Psychiatric medication effects on brain structure

May 8, 2012

It is increasingly recognized that chronic psychotropic drug treatment may lead to structural remodeling of the brain. Indeed, clinical studies in humans present an intriguing picture: antipsychotics, used for the treatment of schizophrenia and psychosis, may contribute to cortical gray matter loss in patients, whereas lithium, used for the treatment of bipolar disorder and mania, may preserve gray matter in patients.

However, the clinical significance of these structural changes is not yet clear. There are many challenges in executing longitudinal, controlled, and randomized studies to evaluate this issue in humans, particularly because there are also many confounding factors, including illness severity, illness duration, and other medications, when studying patients.

It is therefore critical to develop animal models to inform the clinical research. To accomplish this, a group of researchers at King's College London, led by Dr. Shitij Kapur, developed a rat model using clinically relevant and matched clinical dosing in combination with longitudinal . They administered either lithium or haloperidol (a common antipsychotic) to rats in doses equivalent to those received by humans. The rats received this treatment daily for eight weeks, equivalent to 5 human years, and underwent brain scans both before and after treatment.

Dr. Kapur explained their findings, "Using this approach, we observed that chronic treatment with haloperidol leads to decreases in cortical gray matter, whilst lithium induced an increase, effects that were reversible after drug withdrawal." was decreased by 6% after haloperidol treatment, but increased by 3% after .

"These important observations clarify conflicting findings from clinical trials by removing many of the confounding effects," commented Dr. John Krystal, Editor of . "Whether these changes in underlie the benefits or side effects of these medications remain to be seen. However, they point to brain effects of established medications that are not well understood, but which may hold clues to new treatment approaches."

"Whilst these intriguing findings are consistent with available clinical data, it should be noted these studies were done in normal rats, which do not capture the innate pathology of either schizophrenia or bipolar disorder," Kapur added. "Moreover, because the mechanism(s) of these drug effects remain unknown, further studies are required, and one should be cautious in drawing clinical inferences. Nevertheless, our study demonstrates a new and powerful model system for further investigation of the effects of psychotropic drug treatment on brain morphology."

Explore further: Schizophrenia diagnosis associated with progressive brain changes among adolescents

More information: The article is "Contrasting Effects of Haloperidol and Lithium on Rodent Brain Structure: A Magnetic Resonance Imaging Study with Postmortem Confirmation" by Anthony C. Vernon, Sridhar Natesan, William R. Crum, Jonathan D. Cooper, Michel Modo, Steven C.R. Williams, and Shitij Kapur (doi: 10.1016/j.biopsych.2011.12.004). The article appears in Biological Psychiatry, Volume 71, Issue 10 (May 15, 2012)

Related Stories

Schizophrenia diagnosis associated with progressive brain changes among adolescents

January 2, 2012
Adolescents diagnosed with schizophrenia and other psychoses appear to show greater decreases in gray matter volume and increases in cerebrospinal fluid in the frontal lobe compared to healthy adolescents without a diagnosis ...

New study aims to improve long-term treatment for patients with bipolar disorder

May 24, 2011
Patients with bipolar disorder may be eligible for a new clinical research study comparing two medications -- quetiapine (Seroquel), a widely prescribed second-generation antipsychotic mood-stabilizing medication, and lithium, ...

Recommended for you

New study rebuts the claim that antidepressants do not work

August 18, 2017
A theory that has gained considerable attention in international media, including Newsweek and the CBS broadcast 60 minutes, suggests that antidepressant drugs such as the SSRIs do not exert any actual antidepressant effect. ...

Should I stay or should I leave? Untangling what goes on when a relationship is being questioned

August 17, 2017
Knowing whether to stay in or leave a romantic relationship is often an agonizing experience and that ambivalence can have negative consequences for health and well-being.

Kids learn moral lessons more effectively from stories with humans than human-like animals

August 17, 2017
A study by researchers at the Ontario Institute for Studies in Education (OISE) at the University of Toronto found that four to six-year-olds shared more after listening to books with human characters than books with anthropomorphic ...

History of stress increases miscarriage risk, says new review

August 17, 2017
A history of exposure to psychological stress can increase the risk of miscarriage by upto 42 per cent, according to a new review.

Study finds children pay close attention to potentially threatening information, avoid eye contact when anxious

August 17, 2017
We spend a lot of time looking at the eyes of others for social cues – it helps us understand a person's emotions, and make decisions about how to respond to them. We also know that adults avoid eye contact when anxious. ...

Communicating in a foreign language takes emotion out of decision making

August 16, 2017
If you could save the lives of five people by pushing another bystander in front of a train to his death, would you do it? And should it make any difference if that choice is presented in a language you speak, but isn't your ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.