Affective Disorders Flashcards
ICD-10 Diagnostic criteria
DSM-5 diagnostic criteria
Patients are diagnosed with a depressive episode if they experience one of the first two symptoms and at least 5 symptoms total. For at least 2 weeks.
1. Depressed mood
2. Markedly diminished interest or pleasure in almost all activities
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3. Weight loss or change in appetite
4. Insomnia/hypersomnia
5. Psychomotor agitation or retardation
6. Fatigue or loss of energy
7. Feelings of worthlessness or excessive or inappropriate guilt
8. Diminished ability to think or concentrate or general indecisiveness
9. Recurrent thoughts of death, recurrent suicidal ideation, or specific suicide plan/attempt
Somatic symptoms of mdd
2/3 patients suffer from somatic symptoms such as:
- Back ache
- Muscle Aches
- Headache
- Gastrointestinal problems
Inflammation hypothesis of MDD
Hypothesis linking mdd to inflammation in the body. Chronic inflammatory disorders are linked to MDD, and the state of mdd resembles influenza or pneumonia.
Furthermore, 1/3 mdd-patients show elevated markers of inflammatory markers(e.g. C-reactive protein) or pro-inflammatory cytokines (IL-1, IL6, TNF, INF-alpha), and treatment with these cytokines increase rate of depression.
Anti-inflammatory drugs show anti depressive effects, but no specific anti-inflammatory drugs fro mdd has been developed.
What is the prevalence of MDD?
In the EU there is a one year prevalence of 6.9% = 30.3 million people
In Germany 20% of citizens experience mdd during their lifetime. Higher incidence for women (25%).
Monoamine hypothesis of depression
This hypothesis states that the underlying pathophysiological basis of depression is a depletion of serotonin, norepinephrine and/or dopamine in the nervous system.
This hypothesis was developed as a result of discovering tricyclic and monoamine oxidase inhibitor medications having antidepressant effects. However, the underlying pathophysiological basis of depression has been shown to be much more complex.
Which brain areas are hypothesised to be out of balance according to neuro imaging of mdd-patients?
In mdd patients, five major regions have shown dysfunctional activation in mdd-patients. The five are:
Amygdala Hippocampus Nucleus Accumbens HPA-axis Prefrontal cortex (Orbital frontal cortex, dorsolateral prefrontal cortex, medial prefrontal cortex, anterior cingulate cortex)
The dysfunctionality is expressed in either over- or under activation, with the nucleus accumbent and hippocampus being considered underactive, and the HPA-axis and amygdala are overactive. For the prefrontal cortex, both overactivity and under activity has been found, but the general idea is that the prefrontal cortex fails to properly mediate the information coming from the other brain areas. Thus, there is no clear cut psychopathological pattern, but the dysfunctional relationship between these regions is now thought of as a major factor in mdd.
Which hormone has shown elevated plasma levels in patients with mdd?
Cortisol has shown elevated diurnal mean plasma levels in mdd patients. The elevation is stimulated by an increase of corticotropin-releasing hormone and reduced feedback inhibition of the HPA axis.
HPA-axis
The hypothalamic-pituitary-adrenal axis is a complex system of neuroendocrine pathways and feedback loops that function to maintain physiological homeostasis. Abnormal development of the hypothalamic-pituitary-adrenal (HPA) axis can further result in long-term alterations in neuropeptide and neurotransmitter synthesis in the central nervous system, as well as glucocorticoid hormone synthesis in the periphery. Together, these changes can potentially lead to a disruption in neuroendocrine, behavioral, autonomic, and metabolic functions in adulthood.
Postmortem studies of depressed patients have shown increased neurons where?
Paraventricular nucleus of the hypothalamus.
The increase in neurons have been hypothesised to be the driver of overactivity in the HPA-axis, but the underlying reasons are still unclear.
Studies on depressed patients with heightened cortisol levels have showed reduced volume in primarily one brain area. Which one?
Hippocampus.
When cortisol is elevated, it can induce hippocampal atrophy. The hippocampus inhibits the hypothalamic-pituitary-adrenal axis, why hippocampal atrophy “lifts the brake” on the hypothalamic-pituitary-adrenal axis. The resulting cortisol increase induces further hippocampal atrophy, resulting in a vicious circle.
Treatment of depression is thought to preserve or restore original hippocampal volume.
Brain Derived Neurotrophic Factor (BDNF)
One of the most studied neurotrophins which handle regular maintenance of neurons. It is a protein that stimulates nerve growth, and if it is disrupted, this can lead to decrease in cell size and cell loss throughout the brain.
The role of BDNF in MDD patients
Postmortem studies of suicide subjects have shown a marked decrease in BDNF levels in PFC and in the hippocampus. Similarly, treatment with every kind of antidepressant have shown elevated levels of BDNF in rats. This is the first explanation of depression in which one mechanism of action can be seen in all treatments.
This has led to the hypothesis that psychiatric disorders such as MDD can be produced by decreased BDNF levels causing reduction in cell size and cell loss.
Precision psychiatry approach to depression
Precision psychiatry has emerged focusing on enhancing prevention, diagnosis, and treatment of psychiatric disorders through identifying clinical subgroups, suggesting personalized evidence-based interventions, assessing the effectiveness of different interventions, and identifying risk and protective factors for remission, relapse, and vulnerability.
It is based on using large data sources and machine learning techniques that allow more refined subgroups of e.g. MDD.
Circuit taxonomy for depression
In precision psychiatry, large meta-analyses have been used to single out specific symptoms of depression, and propose the neural circuit dysfunction leading to these symptoms, based on neuroimaging.
This is aimed to be used for more effective and personalised treatment of MDD.
