Neurocognition and social cognition in youth and young adults at ultra-high-risk for psychosis and bipolar disorder.

BACKGROUND: Schizophrenia and bipolar disorder are associated with significant deficits in neurocognition and social cognition. Unlike the studies in chronic stages of these disorders, very limited information is available regarding neurocognitive and social-cognitive impairment before the onset of bipolar disorder. Our main aim was to investigate the differences in neurocognition and social cognition between individuals at ultra-high risk for psychosis (UHR-P) and bipolar disorder (UHR-BD). METHODS: This study included 152 help-seeking individuals identified as UHR-P (n = 78) and UHR-BD (n = 74), who were compared with a healthy control group (n = 43). A comprehensive neuropsychological battery was administered to all participants. RESULTS: UHR-P was associated with widespread deficits in all neurocognitive and social-cognitive domains. Effect sizes (Cohen's d) of these deficits ranged from -0.57 to -1.34. UHR-BD was associated with significant deficits in processing speed, executive functions, sustained attention and social cognition (d = -0.48 to-0.70, p < 0.05). UHR-P performed significantly worse than UHR-BD in social cognition, processing speed, verbal memory and executive function domains (d = -0.39 to-0.64, p < 0.05). Negative symptoms were associated with impaired social cognition in the UHR-P group and verbal memory deficits in the UHR-BD group. Cognitive impairment was associated with functional impairment in both groups. CONCLUSIONS: While UHR-P is associated with more widespread cognitive impairment, deficits in processing speed, executive functions, sustained attention and social cognition might be common features of both UHR groups. In early intervention services, cognition should be considered as a target for assessment and intervention not only for individuals at high risk for psychosis but also for bipolar disorder.

Social cognition and neurocognition in first-episode bipolar disorder and psychosis: The effect of negative and attenuated positive symptoms.

BACKGROUND: Schizophrenia and bipolar disorder are associated with neurocognitive and social-cognitive impairments. To date very few studies investigated social cognition in first-episode bipolar disorder (FEBD). Our main aim was to investigate the differences in social cognition and neurocognition between FEBD and first-episode psychosis (FEP). Another aim was to investigate neurocognitive correlates of negative symptoms and attenuated psychotic symptoms in FEBD. METHODS: This study included 55 FEBD, 64 FEP and 43 healthy controls. A comprehensive neuropsychological battery assessing social cognition, processing speed, verbal and visual memory, working memory, sustained attention, and executive functions was administered to all participants. RESULTS: Both FEBD and FEP were associated with widespread deficits in all neurocognitive domains and social cognition. Both FEP (d = -1.19) and FEBP (d = -0.88) were also impaired in social cognition. In FEP, effect sizes (Cohen's d) of neurocognitive deficits ranged from -0.71 to -1.56. FEBD was also associated with relatively milder but similar neurocognitive deficits (d = -0.61 to-1.17). FEBD group performed significantly better than FEP group in verbal and visual memory, processing speed, and executive function domains (d = -0.40 to-0.52). Negative symptoms and social functioning were associated with neuropsychological impairment in both groups. The severity of attenuated psychotic symptoms was associated with poorer verbal memory in FEBD (r = -0.39, p < 0.01). LIMITATIONS: The cross-sectional nature of the current study is the main limitation. CONCLUSIONS: Neurocognitive and social-cognitive deficits are evident in both FEBD and FEP. In FEBD, more severe memory deficits might be markers of clinical overlap and shared neurobiological vulnerability with psychotic disorders.

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.

Diverse glial cell line-derived neurotrophic factor (GDNF) support between mania and schizophrenia: a comparative study in four major psychiatric disorders.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) have essential roles in synaptic plasticity which is involved in pathogenesis and treatment of psychiatric disorders. However, it is not clear whether they act simultaneously during illness states in major psychiatric disorders. METHODS: BDNF and GDNF serum levels were measured concomitantly by enzyme-linked immunosorbent assay (ELISA) method in 171 patients diagnosed with schizophrenia (n=33), bipolar disorder-manic episode (n=39), bipolar/unipolar depression (n=64, 24/40) and obsessive-compulsive disorder (n=35) according to DSM-IV, and 78 healthy volunteers. SCID-I and SCID non-patient version were used for clinical evaluation of the patients and healthy volunteers, respectively. Correlations between the two trophic factor levels, and illness severity scores, duration of illness and medication dosages were studied across different illnesses. RESULTS: While patients had equally lower BDNF levels in all diagnoses, GDNF levels were significantly higher in mania and lower in schizophrenia compared to healthy controls. BDNF levels were negatively correlated to illness severity scores in affective episodes (mania and depression). Longer duration of illness (>5 years) had an impact on lower GDNF levels in schizophrenia. BDNF levels and antipsychotic drug dosages in schizophrenia, and GDNF levels and antidepressant drug dosages in obsessive-compulsive disorder were positively correlated. CONCLUSION: Our data confirmed the evidence of equally deficient neuronal support by BDNF in all major psychiatric illnesses, but suggested a diverse glial functioning between schizophrenia and mania.

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.

Difference between generic and multiple sclerosis-specific quality of life instruments regarding the assessment of treatment efficacy.

Multiple sclerosis (MS) is a chronic and stressful disease, which significantly affects the quality of life (QoL) of patients. QoL instruments provide information which traditional outcome measures of MS do not. It is unclear if the longer disease-specific instruments provide more useful information than the shorter. We aimed to investigate whether there was any difference between general QoL instrument and MS-specific one on the basis of detecting the efficacy of pulse therapy. 112 clinically definite MS patients were included in the study. Patients enrolled in the study were in relapse period treated by 1 g/day methyl-prednisolone for 5 days. World Health Organization Quality of Life Brief Form, Turkish Version (WHOQoL-BREF-TR) was given as a generic measure and Multiple Sclerosis Quality of Life-54 (MSQoL-54) as an MS-specific measure to assess the QoL. The same scales were administered 1 month after the therapy. MSQoL-54 was correlated with the EDSS in the pre-treatment period but WHOQoL-BREF was not. On day 30, there was a significant increase in both WHOQoL-BREF and MSQoL-54 scores. Increase was more prominent in MSQoL-54. There was a weak correlation between WHOQoL-BREF and MSQoL-54 (r=0.17). Correlation between changes in WHOQoL-BREF and MSQoL-54 scores was even weaker (r=0.11). Correlation between WHOQoL-BREF and EDSS was weaker (r=0.13), and correlation between MSQoL-54 and EDSS was still moderate (r=0.46) when compared with day 0. We concluded that although it takes a longer time to administer, MSQoL-54, as a MS-specific QoL instrument, is favorable and reliable for detecting the QoL not only in the remission but also in the relapse period of MS. Our results also indicated that MS-specific measure of QoL might be used for detecting the treatment effects in relapse period of patients with MS.

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.