SSWAHS = SWSLHN and mental health in the Southern Highlands - 9

Brain volume declines with antipsychotic use

15th Feb 2011

Catherine Hanrahan all articles by this author

THE largest and longest study linking the use of antipsychotics to the loss of brain volume has Australian experts divided over the impact of early treatment initiation.

The Iowa Longitudinal Study found the use of antipsychotics was correlated with smaller brain volume after controlling for illness severity, duration of follow-up and substance misuse.

The prospective study, which followed 211 patients with schizophrenia for a median seven years, found higher doses of antipsychotics were associated with smaller brain volume on MRI.

Professor Louise Newman, developmental psychiatrist at Monash University, said the study should flag the need for caution when initiating antipsychotics.

“It suggests very careful consideration of antipsychotic use before we have clearly established symptoms [in individuals],” she said.

The publication of the Iowa study coincides with a British Journal of Psychiatry editorial by Dr Joanna Moncrieff, co-chair of the UK’s Critical Psychiatry Network. She cites mounting evidence that antipsychotics are linked to brain volume reduction, suggesting early use in young people is not justified.

But Professor Patrick McGorry, executive director of Australia’s Orygen Youth Health, said there was no consensus on the clinical significance of brain volume changes. “It would be very destructive to say that just because the brain issue is not clear, young people shouldn’t get any help,” he said.

Professor David Le Couteur, president of the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, said the relevant clinical outcome was long-term cognitive effects.

“[Let’s] see whether these changes in brain volume, which are just a surrogate marker, in fact pan out to have an impact clinically,” he said.

Arch Gen Psychiatry 2011; 68:128-37; B J Psychiatry 2011; 198:85-87

Comments:

big bug
15th Feb 2011
7:06pm

Brain shrinkage in drug-treated psychotic patients (both scz and bipolar) is in no way caused by the genes (which are only for mild schizotypy and benign hypomania). The most likely cause is persistently fatty diet--especially chocolate and cheese--often aggravated by co-morbid anxiety (cortisol alone can shrink the hippocampus, given time). The anxiety--about half of this population--comes from fatty maternal diet, in pregnancy, which also promotes gestational diabetes (which, alone, raises scz risk for offspring SEVEN FOLD). Fatty personal diet, which causes the typical insulin resistance in scz, seems to precipitate acute psychotic episodes, by causing brain inflammation--as in depression. The problem with antipsychotic drugs is that they can increase appetite--for fatty foods already on the menu. The result will be weight gain, diabetes, vascular risk, treatment resistance and a shortened lifespan. Drug-based psychiatry has a poor future. Drug-free management of first-episode psychosis at Soteria House in California led to more patients being employable, after 12 months, compared with hospital-treated cases. To convert scz back to the pure, harmless schizotypy phenotype, use a strict low-fat diet, and for co-morbid anxiety use Inositol supplement 5 gm/day. Using this regimen, I now have 5 formerly scz patients showing obvious improvements in cognition and insight, whose drug doses may now be reduced safely, and even stopped.

Amateur Observer
20th Feb 2011
2:47pm

"Big bug" having just searched the medical literature, I can find no randomized controlled trial of low-fat diet as a treatment. There are also several studies suggesting NO benefit of inositol in chronic schizophrenia. Can you confirm that you practice evidence-based medicine?

sceptical
17th Feb 2011
12:24pm

With all due respect to those who are attempting to treat young schizos, bi-polars, uni-polars, anxiety, we have not been told about the social habits of these unfortunate young people. Perhaps recreational substances use, including alcohol from the legal age of 18 (binge-drinking excluded), are the cause of many falling prey to these mental health disorders?

Amateur Observer
20th Feb 2011
2:52pm

Agree - with almost 100% of schizophrenics being cigarette smokers one would have to be suspicious of nicotine having a role in the pathogenesis (in susceptible individuals).

Richard Cranium
21st Feb 2011
3:48pm

I appreciate your viewpoint Big bug. To Amateur Observer, who would fund a randomized controlled trial of a low fat diet anyway? Who funded the several studies suggesting NO benefit of inositol in chronic schizophrenia? I know on the two occasions I have commented on your comments I have asked you to answer questions but I don't get how someone who is seemingly scientifically minded doesn't ask them also.

It is up to each and every scientist (and I'm not but I am definitely interested) to ask the questions: "Says who and why do they say it?" I'm sure those who take the time to look in to it will find out that there are a number of ways to skin a cat and that some are more humane than others so even if it takes longer and costs more, it's better!

Richard Cranium
21st Feb 2011
3:58pm

I appologise Amateur Observer, it was not your comment I commented on last time, it was a comment made by "Another amateur observer", honest mistake.

big bug
21st Feb 2011
7:53pm

To Amateur Observer: Science, said Charles Darwin, consists in grouping facts, so that general laws and conclusions may be drawn from them. Medicine, with no intellectual appetite for nutritional and epidemiological facts, can do no grouping, so cannot explain or prevent disease, but manages to eke out a living on a meagre diet of Random-allocation Controlled Trials. If you want an RCT of healthy (probably low-fat) diet in scz, check Sherryn Evans, 2005 ("evans s and schizophrenia" on PubMed). Her intensive diet group (in Melbourne!) gained only 2 kg in 6 months on Zyprexa, and reported better energy and mental contentment than the control group given minimal diet advice, who gained 9 kg. We know that fatty diet causes diabetes (H Himsworth, CLIN SCI, 1936: The Diet Of Diabetics Prior To The Onset Of The Disease); that glucose intolerance is common in scz (first reported in 1924); and that scz cases do eat fatty diets (several reports), and often develop diabetes. Malcolm Peet, in the UK, claims to have observed worse scz symptoms when the diet is low in polyunsaturated fatty acids, which agrees with studies showing that sat fats impair cognition, reduce dendritic branching, lower BDNF levels in hippocampus, and cause brain inflammation.
As for Inositol, 2 studies in Israel showed no improvement in ANERGIC (deficit cases--untreatable?) scz cases, given Inositol for only 4 weeks, so longer trials are a must, in more typical cases. Inositol has two potential uses in scz: to treat co-morbid anxiety (up to 65% of cases); and to provide specific anti-ageing benefits (J Barger, 2008) for brain, already shown in caloric restriction animal models--increased neurotrophins like BDNF (to enhance synapse formation and plasticity), increased antioxidant enzymes, enhanced neuronal energy (got to be good!), and increased autophagy and replacement of oxidation-damaged mitochondria. NHMRC-funded low fat diet trials are planned for depression and bipolar in Geelong (Prof M Berk), and clearly should be extended to scz as well.

Amateur Observer
25th Feb 2011
5:28pm

I believe the assertion that "Medicine ... no intellectual appetite for nutritional and epidemiological facts ..." is completely false. And respectfully, the criticism of "medicine managing to eke out a living on RCTs" won't earn you much support here in a GP website!

Surprisingly you didn't even mention the one herbal therapy which has good evidence in reducing actual schizophrenia symptoms (ginseng), but strung together a hodge podge of nearly-related studies not supporting your original view. Regarding glucose-intolerance, this is also an unfortunate, but well-known side effects of common anti-schizophrenia medications (eg Olanzepine) thus the obvious "chicken or the egg?" question.