Lydia Krabbendam

Sex differences in psychosis: normal or pathological?

BACKGROUND Schizophrenia first appears in adolescence, in boys at an earlier age than girls. The interpretation of this key epidemiological finding crucially depends on whether similar age-related sex differences exist in the expression of associated, subclinical psychosis-like experiences. METHODS Findings are based on a population sample of 2548 adolescents and young adults aged 17-28. Subjects were assessed with the core psychosis sections on delusions and hallucinations of the Munich-Composite International Diagnostic Interview. RESULTS The risk of subclinical psychotic experiences was significantly higher for males in the younger half of the cohort (17-21 years), but similar in the older half (22-28 years). CONCLUSIONS These findings suggest that normal maturational changes in adolescence with differential age of onset in boys and girls cause the expression of psychosis, the extreme of which is schizophrenia.

Sex differences in symptoms of psychosis in a non-selected, general population sample

BACKGROUND Little is known about sex differences in psychosis beyond the borders of clinical disorder. METHODS A general population sample of 7,076 subjects was assessed using the Composite International Diagnostic Interview, in order to explore sex differences in the prevalence of any positive and negative symptoms of psychosis, and to examine to what degree any differences could be explained by differences in level of affective symptoms. RESULTS Male sex was associated with higher prevalence of negative symptoms (OR = 1.6, 95% CI = 1.0, 2.5), independent of differences in affective symptoms and presence of DSM-III-R psychotic disorder. Women had higher rates of positive psychotic experiences (OR = 0.8, 95% CI = 0.7, 0.9), but this difference disappeared after adjustment for depressive symptoms (adjusted OR = 1.2, 95% CI = 0.9, 1.5). CONCLUSION The sex differences in psychopathology that are seen in schizophrenia are expressed beyond the clinical phenotype, suggesting sex-dependent continuous and normal variation of several psychosis dimensions. The higher rates of positive psychotic experiences seen in women may be secondary to differences in the rate of affective symptoms.

Functional magnetic resonance imaging of inner speech in schizophrenia

BACKGROUND Auditory verbal hallucinations in schizophrenia have been linked to defective monitoring of ones own verbal thoughts. Previous studies have shown that patients with auditory verbal hallucinations show attenuated activation of brain regions involved with auditory processing during the monitoring of inner speech. However, there are no functional magnetic resonance imaging studies explicitly comparing the perception of external speech with internal speech in the same patients with schizophrenia. The present study investigated the functional neuroanatomy of inner and external speech in both patients with schizophrenia and healthy control subjects. METHODS Fifteen patients with schizophrenia and 12 healthy control subjects were studied using functional magnetic resonance imaging while listening to sentences or imagining sentences. RESULTS Significant interactions between group (control subjects vs. patients) and task (listening vs. inner speech) were seen for the left superior temporal gyrus, as well as regions within the cingulate gyrus. CONCLUSIONS Attenuated deactivation of the left superior temporal gyrus in schizophrenia patients during the processing of inner speech may reflect deficits in the forward models subserving self-monitoring.

Cognition as predictor of current and follow-up depressive symptoms in the general population

Objective:  Previous studies have reported an association between depression and poor cognitive functioning. Unknown is to what degree such associations are merely state‐related or reflect an enduring depression vulnerability. This study examined whether cognitive deficits predict current and/or follow‐up (sub)clinical depressive symptoms in the general population.

Subclinical psychotic experiences and cognitive functioning as a bivariate phenotype for genetic studies in the general population

OBJECTIVE Cognitive deficits may be vulnerability markers for the development of schizophrenia. This study examined whether cognitive deficits are related to specific dimensions of subclinical psychotic experiences and whether associations between these variables are caused by additive genetic, common environmental and/or individual-specific environmental factors. METHOD A general population sample of 298 female twin pairs completed the Community Assessment of Psychic Experiences and a neuropsychological test battery. Associations between subclinical positive and negative psychotic dimensions and neuropsychological factors (episodic memory and information processing speed) were examined. Univariate correlation and structural equation analyses were performed to explore the role of genetic and environmental factors in the phenotypes separately. Bivariate correlation and structural equation analyses were applied to examine the causes of association. RESULTS There were significant correlations between information processing speed and both the positive (r=.11; p<.05) and the negative dimension (r=.10; p<.05). For the negative dimension and for speed of processing, the data suggested a model that included genetic factors. The observed phenotypic correlation between the negative dimension and information processing speed could be solely explained in terms of additive genetic factors. Although the comparison of the correlations for MZ and DZ pairs did not give a clear indication as to the underlying causes of the association, structural equation modelling suggested that the observed phenotypic correlation between the negative dimension and information processing speed could be solely explained in terms of additive genetic factors. CONCLUSION Negative symptoms and information processing speed are associated at the subclinical level and this association appears to be influenced by genetic factors exclusively. Bivariate psychosis phenotypes may represent suitable candidates for molecular genetic studies in the general population.

Auditory P300 and N100 components as intermediate phenotypes for psychotic disorder: Familial liability and reliability

OBJECTIVE Abnormalities of the auditory P300 are a robust finding in patients with psychosis. The purposes of this study were to determine whether patients with a psychotic disorder and their unaffected siblings show abnormalities in P300 and N100 and to establish test-retest reliabilities for these ERP components. METHODS Using an auditory oddball paradigm, P300 and N100 latency and amplitude were acquired from 19 patients with a psychotic disorder, 28 unaffected siblings, and 37 healthy controls, on two separate occasions. ERP components were compared between groups, using multilevel random regression analyses. Intraclass correlations were used to determine consistency of ERP components between the sessions. RESULTS A delayed target N100 latency was found in unaffected siblings. Patients showed significantly delayed P300 latency and diminished P300 amplitude compared to controls. Most ERP parameters showed good test-retest reliability. However, patients did not show sufficient reliability for N100 latency for standard stimuli. CONCLUSIONS The present study failed to find significant P300 abnormalities in unaffected siblings. However, N100 latency is delayed in siblings and can be reliably measured in all groups for target stimuli, suggesting that this component, rather than P300, may serve as liability marker. SIGNIFICANCE N100 latency is a promising biomarker for psychosis liability.

An fMRI study of prefrontal dysfunction and symptomatic recovery in schizophrenia

Smee C, Krabbendam L, O’Daly O, Prins A‐M, Nalesnik N, Morley L, Samson G, Shergill S. An fMRI study of prefrontal dysfunction and symptomatic recovery in schizophrenia.