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  • 1
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    Effects of Low-Dose Risperidone and Low-Dose Zuclopenthixol on Cognitive Functions in First-Episode Drug-Naïve Schizophrenic Patients
    Cambridge University Press (CUP) ; 2004
    In:  CNS Spectrums Vol. 9, No. 5 ( 2004-05), p. 364-374
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    In: CNS Spectrums, Cambridge University Press (CUP), Vol. 9, No. 5 ( 2004-05), p. 364-374
    Abstract: Background: Studies on the effects of antipsychotics on cognitive deficits in schizophrenia mostly suggest a superior effect of atypical over typical compounds, although findings are inconsistent and effect sizes small. Several methodological issues, such as heterogenous patient samples, incomparable drug doses, effects of prior medication, construct validity, and retest effects on neuropsychological tasks, confound most results and the comparability between studies. Consequently, the conclusion concerning effects of antipsychotics on cognition is still equivocal. Objective: The present randomized clinical trial examined the effects on cognition of comparatively low doses of a typical antipsychotic (zuclopenthixol) and an atypical antipsychotic (risperidone) in a homogenous group of drug-naïve first-episode schizophrenic patients in a longitudinal setting. Methods: First-episode schizophrenic patients who had never previously been exposed to antipsychotic treatment (N-25) were randomly allocated to treatment with flexible doses of zuclopenthixol or risperidone in an open-label design. Cognitive functions were examined both when patients were drug-naïve, and after 13 weeks of treatment. A comprehensive neuropsychological battery was used in order to optimize construct validity, and principal components of cognitive functions were extrapolated in order to reduce type I errors. A healthy control group was tested at baseline and after 13 weeks, in order to examine retest effects. The cognitive domains studied were executive functions, selective attention, and reaction time. Results: The patients showed considerable cognitive deficits when drug-naïve. There were few differential effects of risperidone and zuclopenthixol on cognitive deficits, except for a differential significance, respectively, tendency towards improved reaction and movement times in the risperidone group, and a lack of such in the zuclopenthixol group. These differences were no longer significant after covarying for extrapyramidal side effects and anticholinergic medication that were more prevalent in the zuclopenthixol group and the increases after medication were comparable with retest effects in controls. Conclusion: The study underscores the importance of examining impact of factors, such as clinical improvement, extrapyramidal side effects, anticholinergic medication and retest effects in longitudinal efficacy studies. This study does not support efficacy of either risperidone or zuclopenthixol on cognitive functions in drug-naïve schizophrenia patients after 3 months of medication, because neither could be distinguished from retest effects of the healthy control group.
    Type of Medium: Online Resource
    ISSN: 1092-8529 , 2165-6509
    URL: Article
    DOI: 10.1017/S1092852900009354
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2004
    detail.hit.zdb_id: 2149753-9
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  • 2
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    Treatment response after 6 and 26 weeks is related to baseline glutamate and GABA levels in antipsychotic-naïve patients with psychosis
    Cambridge University Press (CUP) ; 2020
    In:  Psychological Medicine Vol. 50, No. 13 ( 2020-10), p. 2182-2193
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    In: Psychological Medicine, Cambridge University Press (CUP), Vol. 50, No. 13 ( 2020-10), p. 2182-2193
    Abstract: Poor response to dopaminergic antipsychotics constitutes a major challenge in the treatment of psychotic disorders and markers for non-response during first-episode are warranted. Previous studies have found increased levels of glutamate and γ -aminobutyric acid (GABA) in non-responding first-episode patients compared to responders, but it is unknown if non-responders can be identified using reference levels from healthy controls (HCs). Methods Thirty-nine antipsychotic-naïve patients with first-episode psychosis and 36 matched HCs underwent repeated assessments with the Positive and Negative Syndrome Scale and 3T magnetic resonance spectroscopy. Glutamate scaled to total creatine (/Cr) was measured in the anterior cingulate cortex (ACC) and left thalamus, and levels of GABA/Cr were measured in ACC. After 6 weeks, we re-examined 32 patients on aripiprazole monotherapy and 35 HCs, and after 26 weeks we re-examined 30 patients on naturalistic antipsychotic treatment and 32 HCs. The Andreasen criteria defined non-response. Results Before treatment, thalamic glutamate/Cr was higher in the whole group of patients but levels normalized after treatment. ACC levels of glutamate/Cr and GABA/Cr were lower at all assessments and unaffected by treatment. When compared with HCs, non-responders at week 6 (19 patients) and week 26 (16 patients) had higher baseline glutamate/Cr in the thalamus. Moreover, non-responders at 26 weeks had lower baseline GABA/Cr in ACC. Baseline levels in responders and HCs did not differ. Conclusion Glutamatergic and GABAergic abnormalities in antipsychotic-naïve patients appear driven by non-responders to antipsychotic treatment. If replicated, normative reference levels for glutamate and GABA may aid estimation of clinical prognosis in first-episode psychosis patients.
    Type of Medium: Online Resource
    ISSN: 0033-2917 , 1469-8978
    URL: Article
    DOI: 10.1017/S0033291719002277
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    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1470300-2
    SSG: 5,2
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  • 3
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    Cerebral blood flow in striatum is increased by partial dopamine agonism in initially antipsychotic-naïve patients with psychosis
    Cambridge University Press (CUP) ; 2023
    In:  Psychological Medicine
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    In: Psychological Medicine, Cambridge University Press (CUP)
    Abstract: Resting cerebral blood flow (rCBF) in striatum and thalamus is increased in medicated patients with psychosis, but whether this is caused by treatment or illness pathology is unclear. Specifically, effects of partial dopamine agonism, sex, and clinical correlates on rCBF are sparsely investigated. We therefore assessed rCBF in antipsychotic-naïve psychosis patients before and after aripiprazole monotherapy and related findings to sex and symptom improvement. Methods We assessed rCBF with the pseudo-Continuous Arterial Spin Labeling (PCASL) sequence in 49 first-episode patients (22.6 ± 5.2 years, 58% females) and 50 healthy controls (HCs) (22.3 ± 4.4 years, 63% females) at baseline and in 29 patients and 49 HCs after six weeks. RCBF in striatum and thalamus was estimated with a region-of-interest (ROI) approach. Psychopathology was assessed with the positive and negative syndrome scale. Results Baseline rCBF in striatum and thalamus was not altered in the combined patient group compared with HCs, but female patients had lower striatal rCBF compared with male patients ( p = 0.009). Treatment with a partial dopamine agonist increased rCBF significantly in striatum ( p = 0.006) in the whole patient group, but not significantly in thalamus. Baseline rCBF in nucleus accumbens was negatively associated with improvement in positive symptoms ( p = 0.046), but baseline perfusion in whole striatum and thalamus was not related to treatment outcome. Conclusions The findings suggest that striatal perfusion is increased by partial dopamine agonism and decreased in female patients prior to first treatment. This underlines the importance of treatment effects and sex differences when investigating the neurobiology of psychosis.
    Type of Medium: Online Resource
    ISSN: 0033-2917 , 1469-8978
    URL: Article
    DOI: 10.1017/S0033291723000144
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    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2023
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  • 4
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    Cortical structures and their clinical correlates in antipsychotic-naïve schizophrenia patients before and after 6 weeks of dopamine D 2/3 receptor antagonist treatment
    Cambridge University Press (CUP) ; 2019
    In:  Psychological Medicine Vol. 49, No. 5 ( 2019-04), p. 754-763
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    In: Psychological Medicine, Cambridge University Press (CUP), Vol. 49, No. 5 ( 2019-04), p. 754-763
    Abstract: Schizophrenia has been associated with changes in both cortical thickness and surface area, but antipsychotic exposure, illness progression and substance use may confound observations. In antipsychotic-naïve schizophrenia patients, we investigated cortical thickness and surface area as well as mean curvature before and after monotherapy with amisulpride, a relatively selective dopamine D 2/3 receptor antagonist. Methods Fifty-six patients and 59 matched healthy controls (HCs) underwent T1-weighted 3T magnetic resonance imaging. Forty-one patients and 51 HCs were re-scanned. FreeSurfer-processed baseline, follow-up values and symmetrized percentage changes (SPC) in cortical structures were analysed using univariate analysis of variance. Clinical measures comprised psychopathology ratings, assessment of functioning and tests of premorbid and current intelligence. We applied false discovery rate correction to account for multiple comparisons. Results At baseline, groups did not differ in cortical thickness or surface area; however, curvature in the left hemisphere was higher in patients ( p = 0.015). In both patients and HCs, higher curvature was associated with lower premorbid ( p = 0.009) and current intelligence ( p 〈 0.001). Lower surface area was associated with lower premorbid intelligence ( p = 0.017). After 6 weeks, the cortical structures did not differ between groups. Amisulpride dose (275.0 mg/day) did not correlate with any cortical structures ( p 〉 0.43). Cortical thickness SPC was negatively associated with symptom improvement ( p = 0.002). Conclusions Schizophrenia appears associated with subtle, yet clinically relevant aberrations in cortical structures. Mean curvature holds promise as a sensitive supplement to cortical thickness and surface area to detect complex structural brain abnormalities.
    Type of Medium: Online Resource
    ISSN: 0033-2917 , 1469-8978
    URL: Article
    DOI: 10.1017/S0033291718001198
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    XA 10000
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2019
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  • 5
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    Associations between P3a and P3b amplitudes and cognition in antipsychotic-naïve first-episode schizophrenia patients
    Cambridge University Press (CUP) ; 2019
    In:  Psychological Medicine Vol. 49, No. 5 ( 2019-04), p. 868-875
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    In: Psychological Medicine, Cambridge University Press (CUP), Vol. 49, No. 5 ( 2019-04), p. 868-875
    Abstract: Cognitive deficits are already present in early stages of schizophrenia. P3a and P3b event-related potentials (ERPs) are believed to underlie the processes of attention and working memory (WM), yet limited research has been performed on the associations between these parameters. Therefore, we explored possible associations between P3a/b amplitudes and cognition in a large cohort of antipsychotic-naïve, first-episode schizophrenia (AN-FES) patients and healthy controls (HC). Methods Seventy-three AN-FES patients and 93 age- and gender-matched HC were assessed for their P3a/b amplitude with an auditory oddball paradigm. In addition, subjects performed several subtests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Results AN-FES patients had significantly reduced P3a/b amplitudes, as well as significantly lower scores on all cognitive tests compared with HC. Total group correlations revealed positive associations between P3b amplitude and WM and sustained attention and negative associations with all reaction time measures. These associations appeared mainly driven by AN-FES patients, where we found a similar pattern. No significant associations were found between P3b amplitude and cognitive measures in our HC. P3a amplitude did not correlate significantly with any cognitive measures in either group, nor when combined. Conclusions Our results provide further evidence for P3a/b amplitude deficits and cognitive deficits in AN-FES patients, which are neither due to antipsychotics nor to disease progress. Furthermore, our data showed significant, yet weak associations between P3b and cognition. Therefore, our data do not supply evidence for deficient P3a/b amplitudes as direct underlying factors for cognitive deficits in schizophrenia.
    Type of Medium: Online Resource
    ISSN: 0033-2917 , 1469-8978
    URL: Article
    DOI: 10.1017/S0033291718001575
    RVK:
    XA 10000
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2019
    detail.hit.zdb_id: 1470300-2
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  • 6
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    Effects of methylphenidate on mismatch negativity and P3a amplitude of initially psychostimulant-naïve, adult ADHD patients
    Cambridge University Press (CUP) ; 2023
    In:  Psychological Medicine Vol. 53, No. 3 ( 2023-02), p. 957-965
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    In: Psychological Medicine, Cambridge University Press (CUP), Vol. 53, No. 3 ( 2023-02), p. 957-965
    Abstract: Deficient information processing in ADHD theoretically results in sensory overload and may underlie the symptoms of the disorder. Mismatch negativity (MMN) and P3a amplitude reflect an individual's detection and subsequent change in attention to stimulus change in their environment. Our primary aim was to explore MMN and P3a amplitude in adult ADHD patients and to examine the effects of methylphenidate (MPH) on these measures. Methods Forty initially psychostimulant-naïve, adult ADHD patients without comorbid ASD and 42 matched healthy controls (HC) were assessed with an MMN paradigm at baseline. Both groups were retested after 6 weeks, in which patients were treated with MPH. Results Neither significant group differences in MMN nor P3a amplitude were found at baseline. Although 6-week MPH treatment significantly reduced symptomatology and improved daily functioning of the patients, it did not significantly affect MMN amplitude; however, it did significantly reduce P3a amplitude compared to the HC. Furthermore, more severe ADHD symptoms were significantly associated with larger MMN amplitudes in the patients, both at baseline and follow-up. Conclusion We found no evidence for early information processing deficits in patients with ADHD, as measured with MMN and P3a amplitude. Six-week treatment with MPH decreased P3a but not MMN amplitude, although more severe ADHD-symptoms were associated with larger MMN amplitudes in the patients. Given that P3a amplitude represents an important attentional process and that glutamate has been linked to both ADHD and MMN amplitude, future research should investigate augmenting MPH treatment of less responsive adults with ADHD with glutamatergic antagonists.
    Type of Medium: Online Resource
    ISSN: 0033-2917 , 1469-8978
    URL: Article
    DOI: 10.1017/S0033291721002373
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    XA 10000
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2023
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  • 7
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    Startle habituation, sensory, and sensorimotor gating in trauma-affected refugees with posttraumatic stress disorder
    Cambridge University Press (CUP) ; 2019
    In:  Psychological Medicine Vol. 49, No. 4 ( 2019-03), p. 581-589
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    In: Psychological Medicine, Cambridge University Press (CUP), Vol. 49, No. 4 ( 2019-03), p. 581-589
    Abstract: Impairments in mechanisms underlying early information processing have been reported in posttraumatic stress disorder (PTSD); however, findings in the existing literature are inconsistent. This current study capitalizes on technological advancements of research on electroencephalographic event-related potential and applies it to a novel PTSD population consisting of trauma-affected refugees. Methods A total of 25 trauma-affected refugees with PTSD and 20 healthy refugee controls matched on age, gender, and country of origin completed the study. In two distinct auditory paradigms sensory gating, indexed as P50 suppression, and sensorimotor gating, indexed as prepulse inhibition (PPI), startle reactivity, and habituation of the eye-blink startle response were examined. Within the P50 paradigm, N100 and P200 amplitudes were also assessed. In addition, correlations between psychophysiological and clinical measures were investigated. Results PTSD patients demonstrated significantly elevated stimuli responses across the two paradigms, reflected in both increased amplitude of the eye-blink startle response, and increased N100 and P200 amplitudes relative to healthy refugee controls. We found a trend toward reduced habituation in the patients, while the groups did not differ in PPI and P50 suppression. Among correlations, we found that eye-blink startle responses were associated with higher overall illness severity and lower levels of functioning. Conclusions Fundamental gating mechanisms appeared intact, while the pattern of deficits in trauma-affected refugees with PTSD point toward a different form of sensory overload, an overall neural hypersensitivity and disrupted the ability to down-regulate stimuli responses. This study represents an initial step toward elucidating sensory processing deficits in a PTSD subgroup.
    Type of Medium: Online Resource
    ISSN: 0033-2917 , 1469-8978
    URL: Article
    DOI: 10.1017/S003329171800123X
    RVK:
    XA 10000
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2019
    detail.hit.zdb_id: 1470300-2
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  • 8
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    Differential effects of age at illness onset on verbal memory functions in antipsychotic-naïve schizophrenia patients aged 12–43 years
    Cambridge University Press (CUP) ; 2021
    In:  Psychological Medicine Vol. 51, No. 9 ( 2021-07), p. 1570-1580
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    In: Psychological Medicine, Cambridge University Press (CUP), Vol. 51, No. 9 ( 2021-07), p. 1570-1580
    Abstract: The typical onset of schizophrenia coincides with the maturational peak in cognition; however, for a significant proportion of patients the onset is before age 18 and after age 30 years. While cognitive deficits are considered core features of schizophrenia, few studies have directly examined the impact of age of illness onset on cognition. Methods The aim of the study was to examine if the effects of age on cognition differ between healthy controls (HCs) and patients with schizophrenia at illness onset. We examined 156 first-episode antipsychotic-naïve patients across a wide age span (12–43 years), and 161 age- and sex-matched HCs. Diagnoses were made according to ICD-10 criteria. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS), and IQ was estimated using subtests from the Wechsler adult- or child-intelligence scales. Multivariate analysis of covariance (MANCOVA) was used to examine linear and quadratic effects of age on cognitive scores and interactions by group, including sex and parental socioeconomic status as covariates. Results There was a significant overall effect of age on BACS and IQ ( p 〈 0.001). Significant group-by-age interactions for verbal memory (for age-squared, p = 0.009), and digit sequencing (for age, p = 0.01; age-squared, p 〈 0.001), indicated differential age-related trajectories between patients and HCs. Conclusions Cognitive functions showing protracted maturation into adulthood, such as verbal memory and verbal working memory, may be particularly impaired in both early- and late-schizophrenia onset. Our findings indicate a potential interaction between the timing of neurodevelopmental maturation and a possible premature age effect in late-onset schizophrenia.
    Type of Medium: Online Resource
    ISSN: 0033-2917 , 1469-8978
    URL: Article
    DOI: 10.1017/S0033291720000409
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    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2021
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  • 9
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    Visual attention in adults with attention-deficit/hyperactivity disorder before and after stimulant treatment
    Cambridge University Press (CUP) ; 2019
    In:  Psychological Medicine Vol. 49, No. 15 ( 2019-11), p. 2617-2625
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    In: Psychological Medicine, Cambridge University Press (CUP), Vol. 49, No. 15 ( 2019-11), p. 2617-2625
    Abstract: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder which frequently persists into adulthood. The primary goal of the current study was to (a) investigate attentional functions of stimulant medication-naïve adults with ADHD, and (b) investigate the effects of 6 weeks of methylphenidate treatment on these functions. Methods The study was a prospective, non-randomized, non-blinded, 6-week follow-up design with 42 stimulant medication-naïve adult patients with ADHD, and 42 age and parental education-matched healthy controls. Assessments included measures of visual attention, based on Bundesen's Theory of Visual Attention (TVA), which yields five precise measures of aspects of visual attention; general psychopathology; ADHD symptoms; dyslexia screening; and estimates of IQ. Results At baseline, significant differences were found between patients and controls on three attentional parameters: visual short-term memory capacity, threshold of conscious perception, and to a lesser extent visual processing speed. Secondary analyses revealed no significant correlations between TVA parameter estimates and severity of ADHD symptomatology. At follow-up, significant improvements were found specifically for visual processing speed; this improvement had a large effect size, and remained when controlling for re-test effects, IQ, and dyslexia screen performance. There were no significant correlations between changes in visual processing speed and changes in ADHD symptomatology. Conclusions ADHD in adults may be associated with deficits in three distinct aspects of visual attention. Improvements after 6 weeks of medication are seen specifically in visual processing speed, which could represent an improvement in alertness. Clinical symptoms and visual attentional deficits may represent separate aspects of ADHD in adults.
    Type of Medium: Online Resource
    ISSN: 0033-2917 , 1469-8978
    URL: Article
    DOI: 10.1017/S0033291718003628
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    XA 10000
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2019
    detail.hit.zdb_id: 1470300-2
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  • 10
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    Accuracy of diagnostic classification algorithms using cognitive-, electrophysiological-, and neuroanatomical data in antipsychotic-naïve schizophrenia patients
    Cambridge University Press (CUP) ; 2019
    In:  Psychological Medicine Vol. 49, No. 16 ( 2019-12), p. 2754-2763
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    In: Psychological Medicine, Cambridge University Press (CUP), Vol. 49, No. 16 ( 2019-12), p. 2754-2763
    Abstract: A wealth of clinical studies have identified objective biomarkers, which separate schizophrenia patients from healthy controls on a group level, but current diagnostic systems solely include clinical symptoms. In this study, we investigate if machine learning algorithms on multimodal data can serve as a framework for clinical translation. Methods Forty-six antipsychotic-naïve, first-episode schizophrenia patients and 58 controls underwent neurocognitive tests, electrophysiology, and magnetic resonance imaging (MRI). Patients underwent clinical assessments before and after 6 weeks of antipsychotic monotherapy with amisulpride. Nine configurations of different supervised machine learning algorithms were applied to first estimate the unimodal diagnostic accuracy, and next to estimate the multimodal diagnostic accuracy. Finally, we explored the predictability of symptom remission. Results Cognitive data significantly classified patients from controls (accuracies = 60–69%; p values = 0.0001–0.009). Accuracies of electrophysiology, structural MRI, and diffusion tensor imaging did not exceed chance level. Multimodal analyses with cognition plus any combination of one or more of the remaining three modalities did not outperform cognition alone. None of the modalities predicted symptom remission. Conclusions In this multivariate and multimodal study in antipsychotic-naïve patients, only cognition significantly discriminated patients from controls, and no modality appeared to predict short-term symptom remission. Overall, these findings add to the increasing call for cognition to be included in the definition of schizophrenia. To bring about the full potential of machine learning algorithms in first-episode, antipsychotic-naïve schizophrenia patients, careful a priori variable selection based on independent data as well as inclusion of other modalities may be required.
    Type of Medium: Online Resource
    ISSN: 0033-2917 , 1469-8978
    URL: Article
    DOI: 10.1017/S0033291718003781
    RVK:
    XA 10000
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2019
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    SSG: 5,2
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