<p>Negative Symptoms in Schizophrenia: A Review and Clinical Guide for Recognition, Assessment, and Treatment</p>

Abstract

Schizophrenia is frequently a chronic and disabling disorder, characterized by heterogeneous positive and negative symptom constellations. The objective of this review was to provide information that may be useful for clinicians treating patients with negative symptoms of schizophrenia. Negative symptoms are a core component of schizophrenia that account for a large part of the long-term disability and poor functional outcomes in patients with the disorder. The term negative symptoms describes a lessening or absence of normal behaviors and functions related to motivation and interest, or verbal/emotional expression. The negative symptom domain consists of five key constructs: blunted affect, alogia (reduction in quantity of words spoken), avolition (reduced goal-directed activity due to decreased motivation), asociality, and anhedonia (reduced experience of pleasure). Negative symptoms are common in schizophrenia; up to 60% of patients may have prominent clinically relevant negative symptoms that require treatment. Negative symptoms can occur at any point in the course of illness, although they are reported as the most common first symptom of schizophrenia. Negative symptoms can be primary symptoms, which are intrinsic to the underlying pathophysiology of schizophrenia, or secondary symptoms that are related to psychiatric or medical comorbidities, adverse effects of treatment, or environmental factors. While secondary negative symptoms can improve as a consequence of treatment to improve symptoms in other domains (ie, positive symptoms, depressive symptoms or extrapyramidal symptoms), primary negative symptoms generally do not respond well to currently available antipsychotic treatment with dopamine D 2 antagonists or partial D 2 agonists. Since some patients may lack insight about the presence of negative symptoms, these are generally not the reason that patients seek clinical care, and clinicians should be especially vigilant for their presence. Negative symptoms clearly constitute an unmet medical need in schizophrenia, and new and effective treatments are urgently needed.

Dopamine Receptor Subtypes, Physiology and Pharmacology: New Ligands and Concepts in Schizophrenia

“…Interestingly, D3 receptor expression is enriched in midbrain ventral striatum (including nAcc) ( Slifstein et al., 2020 ) where the receptor is present on pre- and postsynaptic locations and can also work in cooperation with the receptor D1 (in MSN - AKT signal) ( Castrellon et al., 2019 ; Guitart et al., 2019 ). The D3 receptor has been linked to control of DA firing in VTA, emotion and reward control in animal models ( Takeuchi et al., 2019 ), but the lack of selective D3 ligands has so far hampered specific research on the subject ( Correll and Schooler, 2020 ). Cholinergic interneurons in the ventral striatum, particularly those in the insula major of Calleja are highly enriched in D3 receptor, making these cells extremely sensitive to DA from VTA projections.…”

Regulation of Reactive Oxygen Species-Mediated Damage in the Pathogenesis of Schizophrenia

“…The symptoms of schizophrenia are classified as positive, such as hallucinations and delusions, and negative, such as social withdrawal and flat affect [ 40 , 41 , 42 , 43 , 44 , 45 ]. Cognitive deficits, including the impairment of attention, memory, and executive function, are also hallmarks of schizophrenia; they present from the prodromal phase of the disorder before psychotic symptoms fully intensify [ 28 , 46 , 47 ]. Such cognitive decline can present at an early age among those with schizophrenia, eventually leading to self-care issues and impaired social and occupational function [ 28 , 48 , 49 ].…”

Analysis of the status of drug treatment in 746 inpatients with early-onset schizophrenia in China: a retrospective study

“…However, there is no clear information on the effect of this combination on the negative symptoms or on the mechanism of action. Patients, especially children and adolescents, rarely complain of negative symptoms, and more pressing positive symptoms may distract the clinician [ 37 ]. Clinicians should carefully monitor and actively manage all clinically relevant negative symptoms.…”