Ellen S. Herbener

Pretreatment and longitudinal studies of neuropsychological deficits in antipsychotic-naïve patients with schizophrenia

The early course of neuropsychological dysfunction in schizophrenia and the impact of treatment on these deficits need to be better specified. A sample of 45 patients with schizophrenia underwent five neuropsychological evaluations from prior to treatment with antipsychotic treatment through a 2-year follow-up period. A comparison sample of 33 matched healthy individuals underwent neuropsychological evaluations at similar time points. At baseline, a generalized deficit across cognitive domains was evident for the schizophrenia sample. After 6 weeks of treatment, patients showed modest improvements in visual memory and visual perception, but a decline in verbal memory. Verbal memory performance returned to baseline levels by the 6-month follow-up while deficits in other neuropsychological domains persisted throughout the 2-year period. Relatively static and generalized neuropsychological dysfunction, evident from illness onset, is consistent with neurodevelopmental rather than neurodegenerative models of schizophrenia.

Deficits in Positive Reinforcement Learning and Uncertainty-Driven Exploration Are Associated with Distinct Aspects of Negative Symptoms in Schizophrenia

BACKGROUND Negative symptoms are core features of schizophrenia (SZ); however, the cognitive and neural basis for individual negative symptom domains remains unclear. Converging evidence suggests a role for striatal and prefrontal dopamine in reward learning and the exploration of actions that might produce outcomes that are better than the status quo. The current study examines whether deficits in reinforcement learning and uncertainty-driven exploration predict specific negative symptom domains. METHODS We administered a temporal decision-making task, which required trial-by-trial adjustment of reaction time to maximize reward receipt, to 51 patients with SZ and 39 age-matched healthy control subjects. Task conditions were designed such that expected value (probability × magnitude) increased, decreased, or remained constant with increasing response times. Computational analyses were applied to estimate the degree to which trial-by-trial responses are influenced by reinforcement history. RESULTS Individuals with SZ showed impaired Go learning but intact NoGo learning relative to control subjects. These effects were most pronounced in patients with higher levels of negative symptoms. Uncertainty-based exploration was substantially reduced in individuals with SZ and selectively correlated with clinical ratings of anhedonia. CONCLUSIONS Schizophrenia patients, particularly those with high negative symptoms, failed to speed reaction times to increase positive outcomes and showed reduced tendency to explore when alternative actions could lead to better outcomes than the status quo. Results are interpreted in the context of current computational, genetic, and pharmacological data supporting the roles of striatal and prefrontal dopamine in these processes.

Neurocognitive Allied Phenotypes for Schizophrenia and Bipolar Disorder

Psychiatric disorders are genetically complex and represent the end product of multiple biological and social factors. Links between genes and disorder-related abnormalities can be effectively captured via assessment of phenotypes that are both associated with genetic effects and potentially contributory to behavioral abnormalities. Identifying intermediate or allied phenotypes as a strategy for clarifying genetic contributions to disorders has been successful in other areas of medicine and is a promising strategy for identifying susceptibility genes in complex psychiatric disorders. There is growing evidence that schizophrenia and bipolar disorder, rather than being wholly distinct disorders, share genetic risk at several loci. Further, there is growing evidence of similarity in the pattern of cognitive and neurobiological deficits in these groups, which may be the result of the effects of these common genetic factors. This review was undertaken to identify patterns of performance on neurocognitive and affective tasks across probands with schizophrenia and bipolar disorder as well as unaffected family members, which warrant further investigation as potential intermediate trait markers. Available evidence indicates that measures of attention regulation, working memory, episodic memory, and emotion processing offer potential for identifying shared and illness-specific allied neurocognitive phenotypes for schizophrenia and bipolar disorder. However, very few studies have evaluated neurocognitive dimensions in bipolar probands or their unaffected relatives, and much work in this area is needed.

Failure of positive but not negative emotional valence to enhance memory in schizophrenia.

Abnormalities in the integration of emotion and cognition have long been considered hallmark characteristics of schizophrenia. Study authors used a well-established emotional memory model from the neuroscience literature to assess the facilitative impact of emotional valence of information on long-term memory consolidation in schizophrenia. Participants with schizophrenia (n=33) indicated somewhat higher levels of emotional intensity in response to emotional images than did healthy (n=28) participants. However, when recognition memory was tested 24 hr later, schizophrenia participants did not show enhancement of memory for positive images as was found in healthy participants. Their memory enhancement for negative images did not differ from that of healthy participants. Correlations between self-reported physical and social anhedonia were significantly inversely correlated with intensity ratings of positive stimuli during the encoding phase for healthy participants but were negligible for schizophrenia participants. These results suggest a failure to adequately integrate positive emotional experience in memory consolidation processes in schizophrenia participants, despite appropriate initial response to positive stimuli, which may contribute to symptoms such as anhedonia by reducing the long-term impact of positive experiences in motivating hedonic behavior in day-to-day life.

Change in the relationship between anhedonia and functional deficits over a 20-year period in individuals with schizophrenia.

Although early theorists suggested that deficits in emotional experience be considered a hallmark characteristic of schizophrenia, there has been limited research, and inconsistent findings, on the relationship between anhedonia and functional capacity in individuals after the onset of schizophrenia. Stronger relationships have typically been reported for chronic samples in contrast to first episode samples, although it is not clear whether this is due to selection biases that influence recruitment in these different groups, or whether results reflect a change over the course of illness. The current longitudinal study examined the relationship between physical anhedonia and functional status in a sample of 61 individuals with schizophrenia at regular intervals over a 20-year period. Subjects were recruited into the study during an index hospitalization and completed assessments at 2-, 4.5-, 7.5-, 10-, 15-, and 20-year follow-ups. Analyses indicate that the relationship between anhedonia and impairments increases over time, although mean performance on these measures is stable across this same time period. These results suggest increasing convergence of impairments in emotional, adaptive, and cognitive capacities over time, with physical anhedonia associated with poorer outcome.

The relationship between positive symptoms and instrumental work functioning in schizophrenia: a 10 year follow-up study.

This longitudinal investigation was designed to determine the association between the positive symptoms of psychosis and instrumental work functioning among patients with schizophrenia in comparison to patients with affective disorders. 173 participants were assessed prospectively for the presence of psychosis and concurrent work adjustment using a series of standardized measures at four consecutive follow-ups over a 10 yr period. The data demonstrate a significant relationship between psychosis and increased impairment in work functioning across diagnostic groups for three of the four follow-up periods (p<0.01), with this relationship being most consistent for the schizophrenia patients throughout the course of their disorder (p<0.01). The more severely psychotic patients, regardless of diagnosis, are least likely to be working effectively; however, the debilitating effect of psychosis on work adjustment is most evident for schizophrenia patients.

A prospective longitudinal 10-year study of schizophrenia's three major factors and depression

This study investigated the nature, independence, and stability of schizophrenias syndrome factors and depression at 2, 4.5, 7.5 and 10 years post-index hospitalization. At the four follow-ups, 71 patients (48 with schizophrenia and 23 with schizoaffective disorder) were assessed for symptoms hypothesized to constitute the reality distortion, disorganized, and negative factors of schizophrenia. At the last three follow-ups, the patients were also assessed for symptoms of depression. Factor analyses of schizophrenia symptoms revealed more than three syndrome factors at each follow-up. Longitudinally, reality distortion was a stable and relatively independent factor. The negative syndrome was independent but was bifurcated into two dimensions, interpreted as social/emotional withdrawal and diminished movement/expressiveness. Although signs of disorganization were not unified or independent early in schizophrenias course, speech/thought disorder, disorganized affect, and poverty of speech content coalesced to form a disorganization factor by the 7.5-year follow-up. When depressive symptoms were added to the analyses, depression constituted an independent and stable dimension of schizophrenia over time. Each schizophrenia factor demonstrated a unique longitudinal course. Courses included stable symptom consistency (reality distortion), evolving symptom convergence (disorganization), and recurrent bifurcation and symptom instability (the negative syndrome).

The course of anhedonia during 10 years of schizophrenic illness

Although anhedonia has been proposed to be a trait-like characteristic in schizophrenia patients, its persistence and stability have not been tested using multiple assessments over a multiyear period. Specific definitions of anhedonia vary across studies, and relationships between different types of anhedonia as well as their relationship to schizophrenic symptoms over the course of illness have not been addressed. The current research, using prospectively collected longitudinal data covering a 10-year span for 127 individuals with schizophrenic illness, found that (a) physical, but not depressive, anhedonia is a stable characteristic over a 10-year period; (b) physical anhedonia does not show strong and consistent relationships with psychotic, negative, or depressive symptoms; and (c) the relationship between some premorbid characteristics and physical anhedonia are significant even 10 years into the course of illness.

Emotional Memory in Schizophrenia

Emotional memories play an important role in our day-to-day experience, informing many of our minute-to-minute decisions (eg, where to go for dinner, what are the likely consequences of not attending a meeting), as well as our long-term goal setting. Individuals with schizophrenia appear to be impaired in memory for emotional experiences, particularly over longer delay periods, which may contribute to deficits in goal-related behavior and symptoms of amotivation and anhedonia. This article reviews factors that are known to influence emotional memory in healthy subjects, applies these factors to results from emotional memory studies with individuals with schizophrenia, and then uses extant neurobiological models of emotional memory formation to develop hypotheses about biological processes that might particularly contribute to emotional memory impairment in schizophrenia.

Psychotic symptoms in pediatric bipolar disorder

BACKGROUND There is under-recognition or misdiagnosis of pediatric bipolar disorder with psychotic features. It is of major public health importance to recognize psychosis in bipolar disorder. METHOD Original research on phenomenological description of psychosis and external validators including family history, longitudinal course and treatment effects are systematically reviewed. Age differences, sampling, and interview methods of the studies on pediatric bipolar disorder that reported psychotic features are compared. Critical differentiating features between pediatric bipolar disorder and pediatric schizophrenia are summarized given the presence of overlapping psychotic features. RESULTS Prevalence of psychotic features in pediatric bipolar disorder ranged from 16 to 87.5% based on age and methodological differences. The most common psychotic features are mood congruent delusions, mainly grandiose delusions. Psychotic features appear in the context of affective symptoms in pediatric bipolar disorder as opposed to schizophrenia where psychotic symptoms are independent of them. Family history of affective psychosis aggregated in probands with bipolar disorder. LIMITATIONS There is discrepancy in clinical appraisal of what constitutes psychosis and pediatric bipolar disorder, apart from the differences in methodology and nature of the samples. CONCLUSION Clinicians must be vigilant in identifying psychosis in pediatric bipolar disorder, especially when there is a positive family history of psychosis.