Alex Sumich

Smooth pursuit and antisaccade eye movements in siblings discordant for schizophrenia.

Smooth pursuit eye movement (SPEM) and antisaccade deficits have been proposed as endophenotypes in the search for schizophrenia genes. We assessed these measures in 24 schizophrenia patients, 24 of their healthy siblings, and 24 healthy controls closely matched to the siblings. Between-group differences were assessed using a random effects regression model taking into account the relatedness between patients and siblings. Patients showed reduced SPEM gain, increased frequency of saccades during pursuit, increased antisaccade error rate, and reduced antisaccade gain compared to controls. Siblings performed intermediate, i.e. between patients and controls, on most measures, but were particularly characterised by reduced antisaccade gain. SPEM gain at one target velocity was significantly correlated between patients and siblings, highlighting the necessity of taking into account within-family correlations in the statistical analysis of between-group differences. It is concluded that subtle SPEM and antisaccade deficits are observed in clinically unaffected siblings of schizophrenia patients; these deficits may be useful markers of genetic liability to schizophrenia.

Unreality symptoms and volumetric measures of heschl's gyrus and planum temporal in first- episode psychosis

BACKGROUND Schizophrenia may involve dysfunction to primary auditory, speech, and language processes governed by the superior temporal gyrus (STG). These processes are implicated in hallucinations, delusions, and thought disorder. The current study explored the relationship between unreality symptoms (hallucinations and delusions) and specific STG substructures, including Heschls gyrus (HG) and planum temporale (PT). METHODS Twenty-five right-handed men within their first episode of psychosis were assessed using the Positive and Negative Syndrome Scale (PANSS) for the presence of hallucinations and delusional behavior (a composite score of delusions, grandiosity, suspiciousness, and unusual thought content). T1-weighted magnetic resonance imaging (MRI) scans were acquired using a 1.5 Tesla scanner. Stereological measurements of HG and PT volume were obtained. Linear regression methods explored the relationship between regional volumes and symptoms. RESULTS Reductions in left HG were associated with hallucinations and delusions. Increases in left PT were associated with delusional behavior. CONCLUSIONS Current results implicate HG dysfunction in unreality symptoms in men with recent-onset schizophrenia.

Disruption of Frontal Theta Coherence by Δ9-Tetrahydrocannabinol is Associated with Positive Psychotic Symptoms

The main ingredient in cannabis, Δ9-tetrahydrocannabinol (THC), can elicit acute psychotic reactions in healthy individuals and precipitate relapse in schizophrenic patients. However, the neural mechanism of this is unknown. We tested the hypothesis that THC psychopathology is related to changes in electroencephalography (EEG) power or inter-regional coherence. In a within-subjects design, participants (n=16) were given intravenous THC (1.25 mg) or placebo under double-blind conditions, during EEG recordings. Using fast-Fourier transform, EEG data were analyzed for power and coherence in the delta (1–3.5 Hz), theta (3.5–7 Hz), alpha (8–13 Hz), beta (14–25 Hz), low-gamma (30–40 Hz), and high-gamma (60–70 Hz) bands during engagement in the n-back test of working memory (WM). Compared with placebo, THC evoked positive and negative psychotic symptoms, as measured by the positive and negative syndrome scale (p<0.001) and slowed WM performance (p<0.05). Under THC, theta power was specifically reduced, (p<0.001) regardless of WM load; however, the reduction showed no relationship with psychotic symptoms or WM impairment. Coherence between bi-frontal electrodes in the theta band was also reduced by THC (p<0.05) and these reductions correlated with the change-in positive psychotic symptoms (rho=0.79, p<0.001). Bi-frontal specificity was suggested by the absence of a relationship between psychotic symptoms and fronto-parietal coherence. The results reveal that the pro-psychotic effects of THC might be related to impaired network dynamics with impaired communication between the right and left frontal lobes.

Selective deficit of hippocampal N-acetylaspartate in antipsychotic-naive patients with schizophrenia.

BACKGROUND Studies using proton magnetic resonance spectroscopy in schizophrenia have demonstrated abnormality of N-acetylaspartate but are confounded by the effects of phase of illness and medication. There is mounting evidence that antipsychotic medication influences N-acetylaspartate. METHODS A group of first-episode patients who had received no, or minimal, antipsychotic medication was examined at baseline and after 3 months treatment. Normal comparison subjects were examined at the same interval. Ratios of N-acetylaspartate, creatine plus phosphocreatine, and choline-containing compounds in the left prefrontal cortex, hippocampus, and basal ganglia were measured. RESULTS The mean duration of symptoms for all patients was 31.6 (SD 26.1) weeks. A significant reduction of hippocampal N-acetylaspartate/creatine plus phosphocreatine was found in the antipsychotic-naive group relative to those previously treated and to controls at baseline (F = 7.3, p <.002). No group differences were found at follow-up. CONCLUSIONS Hippocampal N-acetylaspartate/creatine plus phosphocreatine appears to be selectively affected early in the course of illness. The finding of neurochemical differences between treatment naive and previously treated patients confirms the relevance of medication status in proton magnetic resonance spectroscopy studies. Further investigation of the influence of medication at this stage of illness is warranted.

Cognitive functioning in siblings discordant for schizophrenia

Objective:  The objective of this study was to investigate neuropsychological impairment as a genetically mediated risk indicator for schizophrenia while accounting for prevalence of schizotypy signs/symptoms in siblings.

Volumetric Neural Correlates of Antisaccade Eye Movements in First-Episode Psychosis

OBJECTIVE The authors investigated the structural brain correlates of antisaccade performance. METHOD Magnetic resonance imaging was used to measure the volumes of the prefrontal, premotor, sensorimotor, and occipitoparietal cortices as well as the caudate, thalamus, cerebellar vermis, and cerebrum in 20 first-episode psychosis patients and 18 healthy comparison subjects. Antisaccades were recorded by using infrared oculography. RESULTS Groups significantly differed in terms of antisaccade error rate and amplitude gain and tended to differ in terms of latency but not brain region volumes. Premotor cortex volume predicted antisaccade error rate among comparison subjects. In the patient group, caudate volume was related to latency and amplitude gain. Negative symptoms, independent of structural volumes, predicted error rate. CONCLUSIONS These findings point to altered structure-function relationships in first-episode psychosis.

N100 and P300 amplitude to Go and No-Go variants of the auditory oddball in siblings discordant for schizophrenia.

BACKGROUND P300 amplitude reduction is reliably seen in schizophrenia. Inconsistent reports of isolated frontal and/or parietal deficits in unaffected family members may be clarified using a task that places greater load on frontal function. METHOD Go and No-Go versions of the auditory oddball task were performed by eighteen schizophrenia patients, age-matched unaffected siblings and healthy controls matched closely to unaffected siblings on age, sex, education, socioeconomic-status, handedness and ethnicity. Groups were compared on P300 and N100 amplitude and latency. Spearman correlations were used to test the relationship between ERP amplitudes and neuropsychological measures of executive function and memory. The relationship between schizotypy--as measured using the structured interview--and ERPs was explored in a combined group of siblings and controls. RESULTS Independent of task, patients had lower P300 than controls and reduced parietal amplitude compared to siblings. Siblings had enhanced frontocentral N100 compared to controls. No-Go P300 amplitude and N100 latency was associated with executive function measures. There were significant intraclass correlations between patients and siblings for No-Go P300 amplitude, particularly at the central midline electrode. Frontocentral N100 and P300 amplitude were positively correlated with anxiety-related aspects of schizotypy. CONCLUSION Enhanced N100 is present in unaffected siblings. Parietal P300 is intact in unaffected siblings, but reduced in patients. The No-Go-oddball is more sensitive than the Go-oddball to executive function deficits in patients and as an index of heritability.

Neural correlates of deficient response inhibition in mentally disordered violent individuals

In this study, response inhibition and associated neural activation during a motor inhibition paradigm were investigated in (i) men with antisocial personality disorder (APD) with a history of violence (n = 14), (ii) men with schizophrenia with a history of violence (n = 12), (iii) men with schizophrenia without a history of violence (n = 12), and (iv) healthy control subjects (n = 14) using functional magnetic resonance imaging (fMRI). At the behavioural level, individuals with schizophrenia showed impaired performance across all conditions, whereas an increased error rate was seen in the APD group only during the conditions requiring inhibition. At the neural level, both violent groups showed reduced thalamic activity, compared with controls, in association with modulation of inhibition by task demands. In addition, the violent schizophrenia group, compared with controls, showed reduced activity in the caudate nucleus during the condition requiring inhibition. It is concluded that violence may not be specifically associated with impaired voluntary inhibition in schizophrenia but this is likely in APD. Reduced thalamic function, perhaps due to its known association with sensorimotor disturbances, is implicated in violent behaviour across both disorders. In addition, caudate dysfunction may contribute, given its role in timing and temporal processing as well as suppression of motor actions, to deficient inhibition and violent behaviour in schizophrenia.

Event-related potential correlates of depression, insight and negative symptoms in males with recent-onset psychosis

OBJECTIVE The neurobiology of clinical characteristics -in particular depression, insight and negative symptoms- in recent-onset psychosis (ROP) was studied using event-related potentials (ERPs). METHODS Twenty right-handed ROP men and 20 controls completed an auditory-oddball task. ROP men had minimum exposure to antipsychotic medication. N100, N200 and P300 were studied to ascertain the effects of (a) diagnosis (patients versus controls), and (b) clinical characteristics. RESULTS ROP men had significantly lower anterior N100, enhanced N200 at T3, and lower P300 at Pz than controls. Lower right-anterior N100 and enhanced right-anterior N200 amplitude explained 47.7% of negative symptoms. Left-central N100 amplitude explained 30.28% of negative symptoms. Lower left-posterior and higher right-posterior P300 amplitude explained 65.99% of total symptoms. Lower left-central N100, enhanced left-central N200 and depression explained 78.8% of impairments in insight and judgement. Impaired insight/judgement correlated positively with right-anterior N200 and was identified as the most significant co-efficient for depression. CONCLUSIONS Disturbed selective-attention and executive function indexed by N100 and N200, respectively, are associated with poor insight and negative symptoms. A complex interaction exists between insight and depression. SIGNIFICANCE The current results demonstrate a biological basis of insight and depression and a complex interaction between the two, perhaps mediated by executive function, in early psychosis.

Toward an integrated profile of depression: evidence from the brain resource international database

Clinical depression is one of the most common psychiatric disorders in adults, yet non-clinical depression in the community may go unnoticed, despite high prevalence rates and significant psychosocial impairment. The aim of the current study was to classify 1,226 individuals from a community sample on the basis of depression scores (using the Depression Anxiety Stress Scales, DASS) and to determine whether depression in a non-clinical sample differed significantly from healthy controls on a profile of multimodal measures. The data analyzed in this study included personality, emotional intelligence, cognition and psychophysiology. It was predicted that non-clinically depressed participants would differ from healthy controls on measures of personality (increased neuroticism; decreased extraversion), emotional intelligence (decreased), cognition (impairments in executive dysfunction and memory impairment), psychophysiology (increased resting-state, right-frontal activation; diminished skin conductance) after controlling for gender, age, handedness and years of education. Findings provide support for the majority of hypotheses, though no evidence was found for memory impairment or frontal hemispheric asymmetry. Longitudinal studies are needed to determine the extent to which of these findings will have utility for the prediction of depression onset and treatment response/non-response.