Schizophrenia: Why, When, and What to do about it?

Among all of the stigma surrounding mental health, schizophrenia fits right in. People experiencing positive symptoms such as hallucinations and delusions are often labeled as crazy or dangerous; negative symptoms, however, such as lack of motivation and blunted affect can lead those with schizophrenia to also be conceived as lazy or uninterested. Much of this stigma comes from misunderstanding of its symptoms and presentation, but we do not fully understand the underlying causes of this disease either. Even more elusive is the reason behind the age of onset for this disorder, which is between late adolescence and early adulthood. As researchers attempt to find better answers to these questions, improve screening, and offer treatments that do more than just mask symptoms, it will be important to focus on how we view schizophrenia and approach its management. 

Why Schizophrenia Occurs – One Piece of the Puzzle

Like most mental disorders, schizophrenia rises from a combination of biological, environment, and social components. You might have heard about factors such as social isolation or specific genes being risk factors, but the way that the messaging systems inside of our cells communicate can have significant impacts on schizophrenia as well. One particular signaling pathway, the Wnt signaling pathway, has been suggested through different lines of evidence to play a part in the development of schizophrenia. The Wnt signaling pathways have a wide range of roles, but are generally involved in development, including the development of the nervous system. In the canonical Wnt pathway, a protein called GSK3 normally works to lower levels of B-catenin (a protein that helps regulate gene transcription) in the cell by marking them for degradation. When Wnt neurotransmitters bind to receptors of this pathway, they inhibit the activity of GSK3. This means that it would no longer lower levels of B-catenin, ultimately allowing B-catenin to enter the nucleus and mediate gene transcription.  

In schizophrenia, it has been proposed that dopamine can alter this pathway by activating GSK3; this would mean that levels of B-catenin are suppressed and unable to regulate gene transcription as normal. Essentially, too much dopamine signaling and not enough Wnt signaling may be mechanisms of schizophrenia development. Other factors can modulate this pathway too – such as the amount of expression for genes such as DISC1 – and therefore have also been suggested to be involved in this development pathway. 

The Onset of Schizophrenia

Interestingly, symptoms of schizophrenia usually do not appear until around 18 to 25 years old, but reasons why symptoms present around this time are not well established. Onset of schizophrenia in childhood is relatively rare, but there is some agreement among experts that schizophrenia does not present ‘out of the blue’ during late adolescence, like its symptoms can make it seem. Instead, symptoms such as hallucinations or delusions are the result of a buildup of molecular changes that start several years earlier, and eventually progress to psychosis.  

A lot of these molecular changes occurring are related to abnormal brain connectivity; during adolescence there is a major reorganization of connectivity between neurons, so this would in part explain the age of onset that is seen. Researchers have found that the DISC1 gene plays a role in connectivity through a couple of different methods. One of these is through forming dendritic spines- the protein expressed by this DISC1 gene acts as a holding place for a protein called Kal-7, which is a critical component of dendritic spine formation in synaptic plasticity, the physical basis for how our brain forms neural connections and “memories”. 

How to Approach Management of Schizophrenia

Given that we do not yet have a medication that can target the underlying cause of schizophrenia or prevent its development, it’s even more critical that we are careful about how we conceptualize this disorder. For individuals with schizophrenia, receiving the proper treatment and support can turn a prognosis from a person being unable to care for themselves to living a functional and rewarding life, whether in the presence of absence of symptoms. Specifically, though, what should be done? In my view, education is possibly the most important step in creating a strong support system for those with schizophrenia. This includes educating the individual, family members of the individual, and communities as a whole; an active focus on education would not only help the individual feel validated through normalizing their experience, but may help families learn how to help their loved one cope and would overall reduce harmful stigma, of just a few possible benefits. As a society that claims to value those who struggle with mental illness, we must take the steps we can to prove it.