compulsive (disorder)’ symptoms. Psychosis can also be present.
Panic attacks
Recurrent episodes of severe anxiety with association of psychic (feeling anxious) and physical anxiety. This will include a tremor. fast heart rate and sweating
Obsessive compulsive disorder
Recurrent thoughts within the patients consciousness that are the patients own. They tend to be unpleasant like contamination or checking the door is locked. Can be associated with constant acts like excessive cleaning.
Psychosis
Hallucinations or delusions. Normally mood congruent, meaning that the nature of the symptoms are consistent with the mood, for example, when depressed you may get an auditory hallucination saying you are worthless. Psychosis occurs in severe depression.
Hallucinations and delusions
A hallucination is a perception which is not there, this is in the absence of a stimulus. Felt with the same force and character as a normal perception. A delusion is a belief that is contradicted by reality, such as the world is going to end.
Melancholic
Normally anhedonia, a loss of pleasure. Also, a type of insomnia called early morning wakening. Diurnal variation which is when mood is worse first thing in the morning. You also get psychomotor retardation, weight loss and guilt
Atypical depressive symptoms
Increased appetite, hypersomnia, ‘laden paralysis’ where it feels impossible to move.
Severity of depression
ICD-11 describes 3 levels of severity: mild, moderate and sever. This is based on symptom count. It is better to make a clinical judgement on the severity of the symptoms and the degree of functional impairment.
Euthymia
Good mental state
Course of depression
Depression is a relapsing/remitting condition. There is a 50% chance of relapse after 1 episode, 80% after 2. Assess the patients response to treatment they can be in non-response, partial remission and in remission.
A response to depression
In depression response is defined as a 50% improvement in symptoms. Being fully well is in remission. Partial response is when the decrease in symptoms is between no response and full recovery.
PHQ-9
Used to assess the severity of depression. It is based on the DSM criteria. It is not a diagnostic toll but is often used as one. Scoring is based on frequency of symptoms: • 0-5= normal • 5-9= minimal symptoms • 10-14= dysthyma or mild MDE • 15-19= moderate MDE • >20= severe MDE
DSM persistent depressive disorder (dysthymia) / ICD Dysthymic depression
Sub-syndromal symptoms for at least 2 years. Most commonly life long. Tend to have less symptoms but they occur for longer. Can respond to antidepressants but not very well, doesn’t respond to therapy. They are at an increased risk of developing MDD, this is then called double depression (MDD+ dysthymia).
Premenstrual dysphoric disorder
Depression and irritability before menstruation. It is more severe than premenstrual syndrome (PMS)
Sub- syndromal depression and anxiety
ICD criteria, less severe forms of anxiety and deppresion
Bipolar disorders
The patient suffers periods of depression and mania. A diagnosis of bipolar overrules a depressive diagnosis. Diagnosed on the basis of a single manic or hypomanic episode. However, most patients first episode is usually depressive and there are more of them then manic episodes
DSM-5 symptoms for mania/hypomania
- Abnormally and persistent elevated or irritable mood
- Increased energy
- Inflated self esteem or grandiosity
- Decreased need for sleep
- Pressured speech
- Racing thoughts or flight of ideas that are connected
- Distractibility
- Increased activity
- Excess pleasurable or risky activity
DSM-5 criteria for mania/hypomania
You must have 1 +2 and 3 others, 4 if only irritable mood and not elevated mood. This must be for 1 week with functional impairment. Hypomania has the same criteria but less severe, it is still distinct from a non-depressed state. There is no major functional impairment and minimum duration is 4 days.
Types of bipolar disorder
- Bipolar 1- the patient has had at least one manic episode.
* Bipolar 2- the patient has had hypomanic episodes but never a manic one.
Mixed features bipolar disorder
A DSM classification. It means you have symptoms of depression and mania at the same time. Has the highest suicide rate of any mood disorder
Rapid cycling bipolar
When you have more than one episode of any type per year
Cyclothymia
There are sub syndromal ups and downs. Symptoms are not that sever and dont meet that criteria.
