Learning Objectives
By the end of this section, you will be able to:
- Review the functions of the nervous system
- Describe the role of neurotransmitters in human behavior
- Explain the relationship between endocrine functioning and psychological and mental health disorders
In order to understand mental health better, nurses must appreciate the underlying biological structures and mechanisms that guide human behavior. This section presents the fundamentals of neuroanatomy, cellular structures, neurotransmitters, and pathways that are integral in the central and peripheral nervous system. An understanding of these systems and their interactions with pharmacology principles will create a foundation for psychopharmacology in the next section.
Basic Principles of Neurobiology
Neurobiology is the study of the nervous system and how the brain works. The nervous system is made up of the central nervous system and the peripheral nervous system, and affects actions and senses. It is responsible for interacting with the external environment and managing the human internal environment. The nervous system begins developing during the first few days of embryonic growth and is influenced by a variety of maternal factors, such as environmental stress, exposure to toxins and hazards, health status, and nutrition. The brain’s most rapid growth occurs during the third month of gestation through the child’s first year after birth.
Breaking it down, the neuron is the fundamental cell of the nervous system, and it is responsible for receiving and transmitting electrical signals across the synaptic space. A human is born with most all of their neurons at birth though neurogenesis continues through life. Through environmental learning, synaptic growth—a process by which neurons in the brain connect—will occur rapidly during the first six years of life, after which synaptic pruning occurs, which is an automatic brain function that eliminates unused synapses, allowing new growth. Psychotropic medications work across the synapses to affect neurotransmitters, but more on that later.
Cells of the Nervous System
The neuron or the nerve cell is the primary cell or unit of the nervous system. It is responsible for transmitting an electrical and chemical message to other neurons or organs in the human body. It consists of a cell body or soma, which contains a nucleus. Extending from the cell body are multiple dendrites that receive information from other neurons. Once this information is received from other neurons, the information travels to the axon hillock, down the axon (the long narrow part of the neuron where impulses are conducted) to the end that contains the neurotransmitters, called the axon terminus (Figure 4.2). Here, the information either continues or fades.
Three types of neurons transmit information in the brain: (1) sensory or afferent neurons, which send information from the outside to the brain, (2) associational or interneurons, which connect neurons primarily within the CNS, and (3) motor neurons, which take information away from the CNS to effector organs or skeletal muscle at a neuromuscular junction, where muscle fibers and nerves connect.
The other primary cells in the nervous system are called glial cells, or microglia, which provide structure, repair, and scaffolding for the migration of the nerve cells. There are three types of glial cells: astrocytes, oligodendrocytes, and Schwann cells. The astrocytes are only located in the central nervous system and are involved with building new synaptic connections and ensuring an appropriate chemical environment for the neuron. In the central nervous system, the axon hillock is surrounded by a myelin sheath, made up of oligodendrocytes, which maintain and generate this sheath. In the peripheral nervous system, the myelin sheath is made up of Schwann cells, which surround the neuron and keep them alive. This myelin sheath is an insulating layer that allows for an action potential to travel successfully along the length of the axon at the nodes of Ranvier, which are gaps in the myelin sheath. This action potential is called saltatory conduction.
Link to Learning
This Khan Academy video describing and illustrating the structure and function of the nervous system provides an excellent primer and/or review of the anatomy associated with psychopharmaceuticals.
The Synapse
The synapse is the small area where two neurons converge: the terminus of one axon and another postsynaptic neuron. The terminus of one axon is called the presynaptic bulb or knob. Inside the presynaptic bulb are small vesicles of neurotransmitters that are stimulated into release to the synapse. A neurotransmitter is a chemical messenger that carries a message from one neuron to another. These neurotransmitters work like a key in a lock. They unlock an excitatory or inhibitory response by interacting with a receptor in the dendrite at the other end of the synapse. Psychotropic drugs have action at the synaptic space.
There are four types of connections at synapses: axo-axonic, which are between the axons of one neuron to the axon of another neuron; axo-somatic, which are from the axon of one neuron to the soma of another neuron; axo-dendritic, which are from the axon of one neuron to the dendrites of another neuron; and dendro-dendritic, which are dendrite to dendrite.
Link to Learning
This Khan Academy video offering insight into the structure of the synapse provides a review of this critical part of the neurobiology implicated in the use of psychotropic medications.
Neurotransmitters and Human Behavior
Neurotransmitters are chemical messengers that are synthesized and packaged within the neuron; they carry chemical messages across a synaptic cleft and bind to a receptor on a postsynaptic neuron (Figure 4.3). This process advances the excitatory or inhibitory signal. Neurotransmitters can have excitatory effects (they promote the generation of an action potential) or inhibitory effects (they inhibit an action potential). The main types of neurotransmitters are monoamines, amino acids, and neuropeptides.
Link to Learning
This Khan Academy video about the neurotransmitters targeted by psychopharmaceutical medications provides more information.
Monoamines
Monoamines are neurotransmitters that contain a single amino group. They have a broad range of effects on the central and peripheral nervous systems. Four monoamine neurotransmitters relevant to mental health are:
- The neurotransmitter norepinephrine, also known as noradrenaline, promotes alertness, mental focus, pain mitigation, and memory retrieval. Decreased levels of norepinephrine are theoretically responsible for depression and are implicated in fibromyalgia, attention-deficit disorders, and chronic fatigue syndrome. Research suggests that too much norepinephrine is responsible for psychotic states and mania.
- The neurotransmitter serotonin, also known as 5-hydroxytryptamine, is involved with mood and sleep regulation, mitigation of pain, aggression and sexual behavior, stimulation of gastric secretion, and other hormonal behaviors. Decreases in serotonin may result in depressive states, weight gain, sedation, and pain. Increases in serotonin can cause anxiety and, potentially, psychotic states.
- The neurotransmitter dopamine manages mood states, attention and focus, motor control and regulation, sexual gratification, reward and motivation, and lactation. Decreased dopamine is related to depression, attention-deficit disorders, and Parkinson’s disease. Increased dopamine is related to psychotic states and mania.
- The neurotransmitter histamine is responsible for management of awake states, homeostasis, appetite, and smooth muscle contractions. Decreases in histamine cause sleepiness and weight gain, while increases in histamine cause alert states.
Amino Acid Neurotransmitters
The amino acid neurotransmitters include gamma-aminobutyric acid, glycine, and glutamate, which have widespread effects on the brain and spinal cord. These neurotransmitters are involved in most excitatory and inhibitory functions in the nervous system.
- One of the major inhibitory amino acid neurotransmitters in the brain is gamma-aminobutyric acid (GABA). It decreases all sensory impulses, including pain and cognition. Decreases in GABA are responsible for anxiety states and insomnia. Overactivation of GABA through medications, such as hypnotics, benzodiazepines, or alcohol causes central nervous sedation and potential coma or death.
- Glycine has a stimulant as well as inhibitory effect within the central nervous system, which may affect physiological functions, such as immunity, digestion and appetite, pain response, and sleep. Psychosocial effects may appear as alterations in mood and cognition.
- Glutamic acid, or glutamate, is the major excitatory neurotransmitter in the brain. Glutamate is primarily involved with sensory transmission and learning and memory. Research demonstrates that glutamate dysregulation and diminished function at certain glutamate neurons cause hyperactivity in other brain areas and potentially psychosis. Increases in glutamate can cause neurotoxicity and neurodegeneration.
Neuropeptides
Neuropeptides, a third type of neurotransmitters, comprise small chains of amino acids and are widely distributed within the central nervous system (CNS) and peripheral nervous system (PNS). Neuropeptides responsible for pain mitigation include endorphins and enkephalins, which function as neurotransmitters, neuromodulators, or neurohormones in the CNS. These molecules act at opioid receptors and function to block pain signals.
Acetylcholine
The neurotransmitter acetylcholine is responsible for activation at the neuromuscular junction. Decreases in acetylcholine have been implicated in disease states, such as Alzheimer’s, Parkinson’s, and Huntington’s. Increases in acetylcholine, usually caused by cholinergic crisis (overstimulation of receptors at neuromuscular junctions), are manifested by muscular cramping and weakness, increased salivation, lacrimation, paralysis, and blurry vision.
Central and Peripheral Nervous System
Mental health is a product of genetics, the human, the environment, and the interaction between them. Humans are constantly reading information from the environment and interpreting it. Nursing strategies make an impact at varying levels of these interactions, so it is imperative to understand how the brain works and interprets the outside world. Comprehending the organization and function of each brain organ or system provides the nurse with the ability to assess symptoms accurately and target them with effective interventions.
The nervous system is divided into two different systems: the central nervous system (CNS), which includes the brain and spinal cord, and the peripheral nervous system (PNS), which includes the cranial and spinal nerves. Both are specifically affected by the action of psychotropic medications.
The Central Nervous System
The central nervous system is composed of the brain and the spinal cord. The brain comprises millions of interconnected neurons and other structures. It monitors and responds to external and internal environments, stores and retrieves memories, maintains homeostasis, and manages emotions. There are three main divisions within the brain: the forebrain (prosencephalon), the midbrain (mesencephalon), and the hindbrain (rhombencephalon). Table 4.1 parses the functions of the various parts of the brain, which are illustrated in Figure 4.4.
| Structure | Function | |
|---|---|---|
| Forebrain | Cerebrum | Divided into two hemispheres; manages sensory processing, emotions, language, and movement; the right side is more creative, the left side is logical and problem-solving |
| Diencephalon | Intermediary between cerebrum and lower brain structure; manages sensory information to the cerebrum, emotional memories, regulation of appetite and thermoregulation, and emotions | |
| Midbrain | Mesencephalon | Manages vision, hearing, motor control, sleep and wake states, and temperature regulation |
| Hindbrain | Pons | Manages respiration and skeletal muscle tone |
| Medulla | Manages blood pressure, heart rate, respiration, and reflexes | |
| Cerebellum | Manages muscle coordination, posture, and position | |
The other part of the CNS, the spinal cord, transmits sensory information from the periphery to the brain and manages behavioral responses via sensory and motor tracts. The spinal cord originates from the medulla oblongata—which forms the connection between the brainstem and the spinal cord—and ends at the conus medullaris with nerve bundles extended from the structure called the cauda equina, the collection of nerves at the terminus of the spinal cord. The spinal cord is divided into five sections: cervical, thoracic, lumbar, sacral, and coccygeal. The spinal cord has an inner core of gray matter that contains the cell bodies of neurons and an outer core of white matter tracts. These outer tracts are divided into three different functional sections: the posterior or dorsal horn, made of interneurons and sensory neurons (afferent); the anterior or ventral horn, made up of motor neurons (efferent); and the lateral horn, which contains cells involved with the autonomic nervous system.
Memory and Learning
Human memory is recording, retaining, and retrieving environmental stimuli. There are two types of memories. One type is declarative memories, which include episodic and semantic memories of personal events, facts, and experiences. Declarative memories are formed in the prefrontal cortex and the hippocampus. The other type is non-declarative memories, which include those that individuals cannot explicitly recollect consciously, like implicit, performance-based, and motor memories. Four areas of the brain are responsible for managing memory and learning. Inside the brain’s medial temporal lobe are the hippocampus and the amygdala (Figure 4.5). The hippocampus is part of the limbic system and is responsible for encoding memories, learning, and perception of space. Inside the hippocampus are NMDA glutamate receptors that manage memories through long-term potentiation, which is a process of synaptic strengthening through signal increases in the neuron. Stress can cause dendritic pruning in the hippocampus, resulting in memory deficits. The amygdala is a pair of small almond-shaped regions located anterior to the hippocampus and is responsible for the formation and encoding of memories, especially those that are highly emotionally charged, such as trauma. High levels of stress can augment the fear startle response mediated by the amygdala resulting in increased levels of norepinephrine, insomnia, high blood pressure, and increased pulse.
The third area of the brain responsible for managing memories is the diencephalon (Figure 4.6). The diencephalon is the central area of the brain located above the brainstem, including the epithalamus, thalamus, subthalamus, and hypothalamus. Areas within the diencephalon are responsible for forming recognition-based memories. Lesions to the diencephalon can potentially cause amnesia. Finally, the basal ganglia are a group of subcortical nuclei most often associated with managing motor control, primarily sequential movements; the basal ganglia are involved with the formation of procedural memories. Diseases and disorders involved in the basal ganglia include Parkinsonism, problems controlling movements, medication induced disorders, such as akathisia and dystonia, and Huntington’s disease.
Movement
Several areas of the brain manage voluntary control over movement. The first is the motor cortex, which is in the cerebral cortex and is subdivided into three areas: the primary, premotor, and supplementary motor areas. The primary motor cortex is located along the precentral gyrus and is responsible for generating efferent neuronal impulses down the spinal cord to manage movement. The premotor cortex lies rostral to the primary motor cortex and is responsible for managing coordinated motor responses. Finally, the supplementary motor areas lie anterior to the primary motor cortex and manage complex, sequenced movements in proximal muscles. Also involved in movement are the basal ganglia, a group of subcortical nuclei associated with managing motor control. Likewise, the substantia nigra, the most prominent nucleus in the midbrain, contains a dopaminergic nucleus that manages motor control and involves disease states, such as Parkinson’s, Huntington’s, and extrapyramidal symptoms. Finally, the cerebellum is in the basal part of the brain between the cerebrum and the brain stem. It is responsible for balance, walking, standing, and measuring distance and timing.
Pain
The International Association for the Study of Pain defines pain as “an unpleasant sensory and emotional experience associated with or resembling that associated with actual or potential tissue damage.” Pain is a phenomenon that has biological, environmental, and social determinants. It is a personal experience that is memory-driven and emotionally interpreted. Pain has implications for mental health through associations with anxiety, fear, powerlessness, social withdrawal, depression, and substance dependence. The processing of pain is called nociception. Nerve cell endings distributed throughout the body that initiate pain sensation through afferent pathways are nociceptors. They are categorized by the type of pain stimulus that is transmitted. A-Delta (Aδ) fibers transmit pressure, mechanical deformation, and extreme temperature sensations. C fibers transmit burning pain, itch, and dull ache. A-Beta (Aβ) fibers manage touch and vibration sensations. Pain sensations from nociceptors travel to the dorsal horn of the spinal cord, where they synapse with an interneuron and then cross over to the contralateral spinothalamic tract. The afferent sensations then transcend to the brain through the brainstem, the thalamus, and the somatosensory cortex. The somatosensory cortex interprets the existence, location, and intensity of pain. The reticular formation, limbic system, prefrontal cortex, and brainstem interpret the emotional response to pain based on current and past experiences. Finally, the cerebral cortex evaluates pain perception, threshold, and tolerance. The response to pain is called pain modulation, and it can occur during all phases of the pain process. The response to pain from the brain to the periphery is called the descending or efferent pathway. Various excitatory and inhibitory neurotransmitters that work in the central and peripheral nervous systems manage modulating pain, including serotonin, norepinephrine, and inflammatory mediators like bradykinin, interleukins, tumor necrosis factors, and neurokinins.
Sleep
Sleep is a restorative process of decreased mental awareness and physical activity. Several neural circuits and neurotransmitters coordinate the sleep-wake cycle. Sleep is regulated by the circadian cycle, a 24-hour cycle determined by light and dark patterns and internal regulatory functions (Figure 4.7). The pacemaker for the circadian cycle starts in the hypothalamus. Internal body temperature, sleepiness, and the ability to fall asleep are coupled with the circadian cycle. The homeostatic process, a sleep debt model, also regulates sleep. The more awake a human is, the greater demand or debt is required for sleep. The more that the human is asleep, the less demand for sleep there is. That process repeats every day.
There are different phases of sleep that are regulated by neurotransmitters. Awake states are managed by increased firing rates of the monoamines (dopamine, norepinephrine, serotonin, and histamine), orexin, and acetylcholine. The sleep states are regulated by increased firing of GABA and very little firing of the monoamines, orexin, and acetylcholine. The final stage of sleep is REM sleep or rapid eye movement. Most of the time in this stage is spent dreaming. This is a paradoxical sleep as the body is “paralyzed” but the mind is “awake.” In REM sleep, inhibitory neurotransmitters release causing overall reduced sympathetic tone. Blood pressure, heart rate, and respirations vary, and may increase, compared with non-REM sleep, and muscle tone decreases. Sexual arousal may occur during REM sleep, which may be due to dream activity or increased blood flow.
Sleep patterns change as humans age. Newborns sleep between 16 and 18 hours a day. A three- to five-year-old child sleeps nine to ten hours a night. Adults sleep an average of seven to nine hours a night, but less as they age. Older adults begin to go to bed earlier and wake up earlier; they spend more time awake at night. Disruption of sleep and rest can be associated with anxiety, poor concentration, ineffective coping, and role function.
Link to Learning
Sleep can be a complex topic because it involves numerous neurotransmitters and several bodily cycles. Watch this Khan Academy video on sleep to learn more.
The Peripheral Nervous System
The peripheral nervous system contains all nerves outside the central nervous system. It is divided into two different pathways: the ascending or afferent pathway, which brings sensory information to the brain; and the descending or efferent pathway, which takes integrated information from the brain. This means that the afferent pathways take things that the client feels, senses, or perceives to the brain, and the efferent pathway manages the response.
There are also functional divisions in the peripheral nervous system. The somatic nervous system is a part of the PNS that delivers conscious sensory (afferent) information to the CNS and a voluntary motor response (efferent). The autonomic nervous system, regulated by the hypothalamus, manages involuntary homeostatic control over the body’s internal processes, like temperature. The autonomic nervous system has two further divisions: the sympathetic nervous system and the parasympathetic nervous system. The sympathetic nervous system manages the fight or flight response (increase in heart rate, blood pressure, respirations, peripheral vasoconstriction, decreased GI motility). This response is manifested when the client is anxious, having a phobic response, or when experiencing a trauma trigger. In contrast, the parasympathetic nervous system functions to conserve and store energy (decreased heart rate, blood pressure, respirations, peripheral vasodilatation, increased GI motility). This system manifests itself when the client is tired, sleepy, or resting.
Neuroendocrinology
The nervous and endocrine systems work together via hormonal regulation to manage internal and external environments. Groups of molecules that function to send signals to other cellular organisms in the human body are called hormones. They are released in response to chemical factors, such as blood glucose levels; endocrine factors, such as other hormones; or signals from neurons. Psychotropic medications, such as lithium, can have neuroendocrine effects: It has been associated with goiters, hypothyroidism, and hyperthyroidism. Additionally, hormonal disorders, such has hypothyroidism, can mimic mental health symptoms such as anhedonia, depressed mood, and decreased energy and motivation.
Endocrine functioning within the CNS is controlled by the hypothalamus and the pituitary gland. There are two lobes in the pituitary gland: the anterior and posterior. The posterior lobe of the pituitary gland releases two hormones: vasopressin and oxytocin. Both are triggered by neuronal impulses from the hypothalamus. The hormone vasopressin, also known as antidiuretic hormone, is responsible for retaining water and maintaining blood pressure. It is stimulated in the presence of decreased fluid volume, emotional stress, and pain. When released, oxytocin is the hormone responsible for uterine contraction and the stimulation of milk from mammary glands after pregnancy. The anterior lobe of the pituitary stimulates hormones that target other organs. When finished with their actions, they have a negative feedback mechanism that then inhibits the release of the same hormone at the anterior pituitary, causing the diminished effect of that hormone.
The release of prolactin releasing hormone from the hypothalamus stimulates prolactin. It stimulates milk production during pregnancy. Certain medications can affect prolactin levels, such as antipsychotics, and can cause amenorrhea or galactorrhea, which is production of milk from the breast unrelated to pregnancy. Thyrotropin releasing hormone triggers the hypothalamus to release thyroid stimulating hormone (TSH), which targets the thyroid gland to release triiodothyronine (T3) and thyroxine (T4). Optimal thyroid functioning manages temperature regulation, mood states, and food metabolism.
Protein synthesis and growth during child development are managed by growth hormone, or somatotropin. Furthermore, melatonin, responsible for initiating sleep during circadian cycles, is released from the pineal gland after melanocyte stimulating hormone is secreted from the hypothalamus. The release of this hormone is affected by light and dark conditions. Finally, adrenocorticotropic hormone (ACTH) is released and travels to the adrenal glands where cortisol is released. Cortisol is responsible for mobilizing glucose for energy; it increases protein metabolism, immune effects, and systemic anti-inflammatory effects. Overall, the release of cortisol enhances the body’s stress response. Once released, cortisol has the same negative feedback loop to the pituitary, which terminates the response. This is called the hypothalamic-pituitary-adrenal (HPA) axis, or the HPA response. Prolonged stress response and its relationship to the HPA axis has been implicated in disease states, such as post-traumatic stress disorder (PTSD), depression, altered response after traumatic brain injury, and accelerated decline in disease states like Alzheimer’s.
PMH Disorders and Their Relationship to the Nervous System
To contextualize psychiatric disorders biologically and neurologically, it is important to consider both anatomical and neuroendocrine perspectives, genetic determinants, and environmental influences. The stress diathesis model posits that there are genetic traits that, when combined with certain environmental influences, create the potential for a mental health disorder. Take, for example, a child who has a genetic predisposition for depression but is raised in a loving environment without significant stress. The theory posits that this child has less chance of expressing that genetic loading for mental disease. Place the same child in an environment with significant environmental stressors, and the theory posits that there is a higher chance for expression of mental disease. Added to environmental and genetic variances are the structural and neurological determinants for mental health disease. Alterations in the monoamines (norepinephrine, serotonin, dopamine), dysregulation of neurotransmitter receptors, and disruption in growth factors can cause mood disorders, which include major depression, bipolar disorder, dysthymia, mood disorder from a medical condition, and substance-induced mood disorder.
Brain circuits involved in mood disorders include the prefrontal cortex, basal forebrain, striatum, nucleus accumbens, thalamus, hypothalamus, amygdala, hippocampus, brainstem, and cerebellum. Schizophrenia, a mental disorder characterized by “disruptions in thought processes, perceptions, emotional responsiveness, and social interactions,” (National Institutes of Health [NIH] 2022) stems from hyperactive dopamine in the mesolimbic pathways caused by malfunctioning NMDA glutamate receptors and hyperfunctioning serotonin receptors. Environmental exposures, such as viral illness in utero, are also theorized to be determinants of the disease. The neurobiology of fear and anxiety involves the limbic system (amygdala and hippocampus), the HPA axis, and conditioned responses to external stimuli. Neurotransmitters involved with anxiety and fear include the monoamines, GABA, and glutamate. Insomnia, being unable to fall or stay asleep, happens because of the inability to neuromodulate circuits and neurotransmitters associated with awake states. These neurotransmitters include norepinephrine, dopamine, serotonin, acetylcholine, and histamine. Neurocircuits involved with sleep include the basal forebrain, the locus coeruleus, and the thalamus. Attention deficits, characterized by impulsive behaviors, hyperactivity, and/or an inability to focus or pay attention, stem from an imbalance of dopamine and norepinephrine in the orbitofrontal and prefrontal cortex. Impulsive and compulsive behaviors like addiction result from a lack of modulation from the prefrontal cortex to impulsive circuits led by the orbital frontal cortex. The dopaminergic system is integral to this reward-driven behavior.