Cognitive remediation therapy modulates intrinsic neural activity in patients with major depression.

BACKGROUND: Cognitive impairment is a core feature of major depressive disorder (MDD). Cognitive remediation may improve cognition in MDD, yet so far, the underlying neural mechanisms are unclear. This study investigated changes in intrinsic neural activity in MDD after a cognitive remediation trial. METHODS: In a longitudinal design, 20 patients with MDD and pronounced cognitive deficits and 18 healthy controls (HC) were examined using resting-state functional magnetic resonance imaging. MDD patients received structured cognitive remediation therapy (CRT) over 5 weeks. The whole-brain fractional amplitude of low-frequency fluctuations was computed before the first and after the last training session. Univariate methods were used to address regionally-specific effects, and a multivariate data analysis strategy was employed to investigate functional network strength (FNS). RESULTS: MDD patients significantly improved in cognitive function after CRT. Baseline comparisons revealed increased right caudate activity and reduced activity in the left frontal cortex, parietal lobule, insula, and precuneus in MDD compared to HC. In patients, reduced FNS was found in a bilateral prefrontal system at baseline (p < 0.05, uncorrected). In MDD, intrinsic neural activity increased in right inferior frontal gyrus after CRT (p < 0.05, small volume corrected). Left inferior parietal lobule, left insula, left precuneus, and right caudate activity showed associations with cognitive improvement (p < 0.05, uncorrected). Prefrontal network strength increased in patients after CRT, but this increase was not associated with improved cognitive performance. CONCLUSIONS: Our findings support the role of intrinsic neural activity of the prefrontal cortex as a possible mediator of cognitive improvement following CRT in MDD.

Abnormal Cerebellar Volume in Patients with Remitted Major Depression with Persistent Cognitive Deficits.

Cerebellar involvement in major depressive disorder (MDD) has been demonstrated by a growing number of studies, but it is unknown whether cognitive functioning in depressed individuals is related to cerebellar gray matter volume (GMV) abnormalities. Impaired attention and executive dysfunction are characteristic cognitive deficits in MDD, and critically, they often persist despite remission of mood symptoms. In this study, we investigated cerebellar GMV in patients with remitted MDD (rMDD) that showed persistent cognitive impairment. We applied cerebellum-optimized voxel-based morphometry in 37 patients with rMDD and with cognitive deficits, in 12 patients with rMDD and without cognitive deficits, and in 36 healthy controls (HC). Compared with HC, rMDD patients with cognitive deficits had lower GMV in left area VIIA, crus II, and in vermal area VIIB. In patients with rMDD, regression analyses demonstrated significant associations between GMV reductions in both regions and impaired attention and executive dysfunction. Compared with HC, patients without cognitive deficits showed increased GMV in bilateral area VIIIB. This study supports cerebellar contributions to the cognitive dimension of MDD. The data also point towards cerebellar area VII as a potential target for non-invasive brain stimulation to treat cognitive deficits related to MDD.

Cognitive Impairment Along the Course of Depression: Non-Pharmacological Treatment Options.

Major Depressive Disorder (MDD) is one of the most common psychiatric disorders, with a large global impact on both the individual and the society. In this narrative review, we summarize neurocognitive deficits during acute and (partially) remitted states of depression. Furthermore, we outline the potential negative effect of cognitive impairment (CI) on functional recovery, and discuss the role of several variables in the development of CI for MDD patients. Though there is cumulating evidence regarding persistent CI in unipolar depression, research on treatment options specific for this patient group is still scarce. Hence the central aim of our review is to present non-pharmacological interventions, which are thought to reduce CI in affected MDD patients. We discuss cognitive remediation therapy (CRT), physical exercise, yoga, mindfulness-based therapy, and modern neuromodulation approaches like neurostimulation and neurofeedback training. In conclusion, we propose future directions for research on CI in depression. Looking further ahead, we suggest creative interventional designs that include a direct comparison of different non-pharmacological treatment approaches on neurocognition and functional outcome of MDD. Furthermore, additive and synergistic effects of CRT with other treatment approaches should be examined and compared to create multimodal and even personalized intervention programs.

Reasoning in psychosis: risky but not necessarily hasty.

INTRODUCTION: A liberal acceptance (LA) threshold for hypotheses has been put forward to explain the well-replicated "jumping to conclusions" (JTC) bias in psychosis, particularly in patients with paranoid symptoms. According to this account, schizophrenia patients rest their decisions on lower subjective probability estimates. The initial formulation of the LA account also predicts an absence of the JTC bias under high task ambiguity (i.e., if more than one response option surpasses the subjective acceptance threshold). METHODS: Schizophrenia patients (n = 62) with current or former delusions and healthy controls (n = 30) were compared on six scenarios of a variant of the beads task paradigm. Decision-making was assessed under low and high task ambiguity. Along with decision judgments (optional), participants were required to provide probability estimates for each option in order to determine decision thresholds (i.e., the probability the individual deems sufficient for a decision). RESULTS: In line with the LA account, schizophrenia patients showed a lowered decision threshold compared to controls (82% vs. 93%) which predicted both more errors and less draws to decisions. Group differences on thresholds were comparable across conditions. At the same time, patients did not show hasty decision-making, reflecting overall lowered probability estimates in patients. CONCLUSIONS: Results confirm core predictions derived from the LA account. Our results may (partly) explain why hasty decision-making is sometimes aggravated and sometimes abolished in psychosis. The proneness to make risky decisions may contribute to the pathogenesis of psychosis. A revised LA account is put forward.

Predictors for improvement of problem-solving during cognitive remediation for patients with Schizophrenia.

Cognitive remediation is a promising pathway for ameliorating cognitive impairment of patients with schizophrenia. Here, we investigate predictors of improvement in problem-solving ability for two different types of cognitive remediation - specific problem-solving training and training of basic cognition. For this purpose we conducted a re-analysis of a randomized controlled trial comparing these two training approaches. The main outcome measure was improvement in problem-solving performance. Correlational analyses were used to assess the contribution of clinical, cognitive and training-related predictors. In the problem-solving training group, impaired pre-training planning ability was associated with stronger improvement. In contrast, in the basic cognition training group antipsychotic medication dose emerged as a negative predictor. These results demonstrate that predictors for successful cognitive remediation depend on the specific intervention. Furthermore, our results suggest that at least in the planning domain patients with impaired performance benefit particularly from a specific intervention.

What do the teachers want? A targeted needs assessment survey for prospective didactic training of psychiatry medical educators.

Objectives: Physicians and psychologists at psychiatric university hospitals are assigned teaching tasks from the first day of work without necessarily having the prerequisite training in teaching methods. This exploratory survey provides a needs-based analysis for the prospective didactic training of physicians and psychologists at psychiatric hospitals in Germany, Austria and Switzerland. Methods: An online questionnaire was distributed at medical schools via email in German-speaking countries in Europe. All physicians involved in teaching medical students at psychiatry faculties were eligible to participate in the survey. Participants were further requested to recruit eligible participants (snowball sampling). Responses were analyzed descriptively, and differences between groups were calculated using nonparametric Mann-Whitney U tests (p<.05). Results: Overall, 97 respondents (male=55, female=42; mean age= 40.6) from 19 medical schools completed the survey. The respondents consisted of 43 residents, 39 specialists, 6 chief physicians and 9 psychologists. Of the respondents, 97.6% rated didactic competence as either highly relevant or rather relevant for teaching medical students. The highest overall interest was shown for bedside teaching (mode=4; IQR: 2-4) and error culture (mode=3; IQR: 2-4). Respondents expressed the highest training needs for topics regarding presentation and communication (mode=3; IQR: 2-3). Resident physicians were significantly more interested in bedside teaching (U=362.0, p=0.004) and roleplay (U=425.0; p=0.036) than specialist physicians, who were more interested in examination didactics (U=415.0; p=0.022). Chief physicians displayed significantly deeper interest in group dynamics (U=51; p=0.023) than specialist physicians. In-person training was preferred by a majority of respondents, and 27.4% preferred online/web-based training. Conclusions: The majority of physicians and psychologists at psychiatric university hospitals considered professional development for faculty to be helpful for teaching medical students. Bedside teaching and error culture management were the most desired teaching topics for training medical teachers. Tailored educational interventions are recommended, with target-oriented priorities for different hierarchical levels.

Exercise elevates serum brain-derived neurotrophic factor in partially remitted depression.

Brain-derived neurotrophic factor (BDNF) is a pleiotropic cytokine implicated in the pathogenesis of major depressive disorder (MDD). In MDD, serum BDNF levels are attenuated. Healthy adults show BDNF elevation after exercise. To investigate activity-dependent BDNF elevation in MDD, thirty-seven participants with partially remitted MDD were allocated to either a bout of strenuous or light activity. Serum was collected before and after the intervention. BDNF was measured using a highly sensitive and specific enzyme-linked immunosorbent assay. Significant BDNF elevation in the strenuous activity group emerged. This study confirms exercise-dependent serum BDNF elevation in MDD. Preregistration: German Clinical Trials Register (DRKS0001515).

"Don't give me that look" - overconfidence in false mental state perception in schizophrenia.

Dysfunctions in social cognition are implicated in the pathogenesis of schizophrenia and have been extensively replicated over the years. For memory research, the administration of cognitive tasks with metacognitive aspects like confidence ratings has deepened our insight into how impairments contribute to symptoms of the disorder. A total of 76 patients with schizophrenia or schizoaffective disorder and a sample of 30 healthy participants were tested with the Reading the Mind in the Eyes test (Eyes-test). The Eyes-test was complemented with a rating scale requesting response confidence and was administered along with paradigms tapping neuropsychological parameters and cognitive insight. Schizophrenia patients showed impaired abilities on mental state perception. In addition, they committed more high-confidence errors and at the same time made fewer high-confidence correct responses. Impairments were most pronounced in patients with formal thought disorder. The patients displayed a decreased metacognitive awareness for their deficits. The results suggest that adding confidence ratings to the investigation of social cognition promises to advance our understanding of social cognition in schizophrenia. Patients not only show severe impairments in social cognition, but are overconfident in their judgments and lack cognitive insight into their deficits. The results highlight the need for metacognitive therapeutic approaches for the treatment of this population.

Planning and problem-solving training for patients with schizophrenia: a randomized controlled trial.

BACKGROUND: The purpose of this study was to assess whether planning and problem-solving training is more effective in improving functional capacity in patients with schizophrenia than a training program addressing basic cognitive functions. METHODS: Eighty-nine patients with schizophrenia were randomly assigned either to a computer assisted training of planning and problem-solving or a training of basic cognition. Outcome variables included planning and problem-solving ability as well as functional capacity, which represents a proxy measure for functional outcome. RESULTS: Planning and problem-solving training improved one measure of planning and problem-solving more strongly than basic cognition training, while two other measures of planning did not show a differential effect. Participants in both groups improved over time in functional capacity. There was no differential effect of the interventions on functional capacity. CONCLUSION: A differential effect of targeting specific cognitive functions on functional capacity could not be established. Small differences on cognitive outcome variables indicate a potential for differential effects. This will have to be addressed in further research including longer treatment programs and other settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT00507988.

Context representation and thought disorder in schizophrenia.

BACKGROUND: Formal thought disorder (FTD) in schizophrenia is related to a disturbance in the representation of contextual information. This study aimed to assess the extent to which the 'context module' is disturbed in patients with schizophrenia. The context module is needed to mediate an appropriate behavioral response. It comprises 2 cognitive functions, namely working memory and behavioral inhibition, and is linked to networks in the prefrontal cortex. We compared patients with enhanced FTD (n = 15) to ones with low levels and a control group (n = 21, respectively). We hypothesized that FTD patients would have greater degradation of the context module by presenting both working memory and inhibition deficits, while in low FTD patients mild degradation of the context module would be present with working memory deficits only. METHODS: Using a within-subjects design, subjects underwent a battery of neuropsychological tests with different demands on the context module. We also divided patients according to first-episode versus chronic course. RESULTS: Our results confirmed our predictions on FTD. However, first-episode patients showed working memory deficits more than those with several episodes. CONCLUSION: We conclude that the context module is more degraded in FTD patients, although our results have to be interpreted with caution because of the small sample size.

Computer-Assisted Cognitive Remediation in Schizophrenia: Efficacy of an Individualized vs. Generic Exercise Plan.

Computer-assisted cognitive remediation (CACR) is an economical, adjustable, and effective treatment for individuals with schizophrenia. The current randomized controlled study examined whether an individualized or generic exercise plan in CACR is superior in patients with multiple cognitive deficits compared to treatment-as-usual (TAU). Fifty-nine inpatients diagnosed with schizophrenia were randomly assigned to 1) TAU, 2) TAU plus an individualized exercise plan in CACR, or 3) TAU plus a generic exercise plan in CACR. Neuropsychological performance, psychopathology, and functional outcome were assessed at baseline and post-treatment. The results show a medium to large training effect for all neuropsychological performance measures. Contrary to our expectations the neuropsychological improvement over time did not differ between groups. Self-reported depression, global level of functioning, and activity and participation functioning showed a significant improvement from baseline to post-treatment. However no further group, time, or interaction effects for other psychopathology and functional outcome could be demonstrated. Possible implications for clinical use of CACR and future studies are discussed.

Predictors of cognitive remediation therapy improvement in (partially) remitted unipolar depression.

BACKGROUND: There is urgent need for development and evaluation of targeted interventions for cognitive deficits in (partially) remitted major depression. Until now the analyses of the moderators of treatment efficacy were only examined in mixed samples of patients with schizophrenia, affective spectrum and schizoaffective disorders. Thus, the aim of our study was to evaluate the predictors of cognitive remediation therapy (CRT) improvement in a sample of (partially) remitted major depressive disorder patients. METHODS: Reliable Change Index with corrections for practice effects was calculated for each participant as an indicator for training improvement. Thirty eight patients, who were randomized within our previously conducted CRT clinical trial, were divided into "Improvers" and "Nonimprovers" in the attention domain, to compare them on sociodemographic, psychopathological, neurocognitive, psychosocial and training factors. RESULTS: We detected 13 training participants who improved reliably in the attention domain. Illness duration was the only factor which significantly differentiated between Improvers and Nonimprovers. No significant differences between Improvers and Nonimprovers in terms of other clinical variables, sociodemographic and neuropsychological factors were found. LIMITATIONS: Exploratory research results should be taken with caution. Focus on the attention domain could have led to a limited point of view. CONCLUSION: Our findings represent a first analysis of the predictors of cognitive remediation training improvement in (partially) remitted unipolar depression. Much more work should be done to refine cognitive treatment approaches. An initiation of cognitive training in early stages of the disease could be beneficial for the affected patients.

Cognitive remediation therapy for partially remitted unipolar depression: A single-blind randomized controlled trial.

BACKGROUND: There is an urgent need for the development and evaluation of targeted interventions for cognitive impairment (CI) in patients with (partially) remitted major depressive disorder (MDD). The aim of our study was therefore to evaluate the effect of cognitive remediation therapy (CRT) on cognitive and psychosocial functioning in a sample of patients with MDD, taking into account comorbidity, psychopathology, remission status and CI profile. Furthermore, we compared a generalized training (GT) with an individualized training (IT) approach regarding their effects on cognition. METHODS: Sixty-two MDD patients in partial remission with CI were randomly assigned to a control group (CG), IT or GT. Participants of GT trained six cognitive subdomains (divided attention, selective attention, alertness, working memory, planning and response inhibition), whereas participants of IT trained their three most deficient cognitive subdomains as identified at baseline. Participants of both intervention groups trained three times per week over a five-week period. Both training groups received additional 30-minute compensatory-transfer sessions once per week. RESULTS: Attention appeared to be the most frequently impaired cognitive domain as well as the domain which was significantly improved by CRT, with medium to large effect sizes. No difference in improvement was found between IT and GT. The analyses also revealed greater improvement in self-assessed psychosocial functioning in training participants (GT and IT combined) compared to the CG. LIMITATIONS: Due to the small sample size, the present results are preliminary in nature. CONCLUSION: CRT was well accepted, and patients transferred the attentional improvement to real life, as measured by self-assessed psychosocial functioning. IT yielded no additional advantages over GT. We propose CRT as an integral part of the treatment plan for patients with depression suffering from CI.

Analysis of risk communication teaching in psychosocial and other medical departments.

Aims: Teaching students about risk communication is an important aspect at medical schools given the growing importance of informed consent in healthcare. This observational study analyzes the quality of teaching content on risk communication and biostatistics at a medical school.Methods: Based on the concept of curriculum mapping, purpose-designed questionnaires were used via participant observers to record the frequency, characteristics and context of risk communication employed by lecturers during teaching sessions for one semester. The data was analyzed quantitatively and descriptively.Results: Teaching about risk communication was observed in 24.4% (n = 95 of 390) sessions. Prevalence varied significantly among different departments with dermatology having the highest rate (67.9%) but lesser in-depth teaching than medical psychology where risk communication concepts were discussed on a higher scale in 61.4% sessions. Relevant statistical values were not mentioned at all in 69% of these 95 sessions and clinical contexts were used rarely (55.8%). Supplementary teaching material was provided in 50.5% sessions while students asked questions in 18.9% sessions.Conclusions: Students are infrequently taught about communicating risks. When they are, the teaching does not include the mention of core biostatistics values nor does the teaching involve methods for demonstrating risk communication.

What and how are students taught about communicating risks to patients? Analysis of a medical curriculum.

BACKGROUND: Communication is a core competence in medical care. Failure of physicians to properly communicate inherent risks of medical interventions has been linked with inadequate training at school. This study analyses a medical curriculum for assessing the content and quality of teaching risk communication to students. METHODS: A checklist based on the national guidelines of core competencies on risk communication required of physicians was developed. Participant observers surveyed all teaching sessions at a medical school during a semester to record the frequency, characteristics and clinical context used by lectures during classes. Data were analyzed using statistical and descriptive methods to determine the prevalence and quality of teaching content. RESULTS: 231 teaching sessions were surveyed. The inter-rater reliability was 81%. Lecturers mentioned topics of risk communication in 61.5% of teaching sessions (83.7% in surgery, 43.3% in internal medicine) but core biostatistics concepts were not discussed in more than 80% of these sessions. Important topics such as patient safety and preventable diseases were underrepresented. Risk communication was mainly taught in large-group, theoretical sessions and rarely with supplementary teaching material (7.4%). Students asked questions in 15.2% of courses, more often in surgery classes than in internal medicine. CONCLUSION: Statistical and clinical topics relevant for teaching risk communication to medical students are not only underrepresented but also minimally explained by lecturers. Supplementary material on risk communication is rarely provided to students during classes. High-resource demanding, small-group teaching formats are not necessarily interactive as students ask few questions.

Do sex differences affect prefrontal cortex associated cognition in schizophrenia?

UNLABELLED: Cognitive deficits in schizophrenia, especially those related to prefrontal cortex (PFC) functions, influence functional outcome. There is evidence for sex differences in cognition in schizophrenia, but the results in the literature are still controversial. OBJECTIVE: This study evaluated different modalities of working memory (WM) and executive control (EC), functions that are both associated with the PFC, between sexes in schizophrenic patients and controls. METHODS: We used a battery of neuropsychological tests for assessing auditory, spatial, and visual-matching WM and used a dual task for assessing EC. The study included 50 inpatients (25 female) partially remitted and taking atypical neuroleptics, as well as 40 controls (20 female) matched for age and education. RESULTS: Significant sex differences were found in the dual task; female patients detected fewer correct trials than male patients and controls did. Moreover, female patients performed significantly worse in the single visual subtest of the dual task. For the controls, no sex differences were found. Males showed higher positive symptoms than females, but no other differences in psychopathology, disease characteristics, or extrapyramidal symptoms were found between sexes. CONCLUSION: The present study shows an absence of sex differences in WM in healthy subjects and in patients with schizophrenia. However, in the dual task and in the single visual subtest, female patients performed worse than males. This finding suggests that in contrast to males, nonacute female inpatients show an underlying attentional deficit that may contribute to impairment in higher-order functions such as EC.

Neurocognitive performance in patients with depression compared to healthy controls: Association of clinical variables and remission state.

Cognitive impairment in Major Depressive Disorder (MDD) has been postulated to persist into remission. However, inconsistent definitions of clinical remission, patterns and influencing factors, isolated cognitive tasks, and the lack of appropriately matched controls (HCs) present significant limitations of previous studies. Furthermore, studies investigating cognition in partially remitted patients are particularly scarce. This study compares the cognition of MDD patients (N = 65) and HCs (N = 65), matched by one-to-one recruitment strategy for age, sex, and education (ages 19-60). The neuropsychological (NPS) performance was measured via an extensive NPS-test battery and analysed retrospectively, accounting for demographic and clinical variables. Full remission was defined as HAMD cut off ≤7, partial remission as HAMD 8-18. The findings show entire MDD group and partially remitted MDD with significantly poorer NPS performance compared to HCs, while remitted MDD patients did not differ significantly from HCs. This underscores how critical a clear definition of remission is to compare studies on MDD. The clinical variable 'number of hospitalizations' had a significant effect on cognition, whereas current symptom severity did not correlate with performance on any cognitive domain. Higher number of hospitalizations may be associated with higher burden of illness and greater neurobiological "scar effects".

Are we preparing future doctors to deal with emotionally challenging situations? Analysis of a medical curriculum.

OBJECTIVE: Skilful communication by doctors is necessary for healthcare delivery during emotionally challenging situations. This study analyses a medical curriculum for the frequency and intensity of teaching content on communication in emotionally challenging situations. METHODS: A questionnaire with 31 questions ("EmotCog31") was used to evaluate teaching sessions at 17 departments of a medical school for one semester. RESULTS: Teaching content on communication in emotionally challenging situations was observed in 62 of 724 (∼nine percent) teaching sessions. Fifty-six percent of these sessions were within psychosocial specialisations. Lecturers used mental diseases as teaching topics four times more than somatic diseases. Forty-two percent of the 62 sessions were large-group while fifty-eight percent were small-group, interactive sessions. Clinical examples were used in sixty-nine percent of these sessions. Eighty-one percent of the handouts provided and sixty-six percent of simulated patient scenarios used were rated as helpful. Two-thirds of teaching sessions were rated positively when they included practical context. CONCLUSION: There was a considerable lack of teaching on communication skills in an emotional context. Teaching was limited to psychosocial specialties, reducing the impact of available knowledge for other medical specialties. PRACTICE IMPLICATIONS: More interactive, practically oriented teaching methods are useful for teaching emotional communication skills.

Monocausal attribution and its relationship with reasoning biases in schizophrenia.

BACKGROUND: Aberrant attributional styles are counted to a set of circumscribed cognitive biases that are implicated in the pathogenesis of (paranoid) psychosis. However, evidence for a specific profile (e.g., an exaggerated self-serving bias, other-blaming bias) has become equivocal over the years. More recently, one-sided (monocausal) attributions have been reported in patients with psychosis. METHODS: We compared a large sample of patients with diagnosed schizophrenia (n=145) to nonclinical controls (n=30) on a revised version of the Internal, Personal and Situational Attributions Questionnaire (IPSAQ-R). In this task, participants have to assign probability estimates to each of three potential causes (i.e., myself, others, circumstances) for a specific (negative or positive) event. RESULTS: Participants with schizophrenia displayed an abolished self-serving bias and showed a significant preference for one-sided/monocausal attributions, which was neither correlated with jumping to conclusions nor overconfidence in errors. School education correlated with less monocausal attributions. We did not find any congruence between attributional styles with core delusional ideas. CONCLUSIONS: Our study corroborates earlier investigations showing that monocausal attributions may play a role in the pathogenesis of psychosis; this bias unlikely represents an epiphenomenon of established biases. Unexpectedly, attributional styles (e.g., external-blaming) did not shape delusional contents. The true prevalence of monocausal attributions in psychosis is perhaps underestimated in the study, as groups were equated on school education, which was correlated with monocausal attributions.