Cognitive functioning in patients with familial bipolar I disorder and their unaffected relatives

BACKGROUND: Impairments in verbal learning and memory, executive functions and attention are manifest in some euthymic patients with bipolar disorder (BPD). However, evidence is sparse on their putative role as aetiologically important genetic vulnerability markers for the disorder. This population-based study examined the cognitive functions of affected and unaffected individuals in families with BPD. The aim was to discover whether any cognitive function would indicate genetic liability to the disorder and could thus be regarded as endophenotypes of BPD. METHOD: A diagnostic interview and a neuropsychological test battery were administered to 32 familial bipolar I disorder patients, 40 of their unaffected first-degree relatives and 55 controls, all representing population-based samples. RESULTS: Unaffected first-degree relatives showed impairment in psychomotor performance speed and slight impairment in executive function. Bipolar patients were impaired in verbal learning and memory compared with unaffected relatives and controls. They also differed from controls in tasks of executive functions. There were no difference between the groups in simple attention and working memory tasks. CONCLUSIONS: Impaired psychomotor performance speed and executive function may represent endophenotypes of BPD, reflecting possible underlying vulnerability to the disorder. Verbal memory impairments appear to be more related to the fully developed disorder.     

Dissociating medication effects from learning and practice effects in a neurocognitive study of schizophrenia: Olanzapine versus haloperidol

Objective. To contrast the effect of a typical antipsychotic (haloperidol) and an atypical antipsychotic (olanzapine) on neurocognitive functioning in schizophrenia when learning and practice (LP) effects are controlled.

Methods. Two groups of participants were recruited, 27 schizophrenia patients in their first 5 years of illness and 13 normal controls. Prior to double-blind randomisation, all subjects were assessed on four occasions within 5 days (prerandomisation period) on the same neurocognitive battery. Repeated assessment prior to randomisation was chosen as a method to control for LP effects. Patients were then randomised to 56 days of treatment with haloperidol or olanzapine (postrandomisation). All subjects were assessed on neurocognitive measures at Days 28 and 56.

Results. LP effects were present during the prerandomisation period on motor tasks, verbal and visual short-term memory, attention, and on a measure of verbal working memory. There were no changes in performance for patients randomised to treatment with olanzapine or haloperidol or the normal control group during the postrandomisation period.

Conclusions. Once LP effects are controlled, olanzapine and haloperidol do not affect performance on measures of motor functioning, verbal short-term memory, attention, verbal working memory, reaction time, visuospatial short-term memory, and visual working memory beyond that observed from LP effects.     

The influence of emotions on inhibitory functioning in borderline personality disorder

BACKGROUND: Borderline personality disorder (BPD) is characterized by an emotionally unstable and impulsive cognitive and behavioral style. Inhibitory dysfunction has been hypothesized as playing a crucial role in BPD psychopathology. This study aimed to systematically investigate differential inhibitory functions in patients with BPD as compared to healthy controls, and to investigate their expected impairment in the context of aversive emotions by comparing performances in neuropsychological tasks that present both neutral and emotional material. METHOD: Unmedicated female patients with BPD (n=28) were compared with age-matched healthy female controls (n=30) in the following tasks: the emotional Stroop test (inhibition of interference), directed forgetting (intentional, resource-dependent inhibition), and an emotional variant of the negative priming task (automatic, resource-independent inhibition). RESULTS: In comparison with the controls, the BPD patients showed reduced inhibition of negative material in the directed forgetting task and in the negative priming task. No effect was found in the emotional Stroop test. Significant correlations with current affect as well as trait anxiety and anger (but not impulsiveness) were found in the BPD group specifically for negative stimuli, while no such correlations were found in the control group. In addition to inhibitory deficiencies, BPD patients had difficulties remembering positive words in the directed forgetting task. CONCLUSIONS: Our data suggest that individuals with BPD have difficulties in actively suppressing irrelevant information when it is of an aversive nature. Inhibitory dysfunction appears to be closely related to state and trait variables of unstable affect, but not to self-reported impulsiveness.     

Impaired memory consolidation during sleep in patients with functional memory disorder

Functional memory disorder (FMD) is characterized by mnestic and attentional deficits without symptoms of mild cognitive impairment or dementia. FMD usually develops in subjects with high psychosocial stress level and is classified to the somatoform disorders. We assessed memory performance (procedural mirror tracing task, declarative visual and verbal memory task) and other cognitive functions before and after one night of sleep in 12 FMD patients (mean age: 51.7 yrs, 7 females) and 12 healthy subjects matched for age, gender and IQ. Memory performance and other neurocognitive tasks did not differ between the groups at baseline. After one night of sleep, FMD patients showed an impairment of declarative memory consolidation compared to healthy subjects (visual task: p = 0.004; verbal task: p = 0.039). Spectral analysis of sleep-EEG indicated an increased cortical excitation in FMD. We hypothesize that a hyperarousal state in FMD might contribute to sleep disturbance implicating negative effects on declarative memory consolidation.     

Association between a Synaptosomal Protein (SNAP-25) Gene Polymorphism and Verbal Memory and Attention in Patients with Endogenous Psychoses and Mentally Healthy Subjects

Synaptosomal protein SNAP-25 is involved in the process of transmitting nerve spikes in the CNS and in the consolidation of memory traces in the hippocampus. Two independent studies have demonstrated associations between SNAP-25 gene polymorphisms and intellectual functions in a group of mentally healthy subjects and patients with schizophrenia. The aim of the present work was to perform a comparative study of the association between the MnlI polymorphism of SNAP-25 and cognitive functions (verbal memory, attention/executive functions) in 66 patients with endogenous psychoses, 75 of their mentally healthy relatives, and 136 healthy control subjects. Statistical analysis showed that the effectiveness of performing cognitive tests was significantly affected by group assignment (p = 0.00001) and genotype (p = 0.012). The interaction between genotype and group assignment also had an influence (p = 0.02). In all groups, carriers of the TT genotype had worse measures than carriers of other genotypes. The similar nature of the influences of the MnlI polymorphism on variations in measures in all groups indicates that this gene is related to overall intellect.     

Functional MRI correlates of the recall of unresolved life events in borderline personality disorder

BACKGROUND: Patients with borderline personality disorder (BPD) frequently report unresolved life events but it is still poorly understood, how these experiences are represented in the brain. Using functional magnetic resonance imaging (fMRI), the present study aimed at investigating the neural correlates of the recall of unresolved life events in patients with BPD and healthy controls. METHOD: Twenty female BPD patients and 21 healthy control subjects underwent fMRI. During measurement subjects recalled unresolved and resolved negative life events. Individual cue words were used to stimulate autobiographical memory. After scanning, subjects rated their emotional states during the recall of both types of memories. RESULTS: When contrasting unresolved and resolved life events, patients showed significant bilateral activation of frontotemporal areas including the insula, amygdala, and the anterior cingulate cortex, the left posterior cingulate cortex, right occipital cortex, the bilateral cerebellum and the midbrain. In healthy subjects, no differential brain activation was related to these conditions. The 2 x 2 factorial analysis (DeltaBPD - Deltacontrols) revealed similar results with bilateral activation of the frontal cortex including parts of the insula and of the orbitofrontal cortex, temporal activation including the amygdala, activation of the right occipital cortex, and parts of the cerebellum. Patients but not controls reported higher levels of anxiety and helplessness during the unresolved versus resolved memory condition. CONCLUSIONS: The activation of both, the amygdala and prefrontal areas, might reflect an increased effortful but insufficient attempt to control intensive emotions during the recall of unresolved life events in patients with BPD.     

Enhanced emotion-induced amnesia in borderline personality disorder

BACKGROUND: Current biological concepts of borderline personality disorder (BPD) emphasize the interference of emotional hyperarousal and cognitive functions. A prototypical example is episodic memory. Pre-clinical investigations of emotion-episodic memory interactions have shown specific retrograde and anterograde episodic memory changes in response to emotional stimuli. These changes are amygdala dependent and vary as a function of emotional arousal and valence. METHOD: To determine whether there is amygdala hyper-responsiveness to emotional stimuli as the underlying pathological substrate of cognitive dysfunction in BPD, 16 unmedicated female patients with BPD were tested on the behavioural indices of emotion-induced amnesia and hypermnesia established in 16 healthy controls. RESULTS: BPD patients displayed enhanced retrograde and anterograde amnesia in response to presentation of negative stimuli, while positive stimuli elicited no episodic memory-modulating effects. CONCLUSION: These findings suggest that an amygdala hyper-responsiveness to negative stimuli may serve as a crucial aetiological contributor to emotion-induced cognitive dysfunction in BPD.     

A developmental look at the attentional system in the at risk and first episode of psychosis: Age related changes in attention along the psychosis spectrum

Introduction. Neurodevelopmental processes of adolescence, when superimposed on a vulnerable brain, may produce additive effects reflecting the subthreshold psychotic symptoms, cognitive, and functional deterioration that are the hallmark of the early stages of schizophrenia.

Methods. As part of a longitudinal study, we investigated Continuous Performance Task, Identical Pairs Version (CPT-IP) performance in a sample of 301 participants (at risk for psychosis: 109; first episode–FE: 90; and controls: 102). Performance across groups was compared using d' of fast and slow, spatial and verbal conditions over two time points. Age effects were investigated using a regression model.

Results. Across all four CPT-IP conditions FE patients performed significantly worse than controls while AR individuals significantly differed from healthy subjects in the verbal condition. Age-related performance associations across groups significantly differed in the slow verbal condition because the FE sample did not show a significant association with increasing age like the AR and NC samples. CPT performance was stable over time.

Conclusions. Sustained attention in the putative prodrome of psychosis is not only impaired but associated with age. Research focusing on cognitive and neurobiological age-related changes can help to address fundamental questions about the nature of the disorder, including whether the underlying pathophysiology of early psychosis is static or deteriorating.     

Did I say that word or did you? Executive dysfunctions in schizophrenic patients affect memory efficiency,but not source attributions

Introduction. Schizophrenic patients have difficulties in recognising previously presented verbal information and identifying its sources. The antecedents of these recognition and source misattributions are, however, largely unknown. The current study examined to what extent schizophrenic patients’ lack of memory efficiency, their memory errors, and their source misattributions are related to neurocognitive deficits (i.e., executive dysfunctions).

Methods. 23 schizophrenic patients and 20 healthy controls were administered an adapted version of the Deese/Roediger-McDermott (DRM) task from which parameters of memory efficiency, memory errors, source misattributions, and two-high threshold measures were derived. Furthermore, two neurocognitive tasks tapping executive functions were administered: the Wisconsin Card Sorting Test (WCST) and the Behavioural Assessment of the Dysexecutive Syndrome (BADS). Using multiple linear regression analyses, we examined whether these neurocognitive measures predicted various memory parameters.

Results. Patients with schizophrenia showed poorer memory efficiency and were more prone to make internal-external source misattributions with high confidence. However, they did not more often falsely recognise critical lure words than controls. Executive dysfunctions predicted memory efficiency, but not source misattribution performance.

Conclusion. Our findings provide further evidence that schizophrenic patients’ memory impairments are intimately related to fundamental neurocognitive deficits.     

Object‐location memory in schizophrenia: Interference of symbolic threatening content

Introduction. Monitoring environmental stimuli for their emotional relevance is inherently associated with spatial processing. In schizophrenia, deficits in spatial working memory on one hand, and abnormal emotion processing on the other, have been documented, but these have not been related to each other. In the present study, we investigated whether a specific aspect of spatial memory (i.e., object‐location memory), is impaired in patients with schizophrenia. Moreover, we hypothesised that symbolic threatening content of objects would interfere with spatial processing in patients with schizophrenia but not in healthy controls.

Methods. Spatial memory for symbolic pictorial stimuli was assessed in 40 patients with schizophrenia compared to 41 healthy matched control participants using an object‐relocation task.

Results. Patients with schizophrenia performed worse in relocating objects, independent of overall intellectual ability. More specifically, patients were particularly worse in the relocation of objects with a symbolic threatening content.

Conclusions. These results suggest that a threatening semantic emotional content of schematic stimuli can interfere with spatial processing in schizophrenia. We hypothesise that a disproportional influence of the amygdala on other brain areas, such as the hippocampus, might underlie this specific emotional interference.     

Insights from the examination of verbal and spatial memory errors in relation to clinical symptoms of patients with recent-onset schizophrenia

Introduction. Memory deficits in patients with schizophrenia (SZ) are considered as a key feature of the clinical manifestations of the disease. In order to further examine the role and nature of memory deficits in SZ, the pattern of errors in verbal and spatial serial recall tasks committed by SZ patients was compared to that of healthy controls. We also tested the relationship between these memory errors and clinical symptoms.

Methods. Twenty-seven outpatients with recent-onset SZ and 27 age and gender matched healthy controls had to remember sequences of items (digits or localisations) in a serial recall task. Clinical symptoms were assessed with the PANSS and the SAPS.

Results. The results indicate that the number of omissions, intrusions, and transpositions can differentiate patients with SZ from healthy controls. Intrusions and transpositions committed in the verbal domain were associated with the negative subscale of the PANSS. Transposition errors were associated with delusions whether the to-be-remembered information was verbal or spatial.

Conclusion. The examination of the pattern of errors, in particular that of transpositions, is a more informative cognitive index than the mere analysis of overall performance, and provides a promising target for treatment.     

Neuropsychological function in borderline personality disorder

To evaluate the possibility of an underlying dimension of organicity in borderline personality disorder (BPD), a carefully diagnosed group of borderline patients was assessed across a wide range of neuropsychological functions and then was compared to an age-and education-matched non-patient control group. The BPD group had significantly lower Verbal, Performance, and Full Scale IQ scores on the WAIS-R. The BPD group also was impaired significantly on motor skills, figural memory, complex visuo-motor integration, social or interpersonal intelligence, and on a measure of susceptibility to interference. This pattern of deficits localized to the fronto-temporal regions and became more pronounced when a subgroup analysis was performed. This study suggests that subtle organic factors may be operative in some, but not all, BPD patients.     

The Impact of Self-Reported Childhood Trauma on Emotion Regulation in Borderline Personality Disorder and Major Depression

Early life stress is said to play a critical role in the development of borderline personality disorder (BPD) and major depressive disorder (MDD), but the underlying mediating factors remain uncertain. This study aimed to investigate self-reported childhood trauma, emotion regulation difficulties, and their associations in a sample of BPD (n = 49) and MDD (n = 48) patients and healthy control participants (n = 63). Multiple regressions were used to evaluate the impact of the quality and severity of self-reported childhood trauma on self-reported emotion regulation. The results supported an association between self-reported maltreatment experiences, especially emotional abuse and neglect, and emotion regulation difficulties. Additional analyses showed that emotion regulation difficulties influence the association between self-reported emotional abuse and acute symptomatology in the BPD subgroup. Emotion regulation difficulties may be 1 pathway through which early life stress, particularly emotional abuse, increases the risk for developing BPD symptomatology.     

Reductions in Whole-body Ownership in Borderline Personality Disorder – A Phenomenological Manifestation of Dissociation

ABSTRACT

Body ownership, i.e., the certainty that own body parts belongs to oneself, is a fundamental feature of self-consciousness. Patients with borderline personality disorder (BPD) often show symptoms of dissociation, describing a state of detachment from reality including their own body. However, up to now, there is no study that a) quantifies body ownership experiences in BPD, b) compares these experiences between the current and the remitted state of the disorder, and c) relates this kind of experience specifically to dissociation. In the present study, we assessed ownership for 25 body areas in current BPD patients (cBPD) and compared their ratings with those of remitted BPD patients (rBPD) and healthy controls (HC). We further related body ownership to dissociation and other relevant BPD markers on body area and subject level by applying multi-level analyses in the cBPD group. We found significantly reduced body ownership experiences in cBPD compared to HC, while there were no significant differences between these groups and rBPD. In cBPD, reduced body ownership was significantly related to dissociation when controlled for other BPD core features. Reduced body ownership might thus constitute a relevant marker for dissociation in current BPD which could further represent a target for therapeutic approaches.     

Creativity and borderline personality disorder: evidence from a voxel-based morphometry study

Introduction: Throughout the history, various examples of eminent creative people suffering from mental disorders along with some empirical research reports strengthened the idea of a potential link between creativity and psychopathology.

Methods: This study investigated different facets of psychometrically determined creativity in 20 females diagnosed with borderline personality disorder (BPD) relative to 19 healthy female controls. In addition, group differences in grey matter (GM) were examined.

Results: Behavioural findings revealed no significant differences between the BPD group and healthy controls with respect to verbal and figural-graphic creative task performance and creativity-related personality characteristics. Whole-brain voxel-based morphometry analyses revealed a distinct pattern of GM reductions in the BPD group (relative to controls) in a network of brain regions closely associated with various cognitive and emotional functions (including the bilateral orbital inferior frontal gyri and the left superior temporal gyrus), partly overlapping with creativity-related brain regions. Correlation analyses moreover revealed that in the BPD group GM reductions in the orbital parts of the inferior and middle frontal gyri were associated with lower levels of creativity.

Conclusions: This study provides no indications in favour of the putative link between creativity and psychopathology, as sometimes reported in the literature.     

Comparing the symptoms and mechanisms of “dissociation” in dissociative identity disorder and borderline personality disorder

A total of 75 patients were diagnosed with the Structured Clinical Interview for DSM–IV Dissociative Disorders–Revised as having dissociative identity disorder (DID), and 100 patients were diagnosed with the Structured Interview for DSM–IV Personality as having borderline personality disorder (BPD). Both groups were administered the Multidimensional Inventory of Dissociation (MID). DID patients had significantly higher MID scores than BPD patients, different distributions of MID scores, and different MID subscale profiles in 3 ranges of MID scores (0–15, 15–30, 30–45). The core MID symptoms—exhibited at all ranges of MID scores—for DID patients (the presence of alters, identity confusion, and memory problems) and BPD patients (flashbacks, identity confusion, and memory problems) were ostensibly similar but were considered to be mostly produced by different underlying processes. Multiple regression analyses showed that the core MID symptoms of DID patients had different predictors than did the core MID symptoms of BPD patients. Alter identities seemed to generate most—but not all—dissociative phenomena in DID patients, whereas only the 24% highest scoring BPD patients (MID ≥45) seemed to manifest alter-driven dissociative experiences. Most BPD dissociative experiences appeared to be due to 5 other mechanisms: (a) BPD-specific, stress-driven, rapid shifts of self-state; (b and c) nondefensive disruptions of the framework of perceptual organization with or without an accompanying BPD-specific, dissociation-like disintegration of affective/neurocognitive functioning; (d) a defensive distancing or detachment from distress (i.e., simple depersonalization); and (e) Allen, Console, and Lewis’s (1999) severe absorptive detachment.     

Processing of autobiographical memory retrieval cues in borderline personality disorder

BACKGROUND: Affective dysregulation in borderline personality disorder (BPD) in response to both external stimuli and memories has been shown to be associated with functional alterations of limbic and prefrontal brain areas. This study aimed to examine neuronal networks involved in autobiographical memory retrieval using standardized stimuli that gain autobiographical significance by illustrating marked solitary and social situations of human life. METHODS: Using event-related functional Magnetic Resonance Imaging (fMRI), we examined the processing of pictures from the Thematic Apperception Test (TAT) in 14 BPD patients and 14 controls. RESULTS: In both groups, TAT stimuli activated brain areas known to be involved in autobiographical memory retrieval. BPD subjects lacked differential amygdala, orbitofrontal and cingulate activations for TAT versus neutral stimuli. In the TAT condition, compared to controls, BPD subjects displayed increased BOLD responses in the bilateral orbitofrontal and insular regions, in the left anterior cingulate and medial prefrontal cortex, as well as in the parietal and parahippocampal areas, consistent with a more aversive and arousing experience assessed by self-reports. CONCLUSIONS: Increased BOLD responses during TAT processing in BPD subjects were in line with previously reported changes in anterior cingulate and orbitofrontal cortices, which are known to be involved in memory retrieval. However, BPD subjects displayed hyperactivation in these areas for both TAT and neutral stimuli. The deficit of selective activation of areas involved in autobiographical memory retrieval suggests a general tendency towards a self-referential mode of information processing in BPD, or a failure to switch between emotionally salient and neutral stimuli.     

Hallucinatory disorder: Preliminary data for a clinical diagnostic proposal

Introduction.?Chronic hallucinatory psychosis is a psychopathological profile reported in French literature but not included in the current Anglo‐American psychiatric classifications. We compared a group of patients with a clinical picture related to this syndrome to a group of patients with schizophrenia in order to evaluate the possibility of characterising hallucinatory disorder as a diagnostic entity.

Methods.?Nine patients with a clinical profile related to chronic hallucinatory psychosis were compared to a group of nine patients with schizophrenia. All of the patients were clinically evaluated using the measures: SCID‐P, GAF, BPRS, PANSS, SAPS, SANS, HRS‐A, HRS‐D, CDSS, MMSE, and CGI.

Results.?Analysis of the clinical rating scales characterised schizophrenia as comprising three dimensions (positive, negative, and disorganised symptoms), each of which contributes differently to the psychopathological profile of individual patients. However, the patients with hallucinatory disorder seemed to be mainly characterised by auditory verbal hallucinations, with relative sparing of the other functions typically altered in patients with schizophrenia.

Conclusions.?The significant differences between the patients in the two groups seem to support the hypothesis that hallucinatory disorder may be considered as being a separate nosographic entity, in which the clinical picture is dominated by the experience of auditory verbal hallucinations.     

Classification of cognitive performance in bipolar disorder

Objective: To understand the etiology of cognitive impairment associated with bipolar disorder, we need to clarify potential heterogeneity in cognitive functioning. To this end, we used multivariate techniques to study if the correlation structure of cognitive abilities differs between persons with bipolar disorder and controls.

Method: Clinically stable patients with bipolar disorder (type I: n?=?64; type II: n?=?44) and healthy controls (n?=?86) were assessed with a wide range of cognitive tests measuring executive function, speed, memory, and verbal skills. Data were analysed with multivariate techniques.

Results: A distinct subgroup (～30%) could be identified that performed significantly poorer on tests concerning memory function. This cognitive phenotype subgroup did not differ from the majority of bipolar disorder patients with respect to other demographic or clinical characteristics.

Conclusions: Whereas the majority of patients performed similar to controls, a subgroup of patients with bipolar disorder differed substantially from healthy controls in the correlation pattern of low-level cognitive abilities. This suggests that cognitive impairment is not a general trait in bipolar disorder but characteristic of a cognitive subgroup. This has important clinical implications for cognitive rehabilitation and remediation.     

Memory Fragmentation in Dissociative Identity Disorder

ABSTRACT

This study examined the quality of self-reported memories of traumatic experiences in participants with dissociative identity disorder (DID) and compared them with their memories of non-traumatic, but emotionally significant life experiences. Systematic interview data were gathered from 30 DID patients in The Netherlands. All participants reported a history of severe childhood abuse; 93.3% reported some period of amnesia for the index traumatic event, and 33.3% reported periods of amnesia for significant non-traumatic childhood experiences. All participants who had been amnestic for their trauma reported that their memories were initially retrieved in the form of somatosensory flashbacks. This suggests that, like PTSD patients, DID patients at least initially recall their trauma not as a narrative, but as somatosensory re-experiencing. Surprisingly, however, DID participants also recalled emotionally charged non-traumatic life events with significant somatosensory components, a phenomenon that has not been previously reported. This finding raises important issues regarding basic memory processing abnormalities in DID patients.