Prospective Memory Influences Social Functioning in People With First-Episode Schizophrenia: A Network Analysis and Longitudinal Study.

Background: Prospective memory (PM) impairment is associated with impaired social functioning, but evidence is limited to chronic schizophrenia samples and cross-sectional design. The aim of this study was to utilize network analysis to address the complex interplay between PM, psychopathology, and functional outcome.Methods: This longitudinal study recruited 119 people with first-episode DSM-IV schizophrenia and followed up with them for 2 to 6 years. PM and working memory were assessed at baseline (in 2010-2015) using valid computerized tasks and the Letter-Number Span Test, respectively. Psychopathology and social functioning were assessed at endpoint (in 2016-2017) using the Positive and Negative Syndrome Scale (PANSS) and the Social and Occupational Functioning Assessment Scale (SOFAS), respectively. Network analysis examined the effect of baseline PM on SOFAS while accounting for the effects of psychopathology.Results: The resultant network showed that social functioning, PANSS positive symptoms, and PANSS general symptoms clustered together, whereas time-based and event-based PM and working memory formed another cluster. Time-based PM linked event-based PM and working memory with social functioning. Time-based PM (expected influence [EI] = 0.69), event-based PM (EI = 0.65), and working memory (EI = 0.83) demonstrated high values of expected influence, but social functioning (variance explained = 0.685) and PANSS negative (variance explained = 0.657) and general (variance explained = 0.583) subscales demonstrated high values of predictability.Conclusions: Time-based PM is the central node linking neurocognitive functions with social functioning. PM and working memory are "target" nodes for interventions bringing changes to the network, whereas social functioning and psychopathology are "malleable" nodes. PM and working memory are promising intervention targets for functional recovery in schizophrenia.

Cognitive insight is correlated with cognitive impairments and contributes to medication adherence in schizophrenia patients.

OBJECTIVE: Cognitive insight refers to the ability to distance oneself from and evaluate one's own beliefs and interpretations. Little is known about whether cognitive insight could influence medication adherence in schizophrenia patients. This study examined the role of cognitive insight in medication adherence and how it would interact with neuropsychological functions. METHODS: Ninety clinically-stable schizophrenia patients completed the Beck's Cognitive Insight Scale (BCIS) and tasks measuring prospective (PM) and other neurocognitive functions. Medication adherence was estimated using a multi-axial method comprising interview, clinician-rating, pharmacy refill record and pill counting. Correlational and regression analyses were conducted to examine whether cognitive insight and PM would be associated with mediation adherence. Post-hoc mediational analysis was performed to examine the interplay between cognitive insight, PM and medication adherence. RESULTS: Clinical insight and cognitive insight together significantly influenced participants' medication adherence, after neurocognitive functions and psychopathology were accounted for. Time-based PM, compared with other neurocognitive functions, affected medication adherence more strongly. CONCLUSIONS: Cognitive insight complements clinical insight in affecting medication adherence in schizophrenia patients.

Impaired olfactory identification and hedonic judgment in schizophrenia patients with prominent negative symptoms.

Introduction: Evidence suggests that schizophrenia patients have olfactory dysfunctions, but the relationship between olfactory identification, hedonic judgement, and negative symptomatology remains unclear. Few studies have investigated whether co-activation of pleasant and unpleasant emotions are more prevalent in schizophrenia patients.Methods: Thirty schizophrenia outpatients with prominent negative symptoms (PNS), 30 outpatients without PNS, and 30 controls completed the University of Pennsylvania Smell Identification Test, and were asked to identify the odourants and to rate their emotions. The effects of gender and medications on olfactory function were examined.Results: Schizophrenia patients exhibited olfactory identification impairments, even after accounting for gender and medication effects. Patients with PNS demonstrated larger magnitude of deficit than those without. Patients with PNS reported less pleasure to positive-valenced odourants, and less unpleasantness to negative-valenced odourants than controls. Olfactory anhedonia in patients with PNS disappeared after controlling for medication effect. Schizophrenia patients do not exhibit affective ambivalence in olfaction.Conclusions: Schizophrenia patients with PNS exhibit deficits in olfactory identification and hedonic judgement, even after controlling for gender and medication effects. Our findings support the close relationship between olfactory dysfunctions and negative symptoms. Further studies should investigate the effect of dopamine-blocking agents on the olfactory hedonic judgment in schizophrenia patients.

Tractography-based classification in distinguishing patients with first-episode schizophrenia from healthy individuals.

BACKGROUND: Schizophrenia has been characterized as a neurodevelopmental disorder of brain disconnectivity. However, whether disrupted integrity of white matter tracts in schizophrenia can potentially serve as individual discriminative biomarkers remains unclear. METHODS: A random forest algorithm was applied to tractography-based diffusion properties obtained from a cohort of 65 patients with first-episode schizophrenia (FES) and 60 healthy individuals to investigate the machine-learning discriminative power of white matter disconnectivity. Recursive feature elimination was used to select the ultimate white matter features in the classification. Relationships between algorithm-predicted probabilities and clinical characteristics were also examined in the FES group. RESULTS: The classifier was trained by 80% of the sample. Patients were distinguished from healthy individuals with an overall accuracy of 71.0% (95% confident interval: 61.1%, 79.6%), a sensitivity of 67.3%, a specificity of 75.0%, and the area under receiver operating characteristic curve (AUC) was 79.3% (χ2 p < 0.001). In validation using the held-up 20% of the sample, patients were distinguished from healthy individuals with an overall accuracy of 76.0% (95% confident interval: 54.9%, 90.6%), a sensitivity of 76.9%, a specificity of 75.0%, and an AUC of 73.1% (χ2 p = 0.012). Diffusion properties of inter-hemispheric fibres, the cerebello-thalamo-cortical circuits and the long association fibres were identified to be the most discriminative in the classification. Higher predicted probability scores were found in younger patients. CONCLUSIONS: Our findings suggest that the widespread connectivity disruption observed in FES patients, especially in younger patients, might be considered potential individual discriminating biomarkers.

Prospective memory in individuals with first-episode schizophrenia: A two-year longitudinal study.

AIM: The present study aimed to explore the two-year naturalistic trajectory of time- and event-based prospective memory (PM) in patients with first-episode schizophrenia. METHODS: We administered a computer-based dual-task PM paradigm to 57 individuals with first-episode schizophrenia at baseline and after 6 months, 12 months and 24 months. Forty-eight healthy controls were also recruited and completed all the measures at baseline. We compared the trajectories between time-based and event-based PM in first-episode schizophrenia patients using repeated measures ANOVAs, and examined the relationship between PM and clinical symptoms using Spearman's correlation. RESULTS: PM impairments improved significantly after 24 months of follow-up. However, time-based and event-based PM appeared to run different trajectories. After 24 months, first-episode schizophrenia patient performed poorer than healthy controls in time-based but not event-based PM. PM did not appear to be correlated with clinical symptoms, both cross-sectionally and longitudinally. CONCLUSIONS: This is one of the longest follow-up studies investigating PM in first-episode schizophrenia. Our results provide evidence to support that time-based PM is more temporally stable than event-based PM.

Problems in remembering to carry out future actions in first-episode schizophrenia: primary or secondary impairment?

Prospective memory (PM) is the ability to remember to carry out intended actions in the future. Empirical evidence suggests that PM deficits exist in individuals with chronic schizophrenia. However, it is unclear whether PM deficits in first-episode schizophrenia exist independently from other neuropsychological deficits. Moreover, prior research using patients with first-episode has been limited to small inpatient samples. We aimed to clarify the nature and extent of PM deficits in individuals with first-episode schizophrenia, using a large outpatient sample. Participants were 91 clinically stable outpatients with first-episode schizophrenia and 83 healthy controls. PM was assessed using both a subjective self-reported checklist and a laboratory-based task capturing time- and event-based PM. A battery assessing verbal and visuo-spatial working memory, as well as executive functions was also administered. ANOVA analyses showed that patients with first-episode schizophrenia performed significantly poorer than healthy controls in time- and event-based PM. Stepwise linear regression analyses suggested that cognitive flexibility predicted time- and event-based PM; and working memory predicted event-based PM. Subgroup analyses showed that "cognitive-preserved" patients with first-episode schizophrenia tended to perform poorer in time-based PM deficit than healthy controls who were matched in IQ and other neuropsychological functions. Overall, our results provide substantial evidence to support that time-based PM deficits in first-episode schizophrenia are apparent and not entirely attributable to other neuropsychological deficits. PM may constitute a neuropsychological marker for schizophrenia.

Prospective memory in patients with first-onset schizophrenia and their non-psychotic siblings.

This behavioral study used a dual-task paradigm to compare PM performance in 35 patients with first-onset schizophrenia, 40 non-psychotic siblings and 35 healthy controls. It aimed specifically to examine the effect of schizophrenia group status on PM, the differential effect of group status on PM type, and correlations between PM and other neurocognitive functions and clinical data in first-onset schizophrenia. It also aimed to test the hypothesis that non-psychotic siblings had poorer PM performance than controls. The cohort of first-onset schizophrenia patients had relatively short illness durations (M=1.7 years). The three groups of participants were matched in terms of age, gender and years of education. Results of the study confirmed that first-onset schizophrenia status had a primary effect on PM after controlling for other neurocognitive functions. We also found that first-onset schizophrenia status did not differentially affect two different types of PM. In the first-onset schizophrenia cohort, PM was found to correlate significantly with IQ, executive functions and sustained attention. Finally, contrary to the findings of the previous study, this study did not find siblings of schizophrenia patients to have impaired PM. Taking into account the previous findings of PM in chronic schizophrenia, we concluded that schizophrenia has a primary effect on PM regardless of illness duration.

Neuropsychological profiles and short-term outcome in late-onset depression.

OBJECTIVE: Neuropsychological impairments are common in older persons with late-onset depression. This study examined the relationship between neuropsychological profiles and short-term outcome in late-onset depression. METHODS: A total of 54 non-demented Chinese elders presented with their first major depressive episode after 60 years of age participated in this study and were treated according to a standardised protocol. At entry, they were assessed on neurological signs (Parkinsonian features and neurological soft signs) and neuropsychological measures (executive function, psychomotor-speed, attention and working memory, episodic memory, conceptualisation, construction and global cognitive function). The Hamilton Depression Rating Scale (HAM-D) was administered at baseline, the sixth and 12th week of treatment. RESULTS: Abnormal fist-edge-palm (FEP) test, a sign reflecting impairment in motor sequencing, was more common in non-remitters (defined as HAM-D score above 7) at the 12th week of treatment. CONCLUSIONS: The FEP test may be included in the clinical assessment for patients with late-onset depression to identify a susceptible group who may require more intensive treatment. Further research is warranted to ascertain the link between late-onset depression, neuropsychological deficits and prognosis.