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.
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).
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.
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.
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.
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.
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.
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.
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.
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).
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).
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.
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.
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 D2/3 receptor antagonist.
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.
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).
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.
Email your librarian or administrator to recommend adding this to your organisation's collection.