Visual memory uniquely predicts anhedonia in schizophrenia but not bipolar disorder.

OBJECTIVE: Deficits in memory have been suggested as an influential mechanism of anhedonia, because while pleasant experiences may be enjoyed in-the-moment, the cognitive processes involved in reporting anticipated or remembered enjoyable experiences is thought to be impaired. This study will determine whether any aspects of memory, including visual memory, verbal memory or working memory, are significantly predictive of anhedonia in a sample of schizophrenia, psychotic bipolar disorder and healthy controls. METHODS: The study included 38 individuals with schizophrenia, 19 individuals with bipolar disorder with psychosis, and 43 age-matched healthy controls. All participants completed a self-report social and physical anhedonia questionnaire along with a cognitive screening battery, which assessed the domains of attention/vigilance, working memory, verbal learning, visual learning, and reasoning and problem-solving. RESULTS: Anhedonia scores were regressed onto domain scores to determine which areas of cognition uniquely predicted level of anhedonia in each group. For the schizophrenia group, physical anhedonia was significantly predicted by worse visual memory performance. The regression models did not find significant cognitive predictors of physical or social anhedonia in the bipolar disorder or control groups. CONCLUSIONS: This study found a significant relationship between visual memory and physical anhedonia in schizophrenia patients that was not present in a sample of psychotic bipolar patients or healthy controls, adding to an accumulating body of evidence that visual memory is related to anhedonia in schizophrenia. This relationship may be explained by underlying abnormalities in the orbitofrontal cortex in schizophrenia.

Detection of symptom over-reporting on the Neurobehavioral Symptom Inventory in OEF/OIF/OND veterans with history of mild TBI.

OBJECTIVE: As part of routine care at Veterans Affairs facilities, veterans with a service-related traumatic brain injury (TBI) are administered a self-report post-concussive symptom measure, the Neurobehavioral Symptom Inventory (NSI). Interpreting the NSI can be problematic given that over-reporting on self-report measures is often found in both civilian and military patient populations. This study investigates embedded scales on the NSI that identify possible and probable symptom exaggeration. METHOD: 183 veterans with a history of mild TBI were administered the Minnesota Multiphasic Personality Inventory, 2nd edition, Restructured Form (MMPI-2-RF) and the NSI. The participants were divided into symptom validity testing pass and fail groups based on their performance on the MMPI-2-RF symptom validity scales. Cut scores on the NSI Total and Validity-10 scores were then established and applied to two additional veteran populations. RESULTS: Sensitivity and specificity values were derived for all NSI Total and Validity-10 values. Optimal cut scores were determined based on specificity levels of ≥95%. The NSI Total cut score was ≥57 for possible and ≥67 for probable symptom exaggeration and the Validity-10 cut score was ≥22 for possible and ≥27 for probable symptom exaggeration, with sensitivity ranging from 27 to 43%. Applying these cut scores to a broader clinical and research sample resulted in lower rates of suspected exaggeration. CONCLUSIONS: Both the NSI Total and Validity-10 cut scores consistently identified potential symptom exaggeration across three mild TBI samples. Clinicians and researchers who use the NSI are encouraged to utilize either embedded validity measure in their practice.

Working memory predicts presence of auditory verbal hallucinations in schizophrenia and bipolar disorder with psychosis.

OBJECTIVE: The recent dramatic increase in research investigating auditory verbal hallucinations (AVHs) has broadened the former narrow focus on schizophrenia to incorporate additional populations that experience these symptoms. However, an understanding of potential shared mechanisms remains elusive. Based on theories suggesting a failure of top-down cognitive control, we aimed to compare the relationship between AVHs and cognition in two categorical diagnoses of psychosis, schizophrenia and psychotic bipolar disorder. METHOD: A total of 124 adults aged 21-60 participated, of whom 76 had present-state psychosis (schizophrenia, n = 53; bipolar disorder with psychosis, n = 23), and 48 were non-clinical controls. Diagnosis and hallucination presence was determined using the Structured Clinical Diagnostic Interview for DSM-IV TR. AVHs severity was assessed using the Positive and Negative Syndrome Scale. Participants also completed the MATRICS cognitive battery. RESULTS: The bipolar disorder with psychosis group performed better than the schizophrenia group for cognitive domains of Processing speed, Attention, Working memory (WM), and Visual memory. Hierarchical binary logistic regression found that WM significantly predicted presence of AVHs in both psychotic groups, but diagnosis did not significantly increase the predictive value of the model. A hierarchical multiple linear regression found that schizophrenia diagnosis was the only significant predictor of hallucination severity. CONCLUSIONS: The findings of this study-the first, to our knowledge, to compare the relationship between AVHs and MATRICS domains across schizophrenia and bipolar disorder with psychosis-support theories that deficits in WM underly the genesis of AVHs. WM potentially represents a shared mechanism of AVHs across diagnoses, supporting dimensional classifications of these psychotic disorders. However, non-cognitive factors predictive of hallucination severity may be specific to schizophrenia.

Associations between trait anhedonia and emotional memory deficits in females with schizophrenia versus major depression.

Individuals with schizophrenia (SZ) and individuals with major depressive disorder (MDD) demonstrate impaired emotional memory and decreased enjoyment of pleasant experiences (e.g., anhedonia). However, it is unclear whether these impairments reflect similar or different processes in the two diagnostic groups. This study compared emotional memory performance in three groups of females - controls, MDD, and SZ. Given that physical and social trait anhedonia has been shown to differentiate course of illness and emotional functioning within each disorder, the present study also examined whether trait anhedonia related to emotional memory differently in the groups. Participants viewed emotional and neutral images and twenty-four hours later completed an incidental recognition test. SZ participants demonstrated a trend for the worst memory performance. Across all groups, high intensity and negative images were remembered most accurately, while groups were not differentially influenced by the valence of the stimuli. Physical anhedonia was predictive of reduced memory for negative stimuli across all diagnostic groups. Group specific findings indicated that higher levels of social anhedonia were predictive of poorer memory, but only in the SZ group. Effects remained significant when controlling for depressive symptoms. Results are considered in light of the differing role of anhedonia in SZ and MDD.

Evidence of a sex-dependent restrictive epigenome in schizophrenia.

When compared to women, men have a higher incidence of schizophrenia, with increases in negative and cognitive symptoms, and an overall poorer disease course. Schizophrenia is conceptualized as a disorder of aberrant gene transcription and regulation. Thus, epigenetics, the study of environmentally induced changes in gene regulation, could advance our understanding of the molecular underpinnings of schizophrenia. Peripheral histone methyltransferase (HMT) mRNA levels have been previously shown to be significantly increased in patients with schizophrenia and correlate with symptomology. In this independent study, peripheral lymphocytes were extracted and clinical symptoms were measured on 74 participants, (40 patients with schizophrenia (19 women, 21 men) and 34 healthy individuals (19 women, 15 men)). HMT (G9α, SETDB1 and GLP) mRNA levels and their resulting histone modification H3K9me2 were measured with RT-PCR and ELISA respectively. Plasma estradiol levels were also measured via ELISA and correlated with HMT mRNA. Clinical symptoms were measured utilizing the Positive and Negative Syndrome Scale (PANSS) and the Heinrichs Carpenter Quality of Life Scale (QLS). The results indicate that men with schizophrenia expressed the highest levels of G9α, SETDB1 mRNA and H3K9me2 protein levels. Additionally, higher levels of symptom presentation and an overall poorer quality of life were correlated with higher HMT mRNA and H3K9me2 protein levels in a sex-dependent pattern. These data support the hypothesis of a sex-dependent restrictive epigenome contributing towards the etiology of schizophrenia. The histone methyltransferases measured here could be potential future therapeutic targets for small molecule pharmacology.

The impact of social content and negative symptoms on affective ratings in schizophrenia.

The anhedonia paradox has been a topic of ongoing study in schizophrenia. Previous research has found that schizophrenia patients report less enjoyment from various activities when compared to their healthy counterparts; however, the two groups appear to have similar in-the-moment emotional ratings of these events (Gard et al., 2007; Herbener et al., 2007; Horan et al., 2006). This study examined these in-the-moment experiences further, by assessing whether they differed between social and non-social experiences. The data were collected from 38 individuals with schizophrenia and 53 matched healthy controls in the greater Chicago area. In-the-moment emotional experience was measured by self-reported arousal and valence ratings for social and non-social stimuli taken from the International Affective Picture System (IAPS). Clinical ratings for patients were gathered by the Positive and Negative Syndrome Scale. A series of ANOVAs revealed that controls were more aroused by the social than nonsocial unpleasant stimuli, whereas patients did not show this distinction. Further, regression analyses revealed that negative symptom severity uniquely predicted lower arousal responses to unpleasant social, but not nonsocial, stimuli. Our results indicate that both subject and stimulus factors appear to contribute to differences in emotional responses in individuals with schizophrenia.