Bernard Sabbe

Parsing the components of the psychomotor syndrome in schizophrenia

Docx L, Morrens M, Bervoets C, Hulstijn W, Fransen E, De Hert M, Baeken C, Audenaert K, Sabbe B. Parsing the components of the psychomotor syndrome in schizophrenia.

Beneficial factors in family discussion groups of a psychiatric day clinic: perceptions by the therapeutic team and the families of the therapeutic process

This paper reports a pilot investigation of the perception of helpful events by the therapeutic team and the families in two family discussion groups (FDGs) of a psychiatric day clinic. All participants of the FDG, including therapists and observers, filled in questionnaires measuring events helpful for the individual, for the family and for the group after each FDG session. The results showed that the therapeutic team and the families diverged in their overall perception of which factors were important in family discussion group therapy. The therapeutic team saw the relational climate and the structural aspects of the group (including group involvement and support from the group), and specific therapeutic interventions as more helpful than the families. The process aspects in the group members (including the experiencing of communality and gaining insight) were, on the other hand, more frequently mentioned by the families than by the therapeutic team. The clinical implications of these findings and suggestions for future research are discussed.

The use of dried blood spots for quantification of 15 antipsychotics and 7 metabolites with ultra-high performance liquid chromatography-tandem mass spectrometry

Therapeutic drug monitoring of antipsychotics is important in optimizing individual therapy. In psychiatric populations, classical venous blood sampling is experienced as frightening. Interest in alternative techniques, like dried blood spots (DBS), has consequently increased. A fast and easy to perform DBS method for quantification of 16 antipsychotics (amisulpride, aripiprazole, asenapine, bromperidol, clozapine, haloperidol, iloperidone, levosulpiride, lurasidone, olanzapine, paliperidone, pipamperone, quetiapine, risperidone, sertindole and zuclopenthixol) and 8 metabolites was developed. DBS were prepared using 25u2009μL of whole blood and extraction of complete spots was performed using methanol: methyl-t-butyl-ether (4:1). After evaporation, the extract was reconstituted in the mobile phase and 10u2009μL were injected on an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Separation using a C18 column and gradient elution with a flow rate of 0.5u2009mL/min resulted in a 6-min run-time. Ionization was performed in positive mode and a dynamic MRM method was applied. Median recovery was 66.4 % (range 28.7-84.5%). Accuracy was within the acceptance criteria, except for pipamperone (LLOQ and low concentration) and lurasidone (low concentration). Imprecision was only aberrant for lurasidone at low and medium concentration. All compounds were stable during 1u2009month at room temperature, 4u2009°C and -18u2009°C. Lurasidone was unstable when the extract was stored for 12u2009h on the autosampler. Absolute matrix effects (ME) (median 66.1%) were compensated by the use of deuterated IS (median 98.8%). The DBS method was successfully applied on 25-μL capillary DBS from patients and proved to be a reliable alternative for quantification of all antipsychotics except for olanzapine and N-desmethylolanzapine.

The effect of mood-stabilizing drugs on cytokine levels in bipolar disorder: A systematic review.

OBJECTIVESnCytokine level alterations suggest a role for the immune system in the pathophysiology of bipolar disorder (BD). Pharmacotherapy is an important confounding factor in clinical research on cytokine levels. In this systematic review we collate the evidence on blood cytokine levels in medication-free BD and the effects of single mood-stabilizing drugs on these levels.nnnMETHODSnA systematic review was conducted according to the PRISMA statement. We searched the Pubmed and Embase databases for clinical studies reporting either on cytokine levels in medication-free BD or on the effects of single mood-stabilizing drugs on cytokine levels in BD.nnnRESULTSnOf the 564 articles screened, 17 were included. Fourteen articles report on medication-free patients with BD and indicate state-related cytokine alterations. Six articles discuss the effect of lithium. Whereas no data on short-term effects of lithium were found, ≥2 months lithium use in euthymic populations is associated with normal cytokine levels. Two studies report no effect of valproate and no studies were found on carbamazepine, lamotrigine or antipsychotics.nnnLIMITATIONSnThe available studies are characterized by a broad methodological heterogeneity and limited replication between studies.nnnCONCLUSIONSnThis systematic review suggests the presence of state-related cytokine level alterations in medication-free BD with most evidence pointing to a proinflammatory cytokine response in mania. Euthymia and long-term lithium use are associated with normal cytokine levels. To improve our understanding of the impact of mood-stabilizing drugs on cytokine levels, longitudinal studies with medication-free baseline, randomized controlled single-drug treatment protocols and close mood state monitoring are needed.

Are capillary DBS applicable for therapeutic drug monitoring of common antipsychotics? A proof of concept

AIMnDBS sampling has been proposed as an alternative for venous blood collection in therapeutic drug monitoring (TDM) of antipsychotics. For implementation in routine practice, a comparison between capillary and venous blood concentrations is mandatory.nnnRESULTSnA DBS method for quantification of antipsychotics was clinically validated. First, whole blood therapeutic ranges were calculated using the blood:serum ratio. Calculation of DBS:blood ratios and Passing-Bablok regression analysis demonstrated that concentrations obtained by DBS analysis were highly comparable to those obtained by conventional whole blood analysis. Clinical interpretation of serum, whole blood and DBS concentrations were highly identical (sensitivity 91.6-97.6%).nnnCONCLUSIONnThis is the first clinical study demonstrating the value of DBS sampling in TDM of antipsychotics.

Increased orienting to unexpected action outcomes in schizophrenia

Although some recent research has indicated reduced performance monitoring in patients with schizophrenia, the literature on this topic shows some remarkable inconsistencies. While most studies suggest diminished error signals following error responses, some studies reported normal post-error slowing, while others reported reduced post-error slowing. Here we review these studies and highlight the most important discrepancies. Furthermore, we argue that overall error rates are a mostly neglected issue that can at least partly explain these discrepancies. It has been reported previously that post-error slowing depends on the error rates. Participants or patients that make more errors are likely to show decreased post-error slowing. Therefore, when a group of patients is compared to a group of controls, it is extremely important to match error rates. For this purpose, we developed a procedure where we matched individuals error rates. In a task where subjects had to press a response key corresponding to one of four colors we manipulated the difficulty on an individual basis by varying the discriminability between the colors. Schizophrenic patients and a group of controls were tested with this procedure showing that differences in accuracy disappear. Interestingly, we can see that in patients, the color values that were needed to reach similar levels of accuracy correlate with the Positive and Negative Syndrome Scale (PANSS) scale, with higher PANSS requiring more color. Most important, we found that schizophrenic patients have increased rather than decreased post-error slowing when the inter-trial interval (ITI) is short. This result can be interpreted within the framework of the orienting account, as it has been demonstrated previously that schizophrenic patients show increased distractibility.

Conflict adaptation in schizophrenia: reviewing past and previewing future efforts

ABSTRACT Introduction: Cognitive control impairments have been suggested to be a critical component in the overall cognitive deficits observed in patients diagnosed with schizophrenia. Here, we zoom in on a specific function of cognitive control, conflict adaptation. Abnormal neural activity patterns have been observed for patients diagnosed with schizophrenia in core conflict adaptation areas such as anterior cingulate cortex and prefrontal cortex. On the one hand, this strongly indicates that conflict adaptation is affected. On the other hand, however, outcomes at the behavioural level are needed to create a window into a precise interpretation of this abnormal neural activity.Methods. We present a narrative review of behavioural work within the context of conflict adaptation in schizophrenia, focusing on various major conflict adaptation markers: congruency sequence effects, proportion congruency effects, and post-error and post-conflict slowing. The review emphasises both methodological and theoretical aspects that are relevant to the understanding of conflict adaptation in schizophrenia.Results. Based on the currently available set of behavioural studies on conflict adaptation, no clear-cut answer can be provided as to the precise conflict adaptation processes that are impaired (and to what extent) in schizophrenia populations.Conclusions. Future work is needed in state-of-the-art designs in order to reach better insight into the specifics of conflict adaptation impairments associated with schizophrenia.

Multiple family therapy en familiediscussiegroep : Ontwikkeling en een voorbeeld van toepassing in dagbehandeling ()

Multiple family therapy heeft zijn wortels in de theorieën van het vroege familietherapie- en systeemdenken over schizofrenie en blijft verbonden met de figuur van Laqueur, zijn grondlegger. Ondertussen heeft multiple family therapy een hele ontwikkeling doorgemaakt, die geschetst wordt aan de hand van een literatuuroverzicht. Drie ontwikkelingslijnen worden met name besproken: de psycho-educatieve benadering, de uitbreiding van de indicatie naar diverse patiëntenpopulaties en naar diverse behandelsettings. Vervolgens wordt een voorbeeld van een toepassing beschreven binnen een psychiatrische dagkliniek, waarbij narratieve en constructivistische elementen geï?ntegreerd worden. Deze elementen leiden voor de hier beschreven behandeling tot een nieuwe benaming: familiediscussiegroep in plaats van multiple family therapy.

Problem Behaviours and Major Depressive Disorder in Intellectual Disability and Autism: A Contribution of PET and MRI

Background: Previous literature demonstrates a high association between problem behaviours (PB) and major depressive disorder (MDD) in intellectual disability (ID) and autism (ASD). Neuroradiological literature about this topic is still scarce. Aims: The present study aims at integrating neuro-imaging findings (PET, MRI). Methodology: Two groups with mild-to-moderate ID and ASD with PB (n = 30; MDD = 15) and without (n = 12; MDD = 1) were formed. PB was assessed by the Dutch version of Disturbing Behavior Scales for Intellectual Disability. MDD was screened with the use of the DM-ID (Diagnostic Manual-Intellectual Disability). Every patient received a structural MRI (volumetry hippocampus and amygdala) and at least every second patient a PET scan Results: MDD versus no-MDD as a whole (± PB) demonstrated hypermetabolism cerebellum, brainstem, pallidum. Furthermore, MDD in ID, ASD, PB versus no PB correlated with hypermetabolism in cerebellum, and hypometabolism in the middle frontal and precentral gyrus. PB (+/- MDD) first PET scan versus second PET scan (after a minimum 6 months of treatment) demonstrated hypometabolism of the precentral gyrus. In the case of no-PB and MDD versus no-MDD, hypometabolism cerebellum and precentral gyrus could be screened. PB and MDD versus no-PB and no-MDD demonstrated hypermetabolism pallidum. Summarizing the structural MRI results, the volumes of the hippocampus and amygdala did not show a significant correlation with PB or MDD. Conclusion: ASD, PB and MDD in ID are mutually enhancing factors in hypometabolism precentral gyrus and mid-frontal gyrus. MDD and PB in ID and ASD are correlated with hypermetabolism cerebellum and pallidum. PET data are discussed in relation to the high association between PB and MDD in ID and ASD.

James P. McCullough (2000). Treatment for chronic depression: Cognitive behavioral analysis system of psychotherapy. New York: Guilford Press. 326 pp., £19,95

SamenvattingMcCullough is cognitief gedragstherapeut en meent dat zowel de cognitieve therapie volgens het model van Beck, als de interpersoonlijke therapie specificiteit mist voor de behandeling van chronische depressies. Daarom schreef hij een handleiding voor zijn ‘Cognitive behavioral analysis system of psychotherapy’ (CBASP). Deze aanpak is gericht op de groep van ambulante patiënten met een chronische depressie. Het gaat om een empirisch onderbouwd biopsychosociaal model dat rekening houdt met de complexiteit van de factoren die bijdragen tot de ontwikkeling en instandhouding van depressie.