Impairment of verbal memory and learning in antipsychotic-naı̈ve patients with first-episode schizophrenia
Introduction
Verbal memory deficits are well-established in schizophrenia Calev, 1984, Goldberg et al., 1989, Saykin et al., 1991. Some neuropsychological studies have found verbal memory deficits in schizophrenia to be more severe than those evident in other neuropsychological domains Censits et al., 1997, Dickerson et al., 1991, Saykin et al., 1994. Interest in verbal memory dysfunction has increased in recent years because neuroimaging and post-mortem studies have implicated left temporolimbic cortex as a site of neurophysiologic and neuroanatomic abnormalities in schizophrenia Barta et al., 1990, Keshavan et al., 1998, Shenton et al., 1992. Indeed, verbal memory deficits have been linked to physiological abnormalities of mesial temporal cortex in schizophrenia patients (Mozley et al., 1996). In addition, verbal memory deficits have been linked to difficulties with self-generated organizational strategies in which patients fail to use semantic information to facilitate verbal encoding and retrieval (Brebion et al., 1997). This observation raises the possibility that prefrontal dysfunction also contributes to verbal memory impairments. Based on these findings and the significance of verbal memory deficits in day-to-day function (Green, 1996), an important aim of neuropsychological investigations of schizophrenia is to define the specific memory deficits associated with the disorder.
Studies of memory in schizophrenia have been of two general types. Some studies utilized summary scores of overall memory performance to contrast deficits in memory with those in other neuropsychological domains Bilder et al., 2000, Gur et al., 1999, Riley et al., 2000, Saykin et al., 1991, Saykin et al., 1994. Other studies assessed selective aspects of memory and learning. For example, a number of investigators have reported differential deficits in short- and long-term memory (Tamlyn et al., 1992) while others have reported rapid forgetting (Beatty et al., 1993). A pattern of preserved recognition memory despite impaired free recall was found by some authors (Bauman and Murray, 1968) while others found modest deficits in both recognition and recall memory Calev, 1984, Gold et al., 1992. More recently, schizophrenia patients showed abnormal frontotemporal activation during verbal encoding relative to healthy participants, but no differences in word recognition were observed (Ragland et al., 2001). While these studies provide important findings, better understanding of the particular aspects of memory that are most impaired in schizophrenia is needed, particularly early in the course of the disorder prior to antipsychotic treatment which may affect verbal memory abilities Bilder et al., 2002, Schuepbach et al., in press.
The work of Paulsen et al. (1995) is one of few studies providing an in-depth evaluation of verbal memory and learning in schizophrenia. In addition to assessing traditional aspects of verbal memory such as overall learning, and short- and long-term retention, these authors utilized the California Verbal Learning Test (CVLT) to characterize learning styles, strategies, and rate of memory decay (i.e., forgetting). As Paulsen and her colleagues point out, these components are differentially affected by disorders such as Alzheimer's and Parkinson's diseases, and by focal brain lesions to various cortical regions. They found learning, memory, and organizational deficits in their group of schizophrenia participants. However, duration of illness in this chronic sample was relatively long, all patients were apparently receiving antipsychotic medications, and 19% of patients were also receiving anticholinergic drugs that may impact memory performance Strauss et al., 1990, Sweeney et al., 1991. Thus, it is difficult to ascertain whether the observed memory dysfunctions were related to the presence of schizophrenia, chronic effects of the illness, or iatrogenic effects of pharmacotherapy.
One strategy to avoid potential confounds of chronicity and antipsychotic treatment is to investigate schizophrenia early in the course of illness, prior to treatment with psychoactive medications. Previous reports of memory dysfunction in early phases of schizophrenia used summary scores of memory performance to contrast deficits in multiple neuropsychological domains Hoff et al., 1992, Mohamed et al., 1999, Saykin et al., 1994. The goal of the present study was to describe the nature of verbal memory impairments in antipsychotic-naı̈ve schizophrenia patients early in the course of illness by investigating the following aspects of memory: immediate retention; overall learning; short-term, long-term, and recognition memory; rate of forgetting; susceptibility to proactive and retroactive interference; and use of organizational strategies. Thus, this study examined components of memory that are linked to frontal (e.g., semantic organization) and temporal lobe function (e.g., recall; proactive and retroactive interference) to provide in-depth characterization of verbal memory deficits in schizophrenia.
Section snippets
Subjects
Following hospitalization for first-episode psychosis, 62 individuals who met research diagnostic criteria for schizophrenia based on the Structured Clinical Interview for DSM-IV (SCID; APA, 1994) were recruited at the University of Pittsburgh Medical Center. Scheduled follow-up evaluations at 12 months verified diagnosis of schizophrenia (n=54) or schizoaffective disorder (n=9, 7 of whom were depressed type, 2 mixed type). Testing was completed prior to beginning treatment with antipsychotic
Demographic and clinical characteristics
There were no group differences in age, sex, race, parental SES, or intellectual level (Table 1). As expected, and consistent with disrupted educational and occupational pursuits in schizophrenia, patients had less education and lower individual SES than healthy participants. Lateral preference was similar for both groups. Clinical data for the patient group are presented in Table 1.
Memory and learning
Planned analyses were conducted to assess different aspects of memory and are presented below. Relevant means,
Discussion
This study provides new information regarding verbal memory and learning dysfunction in schizophrenia by investigating first-episode patients with schizophrenia prior to treatment with antipsychotic medication, and by systematically assessing the nature of dysfunction across multiple aspects of memory. The present findings indicate that antipsychotic-naı̈ve schizophrenia patients tested early in their course of illness demonstrate significant memory impairment characterized by reduced
Acknowledgments
We thank Dawn Boarts, Jill Brown, Steve Hegedus, Christine Krisky and Eli Merriam for performing cognitive testing, and Joel Greenhouse for statistical consultation.
This research was supported by National Institute of Health grants MH42969, MH45156, and MH01433, and by the National Alliance for Research in Schizophrenia and Affective Disorders.
References (58)
- et al.
Volumetric analysis of frontal lobe regions in schizophrenia: relation to cognitive function and symptomatology
Biol. Psychiatry
(1999) - et al.
Neuropsychological evidence supporting a neurodevelopmental model of schizophrenia: a longitudinal study
Schizophr. Res.
(1997) - et al.
Recall memory deficit in schizophrenia: a possible manifestation of prefrontal dysfunction
Schizophr. Res.
(1989) - et al.
Superior temporal gyrus and the course of early schizophrenia: progressive, static or reversible?
J. Psychiatry Res.
(1998) - et al.
Verbal learning and memory in relatives of schizophrenics: preliminary findings
Biol. Psychiatry
(1995) - et al.
Frontal brain volume and context effects in short-term recall in schizophrenia
Biol. Psychiatry
(1995) - et al.
Relationships between verbal memory performance and the cerebral distribution of flurodeoxyglucose in patients with schizophrenia
Biol. Psychiatry
(1996) - et al.
Planning and spatial working memory following frontal lobe lesions in man
Neuropsychologia
(1990) - et al.
Neuropsychological functioning in first-episode psychosis—evidence of specific deficits
Schizophr. Res.
(2000) - et al.
Stability in cognitive dysfunctions in schizophrenic patients
Psychiatry Res.
(1997)
Generation effect in short-term verbal and visuospatial memory: comparisons between dementia of Alzheimer type and dementia of frontal lobe type
Cortex
Effects of anticholinergic medication on memory in schizophrenia
Schizophr. Res.
Relationships between medication treatments and neuropsychological test performance in schizophrenia
Psychiatry Res.
Diagnostic and Statistical Manual of Mental Disorders IV
The Quick Test (QT): provisional manual
Psychol. Rep.
Scale for the Assessment of Negative Symptoms
Scale for the Assessment of Positive Symptoms
Auditory hallucinations and smaller superior temporal gyral volume in schizophrenia
Am. J. Psychiatry
Schizophrenic short-term memory: a deficit in subjective organization
Can. J. Behav. Sci.
Recognition versus recall in schizophrenia
Can. J. Psychol.
Memory and frontal lobe dysfunction in schizophrenia and schizoaffective disorder
J. Nerv. Ment. Dis.
Neuropsychology of first-episode schizophrenia: initial characterization and clinical correlates
Am. J. Psychiatry
Neurocognitive effects of clozapine, olanzapine, risperidone, haloperidol in patients with chronic schizophrenia or schizoaffective disorder
Am. J. Psychiatry
Mechanisms underlying memory impairment in schizophrenia
Psychol. Med.
Functional anatomical studies of explicit and implicit memory retrieval tasks
J. Neurosci.
Recall and recognition in mildly disturbed schizophrenics: the use of matched tasks
Psychol. Med.
Levels of processing: a framework for memory research
J. Verbal Learn. Verbal Behav.
California Verbal Learning Test: Research Edition—Adult Version
Profiles of demented and amnesic patients on the California verbal learning test: implications for the assessment of memory disorders
Psychol. Assess.
Cited by (105)
Treatment-resistant schizophrenia: Addressing white matter integrity, intracortical glutamate levels, clinical and cognitive profiles between early- and adult-onset patients
2022, Progress in Neuro-Psychopharmacology and Biological PsychiatryAnterior-posterior axis of hippocampal subfields across psychoses: A B-SNIP study
2021, Biomarkers in NeuropsychiatryNeural correlates of cognitive deficits across developmental phases of schizophrenia
2019, Neurobiology of DiseaseMultivariate Relationships Between Cognition and Brain Anatomy Across the Psychosis Spectrum
2018, Biological Psychiatry: Cognitive Neuroscience and Neuroimaging