Forum Discussion: Disease Progression in Schizophrenia

View Lawrie article View Wood article		In our Forum discussion “journal club” series, the editors of Schizophrenia Bulletin provide access to the full text of a recent article. A short introduction by a journal editor gets us started, and then it's up to our readers to share their ideas and insights, questions, and reactions to the selected paper. So read on…
Lawrie SM, McIntosh AM, Hall J, Owens DG, Johnstone EC. Brain structure and function changes during the development of schizophrenia: the evidence from studies of subjects at increased genetic risk. Schizophr Bull. 2008 Mar 1;34(2):330-40. Abstract Wood SJ, Pantelis C, Velakoulis D, Yücel M, Fornito A, McGorry PD. Progressive changes in the development toward schizophrenia: studies in subjects at increased symptomatic risk. Schizophr Bull. 2008 Mar 1;34(2):322-9. Abstract

Background Text
by William T. Carpenter

One view of the course of schizophrenia is that of progressive deterioration often ending in a defect end-state. This view has been refuted by long-term course studies reporting many and varied course types (see theme in Schizophrenia Bulletin:14, 1988) and finding a substantial number of patients with good outcome (for example, see recent report of the WHO outcome studies [Hopper et al., 2007]). The neurodevelopmental view of schizophrenia suggests that primary pathophysiology is present early without progression in later stages of illness. Observations of a number of cohorts are compatible with the view that progression, if it occurs, is in the early years of illness. In fact, clinical and functional improvement is often observed in late-life schizophrenia. Several conceptual issues have made observations to date non-decisive on the issue of disease progression. First is the syndrome status of schizophrenia, with no reason to expect different component illnesses to follow the same course. A view of typical course is meaningless if various diseases within the syndrome have inherently different patterns. A second consideration involves the domains of pathology associated with schizophrenia. In many cases impaired cognition appears years before reality distortion or disorganization symptoms and remains static throughout the course of illness. In the same cases, the later-appearing psychosis may be episodic or continuous with decreasing intensity late in life. Avolitional pathology may begin early and be trait-like, or may develop after psychosis and mark a deteriorating aspect of the illness. The question of progression becomes a question of progression of which psychopathological aspect.

Another consideration is the interaction among pathophysiology, the afflicted individual, and the living environment. Even if the disease is not progressive, the course may suggest deterioration. The person with psychotic symptoms may lose occupation, relationships, independent living, and educational achievement. The future becomes increasingly challenging, and stigma is not the least of the hurdles faced by the person with schizophrenia. The measures used for assessing course and outcome may reflect a downhill course without clarifying whether the disease pathophysiology has progressed.

In this context the March theme issue in Schizophrenia Bulletin is highly informative. Celso Arango and René Kahn are guest editors, and two of the papers are provided to members of the Schizophrenia Research Forum for discussion. Lawrie and colleagues (2008) examine imaging data from several comparative cohorts to address the question of progression early in the disease course. They highlight structural and functional abnormalities observed in schizophrenia and determine whether similar findings are associated with unaffected relatives. They then look at high-risk cohorts to determine if observed abnormalities are present and progressive during the early phases of psychosis development. The second paper, by Wood and colleagues (2008), reviews imaging and neurocognitive data from clinical high risk and ultra-high-risk cohorts to determine early manifestations of brain dysfunction. They find frontal lobe measures and cognitive measures sensitive to prefrontal cortex dysfunction informative and report measures in their longitudinal study which are associated with conversion to psychosis.

Together with the other papers in this theme (i.e., Arango et al., 2008; DeLisi, 2008; Hulshoff and Kahn, 2008), compelling evidence for early onset and progression of the pathophysiologies is presented. We invite the SRF community to discuss the research presented in these papers.

References:
Arango C, Moreno C, Martínez S, Parellada M, Desco M, Moreno D, Fraguas D, Gogtay N, James A, Rapoport J. Longitudinal brain changes in early-onset psychosis. Schizophr Bull. 2008 Mar 1;34(2):341-53. Abstract

DeLisi LE. The concept of progressive brain change in schizophrenia: implications for understanding schizophrenia. Schizophr Bull. 2008 Mar 1;34(2):312-21. Abstract

Hopper K, Harrison G, Janca A, Sartorious N. [Eds.] Recovery From Schizophrenia. An International Perspective. A Report from the WHO Collaborative Project, The International Study of Schizophrenia. Oxford University Press. New York, NY 2007.

Hulshoff Pol HE, Kahn RS. What happens after the first episode? A review of progressive brain changes in chronically ill patients with schizophrenia. Schizophr Bull. 2008 Mar 1;34(2):354-66. Abstract

Lawrie SM, McIntosh AM, Hall J, Owens DG, Johnstone EC. Brain structure and function changes during the development of schizophrenia: the evidence from studies of subjects at increased genetic risk. Schizophr Bull. 2008 Mar 1;34(2):330-40. Abstract

Wood SJ, Pantelis C, Velakoulis D, Yücel M, Fornito A, McGorry PD. Progressive changes in the development toward schizophrenia: studies in subjects at increased symptomatic risk. Schizophr Bull. 2008 Mar 1;34(2):322-9. Abstract

	Comments on Online Discussion
	Comment by:  Nirmala Srinivasan
	Submitted 12 March 2008	Posted 13 March 2008
	I am not a doctor or a psychiatrist. My comment is exclusively as a caregiver. Over the years, we do notice changes and we are told by the treating doctors that there is a tendency for mental illness to change its profile. Whether this is biological and biochemical or due to other factors must be carefully examined, and each case can prove to be different from the other. My layman's belief is that in cases where there is no marked deterioration but improvement, especially in cognitive functionality (through rehab interventions), other aspects of symptom control and coping also take place. In other words, there is a marked improvement in the patient's learning technique. I have a simple (if not a simplistic) explanation for this. I look upon schizophrenia as "delayed adolescence and adulthood" in a bio- and neuropsychological sense, causing changes over the years for better or for worse. As William Carpenter puts it, a lot depends on the nurturing experiences, opportunities to access and catch up with adult milestones, etc. This has serious implications for prognosis; preparation for the future by the patient and families; rehab interventions, etc. Many family caregivers are made to believe only in the neuropathology and deterioration theories. View all comments by Nirmala Srinivasan