Neuropsychological measures of attention and memory function in schizophrenia: relationships with symptom dimensions and serum monoamine activity

Abstract

Background: Some clinical symptoms or cognitive functions have been related to the overall state of monoamine activity in patients with schizophrenia, (e.g. inverse correlation of the dopamine metabolite HVA with delusions or visual-masking performance). However, profiles (as presented here) of the relations of the activity of dopamine, noradrenaline and serotonin to neuropsychologic (dys)functions in major patient sub-groups with their very different symptomatic and cognitive characteristics have not been reported.

Methods: Serum measures of dopamine, noradrenaline and serotonin turnover were examined by regression analyses for the prediction of performance on 10 neuropsychological measures reflecting left- and right-hemispheric and frontal-, parietal- and temporal-lobe function in 108 patients with schizophrenia and 63 matched controls. The neuropsychological battery included tests of verbal fluency, Stroop interference, trail-making, block-design, Mooney faces recognition, picture-completion, immediate and delayed visual and verbal recall. Paranoid and nonparanoid subgroups were based on ratings from the Positive and Negative Syndrome Scale (PANSS). Groups with high and low ratings of ideas-of-reference and thought-disorder were formed from a median split on the Scale for Assessment of Positive Symptoms (SAPS).

Results: Verbal-fluency and Stroop-interference (left frontal and fronto-cingulate function) were negatively associated with noradrenergic turnover in nonparanoid and thought-disordered patients. High dopamine turnover related to speeded trail-making (frontal modulation of set switching) in those with many ideas-of-reference. In contrast, low dopamine turnover predicted poor recall in nonparanoid patients and those with little thought disorder. Serotonin metabolism did not independently contribute to the prediction any measure of cognitive performance. But, with regard to the relative activity between monoaminergic systems, increased HVA/5-HIAA ratios predicted visual-reproduction and Mooney's face-recognition performance (right-hemisphere functions) in highly symptomatic patients. Decreased HVA/MHPG predicted non-verbal recall.

Conclusion: Clinical state and function are differentially sensitive to overall levels of monoamine activity. In particular, right-lateralised cerebral function was sensitive to the relative activities of the monoamines. Increased noradrenergic activity was associated with enhanced frontal but impaired temporal lobe function in nonparanoid syndromes. Low dopaminergic activity predicted poor attentional set control in those with ideas-of-reference, but poor recall in nonparanoid patients. These data, especially the HVA/5-HIAA ratios, provide a basis for planning the nature of antipsychotic treatment aimed at patient specific symptom dimensions and cognitive abilities.

Figure 1

(Top) Serum monoamine and metabolite levels in controls (CON) and in patients treated with typical (TYP), atypical (ATYP) or both types of antipsychotic drug. Atypical > Typical, * P < 0.1; ** P < 0.08; *** P < 0.04; # P < 0.006 (covaried for age, IQ and CPZ). (Bottom) Turnover rates for 3 monoamines, and the ratio of dopamine (DA) to noradrenaline (NA) and serotonin (5-HT) metabolism (HVA/MHPG, HVA/5-HIAA), respectively. Controls (vs. whole patient group) showed less 5-HT TR (P < 0.05) and more HVA vs. 5-HIAA and MHPG (both ## P < 0.002).

Figure 2

Metabolite/monoamine turnover ratios for the whole subject group (bar diagram, left) and for patient sub-groups (tabular, right: PN, paranoid; NP, nonparanoid; ThD, thought disorder [+/-, high/low]; IoR, ideas of reference [+/-, high/low]). #P < 0.08, *P < 0.05, ** P < 0.01. 1 = levels of metabolite. Units: inter-amine ratios ×10; 5-HT TR ×10³; DA and NA TR ×10.

Figure 3

Partial correlations (left) for increased noradrenaline turnover (NA TR: Ln MHPG/NA) with increased Stroop-test interference scores in healthy controls (r = +0.34, P = 0.009), and (middle) for decreased NA TR with increased Stroop interference scores in patients with schizophrenia (r = -0.26, P = 0.01). But, (right) decreases of NA TR are associated with better verbal fluency in patients with schizophrenia (r = -0.29, P = 0.004).

Figure 4

Partial correlations (left) show that reduced dopamine turnover (DA TR: Ln HVA/DA) is associated with enhanced picture completion scores in healthy subjects (r = -0.35, P = 0.01). Increasing DA TR (middle) is associated with improved verbal recall in patients with schizophrenia (r = +0.29, P = 0.008). For patients with high ratings for ideas-of reference (IoR: right) increased DA activity was associated with promoting the speed of switching between sets on the trail-making test (r = +0.34, P = 0.015).