Reduced gray matter volume in the left prefrontal, occipital, and temporal regions as predictors for posttraumatic stress disorder: a voxel-based morphometric study.

The concept of acute stress disorder (ASD) was introduced as a diagnostic entity to improve the identification of traumatized people who are likely to develop posttraumatic stress disorder (PTSD). Neuroanatomical models suggest that changes in the prefrontal cortex, amygdala, and hippocampus play a role in the development of PTSD. Using voxel-based morphometry, this study aimed to investigate the predictive power of gray matter volume (GMV) alterations for developing PTSD. The GMVs of ASD patients (n = 21) were compared to those of PTSD patients (n = 17) and healthy controls (n = 18) in whole-brain and region-of-interest analyses. The GMV alterations seen in ASD patients shortly after the traumatic event (T1) were also correlated with PTSD symptom severity and symptom clusters 4 weeks later (T2). Compared with healthy controls, the ASD patients had significantly reduced GMV in the left visual cortex shortly after the traumatic event (T1) and in the left occipital and prefrontal regions 4 weeks later (T2); no significant differences in GMV were seen between the ASD and PTSD patients. Furthermore, a significant negative association was found between the GMV reduction in the left lateral temporal regions seen after the traumatic event (T1) and PTSD hyperarousal symptoms 4 weeks later (T2). Neither amygdala nor hippocampus alterations were predictive for the development of PTSD. These data suggest that gray matter deficiencies in the left hemispheric occipital and temporal regions in ASD patients may predict a liability for developing PTSD.

Negative schemata about the self and others and paranoid ideation in at-risk states and those with persisting positive symptoms.

BACKGROUND: The objective of this study is to test the conflicting theories concerning the association of negative self and other schemata and paranoid ideation. METHODS: A risk-based approach, including risk stratification, is used to gain insight into the association of the negative self and other schemata that may be shared by individuals or differentiate between individuals at clinical high risk (CHR) for a first-episode psychosis and those with full-blown psychosis. The dataset includes a sample of individuals at CHR (n = 137) and a sample of individuals with persisting positive symptoms (PPS, n = 211). The CHR sample was subdivided according to a prognostic index yielding 4 CHR sub-classes with increasing risk for transition to psychosis. RESULTS: Negative beliefs about the self were associated with paranoid ideation in CHR and a lower risk state. In the highest risk state and full-blown psychosis, there is an association with negative beliefs about others. CONCLUSION: These findings are in line with theories suggesting a switch from a predominantly activated negative self-schema to a malevolent others-schema in association with paranoid ideation along the risk-continuum. However, due to methodological limitations these results should be replicated by future studies.

Posterior and prefrontal contributions to the development posttraumatic stress disorder symptom severity: an fMRI study of symptom provocation in acute stress disorder.

Acute stress disorder (ASD) is predictive of the development of posttraumatic stress disorder (PTSD). In response to symptom provocation, the exposure to trauma-related pictures, ASD patients showed increased activation of the medial posterior areas of precuneus and posterior cingulate cortex as well as of superior prefrontal cortex in a previous study. The current study aimed at investigating which activated areas are predictive of the development of PTSD. Nineteen ASD patients took part in an fMRI study in which they were shown personalized trauma-related and neutral pictures within 4 weeks of the traumatic event. They were assessed for severity of PTSD 4 weeks later. Activation contrasts between trauma-related and neutral pictures were correlated with subsequent PTSD symptom severity. Greater activation in, among others, right medial precuneus, left retrosplenial cortex, precentral and right superior temporal gyrus as well as less activation in lateral, superior prefrontal and left fusiform gyrus was related to subsequently increased PTSD severity. The results are broadly in line with neural areas related to etiological models of PTSD, namely multisensory associative learning recruiting posterior regions on the one hand and failure to reappraise maladaptive cognitions, thought to involve prefrontal areas, on the other.

Attenuated Readiness Potential in the Absence of Executive Dysfunction in Adults With ADHD.

OBJECTIVE: Patients with ADHD display a decreased contingent negative variation in Go/NoGo tasks. It is unclear whether the attenuation is due to deficits of executive function or to disorder of motor planning. The readiness potential (RP) recorded during self-initiated movements could cast light on this question. METHOD: RP was recorded in 25 stably medicated adult ADHD patients and 21 healthy controls matched for age, education, and verbal IQ. Participants also completed neuropsychological tests of executive function. RESULTS: Compared with healthy controls, ADHD patients showed significantly diminished RP peaks and also decreased negativity in preparation of the movement at frontal locations. There were no significant group differences with regard to tests of executive function. CONCLUSION: In adults with ADHD, deficits of motor organization are also manifest in situations not involving external stimulus processing. The attenuated RP occurred in the absence of executive dysfunction. Results are consistent with partial independence between motor and executive dysfunction in ADHD.

The effect of auditory and visual training on the mismatch negativity in schizophrenia.

BACKGROUND: The mismatch negativity (MMN) is an electrophysiological index of early auditory attention and has repeatedly been suggested to be associated with cognitive functioning. Despite the frequently reported finding of reduced MMN amplitude in schizophrenia, up to now, studies assessing the impact of perceptual discrimination training aiming to improve MMN measures in schizophrenia patients are scarce. METHOD: In the present study, the effect of auditory training (AUD, n=14) on the MMN was compared to that of visual-spatial training (VIS, n=14) and a treatment-as-usual (TAU, n=14) condition in schizophrenia patients. Training consisted of ten 50-min sessions over two weeks. Assessments took place before and after training and at a two-month follow-up. They comprised clinical measures and MMN recordings to frequency and duration deviant stimuli. RESULTS: There was a significant main effect for type of stimulus deviance with a more negative MMN to frequency than duration deviants. In contrast to our hypotheses, we did not find training specific effects on MMN amplitude or latency. CONCLUSION: The visual, as well as the auditory training program failed to result in treatment related MMN changes in schizophrenia patients when compared to treatment-as-usual as a control condition. In contrast to reports in healthy subjects, the induction of training related MMN changes in schizophrenia patients may constitute a specific challenge and require more extensive training protocols.

Modality of fear cues affects acoustic startle potentiation but not heart-rate response in patients with dental phobia.

The acoustic startle response (SR) has consistently been shown to be enhanced by fear-arousing cross-modal background stimuli in phobics. Intra-modal fear-potentiation of acoustic SR was rarely investigated and generated inconsistent results. The present study compared the acoustic SR to phobia-related sounds with that to phobia-related pictures in 104 dental phobic patients and 22 controls. Acoustic background stimuli were dental treatment noises and birdsong and visual stimuli were dental treatment and neutral control pictures. Background stimuli were presented for 4 s, randomly followed by the administration of the startle stimulus. In addition to SR, heart-rate (HR) was recorded throughout the trials. Irrespective of their content, background pictures elicited greater SR than noises in both groups with a trend for phobic participants to show startle potentiation to phobia-related pictures but not noises. Unlike controls, phobics showed HR acceleration to both dental pictures and noises. HR acceleration of the phobia group was significantly positively correlated with SR in the noise condition only. The acoustic SR to phobia-related noises is likely to be inhibited by prolonged sensorimotor gating.

Posterior Midline Activation during Symptom Provocation in Acute Stress Disorder: An fMRI Study.

Functional imaging studies of patients with post-traumatic stress disorder showed wide-spread activation of midline cortical areas during symptom provocation, i.e., exposure to trauma-related cues. The present study aimed at investigating neural activation during exposure to trauma-related pictures in patients with acute stress disorder (ASD) shortly after the traumatic event. Nineteen ASD patients and 19 healthy control participants were presented with individualized pictures of the traumatic event and emotionally neutral control pictures during the acquisition of whole-brain data with a 3-T fMRI scanner. Compared to the control group and to control pictures, ASD patients showed significant activation in midline cortical areas in response to trauma-related pictures including precuneus, cuneus, postcentral gyrus, and pre-supplementary motor area. The results suggest that the trauma-related pictures evoke emotionally salient self-referential processing in ASD patients.

Mismatch negativity latency and cognitive function in schizophrenia.

BACKGROUND: The Mismatch Negativity (MMN) is an event-related potential (ERP) sensitive to early auditory deviance detection and has been shown to be reduced in schizophrenia patients. Moreover, MMN amplitude reduction to duration deviant tones was found to be related to functional outcomes particularly, to neuropsychological (working memory and verbal domains) and psychosocial measures. While MMN amplitude is thought to be correlated with deficits of early sensory processing, the functional significance of MMN latency remains unclear so far. The present study focused on the investigation of MMN in relation to neuropsychological function in schizophrenia. METHOD: Forty schizophrenia patients and 16 healthy controls underwent a passive oddball paradigm (2400 binaural tones; 88% standards [1 kHz, 80 db, 80 ms], 11% frequency deviants [1.2 kHz], 11% duration deviants [40 ms]) and a neuropsychological test-battery. Patients were assessed with regard to clinical symptoms. RESULTS: Compared to healthy controls schizophrenia patients showed diminished MMN amplitude and shorter MMN latency to both deviants as well as an impaired neuropsychological test performance. Severity of positive symptoms was related to decreased MMN amplitude to duration deviants. Furthermore, enhanced verbal memory performance was associated with prolonged MMN latency to frequency deviants in patients. CONCLUSION: The present study corroborates previous results of a diminished MMN amplitude and its association with positive symptoms in schizophrenia patients. Both, the findings of a shorter latency to duration and frequency deviants and the relationship of the latter with verbal memory in patients, emphasize the relevance of the temporal aspect of early auditory discrimination processing in schizophrenia.

Why do bad things happen to me? Attributional style, depressed mood, and persecutory delusions in patients with schizophrenia.

Theoretical models postulate an important role of attributional style (AS) in the formation and maintenance of persecutory delusions and other positive symptoms of schizophrenia. However, current research has gathered conflicting findings. In a cross-sectional design, patients with persistent positive symptoms of schizophrenia (n = 258) and healthy controls (n = 51) completed a revised version of the Internal, Personal and Situational Attributions Questionnaire (IPSAQ-R) and assessments of psychopathology. In comparison to controls, neither patients with schizophrenia in general nor patients with persecutory delusions (n = 142) in particular presented an externalizing and personalizing AS. Rather, both groups showed a "self-blaming" AS and attributed negative events more toward themselves. Persecutory delusions were independently predicted by a personalizing bias for negative events (beta = 0.197, P = .001) and by depression (beta = 0.152, P = .013), but only 5% of the variance in persecutory delusions could be explained. Cluster analysis of IPSAQ-R scores identified a "personalizing" (n = 70) and a "self-blaming" subgroup (n = 188), with the former showing slightly more pronounced persecutory delusions (P = .021). Results indicate that patients with schizophrenia and patients with persecutory delusions both mostly blamed themselves for negative events. Nevertheless, still a subgroup of patients could be identified who presented a more pronounced personalizing bias and more severe persecutory delusions. Thus, AS in patients with schizophrenia might be less stable but more determined by individual and situational characteristics that need further elucidation.

[Determinants of direct cost in schizophrenia patients with persistent positive symptoms]. / Determinanten direkter Kosten bei persistierender Positivsymptomatik psychotischer Erkrankungen.

OBJECTIVE: To analyze direct costs and cost determinants in psychotic patients with persistent positive symptoms (PPS). METHODS: A total of 330 patients with PPS were recruited via 6 university clinics and interviewed about service utilization in the previous 3 months. After monetary valuation, costs were analyzed via generalized linear mixed models with gamma distribution and log-link function to identify determinants of direct costs. RESULTS: The mean costs were 7,065 € and resulted predominantly from psychiatric hospital care (63 %), assisted living (17 %) and complementary services (8 %). We found statistically significant associations between direct costs and an increasing score of the negative subscale of the Positive and Negative Syndrome Scale (+ 2,484 € per point, p < 0.001) and experiencing less than one social contact per week (- 2,272 €, p = 0.003). CONCLUSION: PPS incurred substantial direct costs which primarily resulted from hospital treatment, and were strongly associated with symptom severity.

The effect of cognitive training on evoked potentials in schizophrenia.

Electrophysiological indices are sensitive to cognitive dysfunction in schizophrenia but have rarely been used to assess benefits of cognitive remediation. Our aim was to evaluate the effect of specific cognitive training approaches on event-related potentials. Forty-six patients with schizophrenia underwent either auditory (AUD) or visuo-spatial (VIS) cognitive training or treatment-as-usual (TAU). Cognitive training was computer-assisted and administered for 10 sessions within two weeks. Event-related potentials during an active odd-ball paradigm together with clinical and neuropsychological variables were assessed before and after training and again at a two-month follow-up. Compared to the TAU group both the AUD and VIS training groups showed decreased P2 latency following training. At follow-up, the P2-latency reduction was stable in the VIS group but the AUD group experienced a relapse. Training resulted in improved digit-span backward among neuropsychological variables. Increased P2 amplitude was related to more positive symptoms and lower social-occupational functioning and longer P2 latency was associated with greater severity of stereotyped thinking. The more general visuo-spatial training appears to have a longer-lasting effect on P2 latency than the specific auditory training. Alternatively, there may be specific auditory discrimination deficits in schizophrenia requiring more extensive training for a stable change.

Associations between therapy skills and patient experiences of change processes in cognitive behavioral therapy for psychosis.

Despite the promising findings in relation to the efficacy of cognitive behavioral therapy for psychosis (CBTp), little attention has been paid to the therapy skills necessary to deliver CBTp and to the influence of such skills on processes underlying therapeutic change. Our study investigated the associations between general and technical therapy skills and patient experiences of change processes in CBTp. The study sample consisted of 79 patients with psychotic disorders who had undergone CBTp. We randomly selected one tape-recorded therapy session from each of the cases. General and technical therapy skills were assessed by the Cognitive Therapy Scale for Psychosis. The Bern Post Session Report for Patients was applied to measure patient experiences of general change processes in the sense of Grawe's psychological therapy. General skills, such as feedback and understanding, explained 23% of the variance of patients' self-esteem experience, but up to 10% of the variance of mastery, clarification, and contentment experiences. The technical skill of guided discovery consistently showed negative associations with patients' alliance, contentment, and control experiences. The study points to the importance of general therapy skills for patient experiences of change processes in CBTp. Some technical skills, however, could detrimentally affect the therapeutic relationship.

In search of the trauma memory: a meta-analysis of functional neuroimaging studies of symptom provocation in posttraumatic stress disorder (PTSD).

Notwithstanding some discrepancy between results from neuroimaging studies of symptom provocation in posttraumatic stress disorder (PTSD), there is broad agreement as to the neural circuit underlying this disorder. It is thought to be characterized by an exaggerated amygdalar and decreased medial prefrontal activation to which the elevated anxiety state and concomitant inadequate emotional regulation are attributed. However, the proposed circuit falls short of accounting for the main symptom, unique among anxiety disorders to PTSD, namely, reexperiencing the precipitating event in the form of recurrent, distressing images and recollections. Owing to the technical demands, neuroimaging studies are usually carried out with small sample sizes. A meta-analysis of their findings is more likely to cast light on the involved cortical areas. Coordinate-based meta-analyses employing ES-SDM (Effect Size Signed Differential Mapping) were carried out on 19 studies with 274 PTSD patients. Thirteen of the studies included 145 trauma-exposed control participants. Comparisons between reactions to trauma-related stimuli and a control condition and group comparison of reactions to the trauma-related stimuli were submitted to meta-analysis. Compared to controls and the neutral condition, PTSD patients showed significant activation of the mid-line retrosplenial cortex and precuneus in response to trauma-related stimuli. These midline areas have been implicated in self-referential processing and salient autobiographical memory. PTSD patients also evidenced hyperactivation of the pregenual/anterior cingulate gyrus and bilateral amygdala to trauma-relevant, compared to neutral, stimuli. Patients showed significantly less activation than controls in sensory association areas such as the bilateral temporal gyri and extrastriate area which may indicate that the patients' attention was diverted from the presented stimuli by being focused on the elicited trauma memory. Being involved in associative learning and priming, the retrosplenial cortex may have an important function in relation to trauma memory, in particular, the intrusive reexperiencing of the traumatic event.

Mental retrieval of treatment context in dental phobia.

BACKGROUND: The effect of mental retrieval of an exposure session was investigated during a follow-up examination in dental phobia patients. METHOD: The exposure session took place at the psychology unit and the follow-up a week later at the dental clinic prior to dental treatment while patients were seated in the dental chair. During exposure, individuals with dental phobia (N = 72) were shown a video of a dental appointment, after which they were instructed to imagine themselves receiving dental treatment. During follow-up half of the participants received instructions to mentally retrieve the exposure session and the other half were asked to recall everyday activities. Before and after exposure treatment, and after mental retrieval, participants were shown three dental instruments while heart rate (HR) and avoidance and subjective units of discomfort (SUD) were recorded. RESULTS: Questionnaires of phobic anxiety administered before and after treatment indicated significant improvement. Mental retrieval of treatment was moderately superior to the control condition with regard to avoidance. Over 80% of patients underwent the subsequent dental treatment session. Those not adhering showed initially more dysfunctional cognitions and more desire for control. CONCLUSION: There is some evidence that retrieval of treatment context may have a moderately beneficial effect on avoidance.

Sleep-related cognitive function and the K-complex in schizophrenia.

Sleep parameters have been reported to be related to cognitive function in a variety of ways. Problem solving and procedural learning were found to be improved after sleep but training also affected subsequent sleep and some parameters were related to cognitive trait variables, e.g. IQ. Additional to rapid-eye-movement (REM) and slow wave sleep (SWS), micro-architectural features such as spindle activity and K-complexes have recently been the focus of interest. The study aimed at investigating the relationship of neuropsychological variables, problem solving and procedural learning with sleep parameters in stably medicated schizophrenia patients. Twenty schizophrenia out-patients participated in the study. Learning and testing occurred over a randomly balanced waking and sleep interval. The tasks were the Tower of London (ToL) and mirror tracing. Sleep EEG was analysed together with spindle activity and K-complexes. Performance improved with regard to both tasks from learning to testing irrespective of type of interval. Increasing density of K-complexes was related to a higher number of solved ToL tasks pre and post night whereas longer SWS was related to faster completion of the ToL. A higher age was related to less overnight improvement in regard to number of solved ToL tasks. K-complexes are thought to indicate intra-cortical activity paving the way for the uptake of new information. As ToL is considered a test of executive function, K-complexes appear to be linked to this domain, deficits of which are thought to be a core feature of schizophrenia.

A practice-based comparison of brief cognitive behavioural treatment, two kinds of hypnosis and general anaesthesia in dental phobia.

BACKGROUND: A practice-based study was carried out to assess the comparative effectiveness and acceptability of standardised hypnosis, hypnosis with individualised imagery, cognitive behavioural treatment (CBT) and general anaesthesia (GA) in the treatment of dental phobia. METHODS: A 4-group design was used with 4 repeated measurement occasions. Of an initial total of 137 dental phobics, 77 completed the study with sample sizes of between 14 and 29 patients in the 4 groups. Participants completed questionnaires of dental anxiety at the beginning of the trial, before and after the first dental appointment and again before the second dental appointment a week later. RESULTS: Standardised hypnosis evidenced a significantly higher rate of premature termination of treatment than CBT. The completer analysis showed a significant reduction of dental anxiety after CBT and individualised hypnosis compared to the GA condition. The intent-to-treat analysis showed significant improvement only after CBT. CONCLUSIONS: The results suggest that CBT is the treatment of choice in dental phobia when taking both effectiveness and acceptability into account.

Cognitive behavioural therapy versus supportive therapy for persistent positive symptoms in psychotic disorders: the POSITIVE Study, a multicenter, prospective, single-blind, randomised controlled clinical trial.

BACKGROUND: It has been demonstrated that cognitive behavioural therapy (CBT) has a moderate effect on symptom reduction and on general well being of patients suffering from psychosis. However, questions regarding the specific efficacy of CBT, the treatment safety, the cost-effectiveness, and the moderators and mediators of treatment effects are still a major issue. The major objective of this trial is to investigate whether CBT is specifically efficacious in reducing positive symptoms when compared with non-specific supportive therapy (ST) which does not implement CBT-techniques but provides comparable therapeutic attention. METHODS/DESIGN: The POSITIVE study is a multicenter, prospective, single-blind, parallel group, randomised clinical trial, comparing CBT and ST with respect to the efficacy in reducing positive symptoms in psychotic disorders. CBT as well as ST consist of 20 sessions altogether, 165 participants receiving CBT and 165 participants receiving ST. Major methodological aspects of the study are systematic recruitment, explicit inclusion criteria, reliability checks of assessments with control for rater shift, analysis by intention to treat, data management using remote data entry, measures of quality assurance (e.g. on-site monitoring with source data verification, regular query process), advanced statistical analysis, manualized treatment, checks of adherence and competence of therapists. Research relating the psychotherapy process with outcome, neurobiological research addressing basic questions of delusion formation using fMRI and neuropsychological assessment and treatment research investigating adaptations of CBT for adolescents is combined in this network. Problems of transfer into routine clinical care will be identified and addressed by a project focusing on cost efficiency. DISCUSSION: This clinical trial is part of efforts to intensify psychotherapy research in the field of psychosis in Germany, to contribute to the international discussion on psychotherapy in psychotic disorders, and to help implement psychotherapy in routine care. Furthermore, the study will allow drawing conclusions about the mediators of treatment effects of CBT of psychotic disorders.

Effects of additional prolonged exposure to psychoeducation and relaxation in acute stress disorder.

We investigated the effect of prolonged exposure (PE) on the heart rate (HR) and skin conductance response to trauma-related stimuli in acute stress disorder (ASD). Forty recent trauma victims with ASD were randomly assigned to three sessions of either PE or supportive counseling (SC) with both groups also receiving psychoeducation and progressive relaxation. Assessments were carried out before and after treatment and again after 3 months. Four years later, patients were asked by telephone whether they had received further treatment. There were no significant group differences with regard to symptomatic improvement at the end of treatment. Both groups showed initial cardiac acceleration to trauma-related pictures. After treatment the PE group showed attenuation of the HR response and a reduction in spontaneous fluctuations (SF) whereas the SC group showed a decelerative (orienting) response and a marginal increase in SF. Following SC, 43% received further treatment compared to 9% after PE.

Does the cognitive dispute of psychotic symptoms do harm to the therapeutic alliance?

We examined whether the cognitive dispute of psychotic symptoms has a negative impact on the course of the therapeutic alliance. Sixty-seven patients with persistent psychotic symptoms received either cognitive behavioral therapy (CBT) or supportive therapy. Questionnaire-based alliance ratings were repeatedly obtained throughout the course of therapy. Patient and therapist alliance ratings were examined separately. Data analyses comprised repeated measurement analyses of variance and cluster analytic procedures. Neither patient nor therapist alliance ratings showed a differential course throughout the treatments. This was despite the implementation of disputing strategies in later stages of CBT. Irrespective of the treatment condition a cluster with a positive alliance rating and a cluster with a poorer rating were found for therapist and patient ratings, respectively. Baseline symptoms and insight differentiated between the types of clusters. In conclusion, CBT-specific interventions that challenge psychotic symptoms do not necessarily negatively influence the course of the alliance.

Clinical symptoms of major depression are associated with the intensity dependence of auditory event-related potential components.

The intensity (loudness) dependent amplitude change (IDAP) of the auditory event-related potential (ERP) has been shown to be associated with the outcome of treatment with selective serotonin reuptake inhibitors in major depression. The purpose of the present study is to evaluate associations between clinical symptoms of major depression and the IDAP as an indirect indicator of cortical serotonergic function. We assessed 40 in-patients suffering from a major depressive episode (DSM-IV) prior to antidepressant treatment. Psychometric characteristics of depression were assessed by means of psychiatric rating scales (CGI, HDRS, HAMA, STAI and BDI) and evaluated for associations with auditory evoked P1, N1, P2 as well as P1/N1 and N1/P2 peak to peak amplitude slopes. Our data revealed a positive correlation of the intensity dependent N1 amplitude slope with the degree of certain somatic symptoms of depression: loss of appetite and weight, insomnia, and sexual dysfunction. The results of our study might contribute to a more specific clinical basis in the differential indication of serotonergic versus noradrenergic antidepressants.