Schizophrenia (SZ) and bipolar disorder (BD) are psychiatric disorders that make daily life difficult. The two disorders share similar risk factors and outcomes and are both difficult to diagnose and treat. SZ and BD have also been observed to have high rates of comorbidity, which has led researchers to investigate possible links and similarities between them. Neuroimaging studies have found significant correlations between these two conditions in white matter integrity and grey matter volume. Continuing to focus on how mental illnesses such as SZ and BD are related, rather than researching them individually, will contribute to discovering possible underlying causes and developing better ways to treat comorbid disorders.
Schizophrenia (SZ) is a chronic and disabling mental disorder characterized by disruptions in thought processes and emotional responsiveness, distorted perceptions, and abnormal behavior [1,2]. Despite only affecting around 1% of the world’s population, it is among the top fifteen leading causes of disability worldwide, and individuals with SZ have a significantly higher risk of premature mortality . The causes of the disorder remain unclear; genetics, brain chemistry, and environmental factors are all believed to contribute to its development . However, specific risk factors have been identified, such as a family history of SZ, consumption of mind-altering drugs during adolescence and young adulthood, stress, pregnancy, and birth complications .
The wide range of SZ symptoms generally fall under three categories: psychotic, negative, and cognitive . Psychotic symptoms include altered perception, as well as abnormal thinking and behavior that may result in a distorted experience of the world . Negative symptoms are a diminished ability to live normally, as patients may exhibit social withdrawal, lack of motivation, difficulty showing emotions, and disinterest in daily activities [1, 2]. Problems regarding attention, concentration, and memory are categorized as cognitive symptoms . Symptoms of individuals with SZ vary case by case in severity and type over time .
Bipolar disorder (BD), formerly called manic depression, is a mental illness that causes extreme shifts in mood, activity levels, energy, and concentration . Individuals with the condition experience “periods of unusually intense emotion, changes in sleep patterns and activity levels, and uncharacteristic behaviors” called mood episodes. Mood swings include emotional highs and lows known as mania/hypomania and depression respectively, while the experience of both types of symptoms in the same episode is called a mixed episode . BD is the sixth leading cause of disability in the world and is associated with a shorter life span .
Manic symptoms are characterized by heightened energy, creativity, euphoria, impaired judgment, impulsiveness, lack of sleep, and extreme irritability . Hypomania is a less severe form of mania that generally won’t interfere with day-to-day activities but often precedes manic or depressive episodes . Bipolar depression can be identified through symptoms such as loss of energy, feelings of hopelessness and emptiness, irritability, physical and mental sluggishness, concentration and memory problems, suicidal thoughts, and inability to feel pleasure . Severe episodes of mania or depression may include psychotic symptoms such as delusions or hallucinations . Symptoms vary in frequency, severity, and length of time based on the type of BD, which include bipolar I disorder bipolar II disorder, and cyclothymic disorder . Though no single cause has been identified, factors that contribute to developing BD include brain structure and function, stress, and genetics .
Though psychiatric disorders have traditionally been viewed as unrelated to one another, recent studies have demonstrated high levels of comorbidity between multiple illnesses, which suggest that there may be an underlying cause . SZ and BD are both mental illnesses that often occur together and are exacerbated by other conditions. They are also highly associated with depression and anxiety (SZ: 16.7%, BD: 22.4%), and substance use disorders (SZ: 25.1%, BD: 20.1%) [8, 9, 22, 23].
Obsessive-compulsive disorder (OCD) and obsessive-compulsive symptoms (OCS), as well as their high rates of comorbidity with SZ and BD, are also well documented. Up to 30% of patients with SZ report OCS; 12%–14% of them meet the diagnostic criteria for OCD, while 17% of BD patients were found to also have OCD .
A study conducted by the University of Aarhus in Denmark over a 35 year period established a large comorbidity index between SZ and BD along with schizoaffective disorder, a mental illness characterized by symptoms of both SZ and a mood disorder [10, 12]. Risks of the three psychiatric disorders were estimated through a survival analysis method, while the comorbidity index was indicated by measuring the resulting overlap . According to this method, a SZ patient’s risk of also being diagnosed with BD was found to be 20 times higher than that of the general population .
It’s not yet clear whether the high rates of comorbidity represent the frequent occurrence of two independent disorders, the development of symptoms of one disease in a different disease, or the possibility of one being a risk factor for another. However, comorbidity has been observed to negatively influence the course of SZ and BD . Thus, the treatment is highly challenging, as regular measures for a certain disease are consistently less successful when applied to comorbid disorders and may even exacerbate symptoms . As a result, the diagnosis of and recovery from such disorders is impeded.
As evidence suggesting an etiologic overlap—or an overlap in causes and origin—between schizophrenia and bipolar disorder will continue to grow, researchers have turned to neuroimaging techniques, such as MRI scans, to detect and compare distinguishing characteristics in the brains of patients with the two disorders.
White matter (WM) is responsible for neuronal connectivity and is composed of closely packed nerve fibers, or axons, that are coated in myelin sheath. By uniting the different regions of the brain, white matter forms networks that perform various mental operations necessary for normal mental function . Through diffusion tensor imaging, an MRI-based neuroimaging technique, WM can be mapped out in the sense of a skeleton .
Structural neuroimaging studies of BD and SZ suggest white matter integrity deficits and abnormalities are consistently widespread over 30% of areas of the whole-brain WM skeleton in both SZ and BD . Shared white matter abnormalities in SZ and BD were observed in the brain regions uncinate fasciculus, corona radiata, anterior limb of the internal capsule, and anterior and posterior thalamic radiation .
White matter abnormalities were consistently found in the corpus callosum for both disorders, suggesting that disruptions in interhemispheric communication may be a common component in the two diseases . The white matter integrity of the corpus callosum is related to cognitive performance such as sustained attention, processing speed, and problem-solving abilities, which are frequently impeded in SZ and BD . Both conditions also showed impaired integrity of the white matter microstructure between the frontotemporal and frontal-subcortical regions, which are areas associated with emotional and cognitive processes that tend to be disrupted in BD and SZ . The extensive white matter deficits indicate that abnormal structural connectivity may play a key role in the pathology of both disorders . Notably, no significant correlation was found between WM integrity and any type of medication, psychotic symptoms, or manic symptoms in either SZ or BD patients .
SZ and BD have also been found to be associated with grey matter volume reductions, though abnormalities are more widespread in SZ than BD . Various neuroimaging studies have reported extensive grey matter deficits in frontal, temporal and subcortical structures in SZ, while BD has reductions in overlapping brain regions . Shared regional decreases of grey matter volume in the thalamus, dorsal anterior cingulate, and insular lobe have also been documented [13,14].
In the past, mental disorders such as schizophrenia and bipolar disorder have been treated
as separate and unassociated diseases. However, there is growing evidence that SZ and BD share significant similarities in risk factors, symptoms, neurobiological features, and outcomes . Thus, an increasing number of scientists have been shifting towards investigating possible links between the two disorders, with clear commonalities in characteristics having been found through neuroimaging that point towards connections in pathology. Further studies may eventually be helpful in identifying individuals at risk for developing either SZ or BD and make diagnoses more accurate. Findings may also aid in making the treatment of comorbid BD and SZ more effective. Individuals with comorbidity usually have worse symptoms and treatment outcomes, and treating the underlying cause or the comorbid diseases together would likely be more successful than treating them separately . Mental illnesses are more closely correlated than previously thought, and researching them as such may lead to significant progress for scientists and healthcare professionals.
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