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Schizophrenia and Negative Symptoms: Q&A with Dr. Potkin

I have some great news! I was able to ask Dr. Steven G. Potkin, Professor of Psychiatry in the Department of Psychiatry and Human Behavior at the University of California, Irvine (UCI) Medical Center, some questions regarding the negative symptoms of schizophrenia. He is also the Robert R. Sprague Endowed Chair in Brain Imaging. It was a brief, by email interview, but I’m happy to share what I’ve learned with you all! The following is the Q&A:

Kristin: What are negative symptoms?
Dr. Potkin: “Negative” does not refer to a person’s attitude, but instead to a lack of characteristics that should be present. Symptoms include reduced amount and content of speech, even when encouraged to interact (alogia), lack of emotional and facial expression (affective flattening), diminished ability to begin and sustain activities (avolition), decreased ability to find pleasure in everyday life (anhedonia) and social withdrawal (asociality). ^{[1] [2]}

Negative symptoms can appear a few years before other symptoms appear in young adulthood in the so-called “prodromal” stage of the illness.^[3] Unfortunately these symptoms often go undetected because they manifest themselves as issues common among teenagers: social withdrawal, problems with school work, irritability, depression and sleeping problems.^[4]

Kristin: Do all people with schizophrenia have negative symptoms?
Dr. Potkin: No, but at any point in time, negative symptoms can affect approximately 50 percent or more of people with schizophrenia.^{[5] [6]}

Kristin: How do negative symptoms affect a person with schizophrenia? How do they affect their family and friends?
Dr. Potkin: Research suggests that for people living with schizophrenia, negative symptoms are key factors in poor quality of life as well as problems with personal hygiene, school and work performance, maintaining relationships, interacting within the community, and participating in social activities. ^{[7] [8] [9] [10]}

For caregivers of people with schizophrenia, negative symptoms may cause more burden than do other types of symptoms as they see their loved ones life isolated and lacking in meaning or joy. ^[11]

Kristin: How are negative symptoms currently treated?
Dr. Potkin: Current treatments for schizophrenia focus on reducing characteristic symptoms and can include both medication and psychosocial interventions.^[12] No effective medication treatment has yet been approved for specific treatment of negative symptoms. Despite progress in the medication side of treatment, there are still unmet needs in terms of symptom control. A large study found that despite treatment, approximately 57 percent of people receiving treatment for a schizophrenia spectrum disorder still had at least one negative symptom.^[10]

Kristin: What is the research that Genentech is doing regarding negative symptoms?
Dr. Potkin: Researchers at Genentech are pursuing new treatment strategies for schizophrenia, including increasing N-methyl-D-aspartate (NMDA) receptor activity in the brain in order to target the mechanism that may be a common link between the positive, negative and cognitive symptoms of the disorder.^{[7] [9] [11] [12]}

Specifically, through a clinical trial program, Genentech is looking at an investigational medication for people with schizophrenia, including people who experience mostly negative symptoms of schizophrenia, despite taking medication. For more information, please visit www.SearchLyteschizophrenia.com

Kristin: How can family and friends of someone with schizophrenia help someone with negative symptoms?
Dr. Potkin: Caregivers can talk to doctors about interventions including medication, psychosocial rehabilitation (work, school, relationships), medical care and wellness, and therapy (e.g. cognitive behavioral therapy and peer support groups), as well as ongoing clinical trials.^[13] They can work with physicians to find the medications and non-medicine therapies that are right for their loved one. Different medicines may have different side effects. Caregivers can also consider programs from the National Alliance on Mental Illness (NAMI) including:

• NAMI Hearts and Minds

– Online, interactive wellness initiative

www.nami.org/heartsandminds

• NAMI Peer-to-Peer

– Free, 9-week educational course on recovery

www.nami.org/peertopeer

• NAMI Connection

– Recovery support group for adults

www.nami.org/connection

Kristin: Do scientists know the biological mechanisms involved in negative symptoms? If so, what are the areas of the brain and/or mechanisms involved in negative symptoms?
Dr. Potkin: In the 1970s, the “dopamine hypothesis” of schizophrenia emerged, suggesting the biological basis of schizophrenia was an excess of signaling by dopamine, a chemical messenger in the brain. This theory, however, could not explain negative or cognitive symptoms.^[6] In the late 1980′s a newer theory suggested positive, negative and cognitive symptoms could all be due to reduced function of NMDA receptors in the brain. This theory is now known as the “NMDA receptor hypofunction hypothesis.”^{[6] [7] [8] [9]}

Researchers are pursuing new treatment strategies for schizophrenia, including increasing NMDA receptor function in the brain in order to target the mechanism that may be a common link between the positive, negative and cognitive symptoms of the disorder.^{[7] [9] [11] [12]} It is thought that NMDA receptor activity is an important pathway in psychiatric disorders, especially schizophrenia.

End of article.

*Note: I would like to thank Dr. Potkin and Alexandra Squire for helping me put together this interview. This research is very exciting and I hope that negative symptoms can be tackled in this decade! I know how debilitating they can be!

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1.     Gard DE, Kring AM, Gard MG, Horan WP, Green MF. Anhedonia in schizophrenia: distinctions between anticipatory and consummatory pleasure. Schizophr Res. Jul 2007;93(1-3):253-260.

2.     Strauss GP, Gold JM. A new perspective on anhedonia in schizophrenia. Am J Psychiatry. Apr 2012;169(4):364-373.

3.     Stahl SM. Stahl’s Essential Psychopharacology: Neuroscientific Basis and Practical Applications. 3rd ed. New York: Cambridge University Press; 2008.

4.     National Institute of Mental Health. Schizophrenia. 2009; http://www.nimh.nih.gov/health/publications/schizophrenia/complete-index.shtml. Accessed July 7, 2012.

5.     Kirkpatrick B, Fenton WS, Carpenter WT, Jr., Marder SR. The NIMH-MATRICS consensus statement on negative symptoms. Schizophr Bull. Apr 2006;32(2):214-219.

6.     Bobes J, Arango C, Garcia-Garcia M, Rejas J. Prevalence of negative symptoms in outpatients with schizophrenia spectrum disorders treated with antipsychotics in routine clinical practice: findings from the CLAMORS study. J Clin Psychiatry. Mar 2010;71(3):280-286.

7.     Ho BC, Nopoulos P, Flaum M, Arndt S, Andreasen NC. Two-year outcome in first-episode schizophrenia: predictive value of symptoms for quality of life. Am J Psychiatry. Sep 1998;155(9):1196-1201.

8.     Kirkpatrick B, Fenton WS, Carpenter WT, Jr., Marder SR. The NIMH-MATRICS consensus statement on negative symptoms. Schizophr Bull. Apr 2006;32(2):214-219.

9.     Kurtz MM. Symptoms versus neurocognitive skills as correlates of everyday functioning in severe mental illness. Expert Rev Neurother. Jan 2006;6(1):47-56.

10.   Milev P, Ho BC, Arndt S, Andreasen NC. Predictive values of neurocognition and negative symptoms on functional outcome in schizophrenia: a longitudinal first-episode study with 7-year follow-up. Am J Psychiatry. Mar 2005;162(3):495-506.

11.   Provencher HL, Mueser KT. Positive and negative symptom behaviors and caregiver burden in the relatives of persons with schizophrenia. Schizophr Res. Jul 25 1997;26(1):71-80.

12.   National Institute of Mental Health. Schizophrenia. 2009; http://www.nimh.nih.gov/health/publications/schizophrenia/complete-index.shtml. Accessed July 7, 2012.

13.   National Institute of Mental Health. Schizophrenia. 2009; http://www.nimh.nih.gov/health/publications/schizophrenia/complete-index.shtml. Accessed July 7, 2012.