Schizophrenia research

Anastasya Glezerman, Ph.D.

A review of MRI findings in schizophrenia

(Martha E. Shenton, Chandlee C. Dickey, Melissa Frumin and Robert W. McCarley ; Cinical Neuroscience Division, Laboratory of Neuroscience, Department of Psychiatry, Harvard Medical School, Brockton, MA 02301, USA ; Received 12 October 2000; revised 29 December 2000; accepted 2 January 2001 Available online 2 May 2001.)

These findings include ventricular enlargement (80% of studies reviewed) and third ventricle enlargement (73% of studies reviewed). There is also preferential involvement of medial temporal lobe structures (74% of studies reviewed), which include the amygdala, hippocampus, and parahippocampal gyrus, and neocortical temporal lobe regions (superior temporal gyrus) (100% of studies reviewed). When gray and white matter of superior temporal gyrus was combined, 67% of studies reported abnormalities. There was also moderate evidence for frontal lobe abnormalities (59% of studies reviewed), particularly prefrontal gray matter and orbitofrontal regions. Similarly, there was moderate evidence for parietal lobe abnormalities (60% of studies reviewed), particularly of the inferior parietal lobule which includes both supramarginal and angular gyri. Additionally, there was strong to moderate evidence for subcortical abnormalities (i.e. cavum septi pellucidi-92% of studies reviewed, basal ganglia-68% of studies reviewed, corpus callosum-63% of studies reviewed, and thalamus-42% of studies reviewed), but more equivocal evidence for cerebellar abnormalities (31% of studies reviewed). The timing of such abnormalities has not yet been determined, although many are evident when a patient first becomes symptomatic. There is, however, also evidence that a subset of brain abnormalities may change over the course of the illness. The most parsimonious explanation is that some brain abnormalities are neurodevelopmental in origin but unfold later in development, thus setting the stage for the development of the symptoms of schizophrenia. Or there may be additional factors, such as stress or neurotoxicity, that occur during adolescence or early adulthood and are necessary for the development of schizophrenia, and may be associated with neurodegenerative changes.

Neuropsychological Assessment of Schizophrenia

I

The course of cognitive functioning over a 1-year period was examined among a community cohort of individuals presenting with first episode schizophrenia spectrum psychosis. Data were obtained for 83 outpatients at entry to an early intervention program and 12 months later on the National Adult Reading Test, Wechsler Adult Intelligence Scales-Third Edition, Wechsler Memory Scales-Third Edition, Paced Auditory Serial Addition Task, Wisconsin Card Sorting Test, Stroop Colour and Word Test, Trail Making Test, Continuous Performance Task and Thurstone Word Fluency Test. Paired sample t-tests indicated significant and positive changes in verbal and non-verbal intelligence, auditory and visual memory, working memory and some aspects of executive functioning. Processing speed also improved though remained an area of relative weakness for this sample. Findings indicated generally average performance at both assessment periods. Neither gender nor duration of untreated psychosis were related to the degree of change in cognitive functioning for this sample.

(Changes in cognitive functioning following comprehensive treatment for first episode patients with schizophrenia spectrum disorders; Psychiatry Research, Volume 113, Issues 1-2, 15 December 2002, Pages 69-8; Laurel A. Townsend, Ross M. G. Norman, Ashok K. Malla, Anita D. Rychlo and Rashid R. Ahmed)

II

The Wechsler Memory Scale-Revised Visual Memory Span and Digit Span subtests were administered to 46 schizophrenic patients, 32 of their unaffected co-twins, 22 bipolar patients, 16 of their unaffected co-twins, and 100 control twins, representing unselectively nationwide twin samples. Schizophrenic patients and their unaffected co-twins performed significantly worse than control subjects on the spatial working memory task, whereas only the schizophrenic patients performed significantly below the control subjects on the verbal working memory task. Neither bipolar patients nor their unaffected co-twins differed from control subjects on these measures.

(Spatial Working Memory Function in Twins with Schizophrenia and Bipolar Disorder; Biological Psychiatry, In Press, Corrected Proof, Available online 22 August 2005; Tiia Pirkola, Annamari Tuulio-Henriksson, David Glahn, Tuula Kieseppä, Jari Haukka, Jaakko Kaprio, Jouko Lonnqvist and Tyrone D. Cannon)

III

The Greek Verbal Fluency Test was administered to 119 patients with schizophrenia and 150 age-, education-, and gender-matched healthy controls. We calculated the total number of words generated, the number of cluster related words, and the number of switches on the semantic and phonological fluency tasks separately. Patients with schizophrenia generated fewer total words, cluster related words and switches than healthy controls on both fluency tasks. When controlling for the total number of words produced, however, the differences between the two groups in the number of cluster related words and switches disappeared. We found a disproportionate impairment in semantic, compared with phonemic, fluency in schizophrenia for total word production and the number of cluster related words, but not for the number of switches. In conclusion, patients with schizophrenia used the same strategies as healthy controls to perform on a word fluency test, but they used them less effectively. Disproportionate impairment in semantic fluency in schizophrenia resulted from a differential deficit only in clustering. Therefore, disproportionately impaired category fluency in schizophrenia may be primarily due to disorganization and not to inefficient access to and retrieval from semantic store.

(Disproportionate impairment in semantic verbal fluency in schizophrenia: differential deficit in clustering; Schizophrenia Research, Volume 74, Issue 1, 1 April 2005, Pages 51-59; Vasilis P. Bozikas, Mary H. Kosmidis and Athanasios Karavatos)

IV

Seventy-eight consecutive outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for schizophrenia in the stable period were enrolled in this cross-sectional study. Assessment were performed using the Calgary Depression Scale for Schizophrenia, Positive and Negative Syndromes Scale (PANSS), Clinical Global Impression Scale-severity, Social and Occupational Functioning Assessment Scale, Sheehan Disability Scale, and Quality of Life Scale. A neuropsychologic battery including the vocabulary and block design subtests of the Wechsler Adult Intelligence Scale-Revised, Wechsler Memory Scale, Wisconsin Card Sorting Test, and Continuous Performance Test was also administered to the patients. Two multiple regressions were performed testing demographic and clinical factors, rating scales, and cognitive measures as independent variables and Calgary Depression Scale for Schizophrenia and PANSS-negative subscale scores as dependent variables. Four variables were predictors of depressive symptoms in our sample of schizophrenic patients: 2 outcome measures (Sheehan Disability Scale and Quality of Life Scale), gender, and Continuous Performance Test reaction time. Predictors of negative symptoms were the measures of severity of psychopathology (Clinical Global Impression Scale-severity and PANSS-general psychopathology subscale) and the cognitive tests Wechsler Adult Intelligence Scale-Revised block design and Wechsler Memory Scale. We found that depressive symptoms in schizophrenia are mainly a function of the level of social adjustment and quality of life, whereas negative symptoms constitute an indicator of severity of schizophrenia. The 2 symptom dimensions showed also distinct cognitive correlates.

(Depressive and negative symptoms in schizophrenia: different effects on clinical; Comprehensive Psychiatry, Volume 46, Issue 4, July-August 2005, Pages 304-310; Paola Rocca, Silvio Bellino, Paolo Calvarese, Livio Marchiaro, Luca Patria, Roberta Rasetti and Filippo Bogetto)

V

The purpose of the present study is to investigate whether patients with different subtypes of schizophrenia are differentially impaired on measures of attention. Forty-eight patients with schizophrenia (19 paranoid and 29 nonparanoid) and 48 healthy controls (matched on chronological age, sex, and years of education) were administered five measures of attention including the Stroop Color-Word Test (SCWT; Stroop, 1935), the Digit Vigilance Test (DVT; Lewis, 1992), the Symbol Digit Modalities Test (SDMT; Smith, 1982), the Backward Digit Span Test (BDST; Wechsler, 1987), and the Color Trails Test (CTT; D'Elia et al., 1996) to assess selective attention, sustained attention, switching attention, and attentional control processing by the latter two tests respectively. Results from the present study showed that patients with schizophrenia performed poorer on the SCWT, the DVT, and the SDMT, relative to their healthy counterparts. Furthermore, patients with different subtypes of schizophrenia also had different degrees of attentional impairment. While patients with paranoid schizophrenia performed worse on the SCWT, those with nonparanoid schizophrenia performed worse on the SDMT. Nevertheless, these findings may suggest that patients with paranoid and nonparanoid schizophrenia may have different profiles with respect to their performances on measures of attention.

(Differential impairment on measures of attention in patients with paranoid and nonparanoid schizophrenia; Journal of Psychiatric Research, Volume 38, Issue 2, March-April 2004, Pages 145-152; Michelle W. C. Chan, James T. H. Yip and Tatia M. C. Lee)

VI

Thirty-six DSM-IV schizophrenic subjects were assessed using the Purdue Pegboard test, the Modified Wisconsin Card Sorting test, the Tower of London, Schwartz' Reaction Time and Wechsler's Associate Learning and Digit Span tests. Social functioning was measured by the Social and Occupational Functional Assessment Scale. Univariate regression analyses showed that the Purdue Pegboard, the Modified Card Sorting test, the Tower of London and Wechsler's Associate Learning subtest were significantly linked to social functioning. The best fitting multivariate model to explain social functioning included fine motor dexterity and executive functioning. Various neuropsychological measures correlated to social functioning, the correlation involving fine motor dexterity being the strongest one. Future studies of the prediction of social functioning in schizophrenia should include fine motor dexterity.

(Fine motor dexterity is correlated to social functioning in schizophrenia; Schizophrenia Research, Volume 62, Issue 3, 1 August 2003, Pages 269-273; Catherine Lehoux, James Everett, Louis Laplante, Claudia Emond, Johanne Trepanier, Andree Brassard, Linda Rene, Mireille Cayer, Chantal Merette, Michel Maziade and Marc-Andre Roy)

VII

Impaired neuropsychological performance involving abstraction-flexibility, memory, motor function, and attention has frequently been reported in schizophrenia as well as in attention deficit hyperactivity disorder (ADHD). This study represents an attempt to compare groups of adolescents with schizophrenia and ADHD on a comprehensive neuropsychological test battery. Such a comparison affords the opportunity to ascertain differences in the degree, profile, and specificity of impairments. The performance of 19 adolescents with schizophrenia, 20 adolescents with ADHD, and 30 normal adolescents on a broad battery of cognitive tests was compared. The schizophrenic group showed the most pronounced deficits on tests of abstraction, visual memory, and motor function in comparison with the subjects with ADHD, while the ADHD subjects had the most pronounced deficits on measures of attention, verbal memory, and learning. The subjects with schizophrenia appeared to have a more general pattern of brain dysfunction, whereas the impairment of the ADHD subjects seemed to be relatively specific to tests associated with frontal lobe function.

(Neuropsychological Deficits in Adolescent-Onset Schizophrenia Compared With Attention Deficit Hyperactivity Disorder; Am J Psychiatry 156:1216-1222, August 1999; Merete Oie, Ph.D., and Bjorn Rishovd Rund, Ph.D.)

VIII

Neuropsychological impairments are well documented in schizophrenia and are important targets of treatment. Information about the severity and pattern of deficits after treatment for the first psychotic episode and about relationships between these deficits and syndromal characteristics remains limited. Comprehensive neuropsychological assessments including 41 individual tests were given to 94 patients with first-episode schizophrenia after initial stabilization of psychosis (on meds) and to a comparison group of 36 healthy volunteers. Profiles of neuropsychological deficits and the relationship of deficits to sex and handedness were examined. Correlations of neuropsychological deficit with a broad range of historical and clinical characteristics, including outcome, were explored. Patients had a large generalized neuropsychological deficit (1.5 standard deviations compared to healthy volunteers). Patients also had, superimposed on the generalized deficit, subtle relative deficits (less than 0.5 standard deviation compared to their own average profile) in memory and executive functions. Learning/memory dysfunction best distinguished patients from healthy individuals; after accounting for this difference, only motor deficits further distinguished the groups. Patients with higher neuropsychological ability had only memory deficits, and patients with lower ability had both memory and executive deficits. No sex differences were observed beyond the normal advantage for men in motor speed. Dextral patients had less severe generalized deficit. Severity of residual symptoms was associated with greater generalized deficit. Executive and attentional deficits were most linked to global functional impairment and poor outcome. The results document a large generalized deficit, and more subtle differential deficits, in clinically stabilized first-episode patients. Learning/memory deficits were observed even in patients with less severe generalized deficit, but the pattern was unlike the amnestic syndrome and probably reflects different mechanisms. Executive and attentional deficits marked the more severely disabled patients, and may portend relatively poor outcome. Failure to develop typical patterns of cerebral dominance may increase the risk for greater generalized deficit.

Significant symptomatic correlations (no positive symptoms came out significant): Memory deficit x Alogia, Global Assessment Scale, antipsychotic and antiparkinsonian dosage; Attention x Affective flattening, Alogia, Childhood adjustment, Global Assessment, antipsychotic; Executive x Affective flattening, Alogia, Apathy, Global Assessment, antipsychotic; Motor x Apathy, Anhedonia, Global Assessment; Visuospatial x Alogia, Apathy, Global Assessment;

(Robert M. Bilder, Robert S. Goldman, Delbert Robinson, Gail Reiter, Lisa Bell, John A. Bates, Elizabeth Pappadopulos, Deborah F. Willson, Jose Maria J. Alvir, Margaret G. Woerner, Stephen Geisler, John M. Kane, and Jeffrey A. Lieberman; Neuropsychology of First-Episode Schizophrenia: Initial Characterization and Clinical Correlates; Am J Psychiatry, Apr 2000; 157: 549 - 559.)