A New Way Of Thinking For Schizophrenia Treatment

Main Category: Schizophrenia
Also Included In: Psychology / Psychiatry;  Clinical Trials / Drug Trials
Article Date: 22 Apr 2009 - 5:00 PDT

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The effectiveness of psychiatric drugs varies considerably in individuals being treated for depression or schizophrenia. These drugs act on serotonin, a neurotransmitter (chemical messenger) central to the regulation of moods. Scientists from Oxford and Belfast have discovered more about emotional processing and genetic variations that will help to inform treatment strategies.

The long-held view that serotonin levels are low in people with depression has been challenged by Philip Cowen, professor of psychopharmacology at Oxford University. "We asked what evidence is there that the action is abnormal and this stimulated new thinking about how anti-depressants work," he said at the British Neuroscience Association meeting in Liverpool today (21 April).

Research in rats has shown that antidepressants, such as SSRIs (selective serotonin reuptake inhibitors) or SNRIs (selective norepinephine reuptake inhibitors), elevate serotonin levels in the brain leading to a series of brain changes. This cascade of biochemical events can be measured, but less well documented are the psychological effects: how people handle their emotions and how this might translate into improved subjective mood.

"When people are depressed, they have a bias towards negative responses and feelings. They may feel, for example, that their work colleagues are hostile towards them, creating a downward spiral of misery and anxiety," said Professor Cowen.

In a recent randomised double-blind study, 42 healthy men and women who did not is have depression were given antidepressants (SSRIs or SNRIs), or a placebo for seven days. After a few days of treatment with SSRIs, they became more positive in their emotional outlook based on performance on tasks of emotional processing. These positive biases in emotional processing were independent of their reported mood.

"The drugs work quickly to change how people experience the world emotionally. We believe this is due to the effect of the drugs on emotional processing, rather than directly altering mood. Remembering and experiencing events in a more positive light helps to lift a person out of their depression," he said. This mechanism of the action of antidepressants is compatible with cognitive behavioural therapy suggesting that this dual approach will be helpful for people with depression.

Serotonin is also important in schizophrenia. Positive symptoms include hallucinations and distortions of reality, where as depression, lack of empathy and self-care and withdrawal describe negative symptoms. People with schizophrenia are usually given antipsychotic drugs such as risperidone and olanzapine. The newer antipsychotic drugs also act on the serotonin system and genetic variations in this system may affect how well a person responds to the treatment, as well as the side-effects that he or she experiences.

Professor Gavin Reynolds at Queen's University Belfast has been looking for the genetic indicators to determine which patients respond well to treatment, which do not, and those who might experience side-effects such as weight gain. In collaboration with a research team in Spain, 63 people diagnosed with schizophrenia but who had not had treatment took part in the nine month study. They were then given antipsychotic drug treatment.

"We found that after three months a variation in one gene that is important in the serotonin system was associated with whether or not the negative symptoms improved after drug treatment." The side-effects however, are determined by different genes. Their research revealed how variation in other genes involved in the effects of the serotonin system on food intake can predict whether the patient gains weight after antipsychotic drug treatment. The results highlight the importance of interacting genetic factors in determining obesity, which is up to four times more prevalent in people with schizophrenia, and the subsequent risk of metabolic disorders, such as diabetes.

The results will go some way towards genetic tests that will potentially identify those people who will or will not improve with current treatment, and those at risk of problematic side effects like weight gain.

Source: Snell Communications Ltd

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