Relationship between cognition and age at onset of first-episode psychosis: comparative study between adolescents, young adults, and adults.

Psychotic disorders typically manifest from late adolescence to early adulthood, and an earlier onset might be associated with greater symptom severity and a worse long-term prognosis. This study aimed to compare the cognitive characteristics of patients with first-episode psychosis (FEP) by their age at onset. We included 298 patients diagnosed with FEP and classified them as having an early onset (EOS), youth onset (YOS), or adult onset (AOS) based on age limits of ≤ 18 years (N = 61), 19-24 years (N = 121), and ≥ 25 years (N = 116), respectively. Socio-demographic and clinical variables included age at baseline, gender, socio-economic status, antipsychotic medication, DSM-IV diagnoses assessed by clinical semi-structured interview, psychotic symptom severity, and age at onset. Neuropsychological assessment included six cognitive domains: premorbid intelligence, working memory, processing speed, verbal memory, sustained attention, and executive functioning. The EOS group had lower scores than the YOS or AOS groups in global cognition, executive functioning, and sustained attention. Although the scores in the YOS group were intermediate to those in the EOS and AOS groups for most cognitive factors, no statistically significant differences were detected between the YOS and AOS groups. Age at onset results in specific patterns of cognitive interference. Of note, impairment appears to be greater with EOS samples than with either YOS or AOS samples. A longitudinal study with a larger sample size is needed to confirm our findings.

Cognitive reserve as an outcome predictor: first-episode affective versus non-affective psychosis.

OBJECTIVE: Cognitive reserve (CR) refers to the brain's capacity to cope with pathology in order to minimize the symptoms. CR is associated with different outcomes in severe mental illness. This study aimed to analyze the impact of CR according to the diagnosis of first-episode affective or non-affective psychosis (FEP). METHOD: A total of 247 FEP patients (211 non-affective and 36 affective) and 205 healthy controls were enrolled. To assess CR, common proxies have been integrated (premorbid IQ; education-occupation; leisure activities). The groups were divided into high and low CR. RESULTS: In non-affective patients, those with high CR were older, had higher socioeconomic status (SES), shorter duration of untreated psychosis, and a later age of onset. They also showed greater performance in most cognitive domains. In affective patients, those with a greater CR showed a higher SES, better functioning, and greater verbal memory performance. CONCLUSION: CR plays a differential role in the outcome of psychoses according to the diagnosis. Specifically, in order to address the needs of non-affective patients with low CR, cognitive rehabilitation treatments will need to be 'enriched' by adding pro-cognitive pharmacological agents or using more sophisticated approaches. However, a functional remediation therapy may be of choice for those with an affective psychosis and low CR.

Metabolic syndrome or glucose challenge in first episode of psychosis?

Patients with schizophrenia exhibit a reduced life expectancy. Although unhealthy lifestyle or suicide risk plays a role, the main causes are diverse medical conditions such as cardiovascular diseases, type 2 diabetes mellitus and metabolic syndrome. Albeit pharmacological secondary side effects might also trigger previous conditions, studies in naïve patients reflect diverse anomalies at the onset. Patients with a first episode of psychosis, display a wide scope of metabolic abnormalities, ranging from normality till pathological values depending on the parameters studied. We attempted to evaluate the metabolic syndrome and glycemic homeostasis in a subset of antipsychotic-naïve patients with a first episode of non-affective psychosis. Patients (n=84) showed a similar prevalence of metabolic syndrome compared with a matched control sample (n=98) (6% vs 4%, P=0.562), while glucose homeostasis values differed significantly (14% vs. 5%, P=0.034). Our results suggest that metabolic syndrome is not a useful clinical condition to be evaluated in patients before pharmacological treatment. Abnormal glycemic homeostasis at the onset of the disease requires specific diagnostic tools and preventive measures in order to avoid future cardiovascular events. New strategies must be implemented in order to evaluate the cardiovascular risk and subsequent morbidity in patients at the onset of the disease.

Association of the brain-derived neurotrophic factor Val66Met polymorphism with negative symptoms severity, but not cognitive function, in first-episode schizophrenia spectrum disorders.

OBJECTIVE: A functional polymorphism of the brain-derived neurotrophic factor gene (BDNF) Val66Met has been associated with cognitive function and symptom severity in patients with schizophrenia. It has been suggested that the Val66Met polymorphism has a role as a modulator in a range of clinical features of the illness, including symptoms severity, therapeutic responsiveness, age of onset, brain morphology and cognitive function. However, little work has been done in first-episode schizophrenia (FES) spectrum disorders. The objective of this study is to investigate the association of the BDNF Val66Met polymorphism on cognitive function and clinical symptomatology in FES patients. METHODS: Using a cross-sectional design in a cohort of 204 patients with FES or a schizophrenia spectrum disorder and 204 healthy matched controls, we performed BDNF Val66Met genotyping and tested its relationship with cognitive testing (attention, working memory, learning/verbal memory and reasoning/problem-solving) and assessment of clinical symptom severity. RESULTS: There was no significant influence of the BDNF allele frequency on cognitive factor scores in either patients or controls. An augmented severity of negative symptoms was found in FES patients that carried the Met allele. CONCLUSIONS: The results of this study suggest that in patients with a first-episode of schizophrenia or a schizophrenia spectrum disorder, the BDNF Val66Met polymorphism does not exert an influence on cognitive functioning, but is associated with negative symptoms severity. BDNF may serve as suitable marker of negative symptomatology severity in FES patients within the schizophrenia spectrum.

Cognition and psychopathology in first-episode psychosis: are they related to inflammation?

BACKGROUND: Cognitive deficits are present from the onset of psychosis and are considered a core feature of the disorder. Increasing evidence suggests that cognitive function is associated with inflammatory processes. This study evaluated the association between cognition and inflammatory biomarkers in first-episode psychosis (FEP), in order to identify cognitive phenotypes from inflammatory expression profiles. METHOD: A case-control study of 92 FEP patients and 80 matched controls was used. Neurocognitive assessment, including verbal ability, sustained attention, verbal memory, working memory and executive function, was performed. The expression of pro- and anti-inflammatory mediators of the main intracellular inflammatory pathway was measured in peripheral blood mononuclear cells and plasma. RESULTS: FEP patients performed worse in all cognitive domains compared to controls and had higher expression of pro-inflammatory mediators and lower expression of anti-inflammatory mediators. In the FEP group, cognition and psychopathology were associated with inflammation. Hierarchical regression analysis showed that association between the anti-inflammatory prostaglandin 15d-PGJ2 and sustained attention on one hand, and COX-2 expression and executive function on the other, were statistically significant. CONCLUSIONS: Our study provides evidence for an association between anti-inflammatory biomarkers and cognition in FEP. The identification of a subgroup of patients based on these measures could be useful to guide treatment programmes by providing tools to select a personalized treatment approach, but longitudinal studies are needed before. In the future, establishment of biomarkers linked to cognition would be useful to monitor the course of cognitive impairment, but substantially more data will be required. Determination of IκBα, the inhibitory protein of the pro-inflammatory transcription factor NFκB, could be useful in early phases to assess clinical severity.

Evaluation of the Effectiveness of a Psychoeducational Intervention in Treatment-Naïve Patients with Antidepressant Medication in Primary Care: A Randomized Controlled Trial.

BACKGROUND: There is evidence supporting the effectiveness of psychoeducation (PE) in patients with symptoms of depression in primary care (PC), but very few studies have assessed this intervention in antidepressant-naïve patients. The aim of this study is to assess the effectiveness of a PE program in these patients, since the use of antidepressant (AD) medication may interfere with the effects of the intervention. METHODS: 106 participants were included, 50 from the PE program (12 weekly 1.5-hour sessions) and 56 from the control group (CG) that received the usual care. Patients were assessed at baseline and at 3, 6, and 9 months. The main outcome measures were the Beck Depression Inventory (BDI) and remission based on the BDI. The analysis was carried out on an intention-to-treat basis. RESULTS: The PE program group showed remission of symptoms of 40% (P = 0.001) posttreatment and 42% (P = 0.012) at 6 months. The analysis only showed significant differences in the BDI score posttreatment (P = 0.008; effect size Cohen's d' = 0.55). CONCLUSIONS: The PE intervention is an effective treatment in the depressive population not treated with AD medication. Before taking an AD, psychoeducational intervention should be considered.

Hippocampal abnormalities and age in chronic schizophrenia: morphometric study across the adult lifespan.

BACKGROUND: Hippocampal abnormalities have been demonstrated in schizophrenia. It is unclear whether these abnormalities worsen with age, and whether they affect cognition and function. AIMS: To determine whether hippocampal abnormalities in chronic schizophrenia are associated with age, cognition and socio-occupational function. METHOD: Using 3 T magnetic resonance imaging we scanned 100 persons aged 19-82 years: 51 were out-patients with stable schizophrenia at least 2 years after diagnosis and 49 were healthy volunteers matched for age and gender. Automated analysis was used to determine hippocampal volume and shape. RESULTS: There were differential effects of age in the schizophrenia and control samples on total hippocampal volume (group × age interaction: F(1,95) = 6.57, P = 0.012), with steeper age-related reduction in the schizophrenia group. Three-dimensional shape analysis located the age-related deformations predominantly in the mid-body of the hippocampus. In the schizophrenia group similar patterns of morphometric abnormalities were correlated with impaired cognition and poorer socio-occupational function. CONCLUSIONS: Hippocampal abnormalities are associated with age in people with chronic schizophrenia, with a steeper decline than in healthy individuals. These abnormalities are associated with cognitive and functional deficits, suggesting that hippocampal morphometry may be a biomarker for cognitive decline in older patients with schizophrenia.

Assessment of real-world daily-living skills in early-onset schizophrenia trough the Life Skills Profile scale.

BACKGROUND: Adolescents with early-onset schizophrenia (EOS) have marked deficits in their functional outcome. However, few short and reliable instruments for assessing real-world functioning have been specifically validated in EOS. The Life Skills Profile (LSP) is a brief scale widely used in schizophrenia and considered one of the optimal instruments for assessing real-world daily living skills. The purpose of this study was to examine the usefulness and the feasibility of the LSP to assess daily living skills in EOS. METHODS: The sample included 53 clinically and pharmacologically stabilized adolescent patients with EOS and 53 healthy adolescents. Content review of the scale and internal consistency analysis were conducted in the EOS group. A subgroup of 30 patients was re-assessed over a 10-day interval to establish the test-retest reliability. Measures of functional outcome were used to assess convergent validity, and measures of intelligence and symptoms were used to assess divergent validity. Discriminant validity was analyzed through logistic analysis and the receiver-operating characteristic curve. RESULTS: The LSP and its subscales showed high reliability, adequate internal consistency and adequate convergent and divergent validity. The LSP was also found to be a sensitive instrument for detecting differences between patients and healthy adolescents, correctly classifying 84% of the sample. The estimated area under the curve was 0.925 (95% CI 0.875-0.976). CONCLUSIONS: The LSP showed adequate psychometric characteristics in adolescents with EOS and appeared to be a valid, reliable and time-efficient instrument for use in clinical practice and research settings to assess real-world daily-living skills in EOS.

Processing speed and executive functions predict real-world everyday living skills in adolescents with early-onset schizophrenia.

Cognition and clinical variables are known to be among the most predictive factors of real-world social functioning and daily living skills in adult-onset schizophrenia. Fewer studies have focused on their impact in adolescents with early-onset schizophrenia (EOS). The aim of this study is to examine the relationships and the predictive value of cognition and clinical variables on real-world daily living skills in a sample of adolescents with EOS. Cognitive, clinical and real-world everyday living skills measures were administered to 45 clinically and pharmacologically stabilized adolescent outpatients with EOS and 45 healthy control subjects matched by age and sex. Multi-variant analyses to compare cognitive and real-world functioning profiles between patients and controls and regression analysis to identify predictors of real-world functioning scores in patients were used. Adolescents with EOS showed a generalized cognitive and real-world daily living skills dysfunction. Several cognitive and clinical variables significantly correlated with real-world daily living skills functioning but only the processing speed and executive functions emerged as independent predictors of everyday living skills scores, explaining 25.1% of the variance. Slowness in processing information and executive dysfunction showed a significant impact on real-world daily living skills in EOS, independently from clinical symptoms and other cognitive variables. Nevertheless, much of the variance in the daily living skills measure remained unaccounted for, suggesting that other factors were involved as well in this young population.

Neurodevelopmental liability to schizophrenia: the complex mediating role of age at onset and premorbid adjustment.

Large individual variation in the clinical presentation of schizophrenia-spectrum disorders raises key questions regarding their aetiological underpinnings. In this respect, age at onset of the disorder is a particularly interesting marker of liability, as it has been reported to be associated with other signs of developmental compromise, such as male gender, increased presence of familial history of psychosis and poor premorbid adjustment, as well as a more severe clinical outcome in terms of cognition and symptomatology. The association between these variables has encouraged a neurodevelopmental perspective of the aetiological mechanisms involved in the pathophysiology of schizophrenia. However, the complex relationships within neurobiological liability markers, and between these markers and clinical outcome, remain to be understood. In the present study, we used a path-analytic approach to explore: i) the fit of the model to observed data; and both ii) direct and iii) indirect associations between the variables. In a sample of 106 patients with schizophrenia-spectrum disorders, we found a good fit of the model to the observed data, providing further evidence that supports a neurodevelopmental pathway to the disease in a subgroup of patients. However, the most parsimonious model showed complex relationships, where age at onset and premorbid functioning acted as mediators between gender, familial history of psychosis and clinical outcome. These findings refine earlier explanations of the neurobiological basis of schizophrenia, with potential applications in genetic studies based on more homogeneous forms of the disease. We further discuss the putative implications of our results in clinical practice and prevention policies.

Impaired response inhibition in obsessive compulsive disorder.

OBJECTIVE: The present study investigates different three inhibitory control functions in patients with obsessive-compulsive disorder (OCD). Selective motor response inhibition was tested in a GO/NO-GO paradigm, the inhibition of a triggered motor response in a STOP paradigm and the ability to inhibit cognitive interference in a motor STROOP paradigm. METHODS: 27 patients who met DSM-IV criteria for OCD and 25 age, handedness and IQ-matched healthy control subjects were tested in the GO/NO-GO, STOP and motor STROOP tasks. RESULTS: OCD patients performed significantly worse than controls in the selective inhibition of their motor responses (GO/NO-GO) and in the inhibition of cognitive interference (STROOP), and also showed worse performance in suppressing previously triggered motor responses (STOP). CONCLUSION: Patients with OCD are impaired in motor and cognitive inhibitory mechanisms. The findings are consistent with psychobiological and neuropsychological models of OCD suggesting impairment of frontostriatal circuitries that mediate functions of inhibitory control.

[Selective alteration of the declarative memory systems in patients treated with a high number of electroconvulsive therapy sessions]. / Alteracion selectiva de los sistemas declarativos de memoria en los pacientes tratados con un elevado numero de sesiones de terapia electroconvulsiva.

INTRODUCTION: The reversible electrochemical effects of electroconvulsive therapy (ECT) on specific areas of the brain enable the neuroanatomical bases of some cognitive functions to be studied. In research carried out on memory systems, a selective alteration of the declarative ones has been observed after treatment with ECT. Little work has been done to explore the differential alteration of the memory subsystems in patients with a high number of ECT sessions. AIM. To study the declarative and non declarative memory system in psychiatric patients submitted to maintenance ECT treatment, with a high number of previous ECT sessions. PATIENTS AND METHODS: 20 patients submitted to treatment with ECT (10 diagnosed as having depression and 10 with schizophrenia) and 20 controls, who were paired by age, sex and psychopathological diagnosis. For the evaluation of the declarative memory system, the Wechsler Memory Scale (WMS) logical memory test was used. The Hanoi Tower procedural test was employed to evaluate the non declarative system. RESULTS: Patients treated with ECT performed worse in the WMS logical memory test, but this was only significant in patients diagnosed as suffering from depression. No significant differences were observed in the Hanoi Tower test. CONCLUSIONS: A selective alteration of the declarative systems was observed in patients who had been treated with a high number of ECT sessions, while the non declarative memory systems remain unaffected.

Could the hypofrontality pattern in schizophrenia be modified through neuropsychological rehabilitation?

OBJECTIVE: The effects of neuropsychological treatment on cognitive hypofrontality were examined in schizophrenic patients through the score activation. METHOD: Eight subjects (six men and two women) with persistent negative symptoms and cognitive impairments were evaluated with single photon emission computed tomography (SPECT) procedures and neuropsychological battery before and after a neuropsychological treatment group. RESULTS: After treatment an enhancement in neuropsychological performance was found, especially in executive functions. The activation score showed an increase over baseline levels and no cognitive-dependent hypofrontality after treatment was found. Although the prefrontal blood flow changes were small and non-specific, they suggest a reduction of the cognitive hypofrontality after neuropsychological treatment. CONCLUSION: Cognitive improvements after neuropsychological treatment would possibly be related with the diminution of the functional hypoactivity in the prefrontal areas.

Executive function in patients with remitted bipolar disorder and schizophrenia and its relationship with functional outcome.

BACKGROUND: Recent studies have reported that differences in cognitive performance between schizophrenic and bipolar patients seem to be smaller than expected. Patients with schizophrenia have consistently shown frontal executive dysfunctions, but studies regarding executive abilities in bipolar patients are scarce and discrepant. As executive function has been associated with psychosocial functioning in schizophrenia, we wanted to investigate if such a relationship is also present in bipolar disorder and the differences between the two groups. METHODS: Executive function was assessed in 49 euthymic (at least 6 months in remission, Hamilton Depression Rating Scale < or = 8 and Young Mania Rating Scale < or = 6) bipolar and in 49 schizophrenic, residual-type (with at least 1 year without acute exacerbation and predominant negative symptomatology) patients, by the Wisconsin Card Sorting Test (WCST), FAS Test (COWAT) and Trail Making Test. Baseline clinical and psychosocial variables were controlled and psychopathology evaluated by means of the Positive and Negative Syndrome Scale (PANSS). RESULTS: The two groups showed a similar pattern of cognitive deficits in tests of executive function, except for the number of categories achieved in the WCST, which was significantly lower in the schizophrenic group (F = 7.26; p = 0.009). Functional outcome was predicted by the negative syndrome (PANSSN) and perseverative errors (WCST) in schizophrenic patients, and general psychopathology (PANSSG) was the best predictor of functional outcome in the bipolar group. CONCLUSION: Executive function was a good predictor of functional outcome in the schizophrenic group, whereas clinical variables were more predictive of the bipolar one. Patterns of cognitive disturbances in tasks of executive function are similar in both groups but quantitatively more marked in schizophrenia.

Deficit in schizophrenia: the relationship between negative symptoms and neurocognition.

The aim of the study was to analyze the role of clinical and neuropsychological variables in the psychosocial functioning and evolution of negative schizophrenia. We examined a sample of 49 negative schizophrenic outpatients who were pharmacologically stabilized. The subjects were evaluated clinically with the Positive and Negative Syndrome Scale (PANSS) and the Schedule for Affective Disorders and Schizophrenia (SADS), and neuropsychologically with a broad neuropsychological test battery. The correlations between all of the variables were studied and their predictive capacity assessed by linear regression methods. When the neuropsychological impairment criterion was established, we were able to distinguish two groups of patients with similar psychopathologies, but different neuropsychological and prognostic characteristics. Schizophrenic patients with neuropsychological impairment showed worse prognosis, worse evolution, and worse psychosocial adaptation than nonneuropsychologically impaired schizophrenics. Cognitive variables are statistically good predictors of evolution, prognosis, and adaptation. In conclusion, the negative syndrome of schizophrenia is neuropsychologically heterogeneous. Although negative patients present a similar clinical profile, their neuropsychological and prognostic characteristics may differ.

Brain perfusion and neuropsychological changes in schizophrenic patients after cognitive rehabilitation.

The role of cognitive variables was compared in two single cases of schizophrenia hypofrontality. SPECT procedures and neuropsychological tests were used to study frontal brain function. After cognitive rehabilitation, neuropsychological performance were enhanced in both patients, but only one of them showed enhanced the frontal blood flow. The brain perfusion changes after cognitive rehabilitation could be associated with the cognitive-dependent hypofrontality.

[Neuropsychological changes in schizophrenia and its modification]. / Alteraciones neuropsicológicas en la esquizofrenia y su modificación.

The main experimental works about neuropsychological impairments of schizophrenia are reviewed. The underlying mechanisms of the cognitive deficits are set in a framework of the limited capacity model. In second point, the current status of the modificability of the cognitive deficits and the clinical and psychosocial consequences of this deficits are presented. At least, neuropsychological rehabilitation programs are reviewed from a clinical point of view.

[Neuropsychological alteration in schizophrenia and its modification]. / Alteraciones neuropsicológicas en la esquizofrenia y su modificación.

The main experimental works about neuropsychological impairments of schizophrenia are reviewed. The underlying mechanisms of the cognitive deficits are set in a framework of the limited capacity model. In second point, the current status of the modificability of the cognitive deficits and the clinical and psychosocial consequences of this deficits are presented. At least, neuropsychological rehabilitation programs are reviewed from a clinical point of view.