Neurophysiological mechanisms of cortical plasticity impairments in schizophrenia and modulation by the NMDA receptor agonist D-serine.

Schizophrenia is associated with deficits in cortical plasticity that affect sensory brain regions and lead to impaired cognitive performance. Here we examined underlying neural mechanisms of auditory plasticity deficits using combined behavioural and neurophysiological assessment, along with neuropharmacological manipulation targeted at the N-methyl-D-aspartate type glutamate receptor (NMDAR). Cortical plasticity was assessed in a cohort of 40 schizophrenia/schizoaffective patients relative to 42 healthy control subjects using a fixed reference tone auditory plasticity task. In a second cohort (n = 21 schizophrenia/schizoaffective patients, n = 13 healthy controls), event-related potential and event-related time-frequency measures of auditory dysfunction were assessed during administration of the NMDAR agonist d-serine. Mismatch negativity was used as a functional read-out of auditory-level function. Clinical trials registration numbers were NCT01474395/NCT02156908 Schizophrenia/schizoaffective patients showed significantly reduced auditory plasticity versus healthy controls (P = 0.001) that correlated with measures of cognitive, occupational and social dysfunction. In event-related potential/time-frequency analyses, patients showed highly significant reductions in sensory N1 that reflected underlying impairments in θ responses (P < 0.001), along with reduced θ and ß-power modulation during retention and motor-preparation intervals. Repeated administration of d-serine led to intercorrelated improvements in (i) auditory plasticity (P < 0.001); (ii) θ-frequency response (P < 0.05); and (iii) mismatch negativity generation to trained versus untrained tones (P = 0.02). Schizophrenia/schizoaffective patients show highly significant deficits in auditory plasticity that contribute to cognitive, occupational and social dysfunction. d-serine studies suggest first that NMDAR dysfunction may contribute to underlying cortical plasticity deficits and, second, that repeated NMDAR agonist administration may enhance cortical plasticity in schizophrenia.

Confirmatory factor analysis of the Beck Depression Inventory-II in patients with advanced cancer: A theory-driven approach.

OBJECTIVE: The diagnosis and treatment of depression are complicated by the presence of a serious medical illness, such as cancer. The role of inflammation in the pathophysiology of depression remains unknown; however, the symptom cluster of sickness behavior is more clearly related to inflammation. Symptom clusters may provide the specificity needed to improve treatment outcomes. The purpose of this study is to use confirmatory factor analysis to examine the construct of sickness behavior in patients with advanced cancer using the Beck Depression Inventory-II (BDI-II). METHOD: Patients (N = 167) were recruited from chemotherapy clinics and the Department of Psychiatry at Memorial Sloan Kettering Cancer Center. Symptoms were a priori delineated using the factor labels sickness behavior and negative affectivity (two-factor model), and affective, cognitive, and sickness behavior (three-factor model). These data were also fit for a more traditional model using affective, cognitive, and somatic factors. RESULTS: The mean total BDI-II score was 14.74 (SD = 8.52; range = 1-46). Fit statistics for all models were good, but the novel three-factor model with sickness behavior provided the best fit: χ2(186) = 273.624; p < 0.001; root-mean-square error of approximation = 0.053; comparative fit index = 0.949. SIGNIFICANCE OF RESULTS: Both the two- and three-factor models provide support for the unique construct of sickness behavior in patients with advanced cancer. High factor correlations with the BDI-II and other measures of distress were observed, which raises questions about theoretically distinct, but related, constructs.

Neural Substrates of Auditory Emotion Recognition Deficits in Schizophrenia.

Deficits in auditory emotion recognition (AER) are a core feature of schizophrenia and a key component of social cognitive impairment. AER deficits are tied behaviorally to impaired ability to interpret tonal ("prosodic") features of speech that normally convey emotion, such as modulations in base pitch (F0M) and pitch variability (F0SD). These modulations can be recreated using synthetic frequency modulated (FM) tones that mimic the prosodic contours of specific emotional stimuli. The present study investigates neural mechanisms underlying impaired AER using a combined event-related potential/resting-state functional connectivity (rsfMRI) approach in 84 schizophrenia/schizoaffective disorder patients and 66 healthy comparison subjects. Mismatch negativity (MMN) to FM tones was assessed in 43 patients/36 controls. rsfMRI between auditory cortex and medial temporal (insula) regions was assessed in 55 patients/51 controls. The relationship between AER, MMN to FM tones, and rsfMRI was assessed in the subset who performed all assessments (14 patients, 21 controls). As predicted, patients showed robust reductions in MMN across FM stimulus type (p = 0.005), particularly to modulations in F0M, along with impairments in AER and FM tone discrimination. MMN source analysis indicated dipoles in both auditory cortex and anterior insula, whereas rsfMRI analyses showed reduced auditory-insula connectivity. MMN to FM tones and functional connectivity together accounted for ∼50% of the variance in AER performance across individuals. These findings demonstrate that impaired preattentive processing of tonal information and reduced auditory-insula connectivity are critical determinants of social cognitive dysfunction in schizophrenia, and thus represent key targets for future research and clinical intervention. SIGNIFICANCE STATEMENT: Schizophrenia patients show deficits in the ability to infer emotion based upon tone of voice [auditory emotion recognition (AER)] that drive impairments in social cognition and global functional outcome. This study evaluated neural substrates of impaired AER in schizophrenia using a combined event-related potential/resting-state fMRI approach. Patients showed impaired mismatch negativity response to emotionally relevant frequency modulated tones along with impaired functional connectivity between auditory and medial temporal (anterior insula) cortex. These deficits contributed in parallel to impaired AER and accounted for ∼50% of variance in AER performance. Overall, these findings demonstrate the importance of both auditory-level dysfunction and impaired auditory/insula connectivity in the pathophysiology of social cognitive dysfunction in schizophrenia.

Maladaptive daydreaming: Evidence for an under-researched mental health disorder.

This study explores the recently described phenomenon of Maladaptive Daydreaming (MD) and attempts to enhance the understanding of its features. It documents the experiences of 340 self-identified maladaptive daydreamers who spend excessive amounts of time engaged in mental fantasy worlds, in comparison to 107 controls. Our sample included a total of 447 individuals, aged 13-78, from 45 countries who responded to online announcements. Participants answered quantitative and qualitative questions about their daydreaming habits and completed seven questionnaires assessing mental health symptoms. Findings demonstrated that MD differs significantly from normative daydreaming in terms of quantity, content, experience, controllability, distress, and interference with life functioning. Results also demonstrated that Maladaptive Daydreamers endorsed significantly higher rates of attention deficit, obsessive compulsive and dissociation symptoms than controls. In sum, findings suggested that MD represents an under-acknowledged clinical phenomenon that causes distress, hinders life functioning and requires more scientific and clinical attention.

Development and validation of the Maladaptive Daydreaming Scale (MDS).

This study describes the development of the Maladaptive Daydreaming Scale (MDS), a 14-item self-report instrument designed to gauge abnormal fantasizing. Our sample consisted of 447 English-speaking individuals from 45 different countries. A 3-correlated-factors model best presented the underlying dimensions Yearning, Kinesthesia and Impairment, capturing related rewarding experiences as well as psychological impairment of maladaptive daydreaming. MDS scores were associated with obsessive-compulsive behavior and thoughts, dissociative absorption, attention deficit, and high sense of presence during daydreaming, but less with psychotic symptoms. The MDS and its subscale demonstrated good validity, sound internal consistency and temporal stability and discriminated well between self-identified individuals with and without maladaptive daydreaming. Considering the instrument's high sensitivity and specificity levels, it seems an excellent measure for future investigation of MD that will, hopefully, shed light on the etiology and psycho-biological mechanisms involved in this mental condition, as well as on the development of effective MD treatment methods.

Physical, cognitive, social and mental health in near-centenarians and centenarians living in New York City: findings from the Fordham Centenarian Study.

BACKGROUND: Despite their strong increase, the population of the very old, including near-centenarians and centenarians, represent an unstudied and underserved population. Available studies mostly concentrate on predictors of exceptional longevity, but rarely extend their focus to other areas of functioning. Also, little is known about what contributes to experiencing a quality life in very old age. The present population-based study aims at providing a comprehensive picture of key domain of functioning, including physical, cognitive, social and mental function in very old individuals and to determine predictors of mental health indicators. METHODS: A total of 119 individuals aged 95 to 107 living in private dwellings and residential care facilities were recruited based on the New York City Voters Registry. Participants answered questions regarding their health and activities of daily living. Their cognitive functioning was determined using the Mini-Mental State Examination and the Global Deterioration Scale. Social resources were measured with number of children and the Lubben Scale. Mental health was assessed with the Geriatric Depression Scale and the Satisfaction with Life Scale. RESULTS: An unexpectedly large proportion of the sample lived in the community. On average, cognitive functioning was high. Although five diseases were reported on average, participants reported good health. Functional status was reduced. Most participants had at least one person for communication/social support. On average, depression was below cut-off, and most participants reported high life satisfaction. Regression analyses indicated that individual differences in depression were associated with subjective health, IADL and relatives support. For life satisfaction, subjective health, ADL and number of children were most important. Demographic characteristics, number of illnesses or cognitive status were not significant. CONCLUSIONS: Despite reduced levels of physical functioning and social resources, very old participants were in good mental health suggesting high resilience and ability to adapt to age-associated challenges. That a large proportion of them lived in the community further highlights their desire for leading an autonomous life, which may have been facilitated by New York service culture. More research is necessary to provide guidance for the development of well-suited services for this very old population.

Auditory tasks for assessment of sensory function and affective prosody in schizophrenia.

Schizophrenia patients exhibit impairments in auditory-based social cognition, indicated by deficits in detection of prosody, such as affective prosody and basic pitch perception. However, little is known about the psychometric properties of behavioral tests used to assess these functions. The goal of this paper is to characterize the properties of prosody and pitch perception tasks and to investigate whether they can be shortened. The pitch perception test evaluated is a tone-matching task developed by Javitt and colleagues (J-TMT). The prosody test evaluated is the auditory emotion recognition task developed by Juslin and Laukka (JL-AER). The sample includes 124 schizophrenia patients (SZ) and 131 healthy controls (HC). Properties, including facility and discrimination, of each item were assessed. Effects of item characteristics (e.g., emotion) were also evaluated. Shortened versions of the tests are proposed based on facility, discrimination, and/or ability of item characteristics to discriminate between patients and controls. Test-retest reliability is high for patients and controls for both the original and short forms of the J-TMT and JL-AER. Thus, the original as well as short forms of the J-TMT and JL-AER are suggested for inclusion in clinical trials of social cognitive and perceptual treatments. The development of short forms further increases the utility of these auditory tasks in clinical trials and clinical practice. The large SZ vs. HC differences reported here also highlight the profound nature of auditory deficits and a need for remediation.

Valuation of Life Among Old and Very Old Adults: Comparison Between Germany and Japan.

BACKGROUND AND OBJECTIVES: Valuation of life (VOL) represents a construct capturing individuals' active attachment to their life. The majority of studies on VOL were conducted in North America and Europe where personal autonomy and independence are highly valued, leaving open the question about the relevance of this construct in interdependence-oriented cultures. Using a framework of cross-cultural and life-span theories, the present study compared levels and predictors of VOL between the young-old and old-old individuals from Germany and Japan. RESEARCH DESIGN AND METHODS: Two hundred fifty-seven Germans and 248 Japanese, matched by age, gender, education, and IADL, answered a 5-item VOL scale and shared information on sociodemographic, social, and health resources. RESULTS: Germans' VOL levels were higher than in Japanese participants. Both culture- and age-moderated predictions of VOL: education was significant only in the young-old Japanese, and close social partners mattered in the old-old, not in the young-old. Health determined VOL irrespective of culture and age. DISCUSSION AND IMPLICATIONS: The findings suggest that cultural values and aging processes should be considered to better understand how individuals value their life and to help older adults to feel that his/her life is meaningful and worth living.

Reading deficits in schizophrenia and individuals at high clinical risk: relationship to sensory function, course of illness, and psychosocial outcome.

OBJECTIVE: The ability to read passages of information fluently and with comprehension is a basic component of socioeconomic success. Reading ability depends on the integrity of underlying visual and auditory (phonological) systems. This study investigated the integrity of reading ability in schizophrenia relative to the integrity of underlying visual and auditory function. METHOD: The participants were 45 schizophrenia patients, 19 clinical high-risk patients, and 65 comparison subjects. Reading was assessed using tests sensitive to visual or phonological reading dysfunction. Sensory, neuropsychological, and functional outcome measures were also obtained. RESULTS: Schizophrenia patients displayed reading deficits that were far more severe (effect size >2.0) than would be predicted based on general neurocognitive impairments (effect size 1.0-1.4). The deficits correlated highly with both visual and auditory sensory measures, including impaired mismatch negativity generation (r=0.62, N=51, p=0.0002). Patients with established schizophrenia displayed both visual and phonological impairments, whereas high-risk patients showed isolated visual impairments. More than 70% of schizophrenia patients met criteria for acquired dyslexia, with 50% reading below eighth grade level despite intact premorbid reading ability. Reading deficits also correlated significantly (rp=0.4, N=30, p=0.03) with failure to match parental socioeconomic achievement, over and above contributions of more general cognitive impairment. CONCLUSIONS: Patients with schizophrenia display severe deficits in reading ability that represent a potentially remediable cause of impaired socioeconomic function. Such deficits are not presently captured during routine clinical assessment. Deficits most likely develop during the years immediately surrounding illness onset and may contribute to the reduced educational and occupational achievement associated with schizophrenia.

Reduction in tonal discriminations predicts receptive emotion processing deficits in schizophrenia and schizoaffective disorder.

INTRODUCTION: Schizophrenia patients show decreased ability to identify emotion based upon tone of voice (voice emotion recognition), along with deficits in basic auditory processing. Interrelationship among these measures is poorly understood. METHODS: Forty-one patients with schizophrenia/schizoaffective disorder and 41 controls were asked to identify the emotional valence (happy, sad, angry, fear, or neutral) of 38 synthesized frequency-modulated (FM) tones designed to mimic key acoustic features of human vocal expressions. The mean (F0M) and variability (F0SD) of fundamental frequency (pitch) and absence or presence of high frequency energy (HF500) of the tones were independently manipulated to assess contributions on emotion identification. Forty patients and 39 controls also completed tone-matching and voice emotion recognition tasks. RESULTS: Both groups showed a nonrandom response pattern (P < .0001). Stimuli with highest and lowest F0M/F0SD were preferentially identified as happy and sad, respectively. Stimuli with low F0M and midrange F0SD values were identified as angry. Addition of HF500 increased rates of angry and decreased rates of sad identifications. Patients showed less differentiation of response across frequency changes, leading to a highly significant between-group difference in response pattern to maximally identifiable stimuli (d = 1.4). The differential identification pattern for FM tones correlated with deficits in basic tone-matching ability (P = .01), voice emotion recognition (P < .001), and negative symptoms (P < .001). CONCLUSIONS: Specific FM tones conveyed reliable emotional percepts in both patients and controls and correlated highly with deficits in ability to recognize information based upon tone of voice, suggesting significant bottom-up contributions to social cognition and negative symptom impairments in schizophrenia.

Recognition of posed and spontaneous dynamic smiles in young and older adults.

In 2 studies, we investigated age effects in the ability to recognize dynamic posed and spontaneous smiles. Study 1 showed that both young and older adult participants were above chance in their ability to distinguish between posed and spontaneous smiles in young adults. In Study 2, we found that young adult participant performance declined when judging a combination of both young and older adult target smiles, while older adult participants outperformed young adult participants in distinguishing between posed and spontaneous smiles. A synthesis of results across the 2 studies showed a small-to-medium age effect (d = -0.40), suggesting that older adults have an advantage in discriminating between smile types. Mixed stimuli (i.e., a mixture of young and older adult faces) may impact accurate smile discrimination. In future research, both the sources (cues) and behavioral effects of age-related differences in the discrimination of positive expressions should be investigated.