Preventative Psychiatry: Early Intervention in Schizophrenia
It is well accepted that for someone with Schizophrenia, the disorder can lead to a decline in functioning across both interpersonal and occupational domains and on a larger level is a public health concern (Lieberman, J. & Fenton, W., 2000).
Prior to the onset of symptoms diagnostic of schizophrenia is a “premorbid” phase of slight social and cognitive impairment (Keshavan, M. & Amirsadri, A., 2007). This is followed by a “prodromal” period” characterized by vague behaviors that often cannot be differentiated from other mental and behavioral experiences (Lieberman, J. & Fenton, W., 2000). This includes “subtle psychotic-like symptoms” and social withdrawal (Keshavan, M. & Amirsadri, A., 2007). This prodromal period and the first episode of the disorder are viewed as “critical therapeutic” opportunities (Lieberman, J. & Fenton, W., 2000).
So if someone appears to be in a prodromal state of a potentially devastating illness and has risk factors for developing the illness, is there a way to prevent it from progressing? Over the last decade, there is increasing interest in early intervention for Schizophrenia; however, questions remain as to who and when to treat, as many symptoms characteristic of the prodromal period are also characteristic of other mental disorders and life transitions (Keshavan, M. & Amirsadri, A., 2007). These questions have to be weighed against well-established evidence associating a longer time to treatment with a worse prognosis (Keshavan, M. & Amirsadri, A., 2007).
There has been an increasing focus on early intervention programs that aim to identify and treat psychotic disorders sooner with the goals of improving patient prognosis and easing the financial burden of the illness on the healthcare system (Francey, S. et al., 2010). One such program is the Specialized Treatment Early in Psychosis (STEP) program at Yale, which is composed of an interdisciplinary team approach to providing “comprehensive care for individuals who are early in the course of a psychotic illness in order to prevent symptoms from becoming disabling” (Yale School of Medicine, 2015).
Preliminary data suggests that early intervention models, like the one described above, result in fewer hospital admissions, fewer relapses, improved functional outcomes, as well as financial advantages on a societal level (Francey, S. et al., 2010). Controversy exists concerning who should be referred to early intervention programs as well as what treatment modalities should be utilized. Many individuals with prodromal-like behaviors, even those in the age group most at risk for developing schizophrenia (adolescence or early adulthood), do not develop the disease (Lieberman, J. & Fenton, W., 2000). There are benefits though to assessing and treating an illness like Schizophrenia early as earlier stages of the illness appear to be more treatment responsive (Francey, S. et al., 2010). Furthermore, starting psychotropic medication has also been shown to slow the structural brain changes correlated with the illness (Francey, S. et al., 2010). However, the benefits of beginning pharmacological treatment have to be weighed against less intensive treatments with fewer side effects such as therapy alone.
One could argue that not everyone who receives a vaccine would have contracted the illness he or she is being protected against. Preventative medicine is well accepted across many specialties such as vaccination or the use of sunscreen and even when it comes to more invasive measures such as mastectomies. However, it appears to be either less accepted or less known in psychiatry and perhaps this is related to the lack of concrete diagnostic tests such as a blood test or a biopsy. While we know Schizophrenia is more treatment responsive in earlier stages, how do we even know this is going to turn into Schizophrenia? As of now we really do not, leading to those ethical questions with regard to starting medications known to cause serious side effects.
About one half of patients with early psychosis will actually develop chronic schizophrenia and not all individuals with prodromal features will become psychotic (Keshavan, M. S., Berger, G., Zipursky, R., Wood, S., & Pantelis, C., 2005).
Currently referral into an early intervention program is based on both having prodromal tendencies as well as being deemed “at risk”. This includes things like age, family psychiatric history, and trauma. One study looked at neurodevelopmental elements of the illness from a trauma perspective highlighting similarities between the effects of trauma on the developing brain and the structural brain changes in those diagnosed with schizophrenia. This included overactivity of the hypothalamic-pituitary-adrenal axis, ventricular enlargement, and cerebral and hippocampal atrophy (Read, J., Perry, B., Moskowitz, A., & Connolly, J., 2001). However, another analysis found significant hipoocampi volume reductions in first episode patients but an insignificant reduction in hippocampi volume in those deemed high-risk for psychosis, even in the high-risk individuals whom later developed psychosis (Copolov et al., 2000).
Recent literature has focused on neuroimaging using MRI’s to show structural changes that are specific to the prodromal period. These findings have important clinical implications as beginning treatment is more justifiable if one can say that these prodromal tendencies coupled with these brain changes will become Schizophrenia.
Previous research in the area of Schizophrenia has shown a relationship between prolonged untreated psychosis and loss of gray matter and enlarged cerebral ventricles in patients with an established diagnosis of the disorder (Keshavan, M. & Amirsadri, A., 2007). More relevant to early intervention services, is the progression of this gray matter loss. In first-episode patients, there are fewer brain abnormalities whereas in follow-up studies, these patients have more prominent gray-matter loss after several years (Keshavan, M. & Amirsadri, A., 2007).
In a study of 75 prodromal individuals, 23 of whom later became psychotic, those who developed psychosis had less gray matter in the right medial temporal, lateral temporal, and inferior frontal cortex and bilaterally in the cingulate cortex. This shows that disease progression may be occurring while one is “transitioning” into psychosis (Keshavan, M. & Amirsadri, A., 2007). A study completed in an early intervention program measured gray matter loss in participants at risk for developing psychosis and in participants with first-episode psychosis as well as in a control group. Results showed gray matter loss in temporal, orbitofrontal, and cingulate areas in those that had developed psychosis with a “progressive process” occurring in the superior temporal gyrus preceding a psychotic episode (Takahashi, T. 2009). This possible identification of a structural brain change occurring prior to the onset of psychosis is significant when considering pharmacological treatment in an early-intervention setting. Another area of interest is brain metabolism, specifically in membrane phospholipids in the early stage of the illness (Keshavan, M. S., Berger, G., Zipursky, R., Wood, S., & Pantelis, C., 2005). While there is not yet a clear picture of any one structural brain change that is definitive in the development of a future psychotic disorder, the literature does point to indicative progressive changes. Described consistently in the literature is the benefit of early intervention in schizophrenia and the need for more neurobiological research with specific regard to the prodromal period of the illness.
Copolov, D., Velakoulis, D., McGorry, P., Mallard, C., Yung, A., Rees, S…Pantelis, C. (2000). Neurobiological Findings in Early Phase Schizophrenia. Elsevier: Brain Research Reviews, 31(2-3): 157-165. DOI: 10.1016/S0165-0173(99)00033-8.
Francey, S., Nelson, B., Thompson, A., Parker, A., Kerr, M., Macneil, C… Fraser, R.(2010). Who Needs Antipsychotic Medication in the Earliest Stages of Psychosis? A reconsideration of Benefits, Risks, Neurobiology, and Ethics in the Era of Early Intervention. Elsevier: Schizophrenia Research, 119, 1-10. DOI: 10.1016/j.schres.2010.02.1071.
Keshavan, M. S., Berger, G., Zipursky, R., Wood, S., & Pantelis, C. (2005). Neurobiology of Early Psychosis. The British Journal of Psychiatry, 187, s8-s18. DOI: 10.1192/bjp.1987.48.s8.
Keshavan, M. & Amirsadri, A. (2007). Early Intervention in Schizophrenia: Current and Future Perspectives. Current Psychiatry Reports, 9: 325-328. Http://link.springer.com/article/10.1007/s11920-007-0040-8#page-1.
Lieberman, J. & Fenton, W. (2000). Delayed Detection of Psychosis: Causes, Consequences, and Effect on Public Health. Psychiatry Online, 157 (11): 1727-1730. Http://psychiatryonline.org/doi/full/10.1176/appi.ajp.157.11.1727.
Read, J., Perry, B., Moskowitz, A., & Connolly, J. (2001). The Contribution of Early Traumatic Events to Schizophrenia in Some Patients: A Traumagenic Neurodevelopmental Model. Psychiatry, 64(4): 319-345.
Takashashi, T., Wood, S., Yung, A., Soulsby, B., McGorry, P., Suzuki, M…Pantelis, C. (2009). Progressive Gray Matter Reduction of the Superior Temporal Gyrus During Transition to Psychosis. Arch Gen Psychiatry, 66(4): 366-376. DOI:10.1001/archgenpsychiatry.2009.12.
Yale School of Medicine (2015). Specialized Treatment Early in Psychosis. Retrieved from: http://medicine.yale.edu/psychiatry/step/index.aspx.