[Show abstract][Hide abstract] ABSTRACT: Background: It has been shown that persons people with a psychotic
disorder or who are at risk for psychosis may have an aberrant functioning
of the prefrontal cortex. These prefrontal abnormalities have been related
to negative symptoms and cognitive impairments. A decreased quality of
prefrontal neurons and abnormal glutamate levels may cause the prefrontal
abnormalities and concurrent symptoms. In this study we investigated the
levels of N-Acetyl Aspartate (NAA, measure for neuronal integrety) and
glutamate in a large sample of persons with a psychotic disorder or at risk
Methods: We included 106 patients with a diagnosis of schizophrenia
spectrum disorder. In addition, 16 persons with an At Risk Mental State
(ARMS) for psychosis and 36 healthy controls underwent a H-MRS single
voxel spectroscopy scan in the white matter of their left lateral prefrontal
cortex. We used a 2 cm3 voxel with standard PRESS sequence of Philips.
Absolute levels of glutamate (GLU) and NAA were determined in LcModel
by using the water peak as a reference. The concentrations were corrected
for gray matter and CSF content of the voxel. Patients and ARMS subjects
were compared to their matched healthy control subjects. Moreover, the
relations with age, duration of illness, negative symptoms, and cognitive
performance on a planning task were investigated.
Results: We found that NAA and GLU levels were higher in young persons
with a psychosis, but that the levels decreased stronger with increasing
age than in healthy controls. A longer duration of illness was also weakly
associated with lower NAA and GLU levels. In the ARMS subjects, NAA and
GLU levels were lower at a young age, but higher in older subjects, while
there was no effect of age on NAA in the healthy control group and a
negative association with GLU. Moreover, both patients and ARMS subjects
showed a negative association between GLU levels and negative symptoms,
but not for NAA, neither an effect for cognitive performance.
Discussion: In conclusion, patients with a psychosis, levels of NAA and
glutamate may decrease to a stronger extend with increasing age than in
healthy controls. Contrary, patients with a developing psychosis may show
excessive levels of GLU and NAA, though this hypothesis needs further
investigation. Notably, negative symptoms are related to lower prefrontal
levels of glutamate, which is an excitatory neurotransmitter.
4th Biennial Schizophrenia International Research Conference, Florence; 04/2014
[Show abstract][Hide abstract] ABSTRACT: Sexual dysfunction is a frequent side effect of antipsychotics, but information is scant regarding the psychometric properties and clinical usefulness of currently existing questionnaires. This systematic review compares the psychometric properties and content of questionnaires for assessment of sexual functioning in patients using antipsychotics. A systematic literature search was performed using three electronic databases (PubMed, Embase, and PsycINFO) with predefined search terms. We identified six validated instruments for assessment of sexual functioning in patients using antipsychotics: the Antipsychotic Non-Neurological Side Effects Rating Scale (ANNSERS), the Arizona Sexual Experience Scale (ASEX), the Antipsychotics and Sexual Functioning Questionnaire (ASFQ), the Changes in Sexual Function Questionnaire-14 (CSFQ-14), the Nagoya Sexual Function Questionnaire (NSFQ), and the Psychotropic-Related Sexual Dysfunction Questionnaire (PRSexDQ). The ASFQ, CSFQ-14, and PRSexDQ cover all stages of sexual functioning, which makes these questionnaires preferable to the other three questionnaires described. The ASFQ and PRSexDQ are clinician-administered and ask for a change in sexual functioning related to medication. The ASFQ assesses improvement as well as deterioration of sexual functioning, and includes items about hyperprolactinemia. The CSFQ-14 is useful when self-report is desired but contains more items.
The Journal of Sex Research 01/2014; 51(4):383-9. · 2.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study is to describe the psychometric properties of the Antipsychotics and Sexual Functioning Questionnaire (ASFQ). Internal reliability, test-retest reliability, inter-rater reliability, validity and sensitivity to change were calculated in a sample of 30 patients with schizophrenia or a schizophrenia spectrum disorder using antipsychotics. The ASFQ is a semistructured interview, with good face validity and content validity, that takes on average about 10min to complete. The ASFQ has good internal reliability (Cronbach's alpha 0.84) and good test-retest reliability (mean Spearman's rho=.76). The inter-rater reliability is good for questions about libido, orgasm, erection and ejaculation. Correlation coefficients for calculating convergent validity were modest to good when comparing the ASFQ with the corresponding items on the Subject's Response to Antipsychotics (SRA) questionnaire and the Arizona Sexual Experience Scale (ASEX). Based on preliminary evidence, it can be concluded that the Antipsychotics and Sexual Functioning Questionnaire has reasonable reliability and is available for clinical use and research.
Schizophrenia Research 09/2013; · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Monitoring patients' experiences with antipsychotics may help to improve medication adherence and outcome. We aimed to develop a shorter version of a comprehensive 74-item self-report questionnaire suitable for routine monitoring of desired and undesired effects of antipsychotics. METHODS: Included were patients with psychotic disorders from seven mental health care organizations in The Netherlands, using antipsychotic medication, who completed the Subjects' Response to Antipsychotics (SRA-74). Exploratory factor analysis (EFA) and similarity analysis based on mutual information were used to identify the latent factor structure of the SRA. Items were reduced according to their metric properties and clinical relevance upon consensus by an expert panel, using a Delphi procedure of three rounds. We determined the internal consistency of the shorter version using Cronbach's alpha. RESULTS: SRA data of N=1478 patients (mean age of 40years, 31% females) were eligible for analysis. EFA extracted thirteen factors from the SRA-74, including four factors for desired effects (e.g. recovery of psychosis, cognition and social functioning) and nine factors for undesired effects (e.g. weight gain, flattened affect and increased sleep). Based on this solution 12 items were eliminated for statistical reasons. The expert panel eliminated another 28 items with redundant content, resulting in a 34-item version. The SRA-34 includes 10 desired and 24 clinically relevant undesired effects. Both the subscales for desired and undesired effects have a Cronbach's alpha coefficient of 0.82. CONCLUSIONS: The SRA-34 can be used to evaluate desired and undesired effects of antipsychotics in routine clinical practice and research.
Schizophrenia Research 04/2013; · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Negative symptoms of schizophrenia are normally grouped into a single category. However, the diversity of such symptoms suggests that they are actually made up of more than one dimension. The DSM-V proposes two negative symptom domains, namely expressive deficits and avolition/asociality. We investigated whether the negative symptoms do indeed have two dimensions. An exploratory factor analysis was carried out based on interviews with the PANSS (664 patients). We restricted our analysis to items that had been described as negative symptoms in previous factor analyses. The symptom structure was then tested for stability by performing a confirmatory factor analysis on PANSS interviews from a separate cohort (2172 patients). Exploratory factor analysis yielded a two-factor structure of negative symptoms. The first factor consisted of PANSS items Flat affect, Poor rapport, Lack of spontaneity, Mannerisms and posturing, Motor retardation, and Avolition. The second factor consisted of Emotional withdrawal, Passive/apathetic social withdrawal, and Active social avoidance. The first factor could be related to expressive deficits, reflecting a loss of initiative, and the second factor to social amotivation, related to community interaction. This factor structure supports the DSM-V classification and may be relevant for pathophysiology and treatment of schizophrenia and other psychotic disorders.
Journal of Psychiatric Research 03/2013; 47:718-725. · 4.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An updated version of the Dutch multidisciplinary guideline on schizophrenia was published in 2012.
We aim to provide an overview of the psychosocial interventions and nursing care which, according to the guideline, should be included in basic care programmes for patients with schizophrenia. We consider which interventions are effective and which are optional. In addition, we argue for continuous updating of the guideline so that it reflects current developments.
We conducted a systematic review on the basis of specific predefined search terms. We included articles published up to February 2010. We used the method for evidence-based guideline development in order to formulate treatment recommendations.
Cognitive behavioural therapy and family interventions are scientifically proven interventions that should be included in the care programmes. Although there is no clear evidence that psycho-education is effective, it is nevertheless recommended. Optional interventions are peer support groups and, in the case of negative symptoms, psychomotor therapy. Although scientific evidence concerning nursing care is limited, we do make some recommendations. We are strongly in favour of a ‘living guideline’ that is constantly developed and updated.
Tijdschrift voor psychiatrie 01/2013; 55(9):707-14.
[Show abstract][Hide abstract] ABSTRACT: Introduction
Auditory verbal hallucinations (AVH) in schizophrenia (SZ) have been proposed to result from abnormal local, interregional and interhemispheric integration of brain signals in regions involved in language production and perception. This abnormal functional integration may find its base in morphological abnormalities. Structurally, AVHs have been frequently linked to abnormal morphology of the superior temporal gyrus (STG), but only few studies investigated the relation of hallucination presence with both whole-brain gray matter (GM) and white matter (WM) morphometry.
Using a unified voxel-based morphometry – DARTEL approach, we investigated correlates of AVH presence in 51 schizophrenia patients (20 non-hallucinating [SZ-], 31 hallucinating [SZ +]), and included 51 age and sex matched healthy participants. Effects are reported at p < .05 FWE corrected.
Patients showed lower GM volume of the left STG than controls, irrespective of AVH presence. In addition, SZ + showed lower GM volume of the left inferior frontal and right parahippocampal gyrus, and higher WM volume of the left postcentral and superior parietal lobule than controls. Finally, volume of the putamen was lower in SZ + compared to SZ-. No effects on corpus callosum morphometry were observed. Delusion severity, general positive and negative symptomatology, illness duration, and medication status could not explain the results.
Results suggest that STG GM abnormalities underlie the general susceptibility to experience psychotic symptoms and that additional abnormalities in a network of medial temporal, ventrolateral, putaminal, and parietal regions related to verbal memory and speech production may specifically increase the likelihood of experiencing AVH. Future studies should clarify the meaning of morphometry abnormalities for functional interregional communication.
[Show abstract][Hide abstract] ABSTRACT: Auditory-verbal hallucinations (AVHs) are frequently associated with activation of the left superior temporal gyrus (including Wernicke's area), left inferior frontal gyrus (including Broca's area), and the right hemisphere homologs of both areas. It has been hypothesized that disconnectivity of both interhemispheric transfer and frontal and temporal areas may underlie hallucinations in schizophrenia. We investigated reduced information flow in this circuit for the first time using dynamic causal modeling, which allows for directional inference. A group of healthy subjects and 2 groups of schizophrenia patients-with and without AVH-performed a task requiring inner speech processing during functional brain scanning. We employed connectivity models between left hemispheric speech-processing areas and their right hemispheric homologs. Bayesian model averaging was used to estimate the connectivity strengths and evaluate group differences. Patients with AVH showed significantly reduced connectivity from Wernicke's to Broca's area (97% certainty) and a trend toward a reduction in connectivity from homologs of Broca's and Wernicke's areas to Broca's area (93% and 94% certainty). The connectivity magnitude in patients without hallucinations was found to be intermediate. Our results point toward a reduced input from temporal to frontal language areas in schizophrenia patients with AVH, suggesting that Broca's activity may be less constrained by perceptual information received from the temporal cortex. In addition, a lack of synchronization between Broca and its homolog may lead to the erroneous interpretation of emotional speech activity from the right hemisphere as coming from an external source.
[Show abstract][Hide abstract] ABSTRACT: Alexithymia is a trait characterized by a diminished capacity to describe and distinguish emotions and to fantasize; it is associated with reduced introspection and problems in emotion processing. The default mode network (DMN) is a network of brain areas that is normally active during rest and involved in emotion processing and self-referential mental activity, including introspection. We hypothesized that connectivity of the DMN might be altered in alexithymia. Twenty alexithymic and 18 non-alexithymic healthy volunteers underwent a resting state fMRI scan. Independent component analysis was used to identify the DMN. Differences in connectivity strength were compared between groups. Within the DMN, alexithymic participants showed lower connectivity within areas of the DMN (medial frontal and temporal areas) as compared to non-alexithymic participants. In contrast, connectivity in the high-alexithymic participants was higher for the sensorimotor cortex, occipital areas and right lateral frontal cortex than in the low-alexithymic participants. These results suggest a diminished connectivity within the DMN of alexithymic participants, in brain areas that may also be involved in emotional awareness and self-referential processing. On the other hand, alexithymia was associated with stronger functional connections of the DMN with brain areas involved in sensory input and control of emotion.
Social Cognitive and Affective Neuroscience 05/2012; 7(6):660-6. · 5.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Brain circuits involved in language processing have been suggested to be compromised in patients with schizophrenia. This does not only include regions subserving language production and perception, but also auditory processing and attention. We investigated resting state network connectivity of auditory, language and attention networks of patients with schizophrenia and hypothesized that patients would show reduced connectivity. Patients with schizophrenia (n = 45) and healthy controls (n = 30) underwent a resting state fMRI scan. Independent components analysis was used to identify networks of the auditory cortex, left inferior frontal language regions and the anterior cingulate region, associated with attention. The time courses of the components where correlated with each other, the correlations were transformed by a Fisher's Z transformation, and compared between groups. In patients with schizophrenia, we observed decreased connectivity between the auditory and language networks. Conversely, patients showed increased connectivity between the attention and language network compared to controls. There was no relationship with severity of symptoms such as auditory hallucinations. The decreased connectivity between auditory and language processing areas observed in schizophrenia patients is consistent with earlier research and may underlie language processing difficulties. Altered anterior cingulate connectivity in patients may be a correlate of habitual suppression of unintended speech, or of excessive attention to internally generated speech. This altered connectivity pattern appears to be present independent of symptom severity, and may be suggestive of a trait, rather than a state characteristic.
Schizophrenia Research 03/2012; 135(1-3):15-22. · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Decreased prefrontal activation (hypofrontality) in schizophrenia is thought to underlie negative symptoms and cognitive impairments, and may contribute to poor social outcome. Hypofrontality does not always improve during treatment with antipsychotics. We hypothesized that antipsychotics, which share antagonism at dopamine receptors, with a relatively low dopamine receptor affinity and high serotonin receptor affinity may have a sparing effect on prefrontal function compared to strong dopamine receptor antagonists. We systematically investigated the relation between serotonin and dopamine antagonism of antipsychotics and prefrontal functioning by reviewing neuroimaging studies. The weight of the evidence was consistent with our hypothesis that antipsychotics with low dopaminergic receptor affinity and moderate to high serotonergic affinity were associated with higher activation of the prefrontal cortex. However, clozapine, a weak dopamine and strong serotonin antagonist, was associated with decrease in prefrontal activation. Future studies should further elucidate the link between prefrontal activation and negative symptoms using prospective designs and advanced neuroimaging techniques, which may ultimately benefit the development of treatments for disabling negative symptoms.
European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 01/2012; 22(6):387-400. · 3.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lack of insight (unawareness of illness) is a common and clinically relevant feature of schizophrenia. Reduced levels of self-referential processing have been proposed as a mechanism underlying poor insight. The default mode network (DMN) has been implicated as a key node in the circuit for self-referential processing. We hypothesized that during resting state the DMN network would show decreased connectivity in schizophrenia patients with poor insight compared to patients with good insight. Patients with schizophrenia were recruited from mental health care centers in the north of the Netherlands and categorized in groups having good insight (n= 25) or poor insight (n = 19). All subjects underwent a resting state fMRI scan. A healthy control group (n = 30) was used as a reference. Functional connectivity of the anterior and posterior part of the DMN, identified using Independent Component Analysis, was compared between groups. Patients with poor insight showed lower connectivity of the ACC within the anterior DMN component and precuneus within the posterior DMN component compared to patients with good insight. Connectivity between the anterior and posterior part of the DMN was lower in patients than controls, and qualitatively different between the good and poor insight patient groups. As predicted, subjects with poor insight in psychosis showed decreased connectivity in DMN regions implicated in self-referential processing, although this concerned only part of the network. This finding is compatible with theories implying a role of reduced self-referential processing as a mechanism contributing to poor insight.
PLoS ONE 01/2012; 7(8):e42707. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Menstrual disorders are common among women with schizophrenia, particularly when they are being treated with antipsychotics. The occurrence of menstrual disorders is often attributed to the use of prolactin-elevating antipsychotics, although menstrual disorders also occur in patients not using antipsychotics. Therefore we need to find out whether menstrual disorders in schizophrenia are drug-related or whether they have some other connection with schizophrenia.
To identify and discuss studies that investigate the relationship between antipsychotics-induced hyperprolactinemia and menstrual disorders in women with schizophrenia.
We reviewed the literature systematically using PubMed, Psyc, info and the Cochrane Central Register of Controlled Trials.
Very few studies have investigated the connection between antipsychotic-induced hyperprolactinemia and menstrual disorders and most have serious methodological limitations. Only one study was able to demonstrate such a connection.
On the basis of current research no firm conclusions can be drawn about the relationship between the increased frequency of menstrual disorders in women with schizophrenia and elevated prolactin levels resulting from the use of antipsychotics.
Tijdschrift voor psychiatrie 01/2012; 54(10):861-8.
[Show abstract][Hide abstract] ABSTRACT: Clozapine, an atypical antipsychotic, has proved to be superior to other antipsychotics in treating patients with refractory schizophrenia. An increased plasma clozapine level above the therapeutic window may be associated with serious adverse events including paralytic ileus. Clozapine toxicity may occur in association with infection or after drug overdose. In a medical emergency situation, differentiating between a toxic clozapine ingestion and an infection-induced toxicity might be hindered by associated CNS changes and by the clozapine modulation of the inflammatory process. This may delay prompt initiation of a tailored treatment strategy. Here, we report a case of paralytic ileus developed within the context of clozapine toxicity. Although the underlying cause of toxicity was not clinically obvious, giving antimicrobial therapy resulted in an improvement in the patient's clinical condition. This report indicates the value of serum levels of C-reactive protein and desmethylclozapine, major metabolite of clozapine, in the treatment of aetiologically unclear clozapine toxicity.
[Show abstract][Hide abstract] ABSTRACT: Depressive symptoms require accurate recognition and monitoring in clinical practice of patients with schizophrenia. Depression instruments developed for use in depressed patients may not discriminate depressive symptoms from negative psychotic symptoms.
We reviewed depression instruments on their reliability and validity in patients with schizophrenia.
A systematic literature search was carried out in three electronic databases. Psychometric properties were extracted for those instruments of which reliability, divergent, concurrent and predictive validity were reported in one or more publications.
Forty-eight publications described the reliability and validity of six depression instruments in patients with schizophrenia. The only self-report was the Beck Depression Inventory (BDI). The Brief Psychiatric Rating Scale-Depression subscale (BPRS-D), Positive and Negative Syndrome Scale-Depression subscale (PANSS-D), Hamilton Rating Scale for Depression (HAMD), Montgomery Asberg Depression Rating Scale (MADRS) and Calgary Depression Scale for Schizophrenia (CDSS) were clinician rated. All instruments were reliable for the measurement of depressive symptoms in patients with schizophrenia. The CDSS most accurately differentiated depressive symptoms from other symptoms of schizophrenia (divergent validity), correlated well with other depression instruments (concurrent validity), and was least likely to miss cases of depression or misdiagnose depression (predictive validity).
We would recommend to use the CDSS for the measurement of depressive symptoms in research and in daily clinical practice of patients with schizophrenia. A valid self-report instrument is to be developed for the use in clinical practice.
Journal of affective disorders 11/2011; 140(1):38-47. · 3.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Negative symptoms of schizophrenia often predict an unfavorable clinical outcome. Disturbed dopamine transmission in different brain parts may underlie different aspects of negative symptoms, and the effect of antipsychotics on them may also differ. This pilot study investigated the potentially therapeutic effects of the partial dopamine agonist aripiprazole on different negative symptoms.
This pilot study randomly assigned patients with schizophrenia (N=40) to either aripiprazole or risperidone. After 6 weeks of treatment, the severity of negative symptoms was determined by the PANSS. Subscales of self-report questionnaires were used to assess differences in initiative, anhedonia, social functioning and subjective well-being.
Patients treated with aripiprazole showed a significant improvement on measures for anhedonia and subjective wellbeing. Negative symptoms in general, lack of initiative and social inhibition were also lower in the aripiprazole treated group, but without reaching statistical significance.
According to this pilot study, aripiprazole appears to specifically improve anhedonia and subjective wellbeing compared to risperidone. This may be caused by a specific effect of aripiprazole on the limbic branch of the dopamine system. Future studies should replicate this finding with a larger sample size.