Psychopathology

Major depression

• sadness and helplessness most of the day every day for weeks at a time.

  • Less response to reward, attention problems, motivation and memory.

  • Tiredness and sleep problems; enter REM sooner and awaken early (phase-advanced circadian rhythms).

  • Usually episodes of depression and normal moods.

  • Physical over or underactivity

  • Most common in women under 25.

SAD

depression that recurs during particular season like winter, patients have phase-delayed rhythms.

• One treatment is very bright lights for few hours each morning.

Genetics and depression

• Heritability for depression.

• Early-onset depression has a high probobility of other relatives with psychiatric problems.

• Late-onset depression has a high probability of relatives with circulatory problems.

• Depression could be adaptation to conserve energy after defeat.

Biological effects of depression

• Reduced BDNF production

• Hippocampus + prefrontal cortex reduced activity

• Glial cells atrophy.

Stress pathway

• Stress affects the amygdala

• Amygdala effects the hypothalamus activating the anterior pituitary to release conticotropic releasing factor (CRF) and adrenocroticotropic hormone (ACTH)

• The adrenal cortex receives these hormoones and sends out cortisol.

• Cortisol has a positive feedback effect on the prefrontal cortex. body, amygdala and hippocampus.

• After stress has passed, cortisol receptors on hypothalamus and anterior pituitary shut down stress.

Too much stress

A bit of stress leads to synaptic enhancement, too much leads to synaptic suppression, and far too much leads to excitotoxicity (cells overactive, they will die or atriphute).

Proinflammatory cytokines

• When there is inflammation the body releases proinflammatory cytokines (could lead to chronic inflammation).

  • Cytoines may interact with every pathway relevant to depression; neurotransmitter metabolism, neuroendocrine function and neural plasticity.

Antidepressent drugs

Includes tricyclics, selective seratonin reuptake inhibitors, monoamine oxidase inhibitors, and atypical antidepressants.

First gen antidepressants

Monoamine oxidase inhibitors and tricyclics

Monoamine oxidase inhibitors

• block monoamine oxidase (MAO) which breaks down catecholamines and seratonin into inactive forms.

  • Iproniazid (Rivivol), Phrenelizine (Nardil), Selegilime (Emsam).

Tricyclics

• antidepressant drugs that block the reuptake of catecholamines, acetylcholine and seratonin by blocking presynaptic terminals.

  • May also block histamine and certain sodium, leading to dry mouth and difficulty urinating.

  • History: Methylene blue developed from coal tar, derivitave of this process being imipramine.

  • Imipramine (Trofranil), amitriptyline (elavil)

Second gen antidepressants

Selective seratonin reuptake inhibitors (SSRIs), Seratonin norepinephrine reuptake inhibitors (SNRI’s), Norepinephrine and dopamine reuptake inhibitors (NDRI), Norepinephrine reuptake inhibitors (NRI), Atypical antidepressants.

Selective seratonin reuptake inhibitors (SSRIs)

attach to the center of the seratonin transporter protein and lock it into shape to block seratonin from binding to it.

Seratonin norepinephrine reuptake inhibitors (SNRIs)

block reuptake of seratonin and norepinephrine.

Atypical antidepressant

mischellaneous category, one example being bupropion which inhibits the reuptake of dopamine and maybe norepinephrine.

Monoamine hypothesis

depression is low levels of monoamines (dopamine, seratonin etc.) at the synapse.

Issues with monoamine hypothesis

• Depressed people do not have lower levels of seratonin at the synapse

• Seratonin activates autoreceptors that reduces any artificial increases in seratonin at the synapse

• Clinical response takes weeks not minutes or hours.

How antidepressents act

Increasing seratonin and other tranmitters, or faciliating neurotrophins.

• Depression is assocaited with decreased levels of the neurotrophin called brain-derived neurotrophic factor (BDNF), important for synaptic plasticity and learning.

• Depression is associated with impaired learning.

• Standard antidepressants facilitate release of BDNF, but have to accumulate for weeks to reach a high enough brain concentration.

Antidepressent effectivity

• Plotting of studies to examine the effect of placebos versus actual drugs.

• Overall, there is an improvement but it is not much larger than the improvement with placebo.; the improvement is not clinically significant UNLESS the depression is very severe which the placebo becomes less effective but the drug stays the same amount of effectiveness.

Psychadellics + depression

Psychadellics being used for depression showed that LSD, MDMA or psilocybin helps relieve depression, anxiety, PTSD and substance abuse.

• Also enhanced neural plasticity.

• Ketamine decreases depression rapidly, facilitates the BDNF receptor and increases synaptic plasticity, blocks NMDA-type receptors

  • High risk of hallucinations and delusions, also activates AMPA-type glutamate receptors.

Drug side effects

• Tricyclics - suicidality

• Sexual dysfunction - contrastingly, wellbutrin (NDRI) increases libido.

Medication alternatives

CBT, Psychotherapy, Electroconvulsive therapy (ECT), Deep brain stimulation, excersize, sleep.

Bipolar disorder

a condition alternating between depression and mania.

• Full fledged manic episodes are bipolar 1 disorder and mild hypomaniac episodes are bipolar 2 disorder.

Treatment for BPD

• Lithium salts

  • Stabalizes mood, preventing a relapse into mania or depression

  • Reduced hyperactivity of mitochondria.

• Anticonvulsant drugs

• Consistant adequate sleep to stabalize mood.