Mental Disorders (page 426-430)
Fall 2002

Depression

Symptoms include:

unpleasant mood
loss of interests
trouble sleeping
decrease in energy
suicidal thoughts
decrease in sex drive
difficulty concentrating
decrease in appetite
Treatments for depression include:

A. Antidepressant drugs: 3 types:

1) Monoamine Oxidase Inhibitors (MAOI) Monoamines are drugs such as NE, DA, 5-HT.
Monoamine oxidase is an enzyme that degrades monoamines.
Thus, MAOIs block the enzymes that inactivate monoamines.

The net effect is an increase in monoamines.


2) Tricyclics (e.g., imipramine)

Block reuptake of monoamines.

The net effect is more transmitter in the synaptic cleft.


3) Selective Serotonin Reuptake Inhibitors (e.g., Prozac (fluoxetine), Paxil, Zolof)

SSRIs block 5-HT reuptake.

The net effect is an increase in 5HT in the synapse.
 

 These therapies indicate that depression is caused by low levels of monoamines, in particular serotonin & norepinephrine. This hypothesis is too simple, however, as indicated by the following three problems: 1) It takes 2-3 weeks before drugs lift depression, despite altering monoamines immediately.
2) Antidepressants are only effective in 70% of depressed people.
3) Administration of amphetamines cause an increase in monoamines, but do not alleviate depression


B. Electroconvulsive Therapy (ECT)
Passing an electric current across the brain to induce a seizure (6-8 treatments in 2 weeks) alleviates depression in 80-90% of patients. Relief is temporary so ECT is usually followed by antidepressant drugs.

ECT is not as bad as it used to be or as it is portrayed in movies. ECT today uses:   1) lower currents
2) muscle relaxants & anesthetics
3) patient permission   The main side effect is a 1-6 month amnesia and confusion. C. Other treatments for depression: Sleep deprivation
Bright light therapy
Psychotherapy


Bipolar Disorder
Characterized by exaggerated mood swings. Patient cycles between depression and mania (hyperactive, elevated mood). Typical antidepressant drugs are ineffective and can even exacerbate mania by increasing monoamines.

Treatments include:

1) Lithium
There are two primary hypotheses about how lithium levels mood:
a) alters intracellular Ca++ levels
b) decreases release of throid hormones (high levels of thyroid hormones cause an increase in NE activity)
2) Antiseizure drugs (e.g., Depakote (Valproic acid), Gabapentin) These drugs enhance GABA inhibition.


Schizophrenia
Greek for split brain. The split is between emotions and intellect (this is not the same as multiple personality disorder).

Symptoms include:

Hallucinations (typically auditory)
Delusions that may include paranoia
Movement disorders (stereotyped movements or catatonia)
Inappropriate emotions
Disordered thoughts (includes things like word salad)

Symptoms can divided into two types:

Positive symptoms: presence of abnormal behavior (e.g., thought disorders, hallucinations, delusions)
Negative symptoms: absence of normal behavior (flat emotions, social withdrawal, lack of initiative) The Dopamine Hypothesis for Schizophrenia:

The DA hypothesis states that schizophrenia is caused by excess DA in the brain.

Evidence for the DA hypothesis includes:

1. Antipsychotic drugs (e.g. Haloperidol, Clozapine) block DA receptors. In fact, there is a very good correlation between the affinity with which antipsychotic drugs bind to DA receptors and the dose needed to effectively treat schizophrenia (Figure 15.17).
2. Drugs that increase DA levels cause symptoms similar to schizophrenia (e.g., cocaine, amphetamine) Evidence against the DA hypothesis: 1. It takes 2-3 weeks for drugs to alleviate symptoms despite blocking DA immediately.
2. Mixed DA/5-HT antagonists are better at blocking the symptoms of schizophrenia (e.g., Risperidal)


Traditional antipsychotic drugs (DA antagonists) have both short- and long-term side effects

Short term effect: Reduce movement
Long term effect: Tardive Dyskinesia (uncontrolled movements). DA blockers treat schizophrenia and produce motor effects by acting on two different pathways: 1) The nigrostriatal pathway runs from the substantia nigra to the striatum (i.e., caudate nucleus). This pathway mediates the motor effects and uses D2 receptors.

2) The mesolimbic pathway runs from the midbrain to the frontal cortex. This system uses D4 receptors and seems to be involved in schizophrenia.

 Because these two systems use different types of DA receptors, drugs that block D4, but not D2 receptors should be able to treat schizophrenia without producing motor effects. A new class of atypical antipsychotic drugs are selective for D4 receptors. For example, clozapine blocks DA in the mesolimbic pathway without blocking the nigrostriatal pathway. Thus, there are no motor side effects.
 

Frontal Lobotomy was a commonly used treatment for schizophrenia (see Box 16.3 on page 450). This treatment is not used today for several reasons:

1. Treatment did not cure patients.
2. There were many side effects (difficulty planning, engaging in inappropriate behavior).
3. The effects of psychosurgery are permanent.
4. Antipsychotic drugs introduced in the 1950s are much more effective.   Return to Psych 372 Syllabus