Schizophrenia and deficit schizophrenia are accompanied by neurocognitive impairments. The aim of this study was to examine whether a general factor underpins impairments in key Cambridge Neuropsychological Test Automated Battery (CANTAB) probes, verbal fluency test (VFT), world list memory (WLM), True Recall, and mini mental state examination (MMSE).

We recruited 80 patients with schizophrenia and 40 healthy controls. All patients were assessed using CANTAB tests, namely paired-association learning, rapid visual information processing, spatial working memory, one touch stockings of Cambridge, intra/extradimensional set-shifting (IED), and emotional recognition test.

We found that a general factor, which is essentially unidimensional, underlies those CANTAB, VFT, WLM, True Recall, and MMSE scores. This common factor shows excellent psychometric properties and fits a reflective model and, therefore, reflects a general cognitive decline (G-CoDe) comprising deficits in semantic and episodic memory, recall, executive functions, strategy use, rule acquisition, visual sustained attention, attentional set-shifting, and emotional recognition. Partial least squares analysis showed that 40.5% of the variance in G-CoDe is explained by C-C motif ligand 11, IgA to tryptophan catabolites, and increased oxidative toxicity, and that G-CoDe explains 44.8% of the variance in a general factor extracted from psychosis, hostility, excitation, mannerism, negative symptoms, formal thought disorders, and psychomotor retardation, and 40.9% in quality-of-life scores. The G-CoDe is significantly greater in deficit than in nondeficit schizophrenia.

A common core shared by a multitude of neurocognitive impairments (G-CoDe) mediates the effects of neurotoxic pathways on the phenome of (deficit) schizophrenia.

Primary deficit schizophrenia (DS) is characterized by enduring negative symptoms and represents a qualitatively different disease entity with respect to non-deficit schizophrenia (NDS). No studies investigated the association between the enzyme paraoxonase 1 (PON1) and DS and its phenomenology.

In this case-control study, Thai women and men, aged 18 to 65 years, were divided in DS (n = 40) and NDS (n = 40) and were compared to controls (n = 40). PON1 activities against 4-(chloromethyl)phenyl acetate (CMPA) and phenylacetate were determined. Moreover, subjects were genotyped for their PON1 Q192R polymorphism and immunoglobulin A (IgA) levels responses directed to Gram-negative bacteria were measured.

DS is significantly associated with the QQ genotype and the Q allele as compared with NDS and controls. PON1 activities are significantly and inversely associated with negative symptoms, formal thought disorders, psychomotor retardation, excitation and DS. The presence of the Q allele is associated with increased IgA responses to Pseudomonas aeruginosa, Morganella morganii, and Pseudomonas putida as compared with RR carriers.

The PON1 Q allele and lower PON1 activities especially against CMPA are associated with DS, indicating lowered quorum quenching abilities as well as lowered defenses against lipoperoxidation and immune activation. It is suggested that lowered PON1 activity in DS constitutes an impairment in the innate immune system which together with lowered natural IgM may cause lower immune regulation thereby predisposing toward greater neurotoxic effects of immune-inflammatory, oxidative and nitrosative pathways and Gram-negative microbiota.

To examine whether negative symptoms, psychosis, hostility, excitation, and mannerism (PHEM symptoms), formal thought disorders (FTD) and psychomotor retardation (PMR) are interrelated phenomena in major neurocognitive psychosis (MNP) or deficit schizophrenia and whether those domains belong to an underlying latent vector reflecting general psychopathology.

In this study, we recruited 120 patients with MNP or deficit schizophrenia and 54 healthy subjects and measured the above-mentioned symptom domains.

In MNP, there were significant associations between negative and PHEM symptoms, FTD and PMR. A single latent trait, which is essentially unidimensional, underlies these key domains of schizophrenia and MNP and additionally shows excellent internal consistency reliability, convergent validity, and predictive relevance. Confirmatory Tedrad Analysis indicates that this latent vector fits a reflective model. The lack of discriminant validity shows that positive (and PHEM or psychotic) and negative symptoms greatly overlap and probably measure the same latent construct. Soft independent modeling of class analogy (SIMCA) shows that MNP (diagnosis based on negative symptoms) is better modeled using PHEM symptoms, FTD, and PMR than negative symptoms.

In stable phase MNP, which is a restricted sample of the schizophrenia population, negative and PHEM symptoms, FTD and PMR belong to one underlying latent vector reflecting overall severity of schizophrenia (OSOS). The bi-dimensional concept of “positive” and “negative” symptoms cannot be validated and, therefore, future research in stable phase schizophrenia should consider that the latent phenomenon OSOS as well as its reflective manifestations are the key factors of schizophrenia phenomenology.

Patients with the deficit form of schizophrenia (D-SZ) are characterized by severe primary negative symptoms and differ from patients with the non-deficit form of schizophrenia (ND-SZ) in several aspects. No study has measured brain gyrification, which is a potential marker of neurodevelopment, in D-SZ and ND-SZ.

We obtained magnetic resonance scans from 135 schizophrenia patients and 50 healthy controls. The proxy scale for deficit syndrome (PDS) was used for the classification of D-SZ and ND-SZ. The local gyrification index (LGI) of the entire cortex was measured using FreeSurfer. Thirty-seven D-SZ and 36 ND-SZ patients were included in the LGI analyses. We compared LGI across the groups.

SZ patients exhibited hyper-gyral patterns in the bilateral dorsal medial prefrontal and ventromedial prefrontal cortices, bilateral anterior cingulate gyri and right lateral parietal/occipital cortices as compared with HCs. Although patients with D-SZ or ND-SZ had higher LGI in similar regions compared with HC, the hyper-gyral patterns were broader in ND-SZ. ND-SZ patients exhibited a significantly higher LGI in the left inferior parietal lobule relative to D-SZ patients. Duration of illness inversely associated with LGI in broad regions only among ND-SZ patients.

The common hyper-gyral patterns among D-SZ and ND-SZ suggest that D-SZ and ND-SZ may share neurodevelopmental abnormalities. The different degrees of cortical gyrification seen in the left parietal regions, and the distinct correlation between illness chronicity and LGI observed in the prefrontal and insular cortices may be related to the differences in the clinical manifestations among D-SZ and ND-SZ.

The neurobiological underpinnings of avolition in schizophrenia remain unclear. Most brain imaging research has focused on reward prediction deficit and on ventral striatum dysfunction, but findings are not consistent. In the light of accumulating evidence that both ventral striatum and dorsal caudate play a key role in motivation, we investigated ventral striatum and dorsal caudate activation during processing of reward or loss in patients with schizophrenia.

We used functional magnetic resonance imaging to study brain activation during a Monetary Incentive Delay task in patients with schizophrenia, treated with second-generation antipsychotics only, and in healthy controls (HC). We also assessed the relationships of ventral striatum and dorsal caudate activation with measures of hedonic experience and motivation.

The whole patient group had lower motivation but comparable hedonic experience and striatal activation than HC. Patients with high avolition scores showed lower dorsal caudate activation than both HC and patients with low avolition scores. A lower dorsal caudate activation was also observed in patients with deficit schizophrenia compared to HC and patients with non-deficit schizophrenia. Dorsal caudate activity during reward anticipation was significantly associated with avolition, but not with anhedonia in the patient group.

These findings suggest that avolition in schizophrenia is linked to dorsal caudate hypoactivation.