Long established as the preeminent source in its field, the eagerly anticipated fifth edition of Dr Stahl's essential textbook of psychopharmacology is here! With its use of icons and figures that form Dr Stahl's unique 'visual language', the book is the single most readable source of information on disease and drug mechanisms for all students and mental health professionals seeking to understand and utilize current therapeutics, and to anticipate the future for novel medications. Every aspect of the book has been updated, with the clarity of explanation that only Dr Stahl can bring.
Modern psychopharmacology is largely the story of chemical neurotransmission. To understand the actions of drugs on the brain, to grasp the impact of diseases upon the central nervous system, and to interpret the behavioral consequences of psychiatric medicines, one must be fluent in the language and principles of chemical neurotransmission. The importance of this fact cannot be overstated for the student of psychopharmacology. This chapter forms the foundation for the entire book, and the roadmap for one’s journey through one of the most exciting topics in science today, namely the neuroscience of how disorders and drugs act upon the central nervous system.
What is neurotransmission? Neurotransmission can be described in many ways: anatomically, chemically, electrically. The anatomical basis of neurotransmission is neurons (Figures 1-1 to 1-3) and the connections between them, called synapses (Figure 1-4), sometimes also called the anatomically addressed nervous system, a complex of “hard-wired” synaptic connections between neurons, not unlike millions of telephone wires within thousands upon thousands of cables. The anatomically addressed brain is thus a complex wiring diagram, ferrying electrical impulses to wherever the “wire” is plugged in (i.e., at a synapse). Synapses can form on many parts of a neuron, not just from the axon of one neuron to the dendrite of another neuron as axodendritic synapses, but also from the axon of one neuron to the soma of another neuron as axosomatic synapses, and even from one neuron’s axon to another neuron’s axon, especially at the beginning and at the end of the receiving neuron’s axons (axoaxonic synapses) (Figure 1-2). Such synapses are said to be “asymmetric” since communication is structurally designed to be in one direction, i.e., anterograde from the axon of the first neuron to the dendrite, soma, or axon of the second neuron (Figures 1-2 and 1-3). This means that there are presynaptic elements that differ from postsynaptic elements (Figure 1-4). Specifically, a neurotransmitter is packaged in the presynaptic nerve terminal like ammunition in a loaded gun, and then fired at the postsynaptic neuron to target its receptors.
Neurons are the cells of chemical communication in the brain. Human brains are comprised of tens of billions of neurons, and each is linked to thousands of other neurons. Thus, the brain has trillions of specialized connections known as synapses. Neurons have many sizes, lengths, and shapes that determine their functions. Localization within the brain also determines function. When neurons malfunction, behavioral symptoms may occur. When drugs alter neuronal function, behavioral symptoms may be relieved, worsened, or produced.
Although this textbook will often portray neurons with a generic structure (such as that shown in Figures 1-1 to 1-3), the truth is that many neurons have unique structures depending upon where in the brain they are located and what their function is. On the one hand, all neurons have a cell body known as the soma, and are set up structurally to receive information from other neurons through dendrites, sometimes via spines on the dendrites and often through an elaborately branching “tree” of dendrites (Figure 1-2). Neurons are also set up structurally to send information to other neurons via an axon that forms presynaptic terminals as the axon passes by (en passant, Figure 1-1) or as the axon ends (presynaptic axon terminals, Figures 1-1 through 1-4).
Neurotransmission has an anatomical infrastructure, but it is fundamentally a very elegant chemical operation. Complementary to the anatomically addressed nervous system is thus the chemically addressed nervous system, which forms the chemical basis of neurotransmission: namely, how chemical signals are coded, decoded, transduced, and sent along the way. Understanding the principles of chemical neurotransmission is a fundamental requirement for grasping how psychopharmacological agents work, because these agents target key molecules involved in neurotransmission. Drug targeting of specific chemical sites that influence neurotransmission is discussed in Chapters 2 and 3.
Understanding the chemically addressed nervous system is also a prerequisite for becoming a “neurobiologically informed” clinician: that is, being able to translate exciting new findings on brain circuitry, functional neuroimaging, and genetics into clinical practice, and potentially improving the manner in which psychiatric disorders and their symptoms are diagnosed and treated. The chemistry of neurotransmission in specific brain regions and how these principles are applied to various specific psychiatric disorders, treated with various specific psychotropic drugs, are discussed throughout the rest of the book.