Relational memory in first episode psychosis: implications for progressive hippocampal dysfunction after illness onset.

OBJECTIVE: Verbal episodic memory deficits are prominent in schizophrenia and have also been found in first episode psychosis (FEP) and individuals at clinical risk of the disorder. The central role of the hippocampus in verbal memory processing and the consistent findings of hippocampal volume reductions in chronic patients have prompted the suggestion that impaired verbal memory performance may be a biomarker of schizophrenia. However, it is currently unclear as to when, during the early phase of psychosis, verbal memory performance becomes significantly impaired. The current study investigated verbal relational memory in FEP using a novel verbal paired associate task, and tested whether performance was dependent on phase of illness within FEP, where patients with a diagnosis of schizophrenia were considered to be in a more advanced stage than those with schizophreniform disorder. METHOD: Forty-seven currently psychotic FEP patients and 36 healthy non-psychiatric controls, aged 15-25 years old, completed a test comprising four trials of learning and cued recall of word pairs (denoted AB pairs), an interference phase comprising two trials with new second words (AC pairs), and finally cued recall for the original AB pairings. RESULTS: FEP patients performed similarly to controls on the relational memory task. There was no difference in performance between FEP patients who had a diagnosis of schizophrenia and those with a diagnosis of schizophreniform disorder. CONCLUSIONS: Verbal relational memory appears to be intact in FEP. This finding, along with chronic patient literature, suggests that decline in hippocampal and medial temporal lobe functioning occurs during later illness stages. Further research is needed to aid in the development of intervention strategies that may prevent decline in such cognitive domains at this crucial early stage of the illness.

Cognitive decline following psychosis onset: data from the PACE clinic.

BACKGROUND: The origin of cognitive impairments in psychotic disorders is still unclear. Although some deficits are apparent prior to the onset of frank illness, it is unknown if they progress. AIMS: To investigate whether cognitive function declined over the transition to psychosis in a group of ultra-high risk individuals. METHOD: Participants consisted of two groups: controls (n=17) and individuals at ultra-high risk for development of psychosis (n=16). Seven of the latter group later developed psychosis. Neuropsychological testing was conducted at baseline and again after at least a 12-month interval. RESULTS: Both the Visual Reproduction sub-test of the Wechsler Memory Scale-Revised and Trail-Making Test B showed a decline over the follow-up period that was specific to the group who became psychotic. In addition, both high-risk groups showed a decline in digit span performance. No other task showed significant change over time. CONCLUSIONS: These preliminary data suggest that as psychosis develops there may be a specific decline in visual memory and attentional set-shifting, reflecting impairments in efficient organisation of visual stimuli. This may be caused by either the illness itself or treatment with antipsychotic medication.

The effects of click and tone-burst stimulus parameters on the vestibular evoked myogenic potential (VEMP).

Vestibular evoked myogenic potentials (VEMP) are short latency electromyograms (EMG) evoked by high-level acoustic stimuli and recorded from surface electrodes over the tonically contracted sternocleidomastoid (SCM) muscle and are presumed to originate in the saccule. The present experiments examined the effects of click and tone-burst level and stimulus frequency on the latency, amplitude, and threshold of the VEMP in subjects with normal hearing sensitivity and no history of vestibular disease. VEMPs were recorded in all subjects using 100 dB nHL click stimuli. Most subjects had VEMPs present at 500, 750, and 1000 Hz, and few subjects had VEMPs present at 2000 Hz. The response amplitude of the VEMP increased with click and tone-burst level, whereas VEMP latency was not influenced by the stimulus level. The largest tone-burst-evoked VEMPs and lowest thresholds were obtained at 500 and 750 Hz. VEMP latency was independent of stimulus frequency when tone-burst duration was held constant.

Altered depth of the olfactory sulcus in ultra high-risk individuals and patients with psychotic disorders.

A shallow olfactory sulcus has been reported in schizophrenia, possibly reflecting abnormal forebrain development during early gestation. However, it remains unclear whether this anomaly exists prior to the onset of psychosis and/or differs according to illness stage. In the current study, magnetic resonance imaging was used to investigate the length and depth of the olfactory sulcus in 135 ultra high-risk (UHR) individuals [of whom 52 later developed psychosis (UHR-P) and 83 did not (UHR-NP)], 162 patients with first-episode psychosis (FEP), 89 patients with chronic schizophrenia, and 87 healthy controls. While there was no group difference in the length of the sulcus, UHR-P subjects had significantly shallower olfactory sulcus at baseline as compared with UHR-NP and control subjects. The depth of this sulcus became increasingly more superficial as one moved from UHR-P subjects to FEP patients to chronic schizophrenia patients. Finally, the depth of the olfactory sulcus in the UHR-P subjects was negatively correlated with the severity of negative symptoms. These findings suggest that the altered depth of the olfactory sulcus, which exists before psychosis onset, could be predictive of transition to psychosis, but also suggest ongoing changes of the sulcus morphology during the course of the illness.

Attentional set-shifting ability in first-episode and established schizophrenia: Relationship to working memory.

Patients with established schizophrenia perform poorly on attentional set-shifting tasks, due to a failure of inhibitory control and/or perseverative errors. However, attentional set-shifting is also dependent on working memory capacity, which is additionally impaired in schizophrenia. No studies in first-episode psychosis have specifically examined the contribution of working memory to set-shifting ability in schizophrenia. We investigated 48 first-episode schizophreniform psychosis/schizophrenia (FE) and 40 chronic schizophrenia (CHR) patients, compared to 67 comparable healthy subjects (CTL). All subjects were assessed using the CANTAB 'attentional set-shifting (IDED)' and 'spatial working memory (SWM)' tasks. Both FE and CHR made significantly greater errors on the SWM task (p< or =0.001). Compared with CTL, CHR was more likely to fail at intra-dimensional (p<0.05) and extra-dimensional (p<0.01) shifting and reversal stages of IDED; CHR required significantly greater trials to reach criterion, which was not explained by deficits in SWM (p<0.001). FE did not differ from CTL on IDED level reached. However, FE required significantly more trials (p=0.001); this was no longer significant after controlling for SWM deficits (p>0.05). Given that the capacity to be flexible and shift attentional set is intact only at the early stages of illness, 'neurodegenerative' processes may explain the more severe deficits in chronic schizophrenia. In contrast, deficits in SWM identified at all stages of schizophrenia may reflect incomplete maturation prior to illness onset ('neurodevelopmental arrest'). Longitudinal studies assessing these cognitive functions from illness onset or in prepsychotic individuals are required.

Ethyl-eicosapentaenoic acid in first-episode psychosis. A 1H-MRS study.

Ethyl-eicosapentaenoic acid (E-EPA) is an omega-3 fatty acid that has been used in a range of neuropsychiatric conditions with some benefits. However, its mechanism of action is unknown. Here, we investigate its effects on in vivo brain metabolism in first-episode psychosis (FEP). Proton magnetic resonance spectroscopy at 3 T was performed in the temporal lobes of 24 FEP patients before and after 12 weeks of treatment in the context of a larger double-blind, placebo-controlled E-EPA augmentation study. Treatment group effects for glutathione (F1,12=6.1, p=0.03), and a hemisphere-by-group interaction for glutamine/glutamate (F1,20=4.4, p=0.049) were found. Glutathione increased bilaterally and glutamate/glutamine increased in the left hemisphere following E-EPA administration. Improvement in negative symptoms correlated with metabolic brain changes, particularly glutathione (r=-0.57). These results suggest that E-EPA augmentation alters glutathione availability and modulates the glutamine/glutamate cycle in early psychosis, with some of the metabolic brain changes being correlated with negative symptom improvement. Larger confirmatory studies of these postulated metabolic brain effects of E-EPA are warranted.

Fractionation of verbal memory impairment in schizophrenia and schizophreniform psychosis.

OBJECTIVES: The characterization, aetiology, and course of verbal memory deficits in schizophrenia remain ill defined. The impact of antipsychotic medications is also unclear. The purpose of the present paper was to investigate verbal memory performance in established schizophrenia (SZ) and first-episode schizophreniform psychosis (FE). METHOD: Performances of 32 SZ and 33 FE patients were compared to those of 47 healthy volunteers on measures of verbal working memory, verbal associative learning and story recall. RESULTS: Story recall deficits, but not deficits in working memory or paired associate learning, were demonstrated by both patient groups. Patients treated with typical neuroleptics had more impairment in associative learning with arbitrary word pairings than those treated with atypicals, regardless of patient group. CONCLUSIONS: The results are consistent with the notion that some neuropsychological impairment is present at the time of psychosis onset and that this impairment is non-progressive. However, deficits may be specific to subclasses of memory function.

Early processing deficits in object working memory in first-episode schizophreniform psychosis and established schizophrenia.

BACKGROUND: While there are many studies showing working-memory deficits in schizophrenia there are only a few that disentangle impairments for working-memory subprocesses such as perceptual, attentional, mnemonic and executive function. METHOD: In this study of delay-dependent memory, 55 patients with schizophreniform psychosis, 50 with established schizophrenia and 56 healthy controls were investigated. Using the delayed matching-to-sample task from the Cambridge Neuropsychological Test Automated Battery (CANTAB), performance deficits were found in both patient groups after controlling for age and pre-morbid IQ. RESULTS: Even after controlling for simultaneous matching-to-sample ability (i.e. perceptual matching), impaired performance in both patient groups was found as soon as the stimuli were no longer present. Impaired performance was not due to different types of errors in patients versus controls. Performance in both patient groups was comparable, except for a slight decrease of overall task performance. This suggests that the deficit is relatively stable during the course of the illness. CONCLUSIONS: Our results suggest a deficit in patients with psychotic illness in the initial processes necessary to actively maintain information, such as the ability to form an internal representation of complex objects.

The influence of voluntary tonic EMG level on the vestibular-evoked myogenic potential.

Vestibular-evoked myogenic potentials (VEMPs) are proposed as a reliable test to supplement the current vestibular test battery by providing diagnostic information about saccular and/or inferior vestibular nerve function. VEMPs are short-latency electromyograms (EMGs) evoked by high-level acoustic stimuli and recorded from surface electrodes over the tonically contracted sternocleidomastoid muscle. VEMP amplitude is influenced by the EMG level, which must be controlled. This study examined the ability of subjects to achieve the EMG target levels over a range of target levels typically used during VEMP recordings. In addition, the influence of target EMG level on the latency and amplitude of the click- and tone-evoked VEMP was examined. The VEMP amplitude increased as a function of EMG target level, and the latency remained constant. EMG target levels ranging from 30 microV to 50 microV are suggested for clinical application of the VEMP.

Normative data from the CANTAB. I: development of executive function over the lifespan.

The study of executive function within a developmental framework has proven integral to the advancement of knowledge concerning the acquisition and decline of higher skill processes. Still in its early stages, there exists a discontinuity in the literature between the exploration of executive capacity in young children and the elderly. Research of age-related differences utilising a lifespan approach has been restricted by the lack of assessment tools for the measurement of executive skills that are applicable across all age levels. This paper addresses these issues using the computer-based Cambridge Neuropsychological Test Automated Battery (CANTAB) to identify periods of development in executive capacities using a normative sample of 194 participants ranging in age from 8 to 64 years. Findings of executive function in children as young as 8 years of age were extended, with functional gains found in the efficiency of working memory capacity, planning and problem-solving abilities, between the ages of 15 and 19 years and again at 20-29 years of age. Cognitive flexibility was assessed at adult-levels in even the youngest children. Declines in performance on all tasks were revealed for the 50-64 year old sample, providing support for the vulnerability of executive skills to normal aging.