Schizophrenia: symptoms, genetics, and treatment challenges

Schizophrenia

When people think of what it means to 'go crazy,' quite often the common image that comes to mind is that of someone with schizophrenia. Schizophrenia is a serious mental health disorder that can be physically, socially, and personally destabilizing. "Schizophrenia affects men and women equally. It occurs at similar rates in all ethnic groups around the world. Symptoms such as hallucinations and delusions usually start between ages 16 and 30. Men tend to experience symptoms a little earlier than women. Most of the time, people do not get schizophrenia after age 45.Schizophrenia rarely occurs in children, but awareness of childhood-onset schizophrenia is increasing" (Schizophrenia, 2012, NIMH: 2). The disease is fairly rare "about 1% of Americans have this illness," but it is so debilitating the illness warrants further research and attention (Schizophrenia, 2012, NIMH: 2). While symptoms vary with every person, some of the most common include auditory hallucinations and disordered thinking. Movement disorders such as catatonia have also been noted and a 'negative effect' or an inability to respond normally to stimuli as well as the 'positive effect' of responding to stimuli others do not recognize (Schizophrenia, 2012, NIMH: 2).

Another important reason for further research on the topic is the fact that the causation of schizophrenia remains unclear. Genetics seems to play a key component in the development of the disorder. Although it only occurs in 1% of the population, schizophrenia occurs in 10% of persons "who have a first-degree relative with the disorder, such as a parent, brother, or sister" and even having second-degree relatives or distant relatives with schizophrenia significantly increase the likelihood of developing the disorder. "The risk is highest for an identical twin of a person with schizophrenia. He or she has a 40 to 65% chance of developing the disorder" (Schizophrenia, 2012, NIMH: 6).

Yet this raises an intriguing question -- although genetics has a significant impact upon the likelihood of developing the disorder, even in the cases of identical twins not EVERY set of identical twins, raised together, becomes schizophrenic. Environment must play some role in the manifestation of schizophrenia, although the precise impact is unclear. This statistic points to the fact that schizophrenia is caused by multiple environmental factors. "Studies of brain tissue after death also have revealed differences in the brains of people with schizophrenia. Scientists found small changes in the distribution or characteristics of brain cells that likely occurred before birth" but it is uncertain that these brain changes are the result of the illness, or a precursor of the ailment (Schizophrenia, 2012, NIMH: 6).

As well as its complex causation, another motivating factor to study schizophrenia is the fact that treating schizophrenia can be so stubborn and so difficult. The severe and debilitating side effects of the original antipsychotics such as Thorazine and Haldol used to treat schizophrenia led many sufferers to not to take their medications. These antipsychotics caused tardiac dysconesia (Parkinson's disease-like tics) which did not abate even when the medications were discontinued. Another medication called clozapine was developed in the 1990s which did not cause as many symptoms but "can sometimes cause a serious problem called agranulocytosis, which is a loss of the white blood cells that help a person fight infection. People who take clozapine must get their white blood cell counts checked every week or two. This problem and the cost of blood tests make treatment with clozapine difficult for many people" (Schizophrenia, 2012, NIMH: 6: 7). More recent atypical antipsychotics such as Risperdal "can cause major weight gain and changes in a person's metabolism. This may increase a person's risk of getting diabetes and high cholesterol. A person's weight, glucose levels, and lipid levels should be monitored regularly by a doctor while taking an atypical antipsychotic medication" (Schizophrenia, 2012, NIMH: 6: 7).

Cognitive behavioral therapy is often used in conjunction with drug treatments to help schizophrenics 'not listen' to their voices and to teach them psychological coping mechanism to deal with their illness. Other forms of therapy include occupational 'life skills' therapy and group therapy. Still, despite the available psychopharmacological treatments, life expectancies of persons with schizophrenia are 12 to 15 years less than the average person (Saha, Chant, & McGrath, 2007). Whether this is due to a higher suicide rate or side effects of medication remains unclear and further research is being conducted on the subject, some of which has apparently contradictory conclusions (Saha, Chant, & McGrath, 2007). Other factors that may contribute to morbidity lie in the fact that schizophrenics are more likely to be socially isolated than their non-schizophrenic peers and to suffer problems like homelessness (Saha, Chant, & McGrath, 2007).

Literature review

According to Saha, Chant & McGrath (2007) in an article entitled "A systematic review of mortality in schizophrenia: Is the differential mortality gap worsening over time?" from the Archives of General Psychiatry, schizophrenics have substantially compromised mortality compared with the general population in a manner that is directly linked to the rise in atypical antipsychotics to treat the mental illness. "With respect to mortality, a substantial gap exists between the health of people with schizophrenia and the general community. This differential mortality gap has worsened in recent decades. In light of the potential for second-generation antipsychotic medications to further adversely influence mortality rates in the decades to come, optimizing the general health of people with schizophrenia warrants urgent attention" (Saha, Chant & McGrath 2007). The article suggests that new treatments are needed for schizophrenia to address this issue given the discrepancy between the rise of new drug treatments and the increased risk of death for schizophrenics.

The article also points to the fact that although the side effects of medications have been noted, "less widely appreciated is the fact that people with schizophrenia are at increased risk for premature death associated with comorbid somatic conditions. Apart from adverse effects related to medication, schizophrenia can trigger a cascade of socioeconomic and lifestyle factors that, in turn, can translate into adverse physical health outcomes. These comorbid physical conditions contribute to increased mortality risks among people with schizophrenia" (Saha, Chant & McGrath 2007). Social isolation, homelessness, and increased risk for substance abuse are all comorbid with schizophrenia and are all associated with higher mortality rates.

Results

One of the stated weaknesses of the study was the fact that many of the complications associated with the most recent treatments for schizophrenia may take decades to emerge, including clozapine-induced agranulocytosis or and the even more long-term consequences of the metabolic conditions related to the use of antipsychotics, which can cause extreme weight gain, type II diabetes and heart disease. These will, the authors wrote, "take decades to fully emerge" (Saha, Chant & McGrath 2007). The authors gave greater emphasis to lifestyle-related factors such as a lack of social connections, homelessness, an inability to find a stable job and co-morbidity with complaints such as recreational drug use.

However, a 2004 study by Casey (et al.) found that patients with schizophrenia have increased rates of morbidity and mortality "due primarily to cardiovascular disease, compared with the general population. Case reports, case series, observational analytic epidemiologic studies, and randomized trials raise the possibility that some antipsychotic drugs add to this increased risk, likely due to drug-induced weight gain and associated metabolic abnormalities including hyperglycemia, diabetes mellitus, and dyslipidemia." Casey (2004) stated that these findings were troubling, and seriously called into consideration the use of new atypical antipsychotics. Furthermore, while the psychological and social factors targeted by Saha, Chant & McGrath (2007) are admittedly challenging seeking other forms of drug treatment than those currently prescribed is a concrete action that can be reformed through treatment.

A separate study by Enger 2004 on both typical and atypical antipsychotics further confirmed that schizophrenics had significantly higher mortality rates directly connected to heart-related complaints. "1,920 schizophrenic patients were matched by age, sex, date, and health plan to 9,600 persons randomly selected from the health plan general membership. Death, myocardial infarction, arrhythmia, and new-onset diabetes were identified. The adjusted all-cause mortality rate in the group of treated schizophrenics was 4 times higher than in the control group regardless of whether patients were given a typical or an atypical antipsychotic medication." This suggested a direct link between higher mortality rates specifically associated with taking drug treatments. Both typical and atypical antipsychotics have been associated with higher mortality rates.

A more recent study apparently confounds some of the findings of the Saha, Chant & McGrath article. According to Cullen (2012 et al.), taking antipsychotic medications can actually improve the prognosis of patients. Cullen's study was a literature review analyzing data collected between 1994 through 2004 on 2,132 adult Maryland Medicaid beneficiaries with schizophrenia. Cullen found that a 90% or better compliance rate with medication schedules was associated with a 25% lower death rate for patients, versus patients who were 10% compliant. The most interesting facet of the Cullen study, in distinction to other studies, was that rather than comparing schizophrenics with the population at large, Cullen solely compared treatment patterns amongst schizophrenics. Her findings indicate that although schizophrenics, due to lifestyle and medication-related side effects, may have higher mortality rates, schizophrenics who do not receive adequate medication and treatment still fare less well than those who do.

This should perhaps not necessarily be seen as contradictory with the findings of the Saha, Chant & McGrath (2007) study. First of all, Cullen noted that patients on low-dose medications had significantly better outcomes than patients who did not, although it was not noted if patients with lower-dose medications were less symptomatic and thus were more functional to begin with. Additionally, lower-dose medications are also associated with fewer side effects, which could potentially result in greater compliance. Regardless, Cullen strongly suggested that an effectively-managed use of medication dosage was superior to that of no treatment at all, contrary to the apparent findings of Saha, Chant & McGrath (2007) that the proliferation of new medications had done little to reduce the severity of effects from medication.

Discussion

While all studies use statistical analysis, all have apparent weaknesses. The studies which focused on schizophrenics that revealed higher rates of specifically heart-related and metabolic complications due to the drug treatments were relatively narrow in scope; studies like Cullen which focus on schizophrenics who do and do not receive treatment reveal higher mortality rates for untreated patients do not suggest that other aspects of the treatment or characteristics of the treated population might be the reason for the improvement. It seems likely that drugs have undeniable side effects but clearly some form of intervention seems warranted. But it is unclear if patients who receive interventions have other factors (such as more caring parents) that are the real cause of the improved outcomes, not the drug treatments? Saha, Chant & McGrath (2007) suggest that current interventions are still not adequate to improve outcomes, compared with the general population, and that the needs of schizophrenics overall have not been addressed in a manner that is meaningful and substantive enough to decrease mortality, which has only increased (either due to drug treatments or exacerbating social factors such as greater isolation between children and parents). The directions such interventions should take -- whether pharmacological or therapeutic is not full answered by any study. Finally, there may even be greater comorbidity to genetic factors that often accompany a schizophrenic genetic makeup associated with higher mortality rates, although these factors do not cause schizophrenia, given the strong genetic causation of the illness. Current studies seem to confuse more than they illuminate the best ways to treat this disorder.