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Duration of untreated psychosis is associated with orbital-frontal grey matter volume reductions in first episode psychosis.
Schizophr Res 2011; 125(1):13-20SR

Abstract

BACKGROUND

Delay in treatment of psychosis is associated with poor clinical and social outcome and is measured as the duration of untreated psychosis (DUP) prior to treatment of the first episode. It has been suggested that this may be mediated through toxic effects of psychosis on the structure and function of the brain. Equivocal evidence exists regarding association between longer DUP and neuro-anatomical changes such as, reduced grey matter volume in specific regions in the brain and deficits in neurocognitive functions.

OBJECTIVE

To examine if duration of untreated psychosis (DUP) preceding treatment of a first episode of psychosis is associated with structural brain abnormalities and deficits in neurocognitive functions.

METHOD

We investigated the relationship between DUP and grey matter volume using voxel-based morphometry techniques and with multiple domains of cognition. Eighty patients with a first episode of psychosis were separated into two equal sized groups based on a median split (18 weeks) of their DUP.

RESULTS

Compared to the short-DUP group (mean DUP 7.9 weeks ± 5.6), the long-DUP group (mean 113.7 weeks ± 170 .4) showed significant grey matter volume reductions in orbital-frontal regions (bilateral medial frontal gyrus and bilateral rectal gyrus, BA 11) and parietal regions (postcentral gyrus and superior parietal lobule) as well as a significant reduction in whole brain grey matter volume (p<0.04). For schizophrenia spectrum cases only these findings were confined to left rectal gyrus. There were no differences in white matter or cerebral spinal fluid volumes or on cognitive functions. Results are controlled for antipsychotic medication exposure.

LIMITATIONS

The inherent difficulty in separating slow and insidious onset from long-DUP may limit the interpretation of our results and there may be an overlap between DUP and duration of illness (including the prodrome).

CONCLUSION

Patients with a longer delay in treatment of psychosis show a significant reduction in overall grey matter volume with specific reductions in the inferior-orbital region. These results provide some support to a possible neurotoxic effect of prolonged untreated psychosis.

Authors+Show Affiliations

Prevention and Early Intervention Program for Psychoses (PEPP-Montreal), Douglas Mental Health University Institute, Montreal, Canada. ashok.malla@douglas.mcgill.caNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21059482

Citation

Malla, Ashok K., et al. "Duration of Untreated Psychosis Is Associated With Orbital-frontal Grey Matter Volume Reductions in First Episode Psychosis." Schizophrenia Research, vol. 125, no. 1, 2011, pp. 13-20.
Malla AK, Bodnar M, Joober R, et al. Duration of untreated psychosis is associated with orbital-frontal grey matter volume reductions in first episode psychosis. Schizophr Res. 2011;125(1):13-20.
Malla, A. K., Bodnar, M., Joober, R., & Lepage, M. (2011). Duration of untreated psychosis is associated with orbital-frontal grey matter volume reductions in first episode psychosis. Schizophrenia Research, 125(1), pp. 13-20. doi:10.1016/j.schres.2010.09.021.
Malla AK, et al. Duration of Untreated Psychosis Is Associated With Orbital-frontal Grey Matter Volume Reductions in First Episode Psychosis. Schizophr Res. 2011;125(1):13-20. PubMed PMID: 21059482.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Duration of untreated psychosis is associated with orbital-frontal grey matter volume reductions in first episode psychosis. AU - Malla,Ashok K, AU - Bodnar,Michael, AU - Joober,Ridha, AU - Lepage,Martin, Y1 - 2010/11/06/ PY - 2010/05/28/received PY - 2010/09/21/revised PY - 2010/09/23/accepted PY - 2010/11/10/entrez PY - 2010/11/10/pubmed PY - 2011/4/27/medline SP - 13 EP - 20 JF - Schizophrenia research JO - Schizophr. Res. VL - 125 IS - 1 N2 - BACKGROUND: Delay in treatment of psychosis is associated with poor clinical and social outcome and is measured as the duration of untreated psychosis (DUP) prior to treatment of the first episode. It has been suggested that this may be mediated through toxic effects of psychosis on the structure and function of the brain. Equivocal evidence exists regarding association between longer DUP and neuro-anatomical changes such as, reduced grey matter volume in specific regions in the brain and deficits in neurocognitive functions. OBJECTIVE: To examine if duration of untreated psychosis (DUP) preceding treatment of a first episode of psychosis is associated with structural brain abnormalities and deficits in neurocognitive functions. METHOD: We investigated the relationship between DUP and grey matter volume using voxel-based morphometry techniques and with multiple domains of cognition. Eighty patients with a first episode of psychosis were separated into two equal sized groups based on a median split (18 weeks) of their DUP. RESULTS: Compared to the short-DUP group (mean DUP 7.9 weeks ± 5.6), the long-DUP group (mean 113.7 weeks ± 170 .4) showed significant grey matter volume reductions in orbital-frontal regions (bilateral medial frontal gyrus and bilateral rectal gyrus, BA 11) and parietal regions (postcentral gyrus and superior parietal lobule) as well as a significant reduction in whole brain grey matter volume (p<0.04). For schizophrenia spectrum cases only these findings were confined to left rectal gyrus. There were no differences in white matter or cerebral spinal fluid volumes or on cognitive functions. Results are controlled for antipsychotic medication exposure. LIMITATIONS: The inherent difficulty in separating slow and insidious onset from long-DUP may limit the interpretation of our results and there may be an overlap between DUP and duration of illness (including the prodrome). CONCLUSION: Patients with a longer delay in treatment of psychosis show a significant reduction in overall grey matter volume with specific reductions in the inferior-orbital region. These results provide some support to a possible neurotoxic effect of prolonged untreated psychosis. SN - 1573-2509 UR - https://www.unboundmedicine.com/medline/citation/21059482/Duration_of_untreated_psychosis_is_associated_with_orbital_frontal_grey_matter_volume_reductions_in_first_episode_psychosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0920-9964(10)01550-1 DB - PRIME DP - Unbound Medicine ER -