Hallucinations are probably the most recognized symptom of psychiatric disorders, hands down.
Movies like A Beautiful Mind, or Donnie Darko seek to captivate their audiences by offering them a glimpse into the minds of the protagonist’s struggle, as they attempt to claw their way back into reality as we know it. However, Hollywood rarely does its homework to provide a just and accurate depiction of mental illness, which does a huge disservice to people who actually live with psychiatric conditions. Hallucinations can be terrifying, that we know. But they can also be amusing, or even inspiring. They can be audial or visual (and, in rarer cases, olfactory, tactile or kinesthetic). They can last a few minutes or go on for hours, days, months, even years.
But what exactly are hallucinations, and how do they manifest? Does having them automatically mean one is going mad? No, actually. There are many physiological conditions that include hallucinations as symptoms, including Parkinson’s, Alzheimer’s and Charles Bonnet Syndrome. Certain drugs will also trigger the same effects, as will severe sleep deprivation or a high fever. However, in this article we will be focusing specifically on hallucinations caused by schizophrenia and bipolar disorder: what most psychiatrists would refer to as a “psychotic break.” Buckle up.
First off, what is a hallucination? Hallucinations are generally categorized as false or distorted sensory experiences that appear to be genuine. They are generated by the mind, rather than by any external stimuli, and may be seen, heard, felt, smelled or tasted. A hallucination occurs when environmental, emotional, or physical factors cause the mechanism within the brain that helps to distinguish conscious perceptions from internal, memory-based perceptions to misfire.
Ok, but what is this mechanism? It’s actually more like what are these mechanisms, as many different factors weigh in. The brain is an enormously complicated machine, and, like any machine, it requires multiple parts to work in sync with one another in order to function.
Theories about how hallucinations occur can be broadly divided into two categories.
Topological theories emphasize abnormal activity in specific regions of the brain. For example, visual or auditory hallucinations are associated with increased activity in the visual and auditory regions of the brain, respectively, and can be induced by electrical stimulation. This is commonly seen in hallucinations brought on by non-psychiatric conditions, such as Charles Bonnet Syndrome, sleep deprivation, or fever.1
Hodological theories emphasize the changes in activity of pathways connecting different regions of the brain. For example, in schizophrenic patients who are prone to hallucinations, neuroimaging shows changes in the activity of pathways connecting the frontal and temporal lobes. In addition, people with schizophrenia show a marked decrease in white matter cells in the brain. Because so many different areas of the brain are affected, hodological theory explains why it is very difficult to effectively treat these hallucinations in mental illness. But we do know enough about the workings of the schizophrenic and bipolar brains to start putting several crucial pieces together.2
To start, two forces are necessary: excitation and inhibition. Excitatory signaling from one neuron cell to the next makes the latter cell more likely to fire. Inhibitory signaling makes the latter cell less likely to fire. Two types of amino acids, glutamate and GABA (gamma-aminobutyric acid), act as transmitters for the brain’s synapses. Glutamate excites, GABA inhibits. The balance between these two forces is crucial to healthy functioning, and it is known as the E/I balance. According to an article published in Schizophrenia Bulletin, A large number of studies suggest that subtle impairments of the E/I balance are involved in neurological and psychiatric conditions, such as schizophrenia. Emerging evidence also points to a role of the E/I balance in maintaining stable perceptual representations, suggesting it may be a plausible model for hallucinations. In support, hallucinations have been linked to inhibitory deficits as shown with impairment of GABA transmission, as well as other brain functions.3
The next building block in the anatomy of a hallucination is dopamine. Dopamine is a neurotransmitter present in three circuits of the brain: one that regulates movement; a second thought to be important for cognition and emotion; and a third that regulates the endocrine system. Abnormalities in the second circuit have been implicated in schizophrenia. High levels of dopamine tend to enhance concentration and boost mood.
While maintaining sufficient dopamine levels is beneficial for mental health and physical functioning, too much of it can create dysfunction. And that appears to be the problem, particularly in the case of schizophrenia: the brain’s ability to regulate dopamine levels is severely compromised. High levels of dopamine are also found in the brains of people undergoing a manic episode of bipolar disorder, and people who have taken psychostimulants. But scientists believe it is the continuous high levels of dopamine that contribute to the chaotic thinking and hallucinations that are so prevalent in schizophrenia in particular. An imbalance in these levels is also linked to the disruption of circadian rhythms, a common occurrence in bipolar mania.
Colleen McClung is a researcher at the University of Pittsburgh, recently completed a study that shows that mice with a particular mutation in the Clock gene, an essential enforcer of circadian rhythms, cycle between normal behavior at night (when mice ordinarily are awake and active) and manic behavior during the day (when mice ordinarily sleep). In the new study, the researchers found that the key to the daytime behavior was a surge in dopamine levels in the ventral tegmental area (VTA), a major node in the pleasure-seeking circuitry of the brain. VTA dopamine levels spiked because levels of tyrosine hydroxylase—an enzyme that mediates dopamine production—rose sharply.4
So, what happens when you put together an E/I imbalance with heightened levels of dopamine?
Presumably, hallucinations. Because the brain is so complicated, there is no definite, single area (or areas) that we can point at and say, “THIS is the root of the problem.” Unfortunately, while E/I and dopamine imbalances account for a lot of what happens during a schizophrenic or manic hallucination, it’s not the whole story. This is because different levels of the brain are involved in different kinds of hallucinations, and even though the aforementioned imbalances are prevalent throughout, the locations of the brain in which they are malfunctioning differ from illness to illness.
As I previously mentioned, neuroimaging in the schizophrenic brain shows changes in the activity of pathways connecting the frontal and temporal lobes. However, Rusty Gage, a researcher at the Salk Institute and member of the Dana Alliance for Brain Initiatives, found that in the bipolar brain, the dentate gyrus may be a potential target zone. Gage harvested skin cells from Bipolar I patients, and reprogrammed them to become granule neurons of the type normally found in the dentate gyrus of the hippocampus, a key memory- and learning-related region. According to his findings:
“When the researchers exposed these overexcitable neurons to lithium, the first-line therapy for bipolar disorder, their excitability returned to normal—but only for the neurons derived from patients whose bipolar symptoms had responded to lithium therapy. Neurons from lithium non-responders remained abnormal. That hints strongly that the overexcitability seen in the bipolar patient neurons is not just an incidental finding but is relevant to the disorder. The mania experienced by bipolar disorder patients involves an overabundance of restless energy as well as racing thoughts and speech, which plausibly could be driven by overexcitable neurons and their associated networks in the brain”.5
Gage’s research implies that heightened mitochondria activity may be the trigger behind increased excitability in the dentate gyrus neurons, but even then, nothing is certain:
“The scientists are also trying to find out more precisely how the overactivity of dentate gyrus neurons arises. One clue is that mitochondria—the tiny oxygen reactors that fuel most cellular operations and are particularly important for sustaining neurons’ activity and health—are much more active in the neurons from bipolar patients, and are also smaller, making them more swiftly transportable along the neurons’ output stalks (axons). Whether these mitochondrial abnormalities lead or follow the overall neuronal overexcitability remains to be seen. How people who are manic eventually swing back to a normal mood, or even to the lowered mood of depression, remains a mystery.”6
So, if we still don’t quite understand where exactly hallucinations come from, how do we treat them? We go back to dopamine. Antipsychotic medications work by blocking a specific subtype of the dopamine receptor, referred to as the D2 receptor. First generation antipsychotics, block the D2 receptor and improve positive symptoms (hallucinations). A second generation of antipsychotics, commonly referred to as the atypical antipsychotics, block D2 receptors as well as a specific subtype of serotonin receptor, the 5HT2A receptor. It is believed that this combined action at D2 and 5HT2A receptors treats both the positive and the negative symptoms (hallucinations and the “flat affect” commonly seen in schizophrenia). In addition, we’ve seen that lithium, a mood stabilizer, is also helpful in stabilizing the effects of hallucinations, but only in bipolar disorder. Antipsychotics are not just prescribed for schizophrenic hallucinations, either: they are commonly used to combat hallucinations caused by Parkinson’s disease and dementia. Antipsychotics are also prescribed to help with borderline personality disorder, OCD, autism, and several other conditions that don’t normally present with hallucinations as symptoms.
Neuroscience and neuropsychiatry are fascinating, if sometimes frustrating fields, precisely because there’s so much we still don’t know about the human brain. This article has attempted to chip away at some of the mystery shrouding hallucinations as observed in mental illness, but, as you can see, there are still pieces missing. Neuroscience is a relatively new field, all things considered, but research and breakthroughs are being made all the time. Perhaps in a few years, I’ll be able to look back on this piece and fill in the blanks. We can only hope.
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