The wordnetweb.princeton.edu website defines neurotransmitter as "a neurochemical that transmits nerve impulses across a synapse." Such neurochemicals are vital to brain function and an imbalance or dysfunction in their synthesis often results in illness. No two neurons in the brain can communication without transmission of a neurotransmitter. Antonio R. Damasio, in Descartes' Error: Emotion, Reason, and the Human Brain (1994), provides this description of neural communication in the brain.
There are several billion neurons in the circuits of one human brain. The number of synapses formed among those neurons is a least 10 trillion, and the length of the axon cable forming neuron circuits totals something on the order of several hundred thousand miles. [I (Damasio) thank Charles Stevens, a neurobiologist at the Salk Institute, for the informal estimate.] … The time scale for the firing is extremely small, on the order of tens of milliseconds—which means that within one second in the life of our minds, the brain produces millions of firing patterns over a large variety of circuits distributed over various brain regions.
Later, Damasio adds, "…the elementary secrets of mind reside with the interaction of firing patterns generated by many neuron circuits, locally and globally, moment by moment, within the brain of a living organism."
In Affective Neuroscience: The Foundations of Human and Animal Emotions (1998), Jaak Panksepp explains that the
mesolimbic and mesocortical dopamine pathways "tend to energize and coordinate the functions of many higher brain areas that mediate planning and foresight (such as the amygdala, nucleus accumbens, and frontal cortex)." He goes on to say that dopamine activity in these pathways promotes "states of eagerness and directed purpose in both humans and animals." Panksepp cites the mesolimbic and mesocortical pathways as essential components of what he has termed the SEEKING system of the brain.
Regarding the SEEKING system, Panksepp writes: "When this brain system becomes underactive, as is common with aging, a form of depression results. When the system becomes spontaneously overactive, which can happen as a result of various kinds of stress, an animal's behavior becomes excessive and schizophrenic or manic symptoms may follow—especially the 'functional' forms of psychosis that can be treated with traditional antipsychotic medications (which all reduce dopamine activity in the brain), as opposed to the more chronic forms arising from brain degeneration…."
John Allman, in Evolving Brains (2000), writes: "Drugs that decrease the amount of serotonin in synapses increase exploratory, eating, and sexual behavior, as well as fear-induced aggression. Similarly, when the gene that encodes one class of serotonin receptor is inactivated in mice, the mutant mice are grossly obese and prone to dying from sudden seizures. This evidence also suggests that serotonin constrains the responses of neurons and thus stabilizes the activity of the brain during different behaviors."
When it comes to psychiatric disorders, it seems that increases in the catecholamines have something to do with still trying to cope and the effort that involves, where overabundance of glucocorticoids seems more of a signal of having given up on attempting to cope. You can show this with a lab rat. Rats, being nocturnal creatures, don't like bright lights, are made anxious by them. Put a rat in a cage whose edges are dark, just the place a rat likes to hunker down. But the rat is really hungry and there's some wonderful food in the middle of the cage, under a bright light. Massive anxiety
—the rat starts toward the food, pulls back, again and again, frantically tries to figure ways to the food that avoid the light. This is anxiety, a disorganized attempt to cope, and this phase is dominated by catecholamines. If it goes on for too long, the animal gives up, just lies there, in the shaded perimeter. And that is depression, and it is dominated by glucocorticoids.
As previously discussed, the nigrostriatal pathway transmits dopamine from the substantia nigra in the midbrain, one of the locations where neurons produce dopamine, to the corpus striata complex. This pathway is particularly associated with motor control. Degeneration of neurons in the substantia nigra can result in Parkinson's disease. Although they are lost far more quickly in the nigrostriatal pathway, dopamine neurons are also lost in the mesolimbic pathway in Parkinson's Disease. According to the National Institute of Neurological Disorders and Stroke, the primary symptoms of Parkinson's disease are "tremor, or trembling in hands, arms, legs, jaw, and face; rigidity, or stiffness of the limbs and trunk; bradykinesia, or slowness of movement; and postural instability, or impaired balance and coordination." Parkinson's is a progressive disease. As symptoms become more pronounced, "patients may have difficulty walking, talking, or completing other simple tasks."
In 2006, The American Academy of Neurology issued a news release regarding apathy, or lack of motivation, in persons with Parkinson's Disease. As it turns out, damage to dopamine-producing neurons in Parkinson's Disease not only affects motor behavior, it affects cognitive and emotive behaviors. The academy defined apathy as follows:
"Apathy is a mental state characterized by a loss of motivation, loss of interest, and loss of effortful behavior. In apathy, the mood is neutral and there is a sense of indifference. In depression, the mood is negative and there is emotional suffering. Because apathy and depression share some of the same symptoms, the disorders can be misdiagnosed." The news release went on to quote Lindsey Kirsch-Darrow who participates in related research on Parkinson's Disease. She emphasizes that it is "important to educate family members and caregivers about apathy to help them understand that it is a characteristic of Parkinson disease. Apathetic behavior is not something the patient can voluntarily control, and it is not laziness or the patient trying to be difficult—it is a symptom of Parkinson disease."
Between 1915 and about 1924, a severe epidemic of viral encephalitis plagued areas in Europe and North American. Constantin von Economo, both a clinician and a pathologist, studied the outbreak. The infection caused lesions in the substantia nigra. Von Economo described three types of this illness. 1) The symptoms of the somnolent-opthalmoplegic form were somnolence, often leading to coma and death, paralysis of cranial nerves, extremities and eye muscles and expressionless faces. 2) The hyperkinetic form manifested itself with restlessness, motor disturbances as twitching of muscle groups, involuntary movements, anxious mental state and insomnia or inversion of sleep patterns. 3) The amyostatic-akinetic form often lead to a chronic state similar to Parkinson's disease, called postencephalitic Parkinsonism. The symptoms were weakness of muscles, rigidity of movements and insomnia or sleep inversion
To illustrate how infection that damages delicate brain neurocircuitry affects behavior, in The Boy Who Couldn't Stop Washing: The Experience & Treatment of Obsessive-Compulsive Disorder (1989), Judith L. Rapoport cites von Economo's experiences. He observed that his patients did not say "I have a twitch in my hand," as an epileptic patient might say, but rather as a rule said, "I have got to move my hand that way." In other words, patients often perceived that the movement was an act of will and intention. Rapoport writes: "The frequent subjectivization of these processes, experienced as compulsory by the patients, is, I believe one of their characteristic attributes." Rapoport points out that von Economo "went on to worry about how a 'lower' part of the brain, the basal ganglia, could be responsible for such a complex function as that of 'will' and 'intentionality.'"
In Brainscapes: An Introduction to What Neuroscience Has Learned about the Structure, Function, and Abilities of the Brain (1995), Richard M. Restak quotes a psychiatrist's observations of his postencephalitic patient: "He worried over disturbing ideas, whether his employer or his employer's wife was insulted by certain things he might have said, whether he really had closed the window, whether the door of the room was properly closed. He would wash his hands repeatedly during these episodes, look under the bed to see if anyone were hiding there, and dust his chair carefully before seating himself."
The experiences recounted above indicate that infections that damage dopamine neurocircuitry in the brain can somehow produce both Parkinson's-like and obsessive-compulsive symptoms. Later in this narrative, I will discuss infection as a possible etiologic agent in OCD. For now, it is clear that the primary player in the SEEKING system, dopamine, is involved in both the physical aspects of movement and the mental aspects of motivation.
As in Parkinson's disease, the nigrostriatal dopamine pathway is also implicated in tardive dyskinesia, but in a different way. Tardive dyskinesia results as a side effect of larger doses of antipsychotic drugs used to treat schizophrenia and psychotic episodes in other illnesses. The aim of using these medicines is to block dopamine receptors, specifically D2 receptors, in the dopamine pathway associated with illness. Some medicines, however, including older so-called typical antipsychotics as well as some of the newer atypical antipsychotics, block D2 receptors in multiple pathways including the nigrostriatal pathway, which may result in movement problems, especially when medication dosages are high and long-term. The National Institute of Neurological Disorders and Stroke provides the following information: "Tardive dyskinesia is characterized by repetitive, involuntary, purposeless movements. Features of the disorder may include grimacing, tongue protrusion, lip smacking, puckering and pursing, and rapid eye blinking. Rapid movements of the arms, legs, and trunk may also occur. Involuntary movements of the fingers may appear as though the patient is playing an invisible guitar or piano."
In the video embedded here, eighteen-year-old Lydia, has recorded her tardive dyskinesia symptoms. She developed symptoms after taking Seroquel for bi-polar disorder. Lydia illustrates how she can focus on symptoms in order to stop them. When she returns to a task, however, shifting her attention away from symptoms, they often return.
We discuss antipsychotic medications in more detail, especially in relation to attenuating dopamine transmission as a means of preventing obsessions and compulsions, in Part 3 of MyBrainNotes.com, in OCD Treatments Including Antipsychotic Medications.