Depression (neuro) Flashcards
Characteristics of affective disorders
Characteristics of Affective Disorders
– Disorders of mood rather than thought / cognition
– Most common is depression
– Major cause of premature death and disability
Unipolar depression
1) Unipolar Depression – Mood swings in one direction – Most common depressive illness – 75% cases REACTIVE (induced by environmental factors) – 25% cases ENDOGENOUS (genetic)
Bipolar depression
1) Unipolar Depression – Mood swings in one direction – Most common depressive illness – 75% cases REACTIVE (induced by environmental factors) – 25% cases ENDOGENOUS (genetic)
Symptoms of depression
- Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.
- Note: Do note include symptoms that are clearly due to a general medical condition, or mood-incongruent delusions or hallucinations.
1) Depressed mood most of the day, nearly every day (in children irritable mood)
2) Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day.
3) Significant weight loss when not dieting or weight gain, or decrease or increase in appetite nearly every day.
4) A slowing down of thought and a reduction of physical movement (observable by others, not merely subjective feelings of restlessness or being slowed down).
5) Fatigue or loss of energy nearly every day.
6) Feelings of worthlessness or excessive or inappropriate guilt nearly every day.
7) Diminished ability to think or concentrate, or indecisiveness, nearly every day.
8) Recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide.
Symptomology: ICD-10
- Emotional symptoms (Q): • Apathy, pessimism, negativity • Low self esteem, feeling guilty • Loss of motivation • Indecisiveness - Biological symptoms (Q): • Reduced activity • Loss of libido • Sleep disturbance • Loss of appetite
Co-morbidity
General medical conditions in which you often find depression: - Terminal illness - Chronic illness (e.g. chronic pain) - Thyroid dysfunction - Neurological disease - Stroke - Drug abuse - Parkinson’s disease - anxiety
Monamine Theory
Evidence For:
- Overall reduced activity of central noradrenergic and/ or serotonergic systems
- Reserpine depletes brain of NA and 5-HT induces depression
- Main antidepressant drugs increase [amines] in brain (Q devise drugs to treat depression)
Evidence Against:
- Difficult to show deficits in brain [NA] & [5-HT] and functioning/ (-) results from CSF, plasma in depressed /individuals respond better to one AD than another
- Most antidepressant drugs take several weeks for therapeutic effect but in amines acute (secondary adaptive changes more important)
- Some antidepressants weak / no effect on amine uptake (e.g trazodone)/no increase in 5HT and NA but antidepressants!
- Cocaine blocks amine uptake but has no. antidepressant effect
- Decrease in 5HT in dipolar linked to aggression rather than depression
- Due to imbalances between NT (Monoamines, DA, Ach, CRF, CORT ect) producing long term alterations in gene expression, growth factors and NT (upregulation 5HT, NA receptors, HPA hyperfunction and some neuronal loss)
Neuroendocrine Theory
- NAergic & 5-HT neurons input to
hypothalamus - Hypothalamus releases corticotropin-releasing hormone (CRH)
- CRH acts on pituitary – release of adrenocorticotrophic hormone (ACTH)
- Cortisol release from adrenal cortex in response to increased ACTH in blood
Neuroendocrine
- CRH - behavioural effects mimic some depression symptoms
- Evidence of hyperactivity of HPA in depressed patients
• increased [cortisol]plama in depressed patients
• increased [CRH] in the cerebrospinal fluid - There is clear evidence that genes and environment can contribute to this hyperactivity and as such could offer an explanation for how genes x environment interaction can predispose people to mental health conditions (diathesis)
- decreased hippocampal feedback in depression
- decreased glucocorticoid receptors (cortisol receptors) in hippocampus
- Glucocorticoid receptor gene expression regulated by early experience
- Tactile stimulation just after birth activates 5-HT pathways to hippocampus
- 5-HT triggers long-lasting in expression of glucocorticoid receptor gene
- increased in glucocorticoid receptors in hippocampus
•SSRIs increased glucocorticoid receptors in the hippocampus
Neuroplasticity and Neurogenesis
- Evidence of neuronal loss and neuronal activity in
hippocampus and prefrontal cortex (decision making centres) - Antidepressants and electroconvulsive therapy (ECT) promote neurogenesis in these regions
- 5-HT promotes neurogenesis during development (BDNF)
- Increase in Glutamate in Cx of depressed people (NMDA antagonists potential for depression treatment e.g. ketamine)
Psychological treatment
- Cognitive Behavioural Therapy: based on helping depressed individuals to recognise and change their negative cognitive processes and thus improve their mood and their counterproductive behaviours
- Interpersonal Therapy: assumes that depression is multi-factorial but that interpersonal difficulties play a central role in maintaining depressive symptoms
Pharmacological treatment
- Tricyclic antidepressants
• Monoamine oxidase inhibitors
• Selective serotonin reuptake inhibitors - NICE recommends SSRIs for the pharmacological treatment of depression
- Selectively inhibit the reuptake of serotonin in the synapse
- Because they are more selective in the molecules to which they bind, they do not bind to receptors on other classes of neurons (fewer side effects)
Long term neurochemical effects of AD
- Monoamine Oxidase Inhibitors (MAOIs)
- Tricyclic Antidepressant Drugs (TCAs)
- Selective Serotonin Re-uptake Inhibitors (SSRIs)
- Other mixed 5HT/NA reuptake inhibitors (SNRIs)
- NA reuptake inhibitors
- Monoamine receptor antagonists (alpha2, 5HT2c, 5HT3)
- Downregulation alpha2, 5HT1A, beta1, beta2, 5HT2A, 5HT3
MAOIs
- Inhibition of MAO A correlates with AD activity
- MAO-A 5-HT > NA (Q. what about MAOB?)
- MAOIs rapidly increased [5-HT] > [NA] > [DA]
- Increase NA=>Increased euphoria=>Increased motor activity
- Early drugs e.g. phenelzine & isocarboxazid,
irreversible and nonselective (Q. Why problem?) - Downregulation a2, 5HT1A, b1, b2, 5HT2A, 5HT3
MAO-1
- Associated with food and drug interactions
• Tyramine (in cheese and wine) acts as indirect sympathomimetic and increased NA release
• Excess NA destroyed by MAO – if blocked NA will accumulate
• NA accumulation (Incre headache, intracranial haemorrhage => elevation in BP => severe hypertension)
• MAOIs not specific – reduce metabolism of opioid analgesics and alcohol - Reversible MAOIs (RIMA) e.g. moclobemide
• Accumulation of NA displaces the RIMA allowing
degradation of excess NA
• RIMAs safer and selective RIMAs (e.g moclobemide)
better tolerated (no major side effects)
