Depression & Anxiety

Reactive and Pathological Depression

Reactive depression state of sadness in response to situations like loss

of a loved one.

• Does not constitute mental illness, unless symptoms are disproportionate to the event or significantly prolonged.

Pathological depression resembles an emotional state we have all

experienced but differs significantly in intensity and duration.

Diagnosis of Depression

At least 5 of the following symptoms are present during the same 2-week period (and at least

1 of the symptoms must be depressed mood or anhedonia):

Depressed mood

Anhedonia: diminished interest or loss of pleasure in almost all activities

Significant weight change or appetite disturbance

Sleep disturbance (insomnia or hypersomnia)

Psychomotor agitation or slowness

Fatigue or loss of energy

Feeling of worthlessness

Diminished ability to think or concentrate; indecisiveness

Recurrent thoughts of death, suicide

Comorbidity of Anxiety & Depression

The anxiety disorder, particularly generalized or social anxiety,

usually precedes depression.

There is an extensive overlap of depression with anxiety and alcohol

dependence.

Comorbidity is estimated at almost 60 percent.

Imaging of Depression

PET scans of blood flow in brains of depressed patients show increased activity in the orbitofrontal cortex and amygdala. Imaging studies are not used to diagnose depression! They are only used for research purposes.

The Monoamine (dopamine, norepinephrine, serotonin) Hypothesis

Reserpine (drug prescribed for high blood pressure) reduces monoamine levels and causes

depression

monoamines (Down) → depression

Many antidepressants increase levels of monoamines

monoamines (Up) → antidepressant effect

Supplements that increase monoamine levels

“Stress hypothesis” of depression

45% of adults with depression lasting more than 2 years experienced abuse,

neglect, or parental loss as children

Chronic stress can lead to overproduction of cortisol (=stress hormone), associated with depression

in adulthood

Hippocampus and Stress Response

Hippocampus is involved in turning off the stress response: it signals to hypothalamus to turn off production of stress hormones (submissive monkey and dominant monkey). Research studies showed that hippocampus was shrunk in depression.

Therapies for Depression (approved by the FDA)

Pharmacological Treatments: Antidepressants

• Monoamine oxidase inhibitors (MAOIs)

• Tricyclic antidepressants

• Second-generation antidepressants, which include SSRIs.

• 2019: Ketamine – blocks NMDA receptors

Electroconvulsive Therapy (ECT)

• Using electrical current to produce seizures as a treatment for severe depression. Problems: ECT leads to memory loss

Transcranial Magnetic Stimulation (TMS)

• Approved by the FDA in 2018

• Fewer side effects than ECT because the magnetic stimulation can be applied narrowly, to a focal area, rather than diffusely, as in ECT

Cognitive-behavioral therapy

• Problem-focused, action-oriented, structured treatment for eliminating dysfunctional thoughts and maladaptive behavior

Therapies for Depression (not approved by FDA)

Deep Brain Stimulation (DBS)

• Not yet approved by the FDA

• Neurosurgery in which an electrodes implanted in the brain stimulate a targeted area with a low-voltage electrical current to facilitate behavior

Hallucinogen psilocybin is in clinical trials for resistant depression. Trial was scheduled to be completed in 2021.

Light therapy

• For Seasonal Affective Disorder

Sleep deprivation

MAOIs

MAO inhibitors. The normal function of MAO is to metabolize monoamine neuro-transmitters in presynaptic terminals that are not contained in vesicles. Inhibition of MAO increases the amount of neurotransmitter available for release.

Tricylic antidepressants (TCA)

Bind to the presynaptic monoamine transporters and inhibit reuptake of neurotransmitters → longer duration of transmitter action at the synapse.

Mostly block reuptake of serotonin and norepinephrine, much less dopamine