Accentuate the negative: drawing attention to negative symptoms in schizophrenia

Diminished expression and diminished motivation are two aspects of the negative symptoms that so badly affect many people with schizophrenia. And, like two sides of the same coin, they are linked but also distinguishable.

People with apathy show deficits in ability to learn from positive outcomes

Assigning too much weight to the effort required to achieve a goal, for example, contributes to apathy but not to diminished expression. The same is true of patients who do not learn from positive outcomes and so become less likely to engage in goal-directed behavior, Stefan Kaiser (Geneva University Hospitals, Switzerland) explained at the EPA 2018 session on challenges in treating negative symptoms in schizophrenia.

Neural substrates, limited cognitive reserves

Neuroimaging research shows us that the greater the apathy shown by a patient, the less the activation of the ventral striatum. So we know at least a little about the neural substrates underlying this element of negative symptomatology. In terms of moderating the psychological processes involved, cognitive behavioral therapy (CBT) and strategies that reinforce learning have potential to treat these symptoms.

In the case of diminished expression, on the other hand, the problem may lie in more in limited cognitive reserves and problems with the perception of emotions. Low scores on scales assessing global cognition correlate with diminished expression, but they do not correlate with apathy. It may be that when a patient is functioning at the limits of his or her cognitive reserve, emotional expression is down-regulated, however, little is known about what is happening at the neural level. Cognitive remediation and specific training in affect recognition may be potentially useful interventions.

Does emotional unresponsiveness arise from limited processing capacity?

Assessing the inner experiences of patients

Another overlooked aspect in patients with predominantly negative symptoms is the absence of a validated scale for self-assessment. Sonia Dolfuss and colleagues from the University of Caen (Normandy, France) have designed an instrument (Self-Evaluation of Negative Symptoms) that engages the patient, takes little time to complete, and provides information not available to caregivers or clinical staff while focusing on the inner experiences of patients.

New self-assessment scale distinguishes patients from controls

The twenty-item scale has a total score of 40. Using a cut-off of 8 as the threshold of pathology, the scale had a sensitivity of 82% and a specificity of 91% in a trial assessing its value in distinguishing patients from healthy controls. Moving forward and in addition to testing whether the scale is reliable, the scale will also have to demonstrate the ability to pick up changes with time and treatment, if it is to prove helpful in trials of potential therapies for negative symptom schizophrenia.

Beliefs lead to emotions and emotions to behavior

Turning to the challenge of improving the condition of patients – which is the overriding challenge -- Laurent Lecardeur (also of the University of Caen) explored the role of CBT in managing negative symptoms. In its 2014 guidance, NICE recognized CBT as a means of promoting recovery in patients with both positive and negative symptoms, and for people in remission.

The nature of CBT is that it involves a therapeutic alliance, collaborative work with patients, setting objectives, encouraging the testing of beliefs against reality, and use of positive reinforcement and self-evaluation. In relation to apathy in particular, the need is to challenge defeatist thinking. Therapy proceeds through the identification of problematic cognitions and the distortions that underpin them, the rational challenge of “automatic thoughts” and beliefs, and cognitive restructuring.

CBT challenges defeatist thinking; intervention seems more effective when give early rather than late

Group psycho-education can also be helpful since it leads to the sharing of coping strategies. For blunted affect, assertive training is used to adjust the intensity of the voice, encourage looking at the person being talked to, and introduce animation into speech. Techniques include role play, feedback through video recording and, above all, practice. As in many aspects of therapy for schizophrenia, it seems more effective to intervene early.

Patients with predominantly negative symptoms respond poorly to existing antipsychotic medication, Istvan Bitter (Semmelweiss University, Budapest, Hungary) told the symposium audience. This may reflect a different biology, as suggested by the idea that negative symptoms arise from hypoactive mesocortical dopaminergic projection – rather than the hyperactive nigrostriatal projection to associative striatum, which underlies positive symptoms. Given such insights, there is also potential for the development of more effective pharmacological interventions.