Eric Granholm

Substance use and withdrawal: neuropsychological functioning over 8 years in youth.

This study prospectively examined neuropsychological (NP) functioning associated with adolescent substance use and withdrawal. Participants were youths with histories of substance use disorders (n = 47) and demographically comparable youths with no such lifetime histories (n = 26). They were followed with NP testing and substance involvement interviews at 7 time points spanning 8 years, from ages 16 to 24, on average. After controlling for recent use, age, education, practice effects, and baseline NP functioning, substance use over the 8-year follow-up period significantly predicted performances on tests of memory and attention at Year 8. Additionally, withdrawal symptoms during the follow-up predicted visuospatial and attention scores at Year 8. Findings suggest that use and withdrawal may differentially impact neurocognitive functioning during youth, with heavy use leading to learning, retention, and attentional difficulties, and withdrawal leading to problems with visuospatial functioning.

Verbal memory deficits associated with major affective disorders: a comparison of unipolar and bipolar patients

The verbal learning and fluency of patients with unipolar and bipolar depression were compared to those of normal controls and patients with Huntingtons disease. The data demonstrated that the recall and recognition performance of both groups of depressed patients were impaired relative to the performance of normal control subjects. The bipolar patients, however, were more impaired than the unipolar patients on both tasks (P less than 0.024 and P less than 0.022, respectively). In addition, the unipolar patients generated more correct responses on a test of verbal fluency (P less than 0.04). The performance of the bipolar patients was, in fact, similar to that of patients with Huntingtons disease, a progressive degenerative disorder that primarily affects subcortical areas.

Mobile Assessment and Treatment for Schizophrenia (MATS): A Pilot Trial of An Interactive Text-Messaging Intervention for Medication Adherence, Socialization, and Auditory Hallucinations

Mobile Assessment and Treatment for Schizophrenia (MATS) employs ambulatory monitoring methods and cognitive behavioral therapy interventions to assess and improve outcomes in consumers with schizophrenia through mobile phone text messaging. Three MATS interventions were developed to target medication adherence, socialization, and auditory hallucinations. Participants received up to 840 text messages over a 12-week intervention period. Fifty-five consumers with schizophrenia or schizoaffective disorder were enrolled, but 13 consumers with more severe negative symptoms, lower functioning, and lower premorbid IQ did not complete the intervention, despite repeated prompting and training. For completers, the average valid response rate for 216 outcome assessment questions over the 12-week period was 86%, and 86% of phones were returned undamaged. Medication adherence improved significantly, but only for individuals who were living independently. Number of social interactions increased significantly and a significant reduction in severity of hallucinations was found. In addition, the probability of endorsing attitudes that could interfere with improvement in these outcomes was also significantly reduced in MATS. Lab-based assessments of more general symptoms and functioning did not change significantly. This pilot study demonstrated that low-intensity text-messaging interventions like MATS are feasible and effective interventions to improve several important outcomes, especially for higher functioning consumers with schizophrenia.

Mobile Interventions for Severe Mental Illness: Design and Preliminary Data from Three Approaches

Mobile devices can be used to deliver psychosocial interventions, yet there is little prior application in severe mental illness. We provide the rationale, design, and preliminary data from 3 ongoing clinical trials of mobile interventions developed for bipolar disorder or schizophrenia. Project 1 used a personal digital assistant to prompt engagement in personalized self-management behaviors based on real-time data. Project 2 employed experience sampling through text messages to facilitate case management. Project 3 was built on group functional skills training for schizophrenia by incorporating between-session mobile phone contacts with therapists. Preliminary findings were of minimal participant attrition, and no broken devices; yet, several operational and technical barriers needed to be addressed. Adherence was similar to that reported in nonpsychiatric populations, with high participant satisfaction. Therefore, mobile devices seem feasible and acceptable in augmenting psychosocial interventions for severe mental illness, with future research in establishing efficacy, cost effectiveness, and ethical and safety protocols.

Pupillary and reaction time measures of sustained processing of negative information in depression.

BACKGROUND Disruptions of emotional information processing (i.e., attention to, memory for, and interpretation of emotional information) have been implicated in the onset and maintenance of depression. The research presented here investigated cognitive and psychophysiological features of a particularly promising correlate of depression: sustained processing of negative information 4--5 sec after an emotional stimulus. METHODS Pupil dilation data and reaction times were collected from 24 unmedicated depressed and 25 nondepressed adults in response to emotional processing tasks (lexical decision and valence identification) that employed idiosyncratically generated personally relevant and normed stimuli. Pupil dilation was used to index sustained cognitive processing devoted to stimuli. RESULTS Consistent with predictions, depressed individuals were especially slow to name the emotionality of positive information, and displayed greater sustained processing (pupil dilation) than nondepressed individuals when their attention was directed toward emotional aspects of information. Contrary to predictions, depressed participants did not dilate more to negative than positive stimuli, compared to nondepressed participants. CONCLUSIONS These data suggest depressed individuals may not initially attend to emotional aspects of information but may continue to process them seconds after they have reacted to the information.

A Path Model Investigation of Neurocognition, Theory of Mind, Social Competence, Negative Symptoms and Real-World Functioning in Schizophrenia

Problems in real-world functioning are pervasive in schizophrenia and much recent effort has been devoted to uncovering factors which contribute to poor functioning. The goal of this study was to examine the role of four such factors: social cognition (theory of mind), neurocognition, negative symptoms, and functional capacity (social competence). 178 individuals with schizophrenia or schizoaffective disorder completed measures of theory of mind, neurocognition, negative symptoms, social competence, and self-reported functioning. Path models sought to determine the relationships among these variables. Theory of mind as indexed by the Hinting Task partially mediated the relationship between neurocognition and social competence, and negative symptoms and social competence demonstrated significant direct paths with self-reported functioning. Study results suggest theory of mind serves as an important mediator in addition to previously investigated social cognitive domains of emotional and social perception. The current study also highlights the need to determine variables which mediate the relationship between functional capacity and real-world functioning.

Brain activation and pupil response during covert performance of the Stroop Color Word task.

Patterns of brain activation associated with covert performance of the Stroop Color-Word task were studied in young, healthy, adult volunteers using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). Comparisons of the incongruous Stroop condition were made with both color naming and word reading baselines. Areas of the left and right anterior cingulate, the right precuneus, and the left pars opercularis displayed larger BOLD signal responses during the incongruous Stroop condition than during baseline conditions. Activation of BOLD signals in these areas was highly repeatable. In a second experiment, pupil diameter was used to assess cognitive load in 7 individuals studied during overt and covert performance of both Stroop and color naming conditions. Cognitive load was similar in overt and covert response conditions. Results from the BOLD study indicate that brain regions participating in selective visual attention and in the selection of motor programs involved in speech were activated more by the Stroop task than by the baseline tasks. The neural substrate involved in the resolution of the perceptual and motor conflicts elicited by the Stroop Color-Word task does not appear to be a single brain region. Rather, a network of brain regions is implicated, with separate regions within this system supporting distinct functions.

Feasibility and Validity of Computerized Ecological Momentary Assessment in Schizophrenia

Background: Computerized Ecological Momentary Assessment (EMAc) techniques permit the assessment of daily life behaviors and experiences. The present investigation examined the feasibility and validity of this assessment methodology in outpatients with schizophrenia. Methods: Outpatients with schizophrenia or schizoaffective disorder (n = 54) received a battery of standard laboratory clinical and functional outcome measures and then completed electronic questionnaires on a personal digital assistant (PDA) microcomputer 4 times per day for 1 week. Results: Generally good compliance (87%) with EMAc was found, and participants rated their experience with the study positively. The data collected in daily life demonstrated expected patterns across the assessment week and were significantly associated with scores from standard laboratory instruments measuring similar constructs. Conclusions: EMAc is a feasible and valid approach to data collection in community-dwelling people with schizophrenia, and it may provide important information that is inaccessible via standard clinical and functional outcome measures administered in the laboratory.

Associative encoding and retrieval in Alzheimer's and Huntington's disease

The associative encoding and retrieval abilities of patients with dementia of the Alzheimer type (DAT) and patients with Huntingtons disease (HD) were investigated using an encoding specificity paradigm. When compared to age- and education-matched intact control subjects, both patient groups were severely (and equally) impaired on overall memory for word lists. However, the HD and DAT patients showed differential improvement in recall performance with the introduction of associated cues during stimulus presentation and recall. Although the HD patients, like intact subjects, were able to benefit from semantic retrieval cues (strong and weak) which were present during input, the performance of the patients with DAT improved only with the introduction of strong cues at output, regardless of whether the cues were present or absent during initial presentation. These findings suggest that patients with DAT failed to encode the semantic relationship between the to-be-recalled and cue words and simply generated free associations to the cue words during retrieval. Similarities between the performances of the patients with DAT and alcoholic Korsakoff patients are noted and discussed with regard to the neuropathological basis of the disorders.

Real-Time Electronic Ambulatory Monitoring of Substance Use and Symptom Expression in Schizophrenia

OBJECTIVE Despite evidence demonstrating elevated comorbidity between schizophrenia and substance use disorders, the underlying mechanisms of association remain poorly understood. The brief time intervals that characterize interactions between substance use and psychotic symptoms in daily life are inaccessible to standard research protocols. The authors used electronic personal digital assistants (PDAs) to examine the temporal association of diverse forms of substance use with psychotic symptoms and psychological states in natural contexts. METHOD Of 199 community-dwelling individuals with schizophrenia or schizoaffective disorder who were contacted to participate in the study, 92% accepted and 73% completed the study. The 145 participants who completed the study provided reports of substance use, psychotic symptoms, mood, and event negativity multiple times per day over 7 consecutive days through PDAs. RESULTS Participants responded to 72% of the electronic interviews (N=2,737) across daily life contexts. Strong within-day prospective associations were observed in both directions between substance use and negative psychological states or psychotic symptoms, but considerable variation was observed by substance type. Consistent with the notion of self-medication, alcohol use was most likely to follow increases in anxious mood or psychotic symptoms. Cannabis and other illicit substances, demonstrating more complex patterns, were more likely to follow certain psychological states but were also associated with the later onset of psychotic symptoms. CONCLUSIONS The dynamic interplay of substance use and psychotic symptoms is in many cases consistent with both causal and self-medication mechanisms, and these patterns of association should be considered in the design of treatment and prevention strategies.