Our objective in the present study was to conduct the first empirical study of the effects of regular physical activity habits and their relationship with brain volume and cortical thickness in patients in the early phase of schizophrenia. Relationships between larger brain volumes and higher physical activity levels have been reported in samples of healthy and aging populations, but have never been explored in first-episode schizophrenia patients. Method: We collected MRI structural scans in 14 first-episode schizophrenia patients with either self-reported low or high physical activity levels. We found a reduction in total gray matter volume, prefrontal cortex (PFC), and hippocampal gray matter volumes in the low physical activity group compared to the high activity group. Cortical thickness in the dorsolateral and orbitofrontal PFC were also significantly reduced in the low physical activity group compared to the high activity group. In the combined sample, greater overall physical activity levels showed a non-significant tendency with better performance on tests of verbal memory and social cognition. Together these pilot study findings suggest that greater amounts of physical activity may have a positive influence on brain health and cognition in first-episode schizophrenia patients and support the implementation of physical exercise interventions in this patient population to improve brain plasticity and cognitive functioning. (JINS, 2015, 21, 868–879)

Cognitive deficits in schizophrenia are increasingly accepted as core features of this disorder that play a role as vulnerability indicators, as enduring abnormalities during clinical remission, and as critical rate-limiting factors in functional recovery. This article demonstrates the lasting influence of Norman Garmezy through his impact on one graduate student and then through his later collaborative research with colleagues. The promise of core cognitive deficits as vulnerability indicators or endophenotypes was demonstrated in research with children born to a parent with schizophrenia as well as with biological parents and siblings of individuals with schizophrenia. In studies of patients with a recent onset of schizophrenia, cognitive deficits were found to endure across psychotic and clinically remitted periods and to have a strong predictive influence on likelihood of returning successfully to work or school. Converging lines of evidence for the enduring core role of cognitive deficit in schizophrenia have led in recent years to a burgeoning interest in developing new interventions that target cognition as a means of improving functional recovery in this disorder.

Schizophrenia has come to be viewed as a neurodevelopmental disorder that is characterized by genetic vulnerability, stressors during the prenatal period that may be marked by minor physical anomalies and neurobehavioral deficits that emerge in early development. Less is known about the neurodevelopmental origins of schizotypal personality symptoms. The present study examines schizotypal symptoms in Israeli adolescents (mean age = 16.79 years) who have not yet reached the developmental period during which first schizophrenic episode is most likely to emerge: 39 adolescent offspring of parents with schizophrenia, 39 offspring of parents with other psychiatric disorders, and 36 offspring of parents with no history of mental illness. The Semi-Structured Kiddie Interview for Personality Syndromes was used to assess cognitive–perceptual, interpersonal, and disorganized schizotypal symptoms. Interpersonal schizotypal symptoms were more prevalent in the schizophrenia offspring group than in the no-mental-illness offspring group. Among the schizophrenia offspring group, interpersonal, but not cognitive–perceptual, schizotypal symptoms were associated with minor physical anomalies, fine motor dyscoordination, and deficits in executive functioning during adolescence. Among young people whose parents did not have schizophrenia, cognitive–perceptual schizotypal symptoms were correlated with deficits in executive functioning. Adolescent schizotypal symptoms were associated with neurobehavioral symptoms measured during middle childhood in a subgroup of the sample that had been assessed prospectively. Finally, young people who had genetic risk for schizophrenia, minor physical anomalies, and neurobehavioral signs together were at markedly increased risk for symptoms of interpersonal schizotypal symptoms, compared to young people with one or none of these risk factors.

Abnormalities in attention have long been viewed as one of the fundamental underlying cognitive deficits in schizophrenia, likely contributing both to formation of some types of symptoms and particularly to the substantial work and social impairments that often accompany schizophrenia. Yet, the precise nature of the attentional deficits in schizophrenia remains poorly understood. Translating advances in cognitive psychology to clinical research brings paradigms with greater analytic power to the study of attention in schizophrenia. In particular, these paradigms should shed light on whether the attentional dysfunction in schizophrenia is best conceptualized as arising from limitations in amount or allocation of processing capacity or from more specific structural bottlenecks that do not allow certain processes to be carried out in two tasks simultaneously. Certain types of dual-task paradigms are particularly well suited to make distinctive predictions, particularly those involving a psychological refractory period paradigm. The background and design of a series of ongoing studies of prodromal, first-episode, and chronic schizophrenia patients are described that are addressing the developmental course of attentional dysfunction in this disorder. These refined paradigms should substantially increase our understanding of the specific forms of attentional impairment characterizing schizophrenia and their connections to symptom development and functional outcome.

Background. While several personality characteristics are implicated in the etiology and phenotypic expression of schizophrenia, little is known about their trait status or clinical correlates during the early course of this disorder.

Method. The stability of five personality characteristics derived from the MMPI-168 was examined in recent-onset schizophrenia patients (n=59) during a psychotic period at study entry and at two out-patient assessments over the following 15 months and in non-patient controls (n=39) at similar time intervals. Among patients, associations between personality characteristics and clinical symptoms and exposure to stressful life events during the study period were also examined.

Results. Multilevel modeling analyses indicated that the between-subjects or trait-like variance components for these characteristics among patients were substantial, albeit smaller than those found for controls. Patients reported higher mean levels of Neuroticism, Cynicism, and Psychotic Ideation and lower mean levels of Psychopathic Tendencies and Denial of Somatic Complaints than controls. Among patients, several personality characteristics were systematically related to mean clinical symptom levels as well as frequency of exposure to dependent, but not independent, life events.

Conclusions. Stable individual differences in personality are detectable during the early course of schizophrenia and may help account for heterogeneity in clinical symptoms and functional outcome.

Test–retest stability of electrodermal (EDA) variables indexing both general autonomic arousal (e.g., skin conductance level, number of nonspecific skin conductance responses) and attention to external stimuli (e.g., number of skin conductance orienting responses, electrodermal responder/nonresponder status) was assessed in 71 young, recent-onset schizophrenia patients and 36 demographically matched normal subjects. Significant stability over a 1-year period was found for both patients and normal subjects for most EDA variables and for responder/nonresponder status, with test–retest correlations generally being higher for normal subjects. The lower reliability for patients was not attributable to symptomatic fluctuations during the follow-up period and may reflect poorer arousal regulation among the patients. Among measures of responding to nontask stimuli, a simple count of the number of orienting responses occurring was more stable than was a traditional trials-to-habituation measure.

This study of 31 college students employed the startle eye-blink modification (SEM) technique to index both early and later stages of attentional processing during a memory-load version of the Continuous Performance Test (CPT). Participants viewed a series of digits and pressed a button after the digit 7 of each 3–7 sequence. A startling noise burst was presented either 120 or 1,200 ms following three preselected prepulses: target (3), nontarget (non-3 and non-7 digits), or target plus distractor (3 and simultaneous tone distractor). Greater startle inhibition occurred 120 ms following target and target-plus-distractor prepulses compared with nontargets, indicating early selective attention. No difference was observed between SEM during target and target-plus-distractor prepulses, suggesting the distractor was effectively ignored. At 1,200 ms, the three prepulse types produced nondifferential inhibition, suggesting that modality-specific selective attention occurs in anticipation of the presentation of the next CPT prepulse. These findings indicate that SEM distinguishes between different early selective attention and later anticipatory attention subprocesses underlying the CPT.

Attentional functioning was examined in three groups of 7- to 19-year-old male participants with hemophilia: (1) HIV seronegative controls (HIV−, N = 66), (2) HIV seropositive participants with CD4+ lymphocyte counts greater than or equal to 200 (HIV+ CD4+ ≥200, N = 79), and (3) severely immune suppressed HIV seropositive participants (HIV+ CD4+ <200, N = 28). Two measures sensitive to attention deficits were used: the Continuous Performance Test (CPT) and the Span of Apprehension (Span). On the CPT, there was a decrement in attention in both HIV+ groups, as indexed by an increase in false alarm rate from Block 1 to Block 3, that was not present in the HIV− group. The longer the HIV+ children were required to sustain attention to the CPT, the more they responded to the incorrect stimulus. This effect decreased as age increased. Span percent correct and latency to correct were associated with the presence of a premorbid history of intracerebral hemorrhage, but were not sensitive to HIV status or degree of immune suppression in the HIV+ children, suggesting morbidity related to hemophilia. The remaining CPT and Span variables—hit rate, sensitivity, latency, percent correct, and latency to correct—showed the expected associations with age, but none showed conclusive associations with HIV status or immune suppression in the HIV+ participants. (JINS, 2000, 6, 443–454.)

The effect of an attentional manipulation on eye tracking dysfunction (ETD) in the early stages of schizophrenia was examined in 34 recent-onset schizophrenic patients and 24 demographically matched normal subjects over a 1-year period. An attentional enhancement manipulation improved eye tracking performance of recent-onset schizophrenic patients more than that of normal subjects. Eye tracking level also was moderately stable for both groups over the course of 1 year. The possible role of attentional allocation in ETD highlights the need for further examination of the interface between attentional and eye tracking measures of vulnerability to schizophrenia.