Harvard Mental Health Letter

The negative symptoms of schizophrenia

They are pervasive but sometimes invisible — and especially difficult to treat.

Hallucinations and delusions are the most vivid and conspicuous symptoms of schizophrenia. Many people regard imaginary voices in the head and bizarre ideas with no basis in reality as the essence of madness, or mental illness. An eruption of these psychotic symptoms — a psychotic break — is often what brings a person with schizophrenia to treatment for the first time. But the psychotic or "positive" symptoms — exaggerations and distortions of normal perception and thinking — are not necessarily the most important or characteristic ones. Especially with modern treatments, another set of symptoms is much more pervasive and persistent and has a much greater effect on a patient's quality of life.

These "negative" symptoms are so called because they are an absence as much as a presence: inexpressive faces, blank looks, monotone and monosyllabic speech, few gestures, seeming lack of interest in the world and other people, inability to feel pleasure or act spontaneously. In psychiatric terminology: blunted or flat affect (emotional inexpressiveness and apparent unresponsiveness); alogia (poverty of speech); asociality (apparent lack of desire for the company of others); anhedonia (apparent inability to show or feel pleasure); and avolition (lack of will, spontaneity, and initiative). About 25% of patients with schizophrenia have a condition called the deficit syndrome, defined by severe and persistent negative symptoms.

Positive symptoms make treatment seem more urgent, and they can often be effectively treated with antipsychotic drugs. But negative symptoms are the main reason patients with schizophrenia cannot live independently, hold jobs, establish personal relationships, and manage everyday social situations. These symptoms are also the ones that trouble them most. Surveys find that their chief concerns are difficulty in concentrating, thinking, socializing, and enjoying life. In a seven-year follow-up of patients after a first psychotic break, researchers found that those with the best outcome had the least severe negative symptoms.

It is important to distinguish between lack of expression and lack of feeling, between lack of will and lack of activity. When questioned, patients with schizophrenia often express a full range of feelings and desires. They may describe themselves as demoralized, depressed, and anxious. The difference between what they may feel and what they show has to be taken into account in interpreting their facial expressions, speech, and social behavior.

A related complication is secondary negative symptoms — loss of expressiveness, interest, and social drive that results from social anxiety, fear of social stigma, depression (75% of patients with schizophrenia have at least one episode of major depression), or the neurological side effects of antipsychotic drugs.

The cognitive connection

Negative symptoms are closely related to the thinking deficiencies that are attracting increasing attention from schizophrenia researchers. Patients with schizophrenia perform poorly on tests of mental fluency and flexibility, especially word fluency (producing words belonging to a given category) and the capacity to sustain attention and shift its focus when necessary. Studies suggest that these cognitive limitations affect real-world functioning and the outcome of the illness even more than negative symptoms do.

But cognitive failings are "negative" symptoms, too. It's not always easy to tell the difference between a person who chooses not to talk (alogia) and one who is unable to find words, or between a deficit in motivation (avolition) and a deficit in social competence. Poor judgment and lack of initiative are related. The border between negative and cognitive symptoms blurs. The absences could be negative symptoms, cognitive limitations, or the result of anxious social and emotional withdrawal. When lab cognitive tests become more difficult, most people become more engaged, patients with schizophrenia, less engaged. Are they losing interest, or just giving up because they are unable to cope? Eventually mutual influence may become so strong that it's difficult to distinguish the difference.

The schizophrenic spectrum

Schizophrenia-like conditions can occur without hallucinations and delusions — that is, with only negative and cognitive symptoms. One term for these conditions that has fallen out of fashion is simple schizophrenia. Newer terms, as listed in the American Psychiatric Association diagnostic manual, are schizotypal personality and schizoid personality. Both these disorders involve discomfort with or incapacity for social relations, apparent indifference to others, and emotional inexpressiveness — classic schizophrenia symptoms. Schizotypal personality disorder also implies eccentric to bizarre beliefs, habits, and appearance. Schizophrenia in its earliest stages, before the first psychotic break, sometimes looks exactly like schizotypal personality.

Although their symptoms are milder than schizophrenia, these personality disorders run in the same families and probably reflect a similar hereditary vulnerability (with variably interrelating genes or environmental influences). The range of conditions, from schizoid and schizotypal personality to the most severe forms of schizophrenia, is called the schizophrenia spectrum, and it consists mostly of negative symptoms.

Negative symptoms and the brain

The underlying brain malfunction in schizophrenia is complicated and not well understood, but it almost certainly affects the interaction between the centers of judgment and planning in the prefrontal cortex and the centers of emotion and memory in the temporal lobes and limbic system. One theory is that the brain's noise level rises when the excitatory neurotransmitter glutamate becomes overactive in the prefrontal cortex and at the same time stimulates receptors for another neurotransmitter, dopamine, in the limbic region. According to this theory, negative and cognitive symptoms result directly from the glutamate activity — in part as a defense against the noise — and psychotic symptoms are a byproduct of dopamine activity in the limbic system.

But the limbic system also contains the brain's reward circuits — the place where we learn what to desire and how to recognize the cues indicating that something desirable is on hand. If patients with schizophrenia often seem to want too little (avolition), it could be the result of malfunctioning in the reward system.

The original antipsychotic drugs, introduced in the mid-20th century, worked exclusively by suppressing activity at dopamine nerve receptors in the limbic system. Since the 1980s, a new generation of drugs has taken first place on prescription pads and pharmacy shelves. Because these drugs act on the brain in different and more varied ways, some psychiatrists hoped that they would relieve negative as well as positive symptoms. The results have been disappointing. None of the drugs now available is a specific treatment for schizophrenia. All of them are roughly equally good at suppressing psychotic symptoms and equally ineffective against negative symptoms — whether the source of these symptoms is schizophrenia or another disorder.

No drug treatment for negative symptoms is on the near horizon, but the search continues. One approach involves stimulation of the NMDA receptor, which regulates the release of glutamate in the prefrontal cortex. If drugs that affect negative symptoms are found, they might be tested on people with schizotypal or schizoid personality, or even on genetically vulnerable family members who may be in the early stages of schizophrenia.

Psychosocial treatment

Meanwhile, the best we can do for negative symptoms is to provide education, psychotherapy, behavioral training, and help with employment, housing, and family relations. Supportive therapy offers reassurance, morale building, companionship, commonsense advice, and sometimes help with practical problems. Family therapy helps patients with schizophrenia and their families avoid both angry confrontations and equally harmful emotional distancing. In two studies, multiple family groups were particularly effective in reducing negative symptoms.

In behavioral therapy, patients with schizophrenia improve their social skills and put structure in their lives. Through social skills training, they may learn how to make requests, express feelings, and adjust their voices and facial expressions.

Cognitive therapy draws attention to the interplay between cognitive and negative symptoms, using questioning and reasoning exercises to clarify confusion and overcome self-defeating thoughts. Cognitive therapy may also counteract the fear of exposing limitations that makes some people with schizophrenia withdrawn and apathetic. One study found that cognitive therapy was most effective, surprisingly, not for delusions but for severe negative symptoms like poverty of speech.

A form of cognitive therapy designed specifically for schizophrenia is called cognitive rehabilitation, remediation, or enhancement. It is based on the assumption that people with schizophrenia become isolated and withdrawn because others are put off by their apparent inability to express or understand feelings and desires. Patients undertake exercises that require them to pay attention and read social situations. They are taught how to safely communicate their own needs and show that they understand the needs of others.

It now looks as though schizophrenia is not one disorder but several, with genetic roots and brain malfunctions that may be entirely different or overlapping. Psychotic, negative, and cognitive symptoms could result from different underlying processes, each with a genetic basis, that occur separately or together. These processes result in biological traits or markers that are a new focus for schizophrenia research.

These markers are now called endophenotypes ("endo" means internal and a "phenotype" is the visible expression of a genetic type). By studying endophenotypes, scientists hope to learn how these processes work — not only in people with schizophrenia, but in other people who may or may not have a schizophrenia spectrum disorder. As research links subtle signs and symptoms of illness to a person's underlying genetic makeup, we will likely better understand this range of disorders. And that will make it easier to develop specific treatments, along with better ways for clinicians and patients to choose a treatment that works.


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