Limited Progress Made in Schizophrenia Understanding and Treatment

You’ve come a long way, baby. But maybe not long enough, according to Dr Rajiv Tandon, Professor of Psychiatry at the University of Florida College of Medicine and Chief of Psychiatric Services for North Florida/South Georgia Veterans Health System. Dr Tandon shared the evolution of schizophrenia diagnosis and highlighted the current status for attendees at the US Psychiatric and Mental Health Congress in Las Vegas.

Although the disease has been “recognized” for more than 100 years, we have only made a series of baby steps in understanding the etiology, pathology, and treatment of the disease, he said. Psychiatry has moved from very broad definitions, as was found in the DSM II, to extremely narrow definitions, as psychiatry created DSM III in reaction to DSM II. In the 1950s, the idea that “bad mothering” may cause schizophrenia became popular in response to Freud’s influences. With each new revision of the DSM, psychiatry committed to a bit more details in its etiology and pathology.

Starting in the 1980s, for instance, science recognized that genetics played an important role in schizophrenia, but nothing was known about the mode of transmission. In the 1990s, we learned genetics coupled with environment played a role in its etiology. Now, Tandon explained, we know that genetic factors are 60% to 80% liable for the disease. However, science still cannot point to a single or group of major genes responsible for such. On the other hand, he noted, research also demonstrated that some genes may have protective effects for developing schizophrenia. So while understanding of the genetic component has increased, there are still many unanswered questions.

Our understanding of the environmental factors associated with schizophrenia has also increased, Tandon said.¹ The mother role comes up again, but instead of associating schizophrenia with mothers’ over adulation, now we know the concern is with second trimester insults and obstetric complications. Urbanization, migration (especially to a place where the person is very different from the new population), cannabis use (especially in youth), advanced paternal age, childhood abuse/trauma, and social marginalization also have been linked to increased schizophrenia risk.
Nonetheless, the exact neurobiological pathway to pathogenesis and how the various genetic and environmental factors interact still eludes psychiatry, Tandon said.

We’ve also seen advances in the understanding of pathophysiology. In the 1980s, it was understood that there was too much dopamine somewhere in the brain, Tandon explained. Those advances were a result of CT scans showing smaller brains and larger ventricular regions in patients with schizophrenia. By the 1990s, it became evident that too much dopamine in the mesolimbic circuit causes positive symptoms and too little dopamine in mesocortical circuit combined with ventricular enlargement caused the negative symptoms.

Currently, we know there are distinct abnormalities in brain structure and function, he said. However, the differences are not specific and regular enough to be included as part of the diagnosis. Tandon added we are now looking at other neurotransmitters, especially the role of glutamatergic deficiency. Yet he cautioned attendees to be wary of “excessive enthusiasm” for new roles of the neurotransmitters until more is known.

There have been some advances in treatments, too, Tandon added. In the 1980s, there were about 30 to 40 antipsychotics from which clinicians could choose. This number increased in the 1990s with the introduction of the atypical antipsychotics. Similarly, the atypical promised much more efficacious and safer treatment possibilities, he explained. Currently, there are more than 65 different antipsychotics worldwide, with about 40 of them classified as atypicals.

Nevertheless, he cautioned attendees, psychiatry still has many challenges in 2013 in regards to treatment. Treatments are only partially effective, Tandon said, working fairly well for disorganizational and positive symptoms but not as well for other symptoms. In addition, the medications often cause deleterious effects, like worsening of depression and catatonia. Side effects, such metabolic disorder, are a big concern for this patient population, as they have been linked to increased morbidity and possibly mortality. Tandon also noted varying degrees of functional recovery, with very high rates of homelessness and unemployment among patients with schizophrenia.

The need for more understanding and improvements is evident. Schizophrenia is a global disease, with patients found in all areas of the world. The annual worldwide incidence of schizophrenia is 8 to 40 per 100,000 (median = 15 per 100,000), Tandon explained. Point prevalence is considered 2 to 10 per 100,000, and lifetime risk is 0.7%. In the US alone, there are 50,000 new cases per year, and approximately 1.5 million patients have schizophrenia at any one point. These numbers highlight a disturbing reality-based on the statistics and rates, the point prevalence should be closer to 2.3 million. Unfortunately, the high levels of morbidity associated with schizophrenia and the lower lifespan is the reason for this discrepancy. This, he said, emphasizes another concern and area for improvement: helping patients obtain better quality and quantity of life.

References:

1. Tandon R, Keshavan MS, Nasrallah HA. Schizophrenia, “just the facts” what we know in 2008. Epidemiology and etiology. Schizophr Res. 2008;102(1-3).