Neurobiology in Psychiatry

Neurobiology & Neurotransmitters

• The brain consists of a grouping of neurochemical systems.
• It permits the functional and anatomical systems to run.

• Any anatomic subsystem within the brain usually runs on multiple

classes of neurotransmitters.
The Dopamine System
• Dopamine, a catecholamine neurotransmitter, is the first product
synthesized from tyrosine through the enzymatic activity of tyrosin
hydroxylase.

• There are three subsystems within the brain that use dopamine as
their primary neurotransmitter. These all arise in the ventral
tegmental area.
• One group, arising in the substantia nigra, projects to the caudate and
putamen and is referred to as the nigrostriatal pathway.Its
terminations appear to be rich in both D1 and D2 receptors.
• A second tract  mesocortical or mesolimbic (or mesocorticolimbic),
arises in the ventral tegmental area and projects to the prefrontal
cortex and temporolimbic regions such as the amygdala and
hippocampus. The concentration of D2 receptorsin these regions is
minimal, whereas D1 receptors predominate.
• The third component of the dopamine system originates in the
arcuate nucleus of the hypothalamus and projects to the pituitary.
• Schizophrenia was explained by the dopamine hypothesis,
• symptoms of this illness due to a functional excess of dopamine.
• Because the efficacy of many of the antipsychotic drugs used to treat psychosis is
highly correlated with their ability to block D2 receptors, the dopamine hypothesis
also suggested that the abnormality in this illness might specifically lie with D2
receptors. There is a modest but much weaker correlation with their ability to block
D1 receptors.
• there appears to be a rather sparse density of D2 receptors in critical brain
regions that mediate cognition and emotion, such as the prefrontal cortex,
amygdala, and hippocampus.
• These regions are, however, high in D1 and serotonin type 2 receptors (5-
HT2). prominent effects on serotonin and D1 by the new second-
generation antipsychotics, suggest that the traditional dopamine
hypothesis needs revision.
• extrapyramidal side effects 
• consequence of blocking D2 receptors in the nigrostriatal pathway.
• Drugs that have a weak D2 effect (of which clozapine and quetiapine are
examples) thus are more likely to havefewer extrapyramidal (“parkinsonian”)
side effects.
• Psychoactive drugs (e.g., amphetamines, cocaine) ↑ Dopamine in
the brain reward system which might lead to pleasure,
adventuresome and exploratory behaviors.
The Norepinephrine System
• arises in the locus coeruleus and sends projections throughout the
entire brain.

• NE appears to exert effects on almost every brain region in the human

brain, including the entire cortex, the hypothalamus, the cerebellum,
and the brainstem.

• NE may play a major role in mediating symptoms of major mental

illnesses, especially mood disorders.
 The Norepinephrine System
• catecholamine hypothesis of mood disorders is an oversimplification
• depression  functional deficit of NE at nerve endings
• mania  functional excess of NE at nerve endings

• TCA inhibit NE reuptake  ↑ NE to stimulate postsynaptic receptors.

• MAOI’s ↑ NE transmission by inhibiting it’s breakdown.
• many antidepressants have mixed noradrenergic and serotonergic
activities or purely serotonergic effects (e.g. SSRIs).
 • distribution similar to that of norepinephrine
neurons.
• Serotonergic neurons arise in the raphe nuclei,
• They project to a wide range of CNS regions,
The Serotonin including the entire neocortex, the basal
System ganglia, temporolimbic regions, the
hypothalamus, the cerebellum, and the
brainstem.
• As NE system, the serotonin system appears to
be a general modulator.
 • serotonin hypothesis of depression has been
proposed, largely because many antidepressant
The Serotonin medications (e.g., fluoxetine) facilitate
serotonergic transmission by blocking reuptake.
System • These medications are also used in the
treatment of anxiety disorders.
 • A high serotonergic tone has been shown to be
associated with impulsive, violent, or suicidal
behavior.
The Serotonin • Serotonin is probably also involved in
System schizophrenia and other psychotic disorders,
because clozapine and the newer second-
generation antipsychotics (e.g., olanzapine)
have significant effects on the serotonin system.
The Cholinergic System
• Like dopamine, acetylcholine has a relatively more specific localization in
the human brain The cell bodies of
• a major group of acetylcholine neurons are located in the nucleus basalis of
• Meynert, which lies in the ventral and medial regions of the globus
pallidus.
• Neurons from the nucleus basalis of Meynert project throughout the
cortex.
• The second group of acetylcholine projections originating in the diagonal
band of Broca and the septal nucleus project to the hippocampus and
cingulate gyrus. A third group of cholinergic neurons are local circuit
neurons that enter main structures within the basal ganglia.
The Cholinergic System
• The acetylcholine system plays a major role in the encoding of memory.
• Patients with Alzheimer’s disease show losses of acetylcholine projections
both to the cortex and to the hippocampus, and blockade of muscarinic
receptors produces memory impairment.
• Dopamine and acetylcholine share heavy concentrations of activity within
the basal ganglia, and the drugs used to block the extrapyramidal side
effects of antipsychotics are cholinergic agonists; this suggests a possible
reciprocal relationship between dopamine and acetylcholine in the
modulation of motor activity and possibly of psychosis as well.
• Cholinergic agonists also may impair cognitive functions such as learning
and memory in individuals for whom they are prescribed.
The GABA System
• (GABA) is an amino acid neurotransmitter, as is glutamate. These two
major amino acid neurotransmitters serve complementary functions,
with GABA playing an inhibitory role and glutamate playing an
excitatory role.
The GABA System
• GABAergic neurons are a mix of local circuit and long-tract systems
Within the cerebral cortex and the limbic system, GABAergic neurons
are predominately local circuit.
• The cell bodies of GABAergic neurons in the caudate and putamen
project to the globus pallidus and substantia nigra, making them
relatively long tract, and long-tract GABA neuron also occur in the
cerebellum.
• Many of the anxiolytic drugs (e.g., diazepam) act as GABA agonists,
thereby increasing the inhibitory tone within the CNS.
• Loss of the long-tract GABA neurons connecting the caudate to the
globus pallidus releases the later structure from inhibitory control,
thereby permitting the globus pallidus to “run free” and produce the
choreiform movements that characterize Huntington’s disease.
The Glutamate System
• Glutamate, an excitatory amino acid neurotransmitter, is produced by
pyramidal cells throughout the cerebral cortex and hippocampus.
• Maintaining an adequate balance between excessive and inadequate
levels of glutamate tone is crucial for CNS function.
• At high levels it is neurotoxic (as occurs in stroke).
• On the other hand, a hypoactive glutamate system leads to impaired
cognitive performance.
• Two drugs that block N-methyl-D-aspartate (NMDA) receptors within
the glutamate system, phencyclidine (PCP) and ketamine, produce a
syndrome that closely resembles schizophrenia.
• Both can cause a psychosis characterized by withdrawal, stupor,
disorganized thinking and speech, and hallucinations.
Thank you