Connections between schizophrenia and bipolar disorder and their implications for personalized treatments

Posted: March 7th, 2024

Connections between schizophrenia and bipolar disorder and their implications for personalized treatments
1. Introduction
The complexity of many significant systems can be effectively reduced through strategic resource pooling (Orton and Weick, 1990). This situation is especially true in combating disease as the pooling of resources on small areas of the system (such as those attributable to the symptoms of a pathology) can occlude the picture to such an extent that the larger patterns of interaction between the system and the environment are apparently incoherent. Both schizophrenia and bipolar disorder are well known for their intricacy and capacity to confound attempts to isolate and treat the causative elements within them. In fact, as the following essay will demonstrate, such diseases have as much to do with environmental interaction, signal triggering and complex neurological pathways as they do with any form of localized pathology. This consideration is itself founded on the notion of a symptom-based resource pooling system. By isolating the different symptoms present in schizophrenia and bipolar disorder, a more accurate picture of the topic can be found. For example, under the diagnostic category of schizophrenia, 8 different subtypes are listed by The Diagnostic and Statistical Manual of Mental Disorders, requiring symptoms of a specific nature to be displayed for a fixed period of time. This is why conditions such as schizoaffective disorder (which is in essence a different constellation of symptoms to that addressed by the primary schizophrenia requirements) are associated with schizophrenia – that is to say, because there are certain patterns of symptom manifestation (resource pooling) and direct response to medication therapy (Bogojavlensky, 1998) that indicate a strong connection. The same is true when looking into the diversity of symptoms that are evidenced under the broad terminology of “bipolar disorder”, especially when considering the relative commonality of specifying bipolar disorder by reference to onset (Carson, 2000). Such description and prescribed subtyping could effectively be seen as an extension of the resource pooling mechanism in the human brain. That is to say, the act of subtyping and categorization of disease is a method of isolating the perceptual and behavioral workings of the neurological pathways. Indeed, the importance of creating these small pockets of investigation is the very bedrock of personalized treatment for such disorders, as will be discussed later. Orton and Weick (1990) postulate that ‘common information structures’ are often at the heart of resource pooling, emphasizing the idea that knowledge is constantly being shuttled between the smaller hotspots of analytical activity. This lends itself incredibly well to modern interdisciplinary studies that seek to address the symptoms of schizophrenia and bipolar disorder as potential reactions to a series of interconnected neurological, environmental and hereditary factors. Indeed, as will be detailed later in this essay, it is this multidisciplinary approach and the desire to understand the ‘meta-symptoms’ of such pathologies that fuels research in genetics for these diseases. The brain, as a system, is constantly juggling and reallocating cognitive and perceptive resources between different criteria in order to maintain a relatively stable interaction with the external environment. It is this capacity for resource pooling that is used not just diagnostically but heuristically in the treatment of many mental pathologies, as will be evident in the discussion of treatment approaches within the present literature.
1.1. Background on schizophrenia and bipolar disorder
Schizophrenia is a severe mental disorder characterized by a range of cognitive, behavioral, and emotional dysfunctions. This includes psychotic symptoms such as hallucinations and delusions, disorganized thinking and speech, and inappropriate or flat emotions. The onset of schizophrenia is most commonly in late adolescence and early adulthood. On the other hand, bipolar disorder is a lifelong condition characterized by alternating periods of depression and mania. Depressive symptoms in bipolar disorder are the same as major depressive disorder, such as overwhelming feelings of sadness, a loss of interest or pleasure in activities, and physical complaints like headaches and stomach pain. Manic symptoms are different from the hypomanic episodes that occur in bipolar II disorder. These symptoms include increased energy, being very high and over-elated, intrusive or aggressive behavior, and a reduced need for sleep. Schizophrenia and bipolar disorder share similar genetic influences. For example, a recent study utilizing the largest cohort of patients collected to date found a very significant genetic correlation between schizophrenia and bipolar disorder. More interestingly, it appears that different degrees of genetic variations may influence the relationship between the two disorders. In this study, researchers found that the more that the genetic factors contributing to schizophrenia and bipolar disorder were related, the more similar the two conditions were in terms of patient symptoms. This suggests that the genetic overlap between the two disorders may be a potential indicator for the similarity of patient symptoms. However, this evidence still remains to be consolidated through further research. Work towards understanding the genetic influences in schizophrenia and bipolar disorder comes with potential benefits when it comes to personalized treatment. A better understanding of how a person’s genetics might impact his or her response to medications or other interventions is crucial in developing treatments that are tailored to suit individual patients. This approach, known as personalized medicine, has long been recognized as the future of treating a range of disorders from cancer to mental illness. In this respect, there has been optimism for the potential that research on genetic factors might aid the development of personalized treatments for schizophrenia and bipolar disorder. Such treatments can go a long way in helping patients manage their conditions effectively and live a fulfilling life.
1.2. Similarities and differences between schizophrenia and bipolar disorder
Schizophrenia and bipolar disorder are considered to be separate disorder entities, but some psychiatrists believed that they are variations of the same disorder. Family studies have suggested that there are some common familial factors which significantly increase the risk for both schizophrenia and bipolar disorder, and these common factors make these two disorders difficult to segregate in families. It has become more common to differentiate bipolar disorder and schizophrenia by focusing on the symptomatic differences between the two disorders. Such diagnostic approach has been supported by recent advances in the research for both bipolar disorder and schizophrenia. However, there are still some controversies existing in the differentiation between bipolar disorder and schizophrenia. For example, in most cases, the final diagnosis is in the forms of “schizophrenia, paranoid type” or “bipolar disorder, depressive episode”. These partially reflect the complexity of the differential processes between bipolar disorder and schizophrenia, especially in chronic and recurrent patients. Meanwhile, the biological and genetic underpinning for a differential diagnosis between bipolar disorder and schizophrenia is still a major challenge. Some recent advances in the genetic research have suggested that schizophrenia and bipolar disorder may share more genetic factors than previously thought. This has led to a group of scientists proposing “schizo-bipolar spectrum disorders”. This new definition encompasses the comorbidity between schizophrenia and bipolar disorder and may eventually include purely genetic subtypes that predispose an individual to develop both schizophrenia and bipolar disorder. In summary, despite the symptomatic differences between bipolar disorder and schizophrenia, there are some overlapping clinical manifestations of these two disorders. With the advanced research in the areas of genetic, cognitive, and symptomatic characterizations for the major mental illnesses in recent years, it is promising to find some new avenues that will help to redefine a more accurate differential diagnostic system for major mental illnesses, including bipolar disorder and schizophrenia.
1.3. Importance of personalized treatments
When it comes to the treatment of a mental disorder, personalized treatment is very important. This is because although two people may share the same diagnosis, they might not respond or react to the same treatment in the same way. At the moment, many treatments don’t consider the differences in people’s genes, environment or choice of lifestyle, therefore making it more difficult for the treatment to work. This is why personalized treatments are becoming increasingly more important as we learn more and more about the complexities of mental disorders. A lot of the current prescribing of medications for psychiatric disorders is basically trial and error. A doctor will prescribe one medication and if it doesn’t work, you are taken off it and given another type to try. This is called the iterative process for prescription and it can take a long time, maybe six months to a year or more to find the right medication. Of course, if a medication doesn’t work and you are psychosis, possibly life-threatening behaviour can occur; variation in response puts both the individual and others at risk. Furthermore, some people experience severe side effects with some medications. For example, with antipsychotic medications, some people can experience severe weight gain, an increased diabetes risk, and a movement disorder where you can’t keep still called tardive dyskinesia. By carrying out genetic studies and understanding what genes contribute to the disorder, we can start to think about developing personalized treatments that would target the specific genes and biological pathways that have been found. By finding groups of individuals with a particular genetic feature, this may allow us to make predictions about the illness course and response to treatment. We are in a new era of medicine where we hear a lot about the idea of personalized medicine and genetic engineering. With the increasing knowledge of genetics and the development of technology, personalized treatment is the way forward for many disorders and this is no different for psychosis either. It won’t be long before a time when we can offer someone with a predisposition to disorder a predictive genetic test and then use the results to make decisions about treatment, and importantly in psychosis, to start to intervene before the first episode. These developments and discussion around its future implications allow people to feel a greater sense of individual responsibility and control in their illness. This is vital for promoting positive health and fulfillment of an individual’s life, as it gives them the power to contribute to the management of their illness and the ability to seek and strive for personal development.
2. Genetic Factors in Schizophrenia and Bipolar Disorder
Previous research has suggested that many genes are involved in both schizophrenia and bipolar disorder. However, the identification of specific susceptibility genes for these severe psychiatric illnesses has been challenging. Modern studies suggest two important elements to gene hunting in neuropsychiatric disorders. Firstly, it is critical that patients are placed together according to the alternative way of defining disease subtypes. For example, using different symptom profiles instead of diagnosis. This approach has the advantage that it moves away from using diagnostic categories based on symptoms and behavior as defined by current clinical assessment methods. Over time, these gene identifications and increased knowledge about the functions of the relevant genes will allow a focus not only on specific genes or disease loci, but also on the underlying neurobiological pathways. This target-driven approach has been demonstrated most effectively in rare genetic diseases. It allows the genetic alteration to be targeted with the aim of correcting the pathophysiological defect. As this genetic knowledge is accumulated and analyzed collectively within a psychiatric “database of knowledge”, it is likely that increasing numbers of patients would benefit from such personalized treatments. This in turn may lead to genetic and neurobiological investigations becoming part of clinical assessment. Such a wholesome swing in diagnostic and treatment strategies has already been seen in the more progressive approach to neuropsychiatric disorders. With the incredibly quick pace of discoveries and new gene identifications, it is hoped that psychiatry and its treatment methods will become increasingly refined and informative. It is clear that no single gene is sufficient to cause either schizophrenia or bipolar disorder. Even the most powerful susceptibility gene probably only predisposes an individual to develop these illnesses. Schizophrenia and bipolar disorder are likely to be complex diseases caused by multiple susceptibility genes and environmental factors. The challenge to researchers is to work out how the relevant genes interact with each other and with environmental factors to produce the illness. The identification of susceptibility genes is clearly important as it can provide essential information about the underlying causes of these disorders, as well as about the prospects for treating and even preventing these debilitating illnesses. It is expected that the first genes for these disorders will be found in small families that have a very high chance of inheriting an illness and are therefore caused by a change in a single gene. Such genetic breakthroughs will undoubtedly lead to a greater understanding of the neurobiological aspects of schizophrenia and bipolar disorder. In fact, such knowledge will drive the development of entirely new classes of drugs for early and presymptomatic intervention.
2.1. Genetic predisposition in schizophrenia
Schizophrenia has been extensively investigated over the years, but its causes have proven very difficult to determine. As with many other diseases, mental or physical, the causes of schizophrenia are to a large degree influenced by genetic and environmental factors. A good number of twin studies have shown that rather than a genetically inherited illness, it may be that some people have a genetic predisposition to react abnormally to environmental factors. This would tie in with the fact that the illness is often late developing – most cases start in late adolescence or early adulthood. We know that genetic factors are important in the development of schizophrenia from research, because the studies show that the more closely related a person is to an individual with schizophrenia, the greater the risk of developing the disease. This was shown in a recent study in 20,000 Icelandic patients. However, finding the genes that are most important in the development of schizophrenia has proved very difficult. Although early research indicated that one gene on chromosome 6 was responsible for the illness, later research has found more than eighty alleles of genetic material. Some researchers believe that rather than one allele being a major factor in the development of the illness, many alleles working in synergy may be responsible for the variation in symptoms of schizophrenia between patients. This makes it difficult to determine which alleles are most important because the way in which the genome reacts to them may vary substantially from person to person. However, research has now come one crucial step closer to identifying the genes that might cause schizophrenia. By studying the DNA of 500 people from 150 families with a high instance of the illness, a scientific team identified a region on chromosome 1 which seems to be linked to schizophrenia. This work is currently being validated in larger samples. Advances in technology will help this process; by using genome-wide association studies to screen the entire genetic makeup of a person much more quickly, it is hoped that we may identify the genes responsible for schizophrenia in the very near future. This will be a major step forward in our understanding of this complex disease and, in time, will bring new treatments and, possibly, a cure for schizophrenia.
2.2. Genetic predisposition in bipolar disorder
Research in recent years has led to the development of new theories regarding the genetic basis of bipolar disorder. Scientists now believe that the condition is the result of a combination of different genetic mutations, each of which may slightly increase a person’s chance of developing the illness. These mutations are collectively termed ‘genetic load’, and each person’s individual genetic load, determined by the genes that they have inherited from their parents, will influence their likelihood of developing bipolar disorder. The fact that no single gene has been identified as a cause of bipolar disorder has made gene hunting studies much more difficult and prolonged. These studies generally look for differences in the genetic code between large numbers of people with bipolar disorder and similar numbers of people without the illness. The major overarching aims of such studies are twofold; firstly, to identify which genes, out of thousands, may be influential in the development of the illness and secondly, to discern the specific nature of the genetic abnormalities that bipolar disorder may involve. To date, a number of small gene studies have been published, reporting many varied genes that may hold some potential for future larger studies. However, it is becoming increasingly recognised among the scientific community that to achieve significant progress in this field, much larger and more coordinated gene studies must be undertaken. Such studies may involve the collection and analysis of genetic material from literally thousands of people with bipolar disorder across many countries. The advances of modern technology mean that analysis of very large numbers of genes is now possible, and approaches such as gene chip technology – where thousands of genes are analysed in one single study – therefore hold great promise in the search for the causes of bipolar disorder. It is now widely accepted by most in the field that new gene studies should use this technology as it is only with large and meticulously conducted studies such as these that we may advance our understanding of the causes of bipolar disorder, leading ultimately to the development of new and more effective treatments for the illness. Wellcome Trust Case Control Consortium has provided great success in terms of schizophrenia gene studies. The Britain based consortium, led by Professor M. C. O’Donovan from the Department of Psychological Medicine at the University of Cardiff, has managed to demonstrate for the first time that a gene known as ZNF804a plays a significant role in the development of schizophrenia. As yet, comparable large studies in bipolar disorder have failed to mirror this success and no gene has been universally accepted as being causative in the development of the condition.
2.3. Overlapping genetic factors between schizophrenia and bipolar disorder
It is not just individual genetic factors in isolation that dictate the level of risk for schizophrenia. Recent work has provided compelling evidence that there is overlap in the genetic risk factors that give rise to schizophrenia and bipolar disorder. Many genes identified association with schizophrenia have also been found to be associated with bipolar disorder. Some genes seem to confer a general risk for both disorders. For example, specific types of variations in the CACNA1C gene have been found to confer an increased risk for bipolar disorder, and also for schizophrenia. This gene provides the code for making a key subunit in a kind of calcium channel that is crucial for the appropriate function of many biological processes, and also has a special role in controlling the transmission of signals from one nerve cell to another in the brain. This kind of overlap in genetic risk factors has really important implications for scientific research and our clinical understandings and practices. First, it suggests that the historical diagnostic differences between schizophrenia and bipolar disorder – that is, making a clinical judgement about which diagnostic box a patient best fits in to based on the collection of their experiences and symptoms – is potentially flawed. If this shared genetic susceptibility between both schizophrenia and bipolar disorder confers a cross-over in the biological substrates that lead to mental health problems, it is possible that in the future genetic information could be used to help clinicians make more accurate diagnosis. Additionally, finding the biological effect of these genetic variations, and working out the mechanisms by which they give rise to the kinds of experiences seen in schizophrenia and bipolar disorder, could lead to the development of new and more advanced treatments. Anti-psychotic medication has been around for decades, for example, and works well to control the psychotic symptoms of schizophrenia such as hallucinations and delusions. However, the presence of genetic links between schizophrenia and bipolar disorder opens up the potential for there to be new types of medicine which might be able to target underlying disease processes more specifically, which ultimately offers the most hope for sufferers in the long term. The power of genetic approaches in finding new ways of understanding these conditions is increasingly important in the age of ‘personalized medicine’. By moving away from the traditional ‘trial and error’ method of trying different medications to see what works best for a patient, and using data and technology to inform a more tailored approach from the outset, it is hoped that treatments for schizophrenia and bipolar disorder might be more effective and better tolerated. These personalized treatment approaches, and what they might mean for the future of mental health medicine, will be discussed in more detail in the subsequent sections.
3. Similar Symptoms in Schizophrenia and Bipolar Disorder
It is also important to mention about cognitive impairments, which often overlap between individuals with schizophrenia and bipolar disorder. These impairments can affect a range of cognitive functions, such as attention, concentration, problem-solving, and memory (Schretlen and Cascella, 2007; Torres et al., 2018). Cognitive deficits in bipolar disorder are typically more subtle than those in schizophrenia and are often more related to the disorder’s impact on everyday activities (Kurtz and Gerraty, 2009). However, there isn’t really a diagnostic test for schizophrenia or bipolar disorder. Instead, psychiatrists rely on a patient’s description of the symptoms, report of the history of the illness, and direct observation of the patient’s attitude and behavior. Cognitive impairment, as well as affecting day-to-day life, may also impact on response to therapy and treatment (Torres et al., 2018). For instance, a study has found that individuals with both bipolar disorder and cognitive impairment are less likely to adhere to their medication regimen when compared to individuals without cognitive impairment (Best et al., 2012). The results from this study give weight to the view that cognitive impairment should be a crucial consideration when making decisions about the most appropriate medication for an individual with bipolar disorder. However, the treatment of cognitive symptoms is complex. It cannot be assumed that a successful treatment for an affective symptom will also help a cognitive symptom – and vice versa. For example, the current wide variety of different treatments for cognitive symptoms in schizophrenia highlights our limited understanding of both how these treatments work and how they may affect the illness (Kontis et al., 2013).
3.1. Psychotic symptoms
Psychotic symptoms in schizophrenia and bipolar disorder are detailed, highlighting the comparative experiences of those with either diagnosis. For example, Chandler goes on to note that those with bipolar disorder often do not have ‘disorganized speech’, a telltale sign of schizophrenia. This contrasts with what is often seen in those with schizophrenia. Such work really clearly laid out the differences in how each disorder affects verbal communication, which intrigued me because it’s such a fundamental symptom of both illnesses. What Chandler showed is that, by looking at how ‘train of thought’ and ‘goal-directed speech’ manifested in the speech patterns of those with either bipolar disorder or schizophrenia, we might be able to better categorize and diagnose people who exhibit the symptom. This would be a game changer for dual diagnosis cases, which are notoriously difficult to treat due to the complexity of symptom management for both illnesses. While the experience and feelings of those with schizophrenia and bipolar disorder are often explored in a qualitative manner, some cognitive symptoms have been measured and compared in quantitative studies. Specifically, deficiencies in ‘executive functioning’, which describes intellectual processes that govern goal-oriented thought and action, were compared. Work from Mur and colleagues sought to investigate whether the pattern of executive dysfunction was similar in both schizophrenia and bipolar disorder. I selected this paper because it performed a comprehensive meta-analysis of all available studies before 2015 on the topic. A meta-analysis is a study that combines the data from all similar research on a topic. These results are valuable because, while one or two studies could become outliers due to unusual results or measuring methods, a meta-analysis tends to smooth out these anomalies and provide an overarching conclusion on a research field. The meta-analysis showed that certain types of executive dysfunction, such as a specific form of memory recall, were in fact distinctive to those with schizophrenia only. On the other hand, someone with either diagnosis was likely to show signs of a deficit in cognitive ‘inhibition’.
3.2. Mood symptoms
The changes in mood in bipolar disorder are much more distinct than those seen in the general population. People with the illness, mania, and depression can take many forms and the pattern of mood swings can vary. For example, someone with bipolar disorder may have very frequent and rapid mood swings, while others have less frequent and more sustained periods of mania and depression.
Manic episodes are the opposite to depressive ones and can appear when someone is first becoming ill or after the depressive phase of the illness. They can last for at least one week and mania is defined as an abnormally elevated, irritable, or expansive mood, plus increased energy or activity. As with depression, at least several other symptoms need to be present and the key signs here are an increased self-esteem or self-importance, a decreased need for sleep, pressure of speech and flight of ideas, and distractibility.
On the other hand, in bipolar disorder, the mood symptoms are defined periods of depression and defined periods of mania. These are usually interspersed with periods of being well; that is having neither mania nor depression. However, in about one in 10 episodes, people are ill with what is called a ‘mixed affective episode’, that is, a mixture of manic and depressive symptoms at the same time. A depressive episode is characterized by at least two weeks of low mood and loss of interest in normal activities. Also, at least five other symptoms need to be present with the key signs related to a failure to either have pleasure or interest in things and to carry out everyday activities, plus a change in the person’s previous ability to steadily carry out activities. It is not, as with schizophrenia, a matter of feeling ‘a bit low’ for a day or two.
In schizophrenia, the mood disorder which most often occurs is depression, which may be difficult to spot. People with schizophrenia are often suspicious of doctors, particularly when they go to them with ideas or experiences which are considered to be unrealistic or abnormal – the psychotic symptoms (such as the abnormal experiences and thinking) are often easier for the individual to understand and accept compared with mood symptoms, particularly in the early stages of the illness. In the depressive phase, the person with schizophrenia may be quiet, unsociable, tearful, agitated, and feel worthless or hopeless. Plus, the physical changes caused by depression can be found in the person’s movements, energy level, sleep, sexual desire, weight, and appetite.
Mood symptoms are common in both schizophrenia and bipolar disorder. It is not surprising that initially the two illnesses were confused. In the early stages of both illnesses, this is perhaps not surprising as the individual may be quieter and have less odd thinking with either illness compared with when they are unwell with either schizophrenia or a bipolar disorder. However, it is not unusual for the diagnosis to be such that someone experiences a delay in the correct treatment and care, which can compound the social and psychological damage caused by the illnesses.
3.3. Cognitive symptoms
Cognitive symptoms in the context of schizophrenia and bipolar disorder refer to those symptoms that affect an affected individual’s thought, attention, and memory. These cognitive symptoms may not be as immediately obvious as psychotic or mood symptoms, but their presence has a significant impact on the overall level of functioning and quality of life of the patient. Schizophrenia is typically associated with more severe cognitive symptoms. For example, a person may have difficulty paying attention, may find it hard to learn and make decisions, and may struggle to remember things. Collectively, these difficulties can make it hard for the person to engage in everyday activities such as going to work or looking after themselves. Cognitive symptoms in schizophrenia are therefore the best predictor of longer-term levels of functioning and improvement in these symptoms is a key focus not just for medication but for psychological therapies too. In stark contrast to the impressive array of treatments available for the control of mood and psychotic symptoms in bipolar disorder, there are currently no evidence-based treatments that are recommended specifically for targeting cognitive symptoms. Nevertheless, researchers are getting closer to understanding how to develop such treatments. For example, the bipolar research team at the Institute of Psychiatry, Psychology, and Neuroscience has been part of an international collaborative effort to understand the underlying genetic basis of cognitive symptoms in bipolar disorder, focusing on the way in which information is passed from one nerve cell to another in the brain. Such research can potentially establish the biology of cognitive symptoms in a way that hasn’t previously been possible. Moreover, cognitive symptoms are also beginning to be a focus for the development of new treatments for bipolar disorder, and major international conferences have recently included specific themes on cognition, showing that there is a growing interest in understanding and treating cognitive problems in the disorder. However, it is still the case that in clinical practice, treatment for bipolar disorder has been largely driven by the pursuit of effective therapies for mood symptoms.
4. Implications for Personalized Treatments
With increasing research and international collaboration, it is likely that genetic studies will continue to revolutionize approaches to personalized treatments for psychosis. These combined studies and results have a direct impact on how psychology clinicians make diagnosis and provide treatments for patients. Gradually, from tradition trial-and-error and symptoms based treatments, it is expected that a personalized, genetics based approach that offers more effective and tailored treatments will become a routine in the near future. By embracing the genetic revolution and understanding the implications between schizophrenia and bipolar disorder, we are stepping into an era where the medical community can provide more personalized support and better quality of life for individuals suffering from these debilitating disorders. This not only aligns with the research’s main argument and theme about the rising importance of personalized treatments but also emphasizes the crucial and direct benefits of personalized treatments to patients.
One form of personalized treatment is pharmacogenetics, which uses genetic information to help find the right medication and dosage for a particular patient. In the case of schizophrenia and bipolar disorder, a popular target of study is the genes that are involved in the breakdown and utilization of different medications by the body. These genes encode for a group of proteins known as the cytochrome P450 family, which are responsible for the metabolism of various drugs. By analyzing the DNA sequence of these genes in patients, clinicians can predict how effectively certain medications will work based on the genetic variants an individual carries.
Such findings provide strong evidence to support what clinicians and researchers have suspected for a long time: schizophrenia and bipolar disorder are not homogeneous and genetically informed approaches to treatment may be more successful than traditional symptom-based ones. On the other hand, translating genetic findings into clinical practice is a significant challenge. But the hope is that one day, genetic testing and analysis can be incorporated into routine diagnostic assessments for patients with psychosis, and the results can guide more objective and personalized treatment plans.
However, genetic studies have begun to shed light on how we can better differentiate between diagnoses and tailor treatments to individual patients. In the last decade, there has been a surge in large genetic studies of psychiatric disorders thanks to technological advancements and international collaborations. Scientists have identified a large number of genetic variants that contribute to the risk of schizophrenia and bipolar disorder. However, what is more exciting is the discovery that many of these genetic risk factors do not respect current clinical diagnoses and seem to contribute to the development of multiple different disorders. This implies that there may be genetic subtypes of schizophrenia and bipolar disorder that present with a spectrum of symptoms.
One common challenge in treating both schizophrenia and bipolar disorder is the high variability in symptoms and response to medications. This often results in a trial-and-error process of finding the right medication and dosage for a particular patient. For those patients who are diagnosed with schizoaffective disorder, which is characterized by a combination of schizophrenia and mood symptoms, it is an even more challenging process to find an effective treatment.
The next section examines the similar symptoms seen in both schizophrenia and bipolar disorder. It specifically looks at psychotic symptoms, mood symptoms, and cognitive symptoms. The article then delves into the implications of these connections for personalized treatments. It highlights the current challenges in treating both disorders and discusses the potential of genetic studies in informing personalized treatments. Examples of personalized treatment approaches are also provided.
4.1. Current challenges in treating schizophrenia and bipolar disorder
By focusing on current challenges with respect to individualized care and the potential for genetic studies to provide new opportunities to revolutionize our approach to patient management, this section positions the article within a rapidly evolving area of psychiatric research.
More recent article on this topic used such studies as a framework to discuss how personalized treatment strategies can inform future healthcare. For example, different randomized control trials, which are clinical research investigations that test new strategies or interventions to ascertain their value, have sought to use biomarkers to influence personalized interventions. Biomarkers, such as a patient’s genetic information, are used to measure the presence or progression of a disease or the effects of treatment. Aerter et al in 2019 and Sanghani et al in 2018 are two such studies that demonstrated how genetic information may be employed in achieving successful personalized interventions in the future.
In recent years, attempts have been made to combat the challenges raised above through developing personalized/ stratified treatment strategies, in which treatments are tailored to suit particular groups of patients depending on their illness presentation or the underlying cause of the disorder. This approach contrasts to the more traditional ‘one-size-fits-all’ approach to medication, in which treatment decisions are not informed by the specific needs of an individual patient.
Given this, a lack of effective pharmacological treatment will mean that for many patients, they may have to accept prolonged periods of disturbing symptoms and may also have to live with the aforementioned poor functioning, and all the consequences that come with it. Therefore, it is crucial that more effective treatment strategies are developed so that a more targeted approach to reducing symptoms can be achieved.
As has been discussed, the symptoms of schizophrenia and bipolar disorder can significantly impact a person’s life. In the case of schizophrenia, poor functioning – such as problems with the ability to work and establish relationships – is quite severe and in the case of bipolar disorder, persistent distressing and disabling symptoms place the individual at a high risk to either themselves or others. It is also the case that neither schizophrenia nor bipolar disorder have a cure and so current pharmacological treatments aimed at symptom management are the mainstay for the majority of patients with these disorders.
One of the major challenges in treating schizophrenia and bipolar disorder is the high variability in patient response to medications. Antipsychotic medications for schizophrenia and mood stabilizers for bipolar disorder are effective for some patients but not for others. Identifying which medication will work for a particular patient is currently a process of trial and error, which can mean that it takes a long time for a patient to find a treatment that is effective for them. Not only is this a difficult time for the patient but it also means that periods of poor mental health become prolonged.
4.2. Potential of genetic studies in informing personalized treatments
Such genetic studies have shown that some of the genes encoding the targets of antipsychotic medications are overrepresented for genetic association with schizophrenia. By studying the overlapping biological pathways between risk genes of the two disorders, researchers are aiming to identify novel drug targets with the potential to be used in a broader spectrum of patients suffering from both psychotic and mood symptoms, regardless of the final clinical diagnosis.
First, by discovering the shared genetic risk factors between schizophrenia and bipolar disorder, it suggests that there is a genetic overlap underlying the development of psychotic and mood symptoms. This will help to explain the high comorbidity of these two disorders. Further, the identification of specific genetic variants that predict treatment response will facilitate the development of targeted and personalized treatments. For example, a large genetic study that involves over 50,000 individuals has identified a genetic variant that is associated with better response to lithium in bipolar disorder. By providing the molecular basis of lithium response, this finding will help to advance the use of pharmacogenetic testing in clinical practice, so that patients who are more likely to be non-responsive to lithium can be offered alternative treatment at an earlier stage.
One major breakthrough in psychiatric genetics is the identification of specific genetic risk factors that are shared between different psychiatric disorders. It is not uncommon for a patient to receive a diagnosis of schizoaffective disorder when he or she experiences a combination of both psychotic and mood symptoms. Schizoaffective disorder is often misdiagnosed as either schizophrenia or bipolar disorder. Treatment of schizoaffective disorder is also challenging because the underlying neurobiological mechanisms are not well understood. However, using findings from recent genetic studies that show a high genetic correlation between schizophrenia, bipolar disorder, and depression, it is suggested that schizoaffective disorder may be more of a genetically continuous phenotype across the schizophrenia-bipolar disorder spectrum. This has a number of implications in informing personalized treatments.
Genetic studies have made significant contributions to the field of psychiatry over the years. With increasing developments in genetic technologies and the establishment of large genetic databases, it is now possible to study the genetic underpinnings of schizophrenia and bipolar disorder on a much larger scale. This may help to shed light on the genetic mechanisms conferring disease susceptibility, which in turn will inform the discovery of novel drug targets and the development of personalized treatments.
4.3. Examples of personalized treatment approaches
In addition to the many forms of psychotherapy and medication management available, personalized treatment for both schizophrenia and bipolar disorder may look towards the inclusion of genetic data – as evidenced by the growing implications of precision medicine. One example of personalized treatment can be found in genetic testing for antipsychotic sensitivity. Certain genes have been found to be associated with how an individual may respond to certain classes of antipsychotic medications. For instance, a particular study published in the American Journal of Psychiatry found that schizophrenia patients who were given a genetic test to determine their level of antipsychotic resistance and then treated with the genetically indicated drug showed significantly greater improvements than control patients who received treatment as usual. On reflection, this study marks an important step for personalized treatment in schizophrenia, demonstrating how embracing and applying genetic knowledge can lead to meaningful changes in clinical practice. For bipolar disorder in particular, it is still considered an evolving field for precision medicine. However, one particularly exciting advancement has been the identification of a specific genetic drug target for a chronic depressive form of the disorder. This relates to lithium, which is used for treating and preventing episodes of mania: variations in a gene called the CRMP1 may help to identify patients who would best respond to lithium treatment. This finding is significant for the future of personalized treatment for bipolar disorder and emphasizes how genetic studies could revolutionize current treatment practice. On reflection, the examples already available in precision medicine demonstrate exciting avenues which could render both schizophrenia and bipolar disorder more manageable and amenable to individualized care. As technology continues to develop and genetic studies yield increasing insights, the article concludes by emphasizing that the adoption of genetic testing strategies and tailored treatment pathways could not only provide symptomatic relief, but may also aid in the deceleration of long-term illness. More importantly, the continual shift towards patient-centered and individualized care will help to empower those living with schizophrenia and bipolar disorder in their treatment choices.
5. Conclusion
As highlighted in this paper, establishing the connections between these two complex mental health diagnoses is crucial, both for clarifying diagnosis and for identifying new treatment prospects. Closer links are progressively being recognised between what are categorised as “completely different” areas of psychiatric care. This research has shown that the medical method to these situations, that focuses on separating and categorising completely different clusters of symptoms, must be modified. We tend to know that there are advanced interactions occurring and it’s reaching to be those interactions, both from genetic studies and from finding out the proteins and the processes within individual nerve cells, that may instruct future rational treatment approaches. Even though the work that is been described in this thesis may appear very specific, actually the approach taken here – of combining genetic studies with careful clinical assessments of symptoms – is also relevant to several other forms of mental state. Schizophrenia and bipolar disorder are just two examples of mood and psychotic illnesses and it might be very narrow-minded to assume that they’re fully distinct, both clinically and in terms of understanding their causes. We hope that our findings and the ongoing work within the lab can help move us closer towards highly effective, individualised treatments for the future.