W11 - Depression Flashcards
What is Psychiatry?
Psychiatry
– Branch of medicine, diagnosis & treatment of
disorders that affect the mind or psyche
– Disorder of thoughts, moods and fears
considered outside reach of neuroscience
– Now hope that neuroscience will help identify
causes and treatment of mental illness
* Anxiety, depression, schizophrenia
What happens with mental illness?
- Human behaviour
– Product of brain activity - Brain
– Product of genetics and environment
– Experience (trauma / disease)
– Genetic make-up and experience can interact,
making a person more or less susceptible to
future experience
What are some facts about mental illnesses?
- In 2020, of the estimated 971 million people worldwide living with mental or behavioral
disorders, including drug or alcohol dependent, schizophrenia, and depression
(WHO,2020) - 1 in 4 British adults experience at least one diagnosable mental health problem in any
one year (The Office for National Statistics Psychiatric Morbidity report) - One in ten children between the ages of one and 15 has a mental health disorder (The
Office for National Statistics Mental Health in children and young people in Great Britai ) - Depression affect 1 in 5 older people living in the community
- More than 70% of the prison population has two or more mental health disorders (Social
Exclusion Unit quoting Psychiatric Morbidity Among Prisoners In England And Wales)
What is happening with antidepressants?
Millions of prescriptions for SSRIs are written up in the UK each year, but a major study says they’re no better than placebo.
What now for the citizens of Prozac Nation?
-Around 65 million prescriptions of antidepressants given in the UK every year.
What are the types of depression?
- Characteristics of Affective Disorders
– Disorders of mood rather than thought / cognition
– Most common is depression
– Major cause of premature death and disability - 1) Unipolar Depression
– Mood swings in one direction
– Most common depressive illness
– 75% cases REACTIVE (induced by environmental factors)
– 25% cases ENDOGENOUS (genetic) - 2) Bipolar Depression
– Oscillation between depression and mania
– Mania: excessive exuberance, enthusiasm, self confidence, impulsive actions, aggression, irritability, delusions of grandiose
– Type I: More mania episodes with or without depression (1%pop)
– Type II:Hypomania and always episodes of major depression (0.6%)
– Onset usually in adult life
– Strong hereditary tendency (no genes found yet)
What is a major depressive episode? What are some characteristics?
DSM V - Major Depressive Episode
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.
What is the 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
What is 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
What is a major theory of depression?
Monoamine Theory (Schildkraut, 1965)
* 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 increased [amines] in brain (Q devise drugs to treat depression)
What is evidence against the monoamine theory?
- 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 increase 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
What is the 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 increase ACTH in blood - in time this may increase the basal levels of cortisol.
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)
What is the underlying mechanism for children being predisposed to depression? How do genetics interact with the environment?
The HPA axis is regulated by the amygdala and the hippocampus.
Amygdala -> activates HPA = increase cortisol
Hippocampus -> suppress HPA = decreased cortisol
*Decreased’d hippocampal feedback in depression
*Decreased’d 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 increased in
expression of glucocorticoid
receptor gene
*increased in glucocorticoid receptors in hippocampus
*SSRIs increased glucocorticoid receptors in the hippocampus
In rats, pups neglected by mother, has lower levels of glucocorticoid receptors. This means HPA would not be able to activate hippocampus.
What is the neuroplasticity and neurogenesis theory of depression?
- Neuroplasticity & Neurogenesis
– Evidence of neuronal loss and decreased 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). (Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal survival and growth, serves as a neurotransmitter modulator, and participates in neuronal plasticity, which is essential for learning and memory.)
– Increase in Glutamate in Cx of depressed people (NMDA antagonists potential for depression treatment e.g. ketamine)
What is the monoamine theory of depression?
Monoamine main theory of depression but needs to be extended
– 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)
What is brain atrophy in depression?
In fMRIs, there seem to be a loss of neurones in the hippocampus associated in depression.
