Schizophrenia

Definitions & Key takeaways

Schizophrenia is a mental illness characterized by a disconnection from reality and abnormal behaviors. Symptoms are broadly classified as positive symptoms, negative symptoms, or cognitive symptoms. Positive symptoms include delusions, hallucinations, disordered thinking and speech, and unusual behavior; whereas negative symptoms include affective flattening, alogia, apathy, and anhedonia. Cognitive symptoms include things like not being able to remember things, learn new things, or understand others easily. Treatment involves antipsychotic medications and psychotherapy.

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. With schizophrenia, schizo means split, and phrenia means mind.
So schizophrenia is a condition characterized by a disruption in the normal process of thinking, perception, and behavior.
However, it's important to understand that these individuals do not have a split personality or multiple personality disorder.
But before we dive deeper into schizophrenia, let's quickly cover the four main dopaminergic pathways in the brain. The mesolimbic pathway drives reward-based behaviors.
Bursts of dopamine in this pathway create feelings of pleasure and reinforce survival behaviors like eating, socializing, and reproduction.
The mesocortical pathway supports motivation, goal-oriented actions, executive function, attention, and emotional regulation.
Next, the nirostriatal pathway helps control movement and suppress unwanted motor activity, while the tubero infundibular pathway uses dopamine to signal the anterior pituitary to stop prolactin secretion, which is the hormone responsible for milk production.
Now, in schizophrenia, dopamine levels are out of balance in the mesolimbic and mesocortical pathways. We don't fully understand why, but some risk factors increase the odds.
These include obstetric complications such as gestational diabetes, asphyxia, and low birth weight, as well as acute stress during pregnancy like serious trauma.
Also, prenatal infections could play a role. Later in life, experiencing traumas during childhood, using cannabis and having older parents can increase the risk as well.
Genetics matter too. Variations in certain genes, particularly the ones on chromosome 6 that help regulate the immune system like complement C4, can increase the likelihood of schizophrenia.
Although the exact cause remains unclear, we understand the mechanism behind many of its symptoms. First, we have positive symptoms, which occur when the mesolimbic pathway becomes overactive, releasing too much dopamine.
Too much dopamine adds experiences or behaviors that aren't normally present, like hallucinations, delusions, or disorganized speech.
Hallucinations are the most common positive symptom. They are perceptions that occur without any external trigger.
Auditory hallucinations are the most frequent, where a person hears voices that aren't actually there. These voices can criticize their actions or accuse them of things they haven't done.
Some individuals may experience visual hallucinations, seeing things that aren't present. For example, they might see spiders crawling over the laptop screen.
Next are delusions, which are fixed false beliefs that a person holds firmly despite clear evidence against them. Persecutory delusions involve the belief that others are trying to harm them.
A person might think someone is poisoning their food, so they begin avoiding meals altogether. Referential delusions include beliefs that neutral events are directed specifically at them.
They might think that footsteps in the hallway are secret messages meant only for them. Next, bizarre delusions are beliefs that are clearly impossible and cannot be explained by ordinary life experiences.
Someone with bizarre delusions might believe that their thoughts are being withdrawn by an outside force or that their actions are being controlled by someone else.
The last positive symptom is disorganized speech, which can appear as rapidly shifting from one topic to another, or speaking in a way that does not make any sense, often called word salad.
On the other hand, negative symptoms occur because the mesocortical pathway is underactive and doesn't release enough dopamine.
Negative symptoms include avolition, anhedonia, associality, alogia, and affective flattening. Moreover, you can use the 5A pneumonic to remember them.
Avolition refers to a lack of motivation or drive. The person knows exactly what they need to do, but they can't start or complete the task.
Anhedonia means loss of pleasure. Activities that once brought joy start to feel empty, unrewarding, or purposeless.
Asociality describes the lack of motivation to engage in social interactions. As a result, a person often withdraws from others.
Then we have elogia or reduced speech, which involves giving short brief responses and speaking more slowly than usual. Finally, effective flattening describes the reduction in emotional expression, such as minimal facial expressions or little variation in voice tone, even in emotional situations.
In addition to positive and negative symptoms, some individuals might also develop abnormal psychomotor behavior. Some individuals might present with catatonia, a severe, potentially life-threatening neuropsychiatric state in which a person becomes unresponsive to their surroundings and remains nearly motionless, almost like a statue.
Individuals with catatonia can also show unusual movements such as fixed facial grimace or echolalia where they involuntarily repeat words or phrases they hear.
Finally, individuals with schizophrenia can develop cognitive symptoms. These include attention and memory problems where a person struggles to remember instructions or keep track of what was just said.
They may also have slowed processing, taking longer to answer even simple questions. Now, to diagnose schizophrenia, at least two of the following symptoms must be present delusions, hallucinations, disorganized speech, disorganized or catatonic behavior, and negative symptoms.
Importantly, at least one of these must be delusions, hallucinations, or disorganized speech. Next, symptoms must be present for at least 1 month during the active phase of the condition, and the overall condition must continue for at least 6 months.
Also, symptoms must affect daily functioning, whether that's basic self-care, relationships, or work life. But before calling it schizophrenia, we must be sure that the symptoms aren't caused by something else, like another medical condition, substance use, or even a medication.
Only after ruling those out can we confidently make a diagnosis of schizophrenia. Moving on to management, which primarily relies on two main groups of antipsychotics.
Typical antipsychotics, such as haloperidol, chloropromazine, and thioridazine work by blocking dopamine D2 receptors. By targeting D2 receptors in the mesolimbic pathway, they reduce positive symptoms.
However, they cannot selectively target the mesolimbic pathway. Instead, they block D2 receptors throughout the brain.
In the mesocortical pathway, blocking D2 receptors can worsen negative symptoms. In the tubero infundibular pathway, they fail to block prolactin secretion, eventually raising prolactin levels and causing oligomeorrhea, galactorrhea, and gynecomastia.
Lastly, in the nirostriatal pathway, they cause movement side effects called extrapyramidal symptoms. Within hours to days of starting typical antipsychotics, a person might develop dystonia, which shows up as muscle spasms of the tongue, face, neck, and back.
It can also trigger an oculargyric crisis where the spasm of extraocular muscles causes the eyes to lock in an upward and outward position.
A few days to a month there could be akathisia or pseudoparkinsonism. Akathisia refers to an intense relentlessness with a constant urge to move the limbs, while pseudoparkinsonism involves tremor, muscle rigidity, and bradykinesia, or slow movements.
The good news is that up to this point these symptoms usually go away once the medication is stopped. After months to years, tardive dyskinesia can appear.
Tardive dyskinesia involves repetitive, involuntary rhythmic movements, typically affecting the perioral muscles, causing a person to repeatedly smack or purse their lips.
Unlike earlier movement side effects, tardive dyskinesia can be irreversible. Next we have atypical antipsychotics including risperidone, clozapine, and quetiapine, which works by blocking dopamine D2 receptors in the mesolimbic pathway, thereby alleviating positive symptoms.
But they also block serotonin 5 HT2A receptors in the mesocortical pathway. These receptors are found on inhibitory neurons that regulate dopaminergic neurons and decrease dopamine release.
When atypical antipsychotics block them, dopaminergic neurons have no inhibitory signals, so dopamine release increases, eventually alleviating negative symptoms.
This is why atypical antipsychotics are preferred medications over typical antipsychotics. Also, they are less likely to cause extrapyramidal side effects.
However, because they block histamine receptors, they can lead to significant weight gain and metabolic syndrome. All right, as a quick recap, schizophrenia is a condition where the brain's dopamine system gets out of balance, disrupting processes like thinking, perception, and behavior.
High dopamine levels in the mesolimbic pathway cause positive symptoms such as delusions, hallucinations, and disorganized speech.
On the other hand, low dopamine levels in the mesocortical pathway result in negative symptoms, including avolition. Anhedonia, asociality, alogia, and effective flattening treatment primarily relies on antipsychotics which work by blocking dopamine D2 receptors and helping restore balance in