Semantic memory in schizophrenia: association with cell membrane essential fatty acids

Abstract

Introduction: Semantic memory and language deficits are associated with schizophrenia. Understanding how these systems operate in this disorder will likely require a multi-factorial model that explains their linkages with cognition and modulation by dopamine. A biological factor that may provide causal convergence for these connections is cell membrane composition and dynamics.

Methods: N400 is an electrophysiological measure of semantic memory and language that is sensitive to deficits in schizophrenia. Relationships among N400, cognition, dopamine, and cell membrane polyunsaturated fatty acids (PUFAs) were examined for patients tested under medicated (haloperidol only) and unmedicated (placebo) conditions. Relationships between these factors and clinical symptoms were also evaluated. The sample included 37 male schizophrenia inpatients and 34 male normal controls. The N400 priming effect was measured from visual event-related potentials recorded during a semantic priming-lexical decision task, in which semantic association (related versus unrelated words) and presentation rate (Stimulus Onset Asynchrony/SOAs: 350 and 950 ms) were varied.

Results: N400 was associated with cognition (speed, visuoperception, attention) in patients and controls. These relationships were influenced by SOA in both groups, and by pharmacological condition in patients. Levels of total PUFAs and arachidonic acid were associated with N400 in unmedicated patients. Clinical symptoms (paranoia, thought disturbance) were associated with N400, but not with cognition or PUFAs.

Conclusions: Results suggest cell membrane fatty acids are associated with semantic memory and language in schizophrenia. Findings also suggest a series of linkages that are modulated by dopamine: cell membrane fatty acids are associated with N400 semantic priming; N400 semantic priming is associated with clinical symptoms.

Fig. 1

Grand mean event-related potentials elicited by the 350 ms SOA (stimulus onset asynchrony) for normal controls (n=19), and medicated (n=17) and unmedicated (n=9) schizophrenia patients tested under low expectancy (31% associated word pairs) condition. Waveforms represent responses for semantically associated (solid line) and unassociated (dotted line) target words in prime-target pairs. Positivity is downward. The target word was presented at time zero and remained on for the duration of the recording epoch. EOG=electrooculogram. Data adapted from Condray et al., 2003.

Fig. 2

Relationship between WAIS-R Digit Symbol scaled score and log amplitude of N400 priming effect elicited at FZ by the 950 ms SOA in unmedicated (placebo) schizophrenia patients (n=20).

Fig. 3

Relationship between WRAT-R Vocabulary scaled score and amplitude of N400 priming effect elicited at PZ by the 350 ms SOA in unmedicated (placebo) schizophrenia patients (n=20).

Fig. 4

Relationship between BPRS Paranoia and amplitude of N400 priming effect elicited at FZ by the 350 ms SOA in unmedicated (placebo) schizophrenia patients (n=20).

Fig. 5

Relationship between total polyunsaturated fatty acids (PUFAs: nmol/mL packed red blood cell) and log amplitude of N400 priming effect elicited at FZ by the 950 ms SOA in unmedicated (placebo) schizophrenia patients (n=14).

Fig. 6

Relationship between Arachidonic acid (nmol/mL packed red blood cell) and log amplitude of N400 priming effect elicited at FZ by the 950 ms SOA in unmedicated (placebo) schizophrenia patients (n=14).

Fig. 7

Relationship between WAIS-R Picture Completion scaled score and amplitude of N400 priming effect elicited at FZ by the 950 ms SOA in medicated (haloperidol only) schizophrenia patients (n=29).

Fig. 8

Relationship between BPRS Thought Disturbance and amplitude of N400 priming effect elicited at FZ by the 950 ms SOA in medicated schizophrenia patients (n=29).