To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Anxiety is a core symptom of schizophrenia which elicits significant subjective burden of disease and contributes to treatment resistance in schizophrenia. Anxious syndromes might be attributed to incompletely remitted delusions, the negative syndrome, depressive episodes, panic attacks, social phobia, avoidance after hospitalization and down-tapering of benzodiazepine medication. Previous treatment attempts involved several strategies of combination and augmentation.
Pregabalin, an antagonist at the α2δ-subunit of voltage-gated Ca2+-channels, modulates several neurotransmitter systems and was found able to alleviate anxiety in depression and other mental disorders.
In schizophrenia, this treatment option has not been evaluated before.
Here, we report a case series of 11 schizophrenic patients who suffered from treatment-resistant anxiety and received augmentation with pregabalin.
This observational investigation reveals that augmentation with pregabalin was able to significantly reduce scores on the Hamilton anxiety scale; furthermore, we observed improvements of psychotic positive and negative symptoms and mood as assessed by PANSS, SANS and CDSS. After augmentation, both a complete discontinuation of concomitant benzodiazepine (BZD) treatment as well as a dose reduction of antipsychotics could be achieved. We did not observe pharmacokinetic interactions or adverse events.
These observations suggest that treating anxious syndromes in schizophrenia with pregabalin can be effective and tolerable. Further investigations should differentiate schizophrenic sub-syndromes of anxiety and evaluate benefits and risks of pregabalin in comparison to placebo and active competitors.
Patients with psychotic disorders often suffer from intercurrent major depressive episodes (MDEs). Case reports suggested successful antidepressive treatment with duloxetine, a selective dual reuptake inhibitor of serotonin and norepinephrine (SSNRI). We initiated this open prospective clinical trial in order to evaluate efficacy, safety and tolerability of this approach.
Patients with a psychotic lifetime diagnosis suffering from mildly severe MDEs were treated with duloxetine over a period of 6 weeks. We evaluated effects on mood, monitored the psychotic psychopathology and assessed side effects, basal clinical and pharmacological parameters.
Twenty patients were included and experienced a significant improvement of their MDE during the observation period (CDSS: Calgary Depression Scale for Schizophrenia, HAMD: Hamilton Depression scale). Psychotic positive symptoms remained stably absent while negative syndrome and global psychopathology considerably improved (PANSS: Positive and Negative Syndrome Scale). In general, the treatment was well tolerated, serum prolactin levels stayed unchanged, but pharmacokinetic interactions with a number of antipsychotic agents were observed.
This open prospective evaluation revealed antidepressive efficacy of duloxetine in patients with co-morbid psychotic disorders. With regard to the psychotic disorder, the treatment appears to be safe and well tolerable. Further investigations should involve a randomized control group.
Epidemiological studies estimated that amongst patients with schizophrenia a large subgroup of up to 25% also suffers from comorbid obsessive compulsive symptoms (OCS). The association between these comorbid OCS and neuropsychological impairment remains unclear and somewhat contradictory. Longitudinal approaches which investigate the stability of OCS related cognitive deficits are missing.
37 patients with schizophrenia and comorbid OCS and 43 schizophrenia patients without OCS were assessed with a comprehensive cognitive test-battery and compared at baseline and again 12 months later.
Schizophrenia patients with comorbid OCS showed significant pronounced deficits with increasing effect sizes over the 12 month assessment period in specific cognitive areas such as visuo-spatial perception and visual memory (WAIS-R block design, Rey-Osterrieth Complex Figure Test), executive functioning (perseveration in the Wisconsin card sorting test) and cognitive flexibility (Trail making test B). These cognitive domains correlated with OCS severity and are known to be candidate domains in obsessive compulsive disorder (OCD).
OCS in schizophrenia is associated longitudinally stable specific cognitive deficits. Prospective studies involving patients with at risk mental states for psychosis are necessary to decipher the interaction of cognitive impairment and the clinical manifestation of schizophrenia and OCS. This might facilitate the definition of patients at high risk for OCS, an early detection of subclinical levels, therapeutic interventions and clinical monitoring.
Patients with psychosis display the so-called ‘Jumping to Conclusions’ bias (JTC) – a tendency for hasty decision-making in probabilistic reasoning tasks. So far, only a few studies have evaluated the JTC bias in ‘at-risk mental state’ (ARMS) patients, specifically in ARMS samples fulfilling ‘ultra-high risk’ (UHR) criteria, thus not allowing for comparisons between different ARMS subgroups.
In the framework of the PREVENT (secondary prevention of schizophrenia) study, a JTC task was applied to 188 patients either fulfilling UHR criteria or presenting with cognitive basic symptoms (BS). Similar data were available for 30 healthy control participants matched for age, gender, education and premorbid verbal intelligence. ARMS patients were identified by the Structured Interview for Prodromal Symptoms (SIPS) and the Schizophrenia Proneness Instrument – Adult Version (SPI-A).
The mean number of draws to decision (DTD) significantly differed between ARM -subgroups: UHR patients made significantly less draws to make a decision than ARMS patients with only cognitive BS. Furthermore, UHR patients tended to fulfil behavioural criteria for JTC more often than BS patients. In a secondary analysis, ARMS patients were much hastier in their decision-making than controls. In patients, DTD was moderately associated with positive and negative symptoms as well as disorganization and excitement.
Our data indicate an enhanced JTC bias in the UHR group compared to ARMS patients with only cognitive BS. This underscores the importance of reasoning deficits within cognitive theories of the developing psychosis. Interactions with the liability to psychotic transitions and therapeutic interventions should be unravelled in longitudinal studies.
Metamemory describes the monitoring and knowledge about one's memory capabilities. Patients with schizophrenia have been found to be less able in differentiating between correct and false answers (smaller confidence gap) when asked to provide retrospective confidence ratings in previous studies. Furthermore, higher proportions of very-high-confident but false responses have been found in this patient group (high knowledge corruption). Whether and how these biases contribute to the early pathogenesis of psychosis is yet unclear. This study thus aimed at investigating metamemory function in the early course of psychosis.
Patients in an at-risk mental state for psychosis (ARMS, n = 34), patients with a first episode of psychosis (FEP, n = 21) and healthy controls (HCs, n = 38) were compared on a verbal recognition task combined with retrospective confidence-level ratings.
FEP patients showed the smallest confidence gap, followed by ARMS patients, followed by HCs. All groups differed significantly from each other. Regarding knowledge corruption, FEP patients differed significantly from HCs, whereas a statistical trend was revealed in comparison of ARMS and FEP groups. Correlations were revealed between metamemory, measures of positive symptoms and working memory performance.
These data underline the presence of a metamemory bias in ARMS patients which is even more pronounced in FEP patients. The bias might represent an early cognitive marker of the beginning psychotic state. Longitudinal studies are needed to unravel whether metacognitive deficits predict the transition to psychosis and to evaluate therapeutic interventions.
Epidemiological investigations show that up to 30% of schizophrenic patients suffer from obsessive–compulsive symptoms (OCS) associated with negative impact on the general prognosis. It has been proposed that antiserotonergic second-generation antipsychotics (SGAs) might induce OCS, but investigations of large samples integrating psychopathology, neuropsychology and psychopharmacology are missing.
We stratified 70 patients with schizophrenia according to their mode of antipsychotic treatment: clozapine and olanzapine (group I) compared with aripiprazole and amisulpride (group II). The groups were matched according to age, sex, educational levels and severity of the psychotic disorder (Positive and Negative Syndrome Scale). As the primary endpoint, we evaluated OCS severity (Yale–Brown Obsessive–Compulsive Scale).
OCS were significantly more prevalent and severe in group I, in which OCS severity correlated with dosage of clozapine and duration of treatment. Pronounced cognitive deficits in group I were found in visuospatial perception and visual memory (Wechsler Adult Intelligence Scale-Revised block design, Rey–Osterrieth Complex Figure Test), impulse inhibition (go/no-go test), higher perseveration scores (Wisconsin Card Sorting Test) and reduced set-shift abilities (Trail Making Test Part B, Set-shift Task). These cognitive domains correlated with OCS severity.
OCS in schizophrenia are associated with antiserotonergic SGA treatment, but longitudinal studies have to prove causality. Before starting treatment with antiserotonergic SGAs, specific neurocognitive domains should be evaluated, as visuospatial learning and impulse inhibition performance might allow early detection of OCS secondary to antipsychotic treatment in schizophrenia.
Email your librarian or administrator to recommend adding this to your organisation's collection.