The use of deep brain stimulation (DBS) in treatment resistant patients with schizophrenia is of considerable current interest, but where to site the electrodes is challenging. This article reviews ...rationales for electrode placement in schizophrenia based on evidence for localized brain abnormality in the disorder and the targets that have been proposed and employed to date. The nucleus accumbens and the subgenual anterior cingulate cortex are of interest on the grounds that they are sites of potential pathologically increased brain activity in schizophrenia and so susceptible to the local inhibitory effects of DBS; both sites have been employed in trials of DBS in schizophrenia. Based on other lines of reasoning, the ventral tegmental area, the substantia nigra pars reticulata and the habenula have also been proposed and in some cases employed. The dorsolateral prefrontal cortex has not been suggested, probably reflecting evidence that it is underactive rather than overactive in schizophrenia. The hippocampus is also of theoretical interest but there is no clear functional imaging evidence that it shows overactivity in schizophrenia. On current evidence, the nucleus accumbens may represent the strongest candidate for DBS electrode placement in schizophrenia, with the substantia nigra pars reticulata also showing promise in a single case report; the ventral tegmental area is also of potential interest, though it remains untried.
•Use of deep brain stimulation (DBS) is a focus of interest in schizophrenia.•Where to place the electrodes, however, is challenging.•Rationales have been developed for subcortical and one cortical placement.•Some of these have been targeted, but numbers are small (N = 1–4).•Results to date have been mixed but are overall encouraging.
Abstract Background The extent to which socio-demographic, clinical, and premorbid adjustment variables contribute to cognitive deficits in first-episode schizophrenia spectrum disorders remains to ...be ascertained. Aims To examine the pattern and magnitude of cognitive impairment in first-episode psychosis patients, the profile of impairment across psychosis subtypes and the associations with premorbid adjustment. Methods 226 first-episode psychosis patients and 225 healthy controls were assessed in the PEPsCog study, as part of the PEPs study. Results Patients showed slight to moderate cognitive impairment, verbal memory being the domain most impaired compared to controls. Broad affective spectrum patients had better premorbid IQ and outperformed the schizophrenia and other psychosis groups in executive function, and had better global cognitive function than the schizophrenia group. Adolescent premorbid adjustment together with age, gender, parental socio-economic status, and mean daily antipsychotic doses were the factors that best explained patients' cognitive performance. General and adolescent premorbid adjustment, age and parental socio-economic status were the best predictors of cognitive performance in controls. Conclusions Poorer premorbid adjustment together with socio-demographic factors and higher daily antipsychotic doses were related to a generalized cognitive impairment and to a lower premorbid intellectual reserve, suggesting that neurodevelopmental impairment was present before illness onset.
Up to 30% of patients with schizophrenia are resistant to antipsychotic drug treatment, with 60% of such cases also failing to respond to clozapine. Deep brain stimulation (DBS) has been used in ...treatment resistant patients with other psychiatric disorders, but there is a lack of trials in schizophrenia, partly due to uncertainties over where to site the electrodes. This trial aimed to examine the effectiveness of nucleus accumbens (NAcc) and subgenual anterior cingulate cortex (subgenual ACC) targeted DBS; the primary outcome measure was PANSS total score, as assessed fortnightly.
Eight patients with schizophrenia, who met criteria for treatment resistance and were also resistant to/intolerant of clozapine, were randomly assigned using central allocation to receive DBS in the NAcc or subgenual ACC. An open stabilization phase lasting at least six months was followed by a randomized double-blind crossover phase lasting 24 weeks in those who met symptomatic improvement criteria. The primary end-point was a 25% improvement in PANSS total score. (ClinicalTrials.gov Identifier: NCT02377505; trial completed).
One implanted patient did not receive DBS due to complications of surgery. Of the remaining 7 patients, 2/3 with NAcc and 2/4 with subgenual ACC electrode placements met the symptomatic improvement criteria (58% and 86%, and 37% and 68% improvement in PANSS total score, respectively). Three of these patients entered the crossover phase and all showed worsening when the stimulation was discontinued. The fourth patient worsened after the current was switched off accidentally without her or the investigators’ knowledge. Physical adverse events were uncommon, but two patients developed persistent psychiatric adverse effects (negative symptoms/apathy and mood instability, respectively).
These preliminary findings point to the possibility of DBS having therapeutic effects in patients with schizophrenia who do not respond to any other treatment. Larger trials with careful attention to blinding will be necessary to establish the extent of the benefits and whether these can be achieved without psychiatric side-effects.
•Analysis of structural MRI images using a probabilistic atlas for segmentation of several nuclei of the thalamus.•Comparison of chronic patients with schizophrenia, with and without auditory ...hallucinations and matched healthy controls.•Volumetric reductions in patients with AH vs controls: Medial geniculate nucleus, anterior pulvinar nucleus and lateral and medial mediodorsal nuclei.•In patients without AH we found reductions in the volume of the pulvinar and mediodorsal nuclei, but not in the medial geniculate nucleus.•Found also some significant correlations between the volume of these nuclei and the total score of the PSYRATS scale.
The thalamus is a subcortical structure formed by different nuclei that relay information to the neocortex. Several reports have already described alterations of this structure in patients of schizophrenia that experience auditory hallucinations. However, to date no study has addressed whether the volumes of specific thalamic nuclei are altered in chronic patients experiencing persistent auditory hallucinations. We have processed structural MRI images using Freesurfer, and have segmented them into 25 nuclei using the probabilistic atlas developed by Iglesias and collaborators (Iglesias et al., 2018). To homogenize the sample, we have matched patients of schizophrenia, with and without persistent auditory hallucinations, with control subjects, considering sex, age and their estimated intracranial volume. This rendered a group number of 41 patients experiencing persistent auditory hallucinations, 35 patients without auditory hallucinations, and 55 healthy controls. In addition, we have also correlated the volume of the altered thalamic nuclei with the total score of the PSYRATS, a clinical scale used to evaluate the positive symptoms of this disorder. We have found alterations in the volume of 8 thalamic nuclei in both cohorts of patients with schizophrenia: The medial and lateral geniculate nuclei, the anterior, inferior, and lateral pulvinar nuclei, the lateral complex and the lateral and medial mediodorsal nuclei. We have also found some significant correlations between the volume of these nuclei in patients experiencing auditory hallucinations, and the total score of the PSYRATS scale. Altogether our results indicate that volumetric alterations of thalamic nuclei involved in audition may be related to persistent auditory hallucinations in chronic schizophrenia patients, whereas alterations in nuclei related to association cortices are evident in all patients. Future studies should explore whether the structural alterations are cause or consequence of these positive symptoms and whether they are already present in first episodes of psychosis.
First episode of psychosis (FEP) patients display a wide variety of metabolic disturbances at onset, which might underlie these patients' increased morbidity and early mortality. Glycemic ...abnormalities have been previously related to pharmacological agents; however, recent research highlights the impact of early life events. Birth weight (BW), an indirect marker of the fetal environment, has been related to glucose abnormalities in the general population over time. We aim to evaluate if BW correlates with glucose values in a sample of FEP patients treated with different antipsychotics. Two hundred and thirty-six patients were included and evaluated for clinical and metabolic variables at baseline and at 2, 6, 12, and 24 months of follow-up. Pearson correlations and linear mixed model analysis were conducted to analyze the data. Antipsychotic treatment was grouped due to its metabolic risk profile. In our sample of FEP patients, BW was negatively correlated with glucose values at 24 months of follow-up r=-0.167, p=0.037. BW showed a trend towards significance in the association with glucose values over the 24-month period (F=3.22; p=0.073) despite other confounders such as age, time, sex, body mass index, antipsychotic type, and chlorpromazine dosage. This finding suggests that BW is involved in the evolution of glucose values over time in a cohort of patients with an FEP, independently of the type of pharmacological agent used in treatment. Our results highlight the importance of early life events in the later metabolic outcome of patients.
Although previous imaging studies in borderline personality disorder (BPD) have found brain abnormalities, the results have been inconsistent. This study aimed to investigate structural brain ...abnormalities using voxel-based morphometry (VBM) and cortical thickness (Cth) analyses in a large sample of patients with BPD. Additionally, we aimed to determine the correlation between structural abnormalities and clinical severity and to assess its potential value at predicting psychotherapeutic response. Sixty-one individuals with BPD and 19 healthy controls underwent magnetic resonance imaging. Participants with BPD completed several self-report clinical scales, received dialectical-behavioral therapy skills training and post-therapy changes in clinical scores were also recorded. Gray matter volume (GMV) and Cth differences between groups were compared. Within the BPD group, we further characterized the structural brain correlates of clinical severity and investigated the relationship between pre-therapy structural abnormalities and therapeutic response. As potential confounders we included age, sex, educational level, and total intracranial volume (the latter only in VBM analyses). Compared to controls, the BPD group showed a reduced GMV/Cth in prefrontal areas but increased GMV in the limbic structures (amygdala and parahippocampal regions). Prefrontal abnormalities correlated with higher baseline scores on impulsivity and general BPD severity. Increased GMV in the parahippocampal area correlated with a greater emotion dysregulation. Importantly, several baseline structural abnormalities correlated with worse response to psychotherapy. Patients with BPD showed a reduced GMV in the prefrontal areas but a greater GMV in the limbic structures. Several structural abnormalities (i.e. middle and inferior prefrontal areas, anterior insula, or parahippocampal area) correlated with clinical severity and could potentially be used as imaging biological correlates biomarkers to predict psychotherapy response.
Background:
Traumatic life events (TLEs) are one of the most robust environmental risk factors for the onset of first-episode psychosis (FEP).
Aims:
To explore TLEs in FEP patients and healthy ...controls (HC), to analyze gender differences and to examine whether TLEs were associated with sociodemographic, clinical and psychofunctional variables in all FEP sample and split by age.
Methods:
Descriptive and cross-sectional study. Three hundred and thirty-five FEP and 253 HC were recruited at 16 Spanish mental health research centers. The Traumatic Experiences in Psychiatric Outpatients Questionnaire was administered.
Results:
We found a higher number of TLEs in FEP than in HC, and the proportion of individuals with three or more TLEs was significantly higher in the FEP group. No differences were found in terms of gender and age. There was no relationship between total number of TLEs and psychotic symptomatology and functional outcomes.
Conclusions:
The number and cumulative TLEs should be taken into account in the detection, epidemiology and process of recovery in FEP.
Background:
Hyperprolactinemia is a common side-effect of antipsychotics (APs), which may trigger serious secondary problems and compromise the adherence to treatment which is crucial for prognosis, ...especially in patients presenting with a first-episode of psychosis (FEP).
Aims:
We evaluated, in some cases for the first time, the effect of polymorphisms in multiple candidate genes on serum prolactin (PRL) levels in an AP-treated FEP cohort recruited in the multicenter PEPs study (Phenotype − genotype and environmental interaction; Application of a predictive model in first psychotic episodes).
Methods:
PRL concentration was measured in serum from 222 patients. A total of 167 polymorphisms were selected in 23 genes. Genetic association analysis was performed in the whole sample and also in homogenous subgroups of patients treated with APs with a high (N = 101) or low risk (N = 95) of increasing PRL release, which showed significant differences in their PRL levels.
Results:
After Bonferroni correction, polymorphisms in NTRK2, DRD2 and ACE genes were associated with PRL concentration.
Conclusion:
Our results give more support to the impact of DRD2, but also of other genes related to dopamine availability such as ACE. Moreover, this study provides the first evidence for the involvement of NTRK2, which suggests that pathways other than the ones related to dopamine or serotonin may participate in the AP-related PRL levels.
PDF
