Memory Generalization Impaired in Psychosis Disorders

Deficits in memory generalization are present among schizophrenia patients, their relatives, and bipolar patients, compared with healthy controls, reported Dr. Elena I. Ivleva and her colleagues in the June issue of Schizophrenia Research.

The finding "suggests a specific deficit in memory-guided generalizations common to the psychosis probands that is independent of learning or memory for previously learned associations," wrote the authors (Schizophrenia Research 2012;138:74-80).

Dr. Ivleva of the University of Texas Southwestern Medical Center, Dallas, looked at a combination of probands with DSM-IV diagnoses of schizophrenia (n = 33) and bipolar disorder (n = 20), as well as 21 first-degree relatives of schizophrenia patients (who may or may not have had a psychiatric history) and 26 healthy controls. The groups were demographically similar, except for a slightly higher percentage of males in the schizophrenia patient group.

Most probands and three of the schizophrenia relatives underwent treatment with a combination of psychotropic agents during the study period, wrote the authors, including mood stabilizers and antipsychotics.

"Since the proband groups were comparable with respect to active medication status, cognitive outcomes were not adjusted for medication use," they wrote—a possible study limitation, conceded Dr. Ivleva.

All subjects underwent a modified version of the computer-based Acquired Equivalence paradigm (J. Cogn. Neurosci. 2003;15:185-93), which assesses associative learning, memory for learned associations, and memory generalization.

The authors found that there were no differences in overall learning and memory retrieval in either psychosis probands or the relatives of the schizophrenia patients, compared with controls, "although [schizophrenia probands] demonstrated slower initial learning, consistent with prior reports."

However, when it came to the memory generalization portion of the test, "All probands ... showed lower memory generalization performance, compared with healthy controls," wrote the authors, with P = .026.

Separately, there was a statistically significant difference between schizophrenia patients and controls (P = .038) and a trend-level difference between bipolar patients and controls (P = .069), with no differences found between proband groups.

Looking at the schizophrenia relatives, the researchers found that their performance on the memory generalization component of the test was intermediate between that of the schizophrenia patients and the controls, although more similar to the performance of the controls. Their score was not statistically different from either group (vs. probands, P = .09; vs. controls, P = .85).

"No correlations were found between memory generalization and learning across all stages; memory recall; any of the declarative memory tests; Wechsler Test of Adult Reading general intelligence estimate; age; education; total, psychosis and affective Brief Psychiatric Rating Scale scores; Global Assessment of Functioning Scale scores; age of psychosis onset, age at the first psychiatric hospitalization, or lifetime number of hospitalizations in either schizophrenia or bipolar disorder."

Dr. Ivleva wrote that while the specific mechanisms underlying how generalization deficits link to psychosis remain unknown, at least one recent report (Am. J. Psychiatry 2010;167:1178-93) offers a possible model.

That study "suggests that a hypoglutamatergic lesion in [the] dentate gyrus possibly generates alterations in synaptic plasticity in CA3, specifically, a compensatory increase in sensitivity to incoming stimuli in CA3 excitatory synapses, and results in altered memory generalization, associational mistakes and, possibly, psychotic productions," she wrote.

"This model ... is currently being tested."

The authors disclosed that the study was funded by grants from the National Institutes of Mental Health, the Brain and Behavior Research, and the American Psychiatric Foundation. They stated that they had no personal financial conflicts of interest to disclose.

Deficits in memory generalization are present among schizophrenia patients, their relatives, and bipolar patients, compared with healthy controls, reported Dr. Elena I. Ivleva and her colleagues in the June issue of Schizophrenia Research.

The finding "suggests a specific deficit in memory-guided generalizations common to the psychosis probands that is independent of learning or memory for previously learned associations," wrote the authors (Schizophrenia Research 2012;138:74-80).

Dr. Ivleva of the University of Texas Southwestern Medical Center, Dallas, looked at a combination of probands with DSM-IV diagnoses of schizophrenia (n = 33) and bipolar disorder (n = 20), as well as 21 first-degree relatives of schizophrenia patients (who may or may not have had a psychiatric history) and 26 healthy controls. The groups were demographically similar, except for a slightly higher percentage of males in the schizophrenia patient group.

Most probands and three of the schizophrenia relatives underwent treatment with a combination of psychotropic agents during the study period, wrote the authors, including mood stabilizers and antipsychotics.

"Since the proband groups were comparable with respect to active medication status, cognitive outcomes were not adjusted for medication use," they wrote—a possible study limitation, conceded Dr. Ivleva.

All subjects underwent a modified version of the computer-based Acquired Equivalence paradigm (J. Cogn. Neurosci. 2003;15:185-93), which assesses associative learning, memory for learned associations, and memory generalization.

The authors found that there were no differences in overall learning and memory retrieval in either psychosis probands or the relatives of the schizophrenia patients, compared with controls, "although [schizophrenia probands] demonstrated slower initial learning, consistent with prior reports."

However, when it came to the memory generalization portion of the test, "All probands ... showed lower memory generalization performance, compared with healthy controls," wrote the authors, with P = .026.

Separately, there was a statistically significant difference between schizophrenia patients and controls (P = .038) and a trend-level difference between bipolar patients and controls (P = .069), with no differences found between proband groups.

Looking at the schizophrenia relatives, the researchers found that their performance on the memory generalization component of the test was intermediate between that of the schizophrenia patients and the controls, although more similar to the performance of the controls. Their score was not statistically different from either group (vs. probands, P = .09; vs. controls, P = .85).

"No correlations were found between memory generalization and learning across all stages; memory recall; any of the declarative memory tests; Wechsler Test of Adult Reading general intelligence estimate; age; education; total, psychosis and affective Brief Psychiatric Rating Scale scores; Global Assessment of Functioning Scale scores; age of psychosis onset, age at the first psychiatric hospitalization, or lifetime number of hospitalizations in either schizophrenia or bipolar disorder."

Dr. Ivleva wrote that while the specific mechanisms underlying how generalization deficits link to psychosis remain unknown, at least one recent report (Am. J. Psychiatry 2010;167:1178-93) offers a possible model.

That study "suggests that a hypoglutamatergic lesion in [the] dentate gyrus possibly generates alterations in synaptic plasticity in CA3, specifically, a compensatory increase in sensitivity to incoming stimuli in CA3 excitatory synapses, and results in altered memory generalization, associational mistakes and, possibly, psychotic productions," she wrote.

"This model ... is currently being tested."

The authors disclosed that the study was funded by grants from the National Institutes of Mental Health, the Brain and Behavior Research, and the American Psychiatric Foundation. They stated that they had no personal financial conflicts of interest to disclose.

Deficits in memory generalization are present among schizophrenia patients, their relatives, and bipolar patients, compared with healthy controls, reported Dr. Elena I. Ivleva and her colleagues in the June issue of Schizophrenia Research.

The finding "suggests a specific deficit in memory-guided generalizations common to the psychosis probands that is independent of learning or memory for previously learned associations," wrote the authors (Schizophrenia Research 2012;138:74-80).

Dr. Ivleva of the University of Texas Southwestern Medical Center, Dallas, looked at a combination of probands with DSM-IV diagnoses of schizophrenia (n = 33) and bipolar disorder (n = 20), as well as 21 first-degree relatives of schizophrenia patients (who may or may not have had a psychiatric history) and 26 healthy controls. The groups were demographically similar, except for a slightly higher percentage of males in the schizophrenia patient group.

Most probands and three of the schizophrenia relatives underwent treatment with a combination of psychotropic agents during the study period, wrote the authors, including mood stabilizers and antipsychotics.

"Since the proband groups were comparable with respect to active medication status, cognitive outcomes were not adjusted for medication use," they wrote—a possible study limitation, conceded Dr. Ivleva.

All subjects underwent a modified version of the computer-based Acquired Equivalence paradigm (J. Cogn. Neurosci. 2003;15:185-93), which assesses associative learning, memory for learned associations, and memory generalization.

The authors found that there were no differences in overall learning and memory retrieval in either psychosis probands or the relatives of the schizophrenia patients, compared with controls, "although [schizophrenia probands] demonstrated slower initial learning, consistent with prior reports."

However, when it came to the memory generalization portion of the test, "All probands ... showed lower memory generalization performance, compared with healthy controls," wrote the authors, with P = .026.

Separately, there was a statistically significant difference between schizophrenia patients and controls (P = .038) and a trend-level difference between bipolar patients and controls (P = .069), with no differences found between proband groups.

Looking at the schizophrenia relatives, the researchers found that their performance on the memory generalization component of the test was intermediate between that of the schizophrenia patients and the controls, although more similar to the performance of the controls. Their score was not statistically different from either group (vs. probands, P = .09; vs. controls, P = .85).

"No correlations were found between memory generalization and learning across all stages; memory recall; any of the declarative memory tests; Wechsler Test of Adult Reading general intelligence estimate; age; education; total, psychosis and affective Brief Psychiatric Rating Scale scores; Global Assessment of Functioning Scale scores; age of psychosis onset, age at the first psychiatric hospitalization, or lifetime number of hospitalizations in either schizophrenia or bipolar disorder."

Dr. Ivleva wrote that while the specific mechanisms underlying how generalization deficits link to psychosis remain unknown, at least one recent report (Am. J. Psychiatry 2010;167:1178-93) offers a possible model.

That study "suggests that a hypoglutamatergic lesion in [the] dentate gyrus possibly generates alterations in synaptic plasticity in CA3, specifically, a compensatory increase in sensitivity to incoming stimuli in CA3 excitatory synapses, and results in altered memory generalization, associational mistakes and, possibly, psychotic productions," she wrote.

"This model ... is currently being tested."

The authors disclosed that the study was funded by grants from the National Institutes of Mental Health, the Brain and Behavior Research, and the American Psychiatric Foundation. They stated that they had no personal financial conflicts of interest to disclose.