Psychiatrists are experts when it comes to missing boats. Will prevention be the next one?


Neural correlates of binocular depth inversion illusion in antipsychotic-naïve first-episode schizophrenia patients

Abstract

Objectives

Binocular depth inversion illusion (BDII), a visual, ‘top–down’-driven information process, is impaired in schizophrenia and particularly in its early stages. BDII is a sensitive measure of impaired visual information processing and represents a valid diagnostic tool for schizophrenia and other psychotic disorders. However, neurobiological underpinnings of aberrant BDII in first-episode schizophrenia are largely unknown at present.

Methods

In this study, 22 right-handed, first-episode, antipsychotic-naïve schizophrenia patients underwent BDII assessment and MRI scanning at 1.5 T. The surface-based analysis via new version of Freesurfer (6.0) enabled calculation of cortical thickness and surface area. BDII total and faces scores were related to the two distinct cortical measurements.

Results

We found a significant correlation between BDII performance and cortical thickness in the inferior frontal gyrus and middle temporal gyrus (p < 0.003, Bonferroni corr.), as well as superior parietal gyrus, postcentral gyrus, supramarginal gyrus, and precentral gyrus (p < 0.05, CWP corr.), respectively. BDII performance was significantly correlated with surface area in the superior parietal gyrus and right postcentral gyrus (p < 0.003, Bonferroni corr.).

Conclusion

BDII performance may be linked to cortical thickness and surface area variations in regions involved in “adaptive” or “top–down” modulation and stimulus processing, i.e., frontal and parietal lobes. Our results suggest that cortical features of distinct evolutionary and genetic origin differently contribute to BDII performance in first-episode, antipsychotic-naïve schizophrenia patients.

Antisaccade and prosaccade eye movements in individuals clinically at risk for psychosis: comparison with first-episode schizophrenia and prediction of conversion

Abstract

Saccadic eye movements are well-described markers of cerebral function and have been widely studied in schizophrenia spectrum populations. However, less is known about saccades in individuals clinically at risk for schizophrenia. Therefore, we studied individuals in an at-risk mental state (ARMS) (N = 160), patients in their first episode of schizophrenia (N = 32) and healthy controls (N = 75). N = 88 ARMS participants showed an early at-risk mental state (E-ARMS), defined by cognitive-perceptive basic symptoms (COPER) or a combination of risk and loss of function, whereas N = 72 were in a late at-risk mental state (L-ARMS), defined by attenuated psychotic symptoms or brief limited intermittent psychotic symptoms. We examined prosaccades, reflecting overt attentional shifts, and antisaccades, measuring inhibitory control, as well as their relationship as an indicator of the interplay of bottom–up and top–down influences. L-ARMS but not E-ARMS participants had increased antisaccade latencies compared to controls. First-episode patients had higher antisaccade error rates compared to E-ARMS participants and controls, and increased latencies compared to all other groups. Prosaccade latencies did not differ between groups. We observed the expected negative correlation between prosaccade latency and antisaccade error rate, indicating that individuals with shorter prosaccade latencies made more antisaccade errors. The magnitude of the association did not differ between groups. No saccadic measure predicted conversion to psychosis within 2 years. These findings confirm the existence of antisaccade impairments in patients with schizophrenia and provide evidence that volitional response generation in the antisaccade task may be affected even before onset of clinically overt psychosis.

Hypovitaminosis D is associated with negative symptoms, suicide risk, agoraphobia, impaired functional remission, and antidepressant consumption in schizophrenia

Abstract

Hypovitaminosis D has been associated with, respectively, major depressive disorder, schizophrenia (SZ), and cognitive disorders in the general population, and with positive and negative symptoms and metabolic syndrome in schizophrenia. The objective was to determine the prevalence of hypovitaminosis D and associated factors in a non-selected multicentric sample of SZ subjects in day hospital. Hypovitaminosis D was defined by blood vitamin D level < 25 nM. Depressive symptoms were assessed by the Calgary Depression Rating Scale Score and Positive and Negative Syndrome Scale Score. Anxiety disorders and suicide risk were evaluated by the Structured Clinical Interview for Mental Disorders. Functioning was evaluated with the Functional Remission of General Schizophrenia Scale. Hypovitaminosis D has been found in 27.5% of the subjects. In multivariate analysis, hypovitaminosis D has been significantly associated with, respectively, higher suicide risk (aOR = 2.67 [1.31–5.46], p = 0.01), agoraphobia (aOR = 3.37 [1.66–6.85], p < 0.0001), antidepressant consumption (aOR = 2.52 [1.37–4.64], p < 0.001), negative symptoms (aOR = 1.04 [1.01–1.07], p = 0.04), decreased functioning (aOR = 0.97[0.95–0.99], p = 0.01), and increased leucocytosis (aOR = 1.17 [1.04–1.32], p = 0.01) independently of age and gender. No association with alcohol use disorder, metabolic syndrome, peripheral inflammation, insulin resistance, or thyroid disturbances has been found (all p > 0.05). Despite some slight abnormalities, no major cognitive impairment has been associated with hypovitaminosis D in the present sample (all p > 0.05 except for WAIS similarities score). Hypovitaminosis D is frequent and associated with suicide risk, agoraphobia and antidepressant consumption in schizophrenia, and more slightly with negative symptoms. Patients with agoraphobia, suicide risk and antidepressant consumption may, therefore, benefit in priority from vitamin D supplementation, given the benefit/risk profile of vitamin D. Further studies should evaluate the impact of vitamin D supplementation on clinical outcomes of SZ subjects.

Executive dysfunctions differentially predict amotivation in first-episode schizophrenia-spectrum disorder: a prospective 1-year follow-up study

Abstract

Amotivation is a major determinant of functional outcome in schizophrenia but it is understudied in the early course of illness. There is a paucity of longitudinal research investigating predictors of amotivation. In this study, we aimed to examine baseline cognitive and clinical predictors of amotivation at 6 and 12 months of follow-up in patients aged 18–55 years presenting with first-episode DSM-IV schizophrenia-spectrum disorder (FES). Of 145 patients recruited at intake, 116 and 113 completed assessments at 6- and 12-month follow-up, respectively. Amotivation was measured by avolition-apathy and anhedonia-asociality subscale scores of the Scale of the Assessment of Negative Symptoms. Cognitive assessment was administered at baseline. As executive dysfunction has been more consistently found to be associated with negative symptoms and amotivation in prior literature, we adopted fractionated approach to subdivide executive function into distinct components encompassing switching and flexibility, response initiation, response inhibition, planning and strategy allocation, sustained attention and working memory. Our results showed that baseline amotivation (p = 0.01) and switching and flexibility (p = 0.01) were found to independently predict amotivation at 6 months follow-up. Baseline amotivation (p < 0.01) and switching and flexibility (albeit with trend-wise significance, p = 0.06) were also retained in final multivariate regression model for 12-month amotivation prediction. No other executive components or cognitive domains predicted amotivation at follow-up. Findings of our study thus indicate amotivation at initial presentation as a critical determinant of subsequent motivational deficits over 1 year of treatment for FES patients. Cognitive flexibility might be specifically related to the development of amotivation in the early stage of illness.

Specificity proteins 1 and 4 in peripheral blood mononuclear cells in postmenopausal women with schizophrenia: a 24-week double-blind, randomized, parallel, placebo-controlled trial

Abstract

Accumulating evidence suggests that Specificity Protein 1 (SP1) and 4 (SP4) transcription factors are involved in the pathophysiology of schizophrenia. The therapeutic use of selective oestrogen modulators such as raloxifene added to antipsychotic drugs in the treatment of postmenopausal women with schizophrenia has been investigated in a few clinical trials, which reported an improvement in negative, positive, and general psychopathological symptoms. We aimed to investigate the possible association between peripheral SP protein levels and symptom improvement in postmenopausal women with schizophrenia treated with adjuvant raloxifene. In a subgroup of 14 postmenopausal women with schizophrenia from a 24-week, randomized, parallel, double-blind, placebo-controlled clinical trial (NCT015736370), we investigated changes in SP1 and SP4 protein levels in peripheral blood mononuclear cells. Participants were randomized to either 60 mg/day adjunctive raloxifene or placebo. Psychopathological symptoms were assessed at baseline and at week 24 with the Positive and Negative Syndrome Scale (PANSS). The expression of SP proteins was evaluated by immunoblot, and changes in PANSS scores and protein levels were compared at baseline and after 24 weeks of treatment. An improvement in symptoms was observed in the intervention group, but not in placebo group. Post-treatment protein levels of SP4, but not SP1, correlated with improvements in general and total PANSS subscales in the raloxifene intervention group. A reduction in SP4 levels was found after raloxifene treatment. These results suggest that SP4 may be involved in raloxifene symptom improvement in postmenopausal women and could be a potential candidate for future studies investigating blood-based biomarkers for raloxifene effectiveness.

The cognitive, affective motivational and clinical longitudinal determinants of apathy in schizophrenia

Abstract

Apathy is a frequent and debilitating condition with few treatment options available in schizophrenia patients. Despite evidence of its multidimensional structure, most of past studies have explored apathy through a categorical approach. The main objective of this study was to identify the cognitive, emotional, motivational, and clinical factors at baseline that best predicted the three subtypes of apathy dimensions at follow-up. In a longitudinal study, 137 participants diagnosed with schizophrenia underwent different assessments including clinical, motivational, affective and cognitive measurements, at 1-month (referred to as baseline) and 12-month follow-ups. Data were analyzed using partial least squares variance-based structural equation modeling. Three latent variables representing the three previously described domains of apathy reaching consensus in the literature were extracted from the Lille Apathy Rating Scale. Results showed that in addition to baseline apathy, positive symptoms, anticipatory pleasure and sensibility to punishment at baseline predicted cognitive apathy at follow-up. Likewise, both baseline apathy and sensibility to punishment predicted emotional apathy at follow-up. Finally, baseline anhedonia and episodic memory were the main variables the predicted behavioral apathy at follow-up. This is the first study to show specific associations between apathy subtypes and clinical and cognitive motivational dysfunction in individual with schizophrenia, indicating possible distinct underlying mechanisms to these demotivational symptoms. Treatment for apathy should address both types of processes. Importantly, our results demonstrate the interest of multidimensional approaches in the understanding of apathy in schizophrenia.