Neurobiological background of negative symptoms

Abstract

Studies investigating neurobiological bases of negative symptoms of schizophrenia failed to provide consistent findings, possibly due to the heterogeneity of this psychopathological construct. We tried to review the findings published to date investigating neurobiological abnormalities after reducing the heterogeneity of the negative symptoms construct. The literature in electronic databases as well as citations and major articles are reviewed with respect to the phenomenology, pathology, genetics and neurobiology of schizophrenia. We searched PubMed with the keywords "negative symptoms," "deficit schizophrenia," "persistent negative symptoms," "neurotransmissions," "neuroimaging" and "genetic." Additional articles were identified by manually checking the reference lists of the relevant publications. Publications in English were considered, and unpublished studies, conference abstracts and poster presentations were not included. Structural and functional imaging studies addressed the issue of neurobiological background of negative symptoms from several perspectives (considering them as a unitary construct, focusing on primary and/or persistent negative symptoms and, more recently, clustering them into factors), but produced discrepant findings. The examined studies provided evidence suggesting that even primary and persistent negative symptoms include different psychopathological constructs, probably reflecting the dysfunction of different neurobiological substrates. Furthermore, they suggest that complex alterations in multiple neurotransmitter systems and genetic variants might influence the expression of negative symptoms in schizophrenia. On the whole, the reviewed findings, representing the distillation of a large body of disparate data, suggest that further deconstruction of negative symptomatology into more elementary components is needed to gain insight into underlying neurobiological mechanisms.

Preliminary evidence that negative symptom severity relates to multilocus genetic profile for dopamine signaling capacity and D2 receptor binding in healthy controls and in schizophrenia

“…Our results add to existing PET/SPECT (de Haan et al, 2000; Heinz et al, 1998; Lataster et al, 2011; Martinot et al, 1994; Pickar et al, 1996; Uchida et al, 2009; Voruganti et al, 2001; Voruganti and Awad, 2006) and fMRI (Dowd and Barch, 2010, 2012; Galderisi et al, 2015; Goghari et al, 2010; Juckel et al, 2006a; Simon et al, 2010; Strauss et al, 2014; Waltz et al, 2009; Waltz et al, 2010) evidence that negative symptom severity relates to altered subcortical DA signaling and striatal reactivity, respectively. Our findings are also in line with those of other studies in which genetic profile scores reflecting high DA signaling capacity relate to increased brain responsivity to reward (Nikolova et al, 2011; Stice et al, 2012) and lower depressive symptom severity (Pearson-Fuhrhop et al, 2014).…”

Potential Role of Antipsychotic-Galantamine-Memantine Combination in the Treatment of Positive, Cognitive, and Negative Symptoms of Schizophrenia

“…Therefore, use of the galantamine-memantine combination to treat negative symptoms is an additional benefit. Finally, to treat negative symptoms in schizophrenia, medications that target the glutamatergic system and α7nACh receptors are hypothesized to yield positive results [127-129]. …”

Bipolar disorder risk gene FOXO6 modulates negative symptoms in schizophrenia: a neuroimaging genetics study

“…This is not surprising, however, since previous studies have suggested that negative symptoms do not represent a single homogeneous symptom, but perhaps multiple psychopathological constructs influenced by a variety of systems and genetic variants. 60 This suggests that what manifests as behaviourally similar negative symptoms may be caused by abnormalities in disparate underlying pathways.…”