A few months ago I was contacted by a representative from Genentech to participate in a Q&A with Dr. Sarah Atkinson, a psychiatrist at the Finger Lakes Clinical Research (FLCR) facility located in Rochester, New York. At FLCR, Dr. Atkinson conducts clinical studies specializing in central nervous system trials encompassing a broad range of disorders, including severe mental illnesses such as schizophrenia. Dr. Atkinson took the time to answer a few questions about the negative symptoms of schizophrenia in order to clarify the differences between the negative symptoms and the positive symptoms of schizophrenia. She also goes into great detail about current research involving schizophrenia and its negative symptoms, as well as how patients can better manage both the positive and negative symptoms of their illness on a daily basis.
1. How are negative symptoms different than positive symptoms of schizophrenia?
“Positive” refers to overt symptoms that should not be present. These include: hallucinations, delusions, and disorganized thoughts. “Negative” symptoms, on the other hand, refer to a lack of characteristics that should be present. Negative symptoms can 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). Positive symptoms usually become apparent in early adulthood, while negative symptoms may be present a few years earlier in the so-called “prodromal” stage of the illness. 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.
2. Can you explain the biology behind negative symptoms?
In the late 1980s a theory emerged suggesting 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.” NMDA receptors are found on different types of neurons in several regions of the brain. They are activated when they are bound by both glutamate and another molecule, such as glycine. Activation of an NMDA receptor triggers an electrical impulse that travels the length of the neuron on which the receptor is located. Depending on the type of neuron and its location in the brain, a signal is then sent to another specific area of the brain.Signals to some parts of the brain are believed to inhibit dopamine release, helping to keep levels in check. On the other hand, signals to different parts of the brain are thought to do the opposite – they increase dopamine release, which helps keep neuronal activity up at the right levels. If NMDA receptors aren’t activated enough, the signals are not sent to these downstream pathways. This means dopamine levels may get too high in some areas of the brain, which is thought to contribute to the positive symptoms of schizophrenia, such as hallucinations and delusions. At the same time, in other parts of the brain, this means dopamine levels may get too low. This is thought to lead to the negative symptoms of schizophrenia, such as a profound lack of motivation. Researchers are pursuing new treatment strategies for schizophrenia, including improving 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.
3. Does everyone with schizophrenia experience these negative symptoms?
No, not everyone with schizophrenia will experience negative symptoms. Nonetheless, at any given time, negative symptoms may affect up to 60 percent of people with schizophrenia.
4. What are the current treatments for negative symptoms of schizophrenia?
There is currently no standard of care for the treatment of negative symptoms in schizophrenia and options for their treatment with medicines are limited. Current treatments for schizophrenia focus on reducing characteristic symptoms and can include both medication and psychosocial interventions. 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 60 percent of people receiving treatment for a schizophrenia spectrum disorder still had at least one negative symptom.
5. How can caregivers help someone who is experiencing negative symptoms?
The best way for caregivers to help is to 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. 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 Connection: Recovery support group for adults – www.nami.org/connection
NAMI Peer-to-Peer: Free, 9-week educational course on recovery – www.nami.org/peertopeer
NAMI Hearts and Minds: Online, interactive wellness initiative – www.nami.org/heartsandminds
6. What research is Genentech doing in the realm of negative symptoms in schizophrenia?
Researchers at Genentech are pursuing new treatment strategies for schizophrenia, including improving 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. Via a clinical trial program, Genentech is investigating a medication for people with schizophrenia, including those who experience mostly negative symptoms of schizophrenia, despite taking medication. For more information, please visit www.SearchLyteschizophrenia.com.
7. What medications would this doctor think are the most effective antipsychotics for negative symptoms?
Available antipsychotics have limited impact on negative symptoms and are not consistently or fully effective against positive symptoms.
8. What has research shown to be an effective method of improving negative symptoms either through medication, therapy, or other methods?
There are currently no effective medications or alternative standards of care for the treatment of negative symptoms of schizophrenia. Additionally, no therapeutic approach, including adjunct treatment, has been proven to provide improved control of positive symptoms after an initial response to an antipsychotic agent. However, working with a professional or in a group setting can help people living with schizophrenia deal with the everyday challenges of their disorder and help them function within society. Treatments may include –
- Training to recognize the signs of a relapse and what to do
- Rehabilitation that emphasizes social and vocational skills
- Self-help support groups
- Substance abuse counseling
- Cognitive behavioral therapy
Antipsychotics are the medications primarily used to treat schizophrenia and work mainly by
reducing the amount of dopamine signaling in the brain; they are mostly effective against the positive
symptoms of the disorder. The effect on negative symptoms has been shown to be modest.
9. How do you tell the difference between the negative symptoms of psychosis and depression?
Although they may appear similar, the negative symptoms of schizophrenia are clinically different from depression. The common signs and symptoms of depression include depressed or sad mood and/or loss of interest in activities that were once interesting or enjoyable. Additional symptoms include changes in appetite, weight, sleep, concentration, energy and thoughts of self-reproach or guilt.
Common negative symptoms of schizophrenia include reduced 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). As they are different medical conditions, a person with schizophrenia may also have depression.
10. What does she recommend people do to cope with negative symptoms? For example, one woman made a scrapbook of simple instructions to follow when she is staring at the wall and not functioning.
Outside of medication, there are alternative methods of treatment that can potentially help people with schizophrenia cope with negative symptoms. Some examples are:
- Social skills training
- Supported employment Therapy
- Cognitive Behavioral Therapy (CBT)
- Peer support groups
- What Are the “Negative” Symptoms of Schizophrenia?
- What is Schizophrenia (Disorganized, Catatonic, Paranoid Types, Symptoms, Diagnosis, Treatment)?
- e-CAeSAR Clinical Trial Investigates Brain Plasticity, Inc.’s New Treatment For Schizophrenia And Schizoaffective Disorder
- Sleep and Schizophrenia Linked: NCBI
- Understanding Schizoaffective Disorder vs Schizophrenia