Peeking into the shadows of negative symptoms: Avolition plays the lead role?

Negative symptoms are one of the most difficult to treat traits of psychiatric disorders. This calls for a better understanding of their mechanisms which can pave way for better treatment strategies in the future. The current concept of negative symptoms in schizophrenia and related disorders encompasses the following domains:

(1) Blunted affect: a decrease in the outward expression of emotion in relation to facial expression, vocal expression, and body gestures.

(2) Alogia: a reduction in the quantity of speech or amount of spontaneous elaboration.

(3) Anhedonia: reductions in the intensity and/or frequency of pleasurable experiences across activity domains (e.g., social, physical, recreational, work/school).

(4) Asociality: a reduction in the frequency of social interaction and interest in forming close relationships with others.

(5) Avolition: a reduction in the initiation of and persistence in goal-directed activities, and the desire to perform such activities. It is both a subjective reduction in interests and desires (internal experience) and a behavioral reduction of self-initiated and purposeful acts, which should only be considered negative symptoms if the behavior is a direct consequence of the internal state.

How avolition dominates the negative symptoms cluster?

Avolition ranges restraining oneself from a wide range of activities, from elementary ones, such as grooming, personal hygiene, or preparing food, and extending to more complex acts, such as going to work and/or school and engaging in social activities. A person experiencing avolition may stay at home, staring at the TV for hours and days, hardly following the content, rather than seek work or peer interaction. Differently from a person experiencing a major depression associated with unipolar or bipolar disorder, a person experiencing avolition would not necessarily complain of depressed mood, insomnia, guilt, or suicidal thoughts. Even anxious mood seems absent in people experiencing avolition, suggesting a general experiential emptiness.

The most common and severe manifestation of avolition is found in schizophrenia and schizophrenia-spectrum disorder. However, it has also been described in autism and all ranges of affective and personality disorders.

Avolition seems to be associated with poor premorbid social adjustment during childhood, insidious onset of psychosis, deficits in executive functioning and abstraction flexibility, and male gender. It is observed that, patients with schizophrenia experience levels of pleasure similar to healthy controls when engaging in pleasant activities. However, they less frequently engage in behaviors aimed at obtaining rewards and goal-directed outcomes because they have decreased capacity to anticipate future rewards.

The concept of network analysis and redefining the role of avolition:

The central role of avolition in schizophrenia patients with negative symptoms is supported by network analysis. It is established that psychiatric disorders emerge from the interactions among symptoms in a network; hence the presence of one symptom increases the probability that a related set of symptoms will also manifest. Symptoms are viewed in terms of their density, and dense networks are closely interconnected and co-activate once symptoms exacerbate, forming closely joined clusters of psychopathologies that support each other and become self-sustaining. Often, an individual symptom, avolition for example, will be more central than others in a network, with strong interconnections to other symptoms that cause those symptoms to emerge whenever the central symptom is manifested.

Like avolition is a determinant of decreased speech output (alogia), reductions in facial and vocal expression of emotion (blunted affect), slow movements, diminished pursuit of pleasurable activities or the ability to enjoy them (anhedonia), and limited engagement in social interactions (asociality) due to a common amotivational substrate. In tightly connected networks, the activation of a central symptom may lead to the activation of other symptoms, even after the factors that triggered it had disappeared. This process may account for the symptom's chronicity. Rather than examine each symptom individually, as a single effect of a causal disorder, network analysis considers the interaction between each symptom and all the other ones.

Thus drugs targeted to relieve avoltion, which is the central symptom in schizophrenia, will help to alleviate the burden of negative symptoms substantially.

Unfortunately, efforts to identify biological targets that will inform the development of drugs for avolition and reduced social engagement across syndromes has been unsuccessful. Focusing on this most central component of negative symptoms may be key to observing widespread improvements in negative symptoms.

Source: Nature journal: npj Schizophrenia (2021) 7:16 ; https://doi.org/10.1038/s41537-021-00145-4