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Chapter 15
The Biological Basis of Affective Disorders and
Schizophrenia
Affective Disorders
An affective disorder is a
mental disorder, characterized
by one or both of two mood
states: depression and/or mania.
 Depression - An affective disorder characterized
by an intense, continuing feeling of sadness and
worthlessness.
 Mania – an elevated, expansive, or irritable mood
and inflated self-esteem or grandiosity.
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Affective Disorders:
Depressive Disorders
Depressive disorder - A type of affective disorder in
which depression is the only mood state.
 Depression - An affective disorder characterized by an
intense, continuing feeling of sadness and
worthlessness.
 Major depression - A type of depressive disorder
characterized by a depressed mood of at least two
weeks in duration.
 Dysthymia - Chronic form of depression; usually lowlevel
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Depressive
Disorders:
Ten
Characteristics
Affective Disorders:
Bipolar Disorders
Bipolar disorders - A type of affective disorder
characterized by episodes of mania and
depression that typically continue throughout a
person’s lifetime.
 Cyclothymia - One of the bipolar disorders
characterized by less intense episodes of mania
and depression than are seen in the bipolar
disorder.
 Hypomania - A milder form of mania in which
occupational or social functioning is not
impaired.

Symptoms of
Mania
Affective Disorders:
Neural Changes

Structural abnormalities in the brain
 Reduction of gray matter of orbital frontal cortex
 Prefrontal cortex has significant gray matter reduction in
bipolar individuals
 Reductions of volume of brain tissue in amygdala,
hippocampus, entorhinal cortex, basal ganglia, and
thalamic nuclei.
 Volume of gray matter
ventral to beginning of
the corpus callosum
with familial affective
disorders.
Affective Disorders:
Metabolic Activity in the Brain
PET scans reveal lower-than-normal activity
during depressive episodes and higher-thannormal activity during manic episodes.
 In depression, the reduction is especially
apparent in the left frontal cortex.
 Decreased blood flow and metabolism have also
been found in the cingulate gyrus and the basal
ganglia of depressed individuals.

Models of Depression:
The Role of Neurotransmitters
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Monoamine hypothesis of depression - the idea that
depression is caused by decreased activity in the
monoamine neurotransmitter synapses
Norepinephrine and serotonin, but not dopamine
A serotonin metabolite (5-HIAA) is lower in people with
major depression.
Low levels of CSF 5-HIAA are associated with suicide.
A norepinephrine metabolite (MHPG) is lower in people
with major depression.
As NE metabolites increase, subjects with bipolar
disorder become manic.
Role of Norepinephrine and the
Locus Coeruleus
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A major site of NE synthesis, located in pons and
connected to the hypothalamus, hippocampus, and
cerebral cortex.
Stimulation of the locus coeruleus produces arousal,
hypervigilance, and suppression of exploratory activity in
primates.
Antidepressant drugs
decrease the firing rate
in the locus coeruleus
and reduce the levels of
MHPG, a NE metabolite,
in the CNS.
The Role of GABA and
Acetylcholine
Depressed patients may have hyperresponsive
cholinergic systems. ACh stimulates the locus
coeruleus increasing brain activity.
 Many depressed people have low levels of GABA
and administration of GABA agonists have
antidepressant effects.
• GABA inhibits the firing of noradrenergic neurons
in the locus coeruleus and a decrease in GABA
levels would increase activity in the locus
coeruleus, possibly leading to depression.

Affective Disorders:
Drug Treatments
Tricyclic compounds - drugs that increase NE
and serotonin levels by interfering with their
reuptake after the neuron fires.
 Monoamine oxidase inhibitors (MAOIs) increase NE and serotonin by preventing their
breakdown.
 Serotonin-specific reuptake inhibitor (SSRI) e.g., Prozac, decreases serotonin reuptake.

Drug Treatments: Synaptic Effects
Affective Disorders:
Vagus Nerve Stimulation
Similar to a pacemaker
 Drug resistant epilepsy
and depression
 Sends signals to brain
through afferent fibers
 Targets the locus
coeruleus
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Affective Disorders:
ECT Treatment
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Used for drug-resistant depression
May work by inhibiting locus coeruleus activity
Disadvantages: relapse rate, memory deficits
A new promising alternative treatment is repetitive
transcranial magnetic stimulation (rTMS)
Clinical trials - TMS Therapy is showing promise for a
number of conditions including Parkinson’s disease,
schizophrenia, epilepsy, chronic pain, traumatic brain injury,
stroke, post traumatic stress disorder, migraine headaches,
chronic pain, tinnitus, autism, and Alzheimer’s disease
Tribal variations
Affective Disorders:
The Role of Genetics

Concordance rate - The rate at which any characteristic
occurs in both members of a pair of relatives

Bipolar disorder
 Concordance rates for identical twins ranges from 20%
to 75%, fraternal twins from 0% to 8%

Major depression
 Concordance rates for identical twins is about 50%
 Concordance rates for fraternal twins is about 20%

Genetic connection may be as much as five times higher
for bipolar disorder than for major depression.
Affective Disorders:
The Role of Environment
Learned helplessness - A pattern of depressionlike behavior produced by repeated exposure to
an inescapable noxious event.
 Associated with a heightened locus coeruleus
activity, manifested as the behavioral changes
associated with depression.
 Also associated with anxiety, phobias, shyness and
loneliness which can all be exacerbated by
learned helplessness
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Seasonal Affective Disorder
Sleep and Depression
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Sleep disorders such as insomnia and hypersomnia are
reported by people suffering from depression.
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REM sleep occurs earlier than normal and total sleep time
is shortened.
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Advancing the sleep-wake cycle may help alleviate
symptoms of depression.
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Testing whether Aricept can change sleep patterns. Aricept
boosts the amount of the brain chemical acetylcholine,
which triggers REM sleep and improves memory.
Stages of the Full Sleep Cycle
Biochemical Markers
for Depression
Any hormone, enzyme, antibody, or other substance that
is detected in the urine, blood, or other body fluids or
tissues that may serve as a sign of a disease or other
abnormality
 Depressed people often have hypercortisolism.
 Hypocholesterolemia - total cholesterol levels are below
120 mg/dL
 High incidence of folate deficiency in depression
 Low levels of B12 are associated with depression
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