We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Perspectives |

Neurotoxicity, Neuroplasticity, and Magnetic Resonance Imaging Morphometry What Is Happening in the Schizophrenic Brain?

Daniel R. Weinberger, MD; Robert K. McClure, MD
Arch Gen Psychiatry. 2002;59(6):553-558. doi:10.1001/archpsyc.59.6.553.
Text Size: A A A
Published online


In an era of dramatic discoveries in neuroscience and genetics, it is likely that many popular theories and formulations about mental illness will need to be revised, if not discarded. The "neurodevelopmental hypothesis" is one of the popular theories about the origins of schizophrenia, which posits that abnormalities of early brain development increase risk for the subsequent emergence of the clinical syndrome.13 An early piece of evidence in support of this hypothesis was the apparent lack of progression of cerebral ventricular enlargement observed with computed tomography during illness.49 An important assumption of the neurodevelopmental hypothesis is that the putative primary pathologic condition of the brain is a reflection of abnormalities of early development. The neurodevelopmental hypothesis thus assumes that developmental neuropathologic conditions should arrest early in life and not continue to progress. The computed tomography results showing no apparent progression seemed consistent with this assumption. However, a recent series of magnetic resonance imaging (MRI) studies has called into question this assumption, by revealing changes in measurements of brain structures over short periods in patients who have been ill for varying durations and at various stages of life. These recent studies1014 have generated enthusiasm for a "neurodegenerative hypothesis," harkening back to proposals of Kraepelin and other neuropathologists during the first quarter of the 20th century that there is destruction of neural tissue associated with psychosis. In fact, results of MRI measurements have been cited as support for a much broader conceptual revolution in psychiatry, a "neurotoxicity hypothesis" for many psychiatric illnesses, including affective disorders15,16 and anxiety and stress disorders1719 and even jet lag.20 This recent trend has been bolstered by basic discoveries about the adaptability of neuronal connections21 and the viability and reproducibility of neurons in the adult brain (eg, apoptosis and neurogenesis).22,23 These developments have led some to opine that the neurodegenerative hypothesis of schizophrenia may have been unjustly overshadowed by the ascendancy of the neurodevelopmental hypothesis.24

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

First Page Preview

View Large
First page PDF preview





Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.


Some tools below are only available to our subscribers or users with an online account.

189 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
Original Article: Does This Patient Have a Torn Meniscus or Ligament of the Knee?

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis