Lecture psychiatric disorders 9: depression Flashcards
What are diagnostic criteria for depression?
- Decreased or irritable mood
- Decreased interest in pleasurable activiteit and ability to experience pleasure
- Significant wight gain or loss
- Insomnia or hypersomnia
- Psychomotor agitation or retardation
- Fatigue or loss of energy
- Feelings of worthlessness or excessive guilt
- Diminished ability to think or concentrate
- Recurrent thought of death or suicide.
What is a lifestyle disease?
A disease that appears to increase in frequency as countries become more industrialized and people live longer.
Is depression a lifestyle disease?
No, it’s not a lifestyle disease. The WHO performed a study in 15 cities (including cities in Africa and China). There was a hugh variation in depression prevalence, but this was not related to sociodemographic variables.
What is hard about diagnosing depression?
- There’s lack of objective diagnostic tests, since depression is a compilation of symptoms.
- Diagnosis is variable, due to the heterogeneity of the illness.
- There’s no clear line in distinguishing people with mild clinical depression from those having a tough time in the course of their normal life.
- Diagnostic categories are solely based on verbal information. There’s a need for biomarkers.
What is the monoamine hypothesis?
It states that the underlying pathophysiologic basis of depression is a depletion in the levels of serotonin, norepinephrine and/or dopamine.
Why was it thought that the monoamine hypothesis laid base to the underlying causes of depression?
Because drugs that act on serotonin and/or noradrenalin pathways relieve symptoms of depression within few weeks. Only, this was way to simplistic
What is a new paradigm thought to be important in depression?
That depressive symptoms are increasingly linked to malfunctioning specific brain circuits. This could be due to genes and environmental risk factors that conspire to produce inefficient information processing in neuronal circuitry.
Study picture for an overview of all current hypothesises for the etiology of depression. Most of them will be discussed here.
Ok
What would be the relationship between depression and an overactive amygdala? What other brain region is involved in this?
It is seen that saying positive, negative or neutral words to depressed people results in a bigger and overactive response of the amygdala and a decreased response of the prefrontal cortex compared to non-depressed people. This overactivation of the amygdala and decreased activity of the prefrontal cortex makes sense, since they’re connected in a circuit.
So depression is characterized by an increased and sustained emotional reactivity. What does this result in (especially in response to emotional information)?
Involuntary elaboration on the negative topics.
What’s interesting about the decreased activity of the dorsolateral prefrontal cortex (DL-PFC) in response to cognitive tasks?
That there are no performance deficits
What can be the interaction between the amygdala and the dorsolateral PFC?
That the amygdala is responsible for the inhibition of the DL-PFC and that there might be insufficient communication between the two brain regions.
It is also seen that patients with depression have an attenuated response to sad faces.
Two studies were performed that had a similar effect on depression. The first was the administration of Selective Serotonin Reuptake Inhibitors (SSRIs) to patients with depression. The other study used cognitive behavioral therapy. What were the conclusions of these studies?
That administration of SSRIs decreased the amygdala activity, the patients felt better and their facial sadness expression recognition normalizes.
So pharmacotherapy and behavioral therapy can normalize amygdala and PFC functioning.
Some studies found a reduction in hippocampal volume in patients with Major Depressive Disorder (MDD), others did not. What is a possible explanation of these contradictory results?
- Hippocampal volume is dependent upon suptype of depression.
- It might be that reduced hippocampal volume is a characteristic for depression, but normal hippocampal volume is restored when successfully treated. And that the hippocampal volume is also normal in healthy non-depressed people.
- Reduced hippocampal volume might be an indicator for vulnerability for depression in healthy people.
What was found in a study where they researched healthy girls at (familial) risk for depression (due to mothers having recurrent episodes of depression)?
That compared with individuals at low familial risk of the development of depression, high-risk individuals have a reduced hippocampal volume.
This supports what has been discussed in the previous question, namely that reduced hippocampal volume might be an indicator for vulnerability for depression in healthy people.
Another study focused on hippocampal anatomy, where the volume of hippocampal subregions was measured (head, body and tail). What was found?
- That a decreased hippocampal tail and head volume could be trait changes (i.e. vulnerability markers).
- Hippocampal body changes may be dependent on actual mood state or in other words: dependent on if someone is depressed or treated/non-depressed.
- Long-term antidepressant not only enhance mood, but also restore/affect hippocampal volume in depressed patients.
What could be the cause of the reduction in volume of the hippocampus and PFC?
- Loss of volume neurons → dendritic atrophy, spine loss and decreased neuronal synapses
- Loss of number of neurons → inhibition of neurogenesis (in hippocampus)
The stress systems of our body are made up of two systems: the fast- and slow-acting pathway. What system is usually activated in what situation?
The fast-acting pathway is responsible for responding to short stress stimuli. If these stress stimuli become prolonged, the slow-acting pathway is activated.
Descibe the slow-acting pathway and explain what happens when you’re depressed.
When stress is prolonged, the slow-acting pathway is activated. The HPA axis is activated, where the hypothalamus releases corticotropin releasing hormone (CRH) and AVP. CRH stimulates the pituitary gland to release ACTH, which stimulates adrenal gland to produce glucocorticoids like cortisol. Cortisol is able to interact with almost every bodily cell.
Normally cortisol is able to inhibit its own production, through a negative feedbackloop to the brain. Here, it binds to glucocorticoid receptors (GR) in the hypothalamus and pituitary. In depression, this negative feedbackloop fails and cortisol production is continued, which causes chronic stress.
So what things are found in (some suptypes of) depression in regard to the HPA-axis?
- A persistent finding is overactivation of the HPA-axis in some suptypes of depression.
- Increased peripheral plasma cortisol concentrations
- Elevated levels of CRH in the brain
- Reduced glucocorticoid receptors (GR) in hippocampus and hypothalamus
- Negative feedback loop unable to shut down stress system
Fill in:
A healthy stress system is a stress system with plenty of … (1)
A healthy stress system is a stress system with plenty of glucocorticoid receptors (in the brain).
What are symptoms of chronic stress via cortisol and CRH?
Decreased appetite, weight loss and loss of libido.
How can these symptoms of chronic stress be explained?
Since the negative feedbackloop of cortisol isn’t working, also the concentrations of CRH (also known as CRF) are increased in the brain. And also CRH can interact with receptors in certain brain areas. There are two variants of CRF which stimulate pathways in the brain that are responsible for these symptoms. See picture.
So it’s clear that normalization of the HPA-axis is a necessity for stable remission of symptoms. How can this be done?
Already is stated that a healthy stress system, a stress system is with plenty of cortisol receptors in the brain. Antidepressants and psychotherapy can be used to restore efficient negative feedback by increasing gene/protein expression of the cortisol receptor in the brain.
Why does ketamine work so fast?
Because ketamine can induce synaptogenesis and neurogenesis via a complex pathway (mTOR). This targets the core problems of depression (i.a. reduced neurogenesis in hippocampus).
Name 3 genes for which there is strong evidence of a link to depression.
FKBP5, HTR2A, GRIK4
What was the outcome of this influential prospective study by Caspi et al. that looked for the influence of life stress on depression?
Of the three genotypes/variants of the 5-HTT, the homozygous variant for allele S (S/S) was associated with an increased chance of depression when the amount of stressful life events increased. The homozygous variant for allele L (L/L) showed the lowest chances of developing depression when the amount of stressful life events was high. So you could state that genotype L/L is resilient to life stress.
So the previous study, looked into one genetic-environmental interaction. Another study looked for a broader correlation, between the 5-HTT and BDNF genotype and whether the genotype in combination with the degree of life adversity (here; maltreatment of children) would indicate higher chances of the development of depression.
What was the outcome of this study in regard to the control and maltreated group of people?
That there was a significant three-way interaction between the BDNF genotype, 5-HTTL genotype and maltreatment history.
- Children with the BDNF gene val66met polymorphism and the S/S 5-HTT genotype had the highest depression scores.
- Vulnerability associated with these genotypes was only elevated in maltreated children.
So the previous study, looked into one genetic-environmental interaction. Another study looked for a broader correlation, between the 5-HTT and BDNF genotype and whether the genotype in combination with the degree of life adversity (here; maltreatment of children) would indicate higher chances of the development of depression.
Now they also looked at the degree of social support in combination with the degree of maltreatment. What was the outcome of this study in regard to the maltreated group (high social support vs low social support)?
Here, a significant four-way interaction emerges.
- The depression scores of the maltreated children with high social support were close to the mean depression score of the control subjects, regardless of genotype.
- The S/S genotype was associated with an increase in maltreated children’s depression scores, which was greatest for the children without social support. If this was in combination with the Val66Met genotype, the depression score would be even higher.
