Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum.

AIMS: Psychosis spectrum disorder has a complex pathoetiology characterised by interacting environmental and genetic vulnerabilities. The present study aims to investigate the role of gene-environment interaction using aggregate scores of genetic (polygenic risk score for schizophrenia (PRS-SCZ)) and environment liability for schizophrenia (exposome score for schizophrenia (ES-SCZ)) across the psychosis continuum. METHODS: The sample consisted of 1699 patients, 1753 unaffected siblings, and 1542 healthy comparison participants. The Structured Interview for Schizotypy-Revised (SIS-R) was administered to analyse scores of total, positive, and negative schizotypy in siblings and healthy comparison participants. The PRS-SCZ was trained using the Psychiatric Genomics Consortiums results and the ES-SCZ was calculated guided by the approach validated in a previous report in the current data set. Regression models were applied to test the independent and joint effects of PRS-SCZ and ES-SCZ (adjusted for age, sex, and ancestry using 10 principal components). RESULTS: Both genetic and environmental vulnerability were associated with case-control status. Furthermore, there was evidence for additive interaction between binary modes of PRS-SCZ and ES-SCZ (above 75% of the control distribution) increasing the odds for schizophrenia spectrum diagnosis (relative excess risk due to interaction = 6.79, [95% confidential interval (CI) 3.32, 10.26], p < 0.001). Sensitivity analyses using continuous PRS-SCZ and ES-SCZ confirmed gene-environment interaction (relative excess risk due to interaction = 1.80 [95% CI 1.01, 3.32], p = 0.004). In siblings and healthy comparison participants, PRS-SCZ and ES-SCZ were associated with all SIS-R dimensions and evidence was found for an interaction between PRS-SCZ and ES-SCZ on the total (B = 0.006 [95% CI 0.003, 0.009], p < 0.001), positive (B = 0.006 [95% CI, 0.002, 0.009], p = 0.002), and negative (B = 0.006, [95% CI 0.004, 0.009], p < 0.001) schizotypy dimensions. CONCLUSIONS: The interplay between exposome load and schizophrenia genetic liability contributing to psychosis across the spectrum of expression provide further empirical support to the notion of aetiological continuity underlying an extended psychosis phenotype.

Neurocognitive impairment in deficit and non-deficit schizophrenia: a meta-analysis.

BACKGROUND: Most studies suggested that patients with deficit schizophrenia have more severe impairment compared with patients with non-deficit schizophrenia. However, it is not clear whether deficit and non-deficit schizophrenia are associated with differential neurocognitive profiles. METHODS: The aim of this meta-analytic review was to compare cognitive performances of deficit and non-deficit patients with each other and with healthy controls. In the current meta-analysis, differences in cognitive abilities between 897 deficit and 1636 non-deficit patients with schizophrenia were examined. Cognitive performances of 899 healthy controls were also compared with 350 patients with deficit and 592 non-deficit schizophrenia. RESULTS: Both deficit (d = 1.04-1.53) and non-deficit (d = 0.68-1.19) schizophrenia were associated with significant deficits in all cognitive domains. Deficit patients underperformed non-deficit patients in all cognitive domains (d = 0.24-0.84) and individual tasks (d = 0.39-0.93). The relationship between deficit syndrome and impairment in olfaction, social cognition, verbal fluency, and speed-based cognitive tasks were relatively stronger. CONCLUSIONS: Our findings suggest that there is consistent evidence for a significant relationship between deficit syndrome and more severe cognitive impairment in schizophrenia.

The relationship between cognitive impairment in schizophrenia and metabolic syndrome: a systematic review and meta-analysis.

BACKGROUND: Individuals with schizophrenia are at greater risk for metabolic syndrome (MetS) which is associated with cognitive deficits in the general population. MetS might be potentially an important contributing factor to cognitive impairment in schizophrenia. METHOD: In the current systematic review and meta-analysis, the findings of 18 studies investigating the association between MetS (and its components) with cognitive impairment in schizophrenia are reviewed. RESULTS: Co-morbidity of MetS (d = 0.28) and diabetes mellitus (d = 0.28) were both associated with more severe cognitive deficits in schizophrenia. There was also evidence for a significant relationship between cognitive impairment in schizophrenia and each of the components of MetS including hypertension, dyslipidemia, abdominal obesity and diabetes. CONCLUSIONS: MetS is significantly associated with cognitive impairment in schizophrenia and can potentially contribute to functional decline observed in some patients with schizophrenia throughout the course of illness.

Evidence that the wider social environment moderates the association between familial liability and psychosis spectrum outcome.

BACKGROUND: Familial liability to both severe and common mental disorder predicts psychotic disorder and psychotic symptoms, and may be used as a proxy in models examining interaction between genetic risk and the environment at individual and contextual levels. METHOD: In a representative general population sample (n=4011) in Izmir, Turkey, the full spectrum of expression of psychosis representing (0) no symptoms, (1) subclinical psychotic experiences, (2) low-impact psychotic symptoms, (3) high-impact psychotic symptoms and (4) full-blown clinical psychotic disorder was assessed in relation to mental health problems in the family (proxy for familial liability) and the wider social environment. Quality of the wider social environment was assessed in an independent sample using contextual measures of informal social control, social disorganization, unemployment and low income, aggregated to the neighbourhood level. RESULTS: The association between familial liability to severe mental illness and expression of psychosis spectrum was stronger in more deprived neighbourhoods [e.g. this association increased from ß=0.33 (p=0.01) in low-unemployment neighbourhoods to ß=0.92 (p<0.001) in high-unemployment neighbourhoods] and in neighbourhoods high in social control, while neighbourhood variables did not modify the association between familial liability to common mental disorder and the psychosis outcome. Neighbourhood variables mediated urbanicity effects. CONCLUSIONS: Contextual effects may be important in moderating the expression of psychosis liability in populations, representing a specific pathway independent of the link between common mental disorder and psychosis.

Effect of thought disorders on quality of life in patients with schizophrenia.

OBJECTIVE: The aim of the present study was to investigate the impact of thought disorder on quality of life in patients with schizophrenia. METHODS: Seventy two patients with schizophrenia and 46 healthy subjects were included in the study. World Health Organization Quality of Life Instrument Short Forum (WHOQOL-BREF) was given to patients and healthy subjects to assess quality of life. Thought and Language Index (TLI) for thought disorders, Positive and Negative Syndrome Scale (PANNS) for symptom and Calgary Depression Scale (CDS) for depressive symptoms were administered to the patients. RESULTS: The comparison of quality of life between patients and healthy subjects showed a significant difference except environmental domain. There were no significant correlations between thought disorder and quality of life in patients with schizophrenia. CONCLUSION: The present study revealed that quality of life was lower in patients with schizophrenia compared to healthy subjects. There was no relation between thought disorders and quality of life in schizophrenia. Patients with schizophrenia were aware of their quality of life perception.

Utilization of the auditory consonant trigram test to screen for cognitive impairment in patients with multiple sclerosis: comparison with the paced auditory serial addition test.

Several screening methods have been evaluated, but most of them are insensitive to MS-related cognitive impairment. The Auditory Consonant Trigram (ACT) test, which contains core features required for a working memory task, has been used to test neuro-cognitive function in different samples of patients to examine the status of working memory. The aim of the present study was to investigate the correlation between ACT and the Paced Auditory Serial Addition Test (PASAT), and the usefulness of ACT for evaluating the cognitive impairment in MS in a brief visit A total of 109 consecutive patients with definite MS were included. The patients were administered ACT, PASAT and EDSS. Mean PASAT score and mean ACT score were 46.19 +/- 8.51 and 45.30 +/- 9.07, respectively. Correlations between EDSS and PASAT, and EDSS and ACT were moderately strong. The correlation between ACT and PASAT was very strong (r = 0.831, P < 0.01). The mean time required to perform ACT was significantly shorter than PASAT (7.25 +/- 4.72 and 14.70 +/- 6.97 minutes, respectively). In conclusion, as a relatively brief measure of working memory, ACT was well accepted by MS patients and has a strong correlation with PASAT. Thus, ACT might be used for rapid evaluation of cognitive impairment in patients with multiple sclerosis.

Autoerythrocyte sensitization (Gardner-Diamond) syndrome mimicking compartment syndrome.

We report a case with an unusual manifestation of autoerythrocyte sensitization syndrome (Gardner-Diamond syndrome). The patient had the clinical signs of compartment syndrome of the forearm requiring fasciotomy. Dermatological signs identical to Gardner-Diamond syndrome should alert the physician to avoid unnecessary fasciotomy, as these patients respond well to psychiatric treatment as in the present case.

Quetiapine-induced improvement of tardive dyskinesia in three patients with schizophrenia.

There are very rare cases indicating the effectiveness of the atypical antipsychotics in the treatment of tardive dyskinesia except clozapine. We report three patients with schizophrenia who demonstrated improvement of tardive dyskinesia following treatment with quetiapine; two of them were unable to use clozapine because of intolerable side-effects.

Tc-99m HMPAO brain perfusion SPECT in drug-free obsessive-compulsive patients without depression.

The aim of this study was to confirm prior results of brain-imaging studies on obsessive-compulsive disorder (OCD) in a sample of Turkish patients, as a cross-cultural study. Tc-99m HMPAO brain perfusion SPECT imaging was performed in nine drug-free OCD patients without depression and six controls. The patients' Hamilton Depression Rating Scale scores were <16. The severity of obsessive-compulsive symptoms was rated with the Yale-Brown Obsessive-Compulsive Rating Scale (YBOCS). Quantitative evaluation of regional cerebral blood flow revealed that right thalamus, left frontotemporal cortex and bilateral orbitofrontal cortex showed significant hyperperfusion in patients with OCD compared with controls. YBOCS scores did not show any correlation with hyperperfusion in regional cerebral blood flow in these areas. Results of this cross-cultural study may support orbitofrontal and thalamic dysfunction in OCD in a sample of Turkish patients.