Depressive Disorders Flashcards
Anhedonia
Loss of the capacity to experience pleasure
Clinical depression(also known as major depressive disorder)
When people for 2 weeks or longer experience deep depression often with no apparent reason.
Depression is often divided into two categories
- Reactive depression –> depression triggered by an obvious negative experience
- Endogenous depression –> depression with no apparent cause
Comorbid
The tendency for two health conditions to occur together in the same individual
There are two subtypes of major depressive disorder whose cause is more apparent because of the timing of the episodes.
- Seasonal affective disorder (SAD) –> in which episodes of depression and lethargy typically recur during particular seasons—usually during the winter months.
- Peripartum depression –> the intense, sustained depression experienced by some women during pregnancy, after they give birth, or both. Although estimates vary, the disorder seems to be associated with about 19 percent of pregnancies.
Two lines of evidence suggest that the episodes of SAD are triggered by the reduction in sunlight.
- Incidence of the disorder is higher in Alaska (9 percent) than in Florida (1 percent) where the winter days are longer and brighter.
- Light therapy (e.g., exposure to 15-30 minutes of very bright light each morning) is often effective in reducing the symptoms of SAD.
Five major classes of drugs have been used for the treatment of depressive disorders
- Monoamine oxidase inhibitors,
- Tricyclic antidepressants,
- Selective monoamine-reuptake inhibitors,
- Atypical antidepressants,
- NMDA-receptor antagonists.
Iproniazid
Iproniazid is a monoamine agonist; it increases the levels of monoamines (e.g., norepinephrine and serotonin) by inhibiting the activity of monoamine oxidase (MAO).
MAO inhibitors dangerous side effect (cheese effect)
Foods such as cheese, wine, and pickles contain an amine called tyramine, which is a potent elevator of blood pressure. Normally, these foods have little effect on blood pressure because tyramine is rapidly metabolized in the liver by MAO. However, people who take MAO inhibitors and consume tyramine-rich foods run the risk of stroke caused by surges in blood pressure.
Monoamine oxidase
The enzyme that breaks down monoamine neurotransmitters in the cytoplasm (cellular fluid) of the neuron.
Tricyclic antidepressants
So named because of their antidepressant action and because their chemical structures include three rings of atoms. Tricyclic antidepressants block the reuptake of both serotonin and norepinephrine, thus increasing their levels in the brain. They are a safer alternative to MAO inhibitors.
Imipramine
The first tricyclic antidepressant, was initially thought to be an antipsychotic drug. However, when its effects on a mixed sample of psychiatric patients were assessed, it had no effect against schizophrenia but seemed to help some depressed patients.
Selective serotonin-reuptake inhibitors (SSRIs)
- Are serotonin agonists that exert their agonistic effects by blocking the reuptake of serotonin from synapses.
- The success of the SSRIs spawned the introduction of a similar class of drugs, the selective norepinephrine-reuptake inhibitors (SNRIs). Have proven to be just as effective as the SSRIs in the treatment of depression.
Fluoxetine (marketed as Prozac)
Was the first SSRI to be developed.
Atypical antidepressants
- A new class of antidepressant medications emerged that is really just a catchall class comprising drugs that have many different modes of action.
Bupropion
Atypical antidepressant: Several effects on neurotransmission: It is a blocker of dopamine and norepinephrine reuptake, and it is also a blocker of nicotinic acetylcholine receptors.
Dissociative hallucinogen ketamine
- Antagonizing the glutamate NMDA receptor on depressive disorders
- Even single low dose of ketamine rapidly reduces depression, even in patients who had been experiencing a severe episode
- However, because ketamine has undesirable side effects, researchers are now in the process of trying to identify more selective NMDA-receptor antagonists with fewer side effects.
How effective are antidepressants?
- About 50% of clinically depressed patients improved. This rate seems quite good; however, control groups showed a 25 percent rate of improvement, so only 25 percent of depressed individuals were actually helped by the antidepressants.
- Antidepressants were not significantly better than placebo in treating patients with mild or moderate depression. Only the severely depressed seemed to benefit.
What is observed in structural MRI studies of the brains of depressed patients?
- Consistent reductions in gray matter volumes in the prefrontal cortex, hippocampus, amygdala, and cingulate cortex.
- Atypical activity in frontal, cingulate, and insular cortices as well as in the amygdala, thalamus, and striatum.
- Communication amongst these structures has been found to be atypical during a variety of cognitive states.
Monoamine theory
Depression is associated with underactivity at serotonergic and noradrenergic synapses.
Up-regulation
When an insufficient amount of a neurotransmitter is released at a synapse, there is usually a compensatory increase in the number of receptors for that neurotransmitter.
Two recent lines of evidence have challenged the monoamine theory of depression.
- Monoamine agonists not effective in the treatment of most depressed patients. When effective, only slightly better than placebo.
- Other neurotransmitters (e.g., GABA, glutamate, acetylcholine) play a role in the development of depression.
Neuroplasticity theory
Depression results from a decrease of neuroplastic processes in various brain structures (e.g., the hippocampus), which leads to neuron loss and other neural pathology.
Support for the neuroplasticity theory of depression comes from two kinds of research
- Research showing that stress and depression are associated with the disruption of various neuroplastic processes (e.g., a reduction in the synthesis of neurotrophins, a decrease in adult hippocampal neurogenesis).
- Research showing that antidepressant treatments are associated with an enhancement of neuroplastic processes (e.g., an increase in the synthesis of neurotrophins, an increase in synaptogenesis, and an increase in adult hippocampal neurogenesis)
Biomarker
A biological state that is predictive of a particular disorder
Brain-derived neurotropic factor (BDNF)
- Interest to researchers because treatments that improve depression (both pharmacological and non-pharmacological) have been found to increase BDNF levels in those patients who show improvement.
- Decreased blood levels of BDNF might be a biomarker for depression, increased blood levels of BDNF might be a biomarker for the successful treatment of depression
- Hypothesized that antidepressants increase BDNF levels, which in turn increase certain neuroplastic processes (e.g., increase adult hippocampal neurogenesis) that lead to the alleviation of depression.
Where is the monoamine theory based on?
- Based on the fact that monoamine oxidase inhibitors, tricyclic anti depressants, selective serotonin-reuptake inhibitors, and selective norepinephrine-reuptake inhibitors are all agonists of serotonin, norepinephrine, or both.
- Autopsy studies. Norepinephrine and serotonin receptors have been found to be more numerous in the brains of deceased depressed individuals who had not received pharmacological treatment.
- -> up-regulation
Repetitive transcranial magnetic stimulation (rTMS)
- Involves the noninvasive delivery of repetitive magnetic pulses at either high frequencies (e.g., five pulses per second) or low frequencies (e.g., less than one pulse per second) to specific cortical areas—usually the prefrontal cortex.
- High frequency rTMS and low frequency rTMS are believed to stimulate and inhibit, respectively, activity within those brain regions to which they are applied.
- Meta-analyses have shown reliable improvement of depressive symptoms after either low frequency or high-frequency rTMS when compared with sham rTMS.
Deep brain stimulation
Chronic brain stimulation through an implanted electrode –>
Lozano and colleagues (2008) implanted the tip of a stimulation electrode into an area of the white matter of the anterior cingulate gyrus in the medial prefrontal cortex. Electrode delivered continual pulses of electrical stimulation that could not be detected by the patients. The results were strikingly positive.
Remarkable popularity of fluoxetine and other SSRIs is attributable to two things:
- Have fewer side effects than tricyclics and MAO inhibitors
- Act against a wide range of psychological disorders in addition to depression.
