A phenomenological comparison of auditory hallucinations between borderline personality disorder and schizophrenia: A systematic review.

OBJECTIVE: Borderline personality disorder (BPD) with auditory hallucinations (AHs) may inadvertently be misdiagnosed with a primary psychotic disorder, such as schizophrenia (SZ). This misidentification can lead to challenges in providing effective psychological treatment. This review therefore aims to identify the phenomenological characteristics of AHs in BPD in comparison to SZ, as well as psychological interventions that explicitly target AHs in BPD. METHODS: A systematic review was conducted to summarise the existing evidence base regarding the phenomenological similarities and differences of AHs in BPD and SZ, along with the identification of psychological interventions for AHs in BPD. RESULTS: Eighteen studies were eligible for inclusion. Compared to the SZ group, BPD clients were characterised by more persistent and repetitive AHs, significantly more voice-related distress and appraisals of omnipotence, and an earlier age of onset of AHs. The BPD group also reported more severe depression and anxiety, a higher incidence of childhood trauma, and more negative self-schema. Cognitive Behaviour Therapy Coping Strategy Enhancement (CBT-CSE) might be a promising intervention to reduce AH-related distress in BPD, although further studies are required to determine its effectiveness. CONCLUSION: In order to prevent misdiagnosis of AHs in BPD, the DSM-5 may need to acknowledge the broader and more frequent occurrence of psychosis symptoms in BPD clients. Such clarification may enhance diagnostic practices and facilitate more timely access to treatment. There is also a need to develop and trial psychological interventions that explicitly target AHs in BPD.

The role of culture on the phenomenology of hallucinations and delusions, explanatory models, and help-seeking attitudes: A narrative review.

AIM: Culture has been posited to be involved in the formation and maintenance of delusions and hallucinations. The extent of these differences and how they affect explanatory models of psychosis and help-seeking attitudes remains to be understood. This review aims to present a cultural formulation to account for psychosis onset, symptom maintenance, and help-seeking attitudes. METHODS: A narrative review was conducted to summarize the existing evidence base regarding cross-cultural differences in hallucinatory and delusional prevalence, explanatory models, and help-seeking attitudes in First Episode Psychosis (FEP) and Non-FEP Schizophrenia samples. RESULTS: Sixteen studies were eligible for inclusion. In terms of positive symptom specificity, cross-cultural differences were found. Specifically, auditory and visual hallucinations occurred most frequently in African patients, persecutory and grandiose delusions occurred at higher rates in African, Pakistani, and Latino patients, while delusions of reference were most prevalent in White-British groups. Three explanatory models were identified. Westerners tended to endorse a bio-psychosocial explanation, which was associated with increased help-seeking, engagement, and positive medication attitudes. Asian, Latino, Polish, and Maori patients endorsed religious-spiritual explanatory models, while African patients opted for a bewitchment model. The religious-spiritual and bewitchment models were associated with a longer duration of untreated psychosis (DUP) and poorer engagement with mental health services. CONCLUSIONS: These findings highlight the important influence of culture in the formation and maintenance of positive symptoms of psychosis, engagement, and help-seeking attitudes across different ethnic groups. The incorporation of cultural beliefs in formulation development could facilitate enriched CBTp practices and improved engagement amongst different cultural groups with Early Intervention Services.

Thinking biases and their role in persecutory delusions: A systematic review.

AIM: Thinking biases are posited to be involved in the genesis and maintenance of delusions. Persecutory delusions are one of the most commonly occurring delusional subtypes and cause substantial distress and disability to the individuals experiencing them. Their clinical relevance confers a rationale for investigating them. Particularly, this review aims to elucidate which cognitive biases are involved in their development and persistence. METHODS: MEDLINE, Embase, PsycINFO and Global Health were searched from the year 2000 to June 2020. A formal narrative synthesis was employed to report the findings and a quality assessment of included studies was conducted. RESULTS: Twenty five studies were included. Overall, 18 thinking biases were identified. Hostility and trustworthiness judgement biases appeared to be specific to persecutory delusions while jumping to conclusions, self-serving attributional biases and belief inflexibility were proposed to be more closely related to other delusional subtypes. While the majority of the biases identified were suggested to be involved in delusion maintenance, hostility biases, need for closure and personalizing attributional biases were believed to also have aetiological influences. CONCLUSIONS: These findings show that some cognitive biases are specific to paranoid psychosis and appear to be involved in the formation and/or persistence of persecutory delusions.

Modifying illness beliefs in recent onset psychosis carers: Evaluating the impact of a cognitively focused brief group intervention in a routine service.

AIMS: At first-episode psychosis (FEP), many patients will be routed within familial networks and supported by informal carers who are predominately close family members such as parents. Carer burden, distress and poorer coping styles are associated with different illness beliefs. The current study sought to examine the impact and acceptability of a 3 session, cognitively informed, group intervention targeting illness beliefs previously linked to distress and poorer caregiving experiences in FEP carers. METHODS: Carers attending a routine FEP service were invited to attend the group intervention and completed a measure of illness beliefs at baseline and post intervention. RESULTS: Data on 68 carers with complete datasets are presented. Carers were predominately females (64.2%). Group attendance was linked to positive improvements in carer baseline beliefs about the negative consequences of the illness for the patient and themselves, attributions of blame about the illness to the patient and themselves and their overall understanding about the illness. Significant improvements in their understanding of the illness timeline and course, and confidence in dealing with difficulties were also identified. CONCLUSIONS: A cognitively informed group approach to targeting the less adaptive illness beliefs reported by FEP carers may offer an effective and acceptable pathway to facilitate their understanding of the illness and adjustment. Further studies using controlled designs are required.

New insights into the endophenotypic status of cognition in bipolar disorder: genetic modelling study of twins and siblings.

BACKGROUND: Twin studies have lacked statistical power to apply advanced genetic modelling techniques to the search for cognitive endophenotypes for bipolar disorder. AIMS: To quantify the shared genetic variability between bipolar disorder and cognitive measures. METHOD: Structural equation modelling was performed on cognitive data collected from 331 twins/siblings of varying genetic relatedness, disease status and concordance for bipolar disorder. RESULTS: Using a parsimonious AE model, verbal episodic and spatial working memory showed statistically significant genetic correlations with bipolar disorder (rg = |0.23|-|0.27|), which lost statistical significance after covarying for affective symptoms. Using an ACE model, IQ and visual-spatial learning showed statistically significant genetic correlations with bipolar disorder (rg = |0.51|-|1.00|), which remained significant after covarying for affective symptoms. CONCLUSIONS: Verbal episodic and spatial working memory capture a modest fraction of the bipolar diathesis. IQ and visual-spatial learning may tap into genetic substrates of non-affective symptomatology in bipolar disorder.

Heritability of the limbic networks.

Individual differences in cognitive ability and social behaviour are influenced by the variability in the structure and function of the limbic system. A strong heritability of the limbic cortex has been previously reported, but little is known about how genetic factors influence specific limbic networks. We used diffusion tensor imaging tractography to investigate heritability of different limbic tracts in 52 monozygotic and 34 dizygotic healthy adult twins. We explored the connections that contribute to the activity of three distinct functional limbic networks, namely the dorsal cingulum ('medial default-mode network'), the ventral cingulum and the fornix ('hippocampal-diencephalic-retrosplenial network') and the uncinate fasciculus ('temporo-amygdala-orbitofrontal network'). Genetic and environmental variances were mapped for multiple tract-specific measures that reflect different aspects of the underlying anatomy. We report the highest heritability for the uncinate fasciculus, a tract that underpins emotion processing, semantic cognition, and social behaviour. High to moderate genetic and shared environmental effects were found for pathways important for social behaviour and memory, for example, fornix, dorsal and ventral cingulum. These findings indicate that within the limbic system inheritance of specific traits may rely on the anatomy of distinct networks and is higher for fronto-temporal pathways dedicated to complex social behaviour and emotional processing.

Age-Related Differences and Heritability of the Perisylvian Language Networks.

Acquisition of language skills depends on the progressive maturation of specialized brain networks that are usually lateralized in adult population. However, how genetic and environmental factors relate to the age-related differences in lateralization of these language pathways is still not known. We recruited 101 healthy right-handed subjects aged 9-40 years to investigate age-related differences in the anatomy of perisylvian language pathways and 86 adult twins (52 monozygotic and 34 dizygotic) to understand how heritability factors influence language anatomy. Diffusion tractography was used to dissect and extract indirect volume measures from the three segments of the arcuate fasciculus connecting Wernicke's to Broca's region (i.e., long segment), Broca's to Geschwind's region (i.e., anterior segment), and Wernicke's to Geschwind's region (i.e., posterior segment). We found that the long and anterior arcuate segments are lateralized before adolescence and their lateralization remains stable throughout adolescence and early adulthood. Conversely, the posterior segment shows right lateralization in childhood but becomes progressively bilateral during adolescence, driven by a reduction in volume in the right hemisphere. Analysis of the twin sample showed that genetic and shared environmental factors influence the anatomy of those segments that lateralize earlier, whereas specific environmental effects drive the variability in the volume of the posterior segment that continues to change in adolescence and adulthood. Our results suggest that the age-related differences in the lateralization of the language perisylvian pathways are related to the relative contribution of genetic and environmental effects specific to each segment. SIGNIFICANCE STATEMENT: Our study shows that, by early childhood, frontotemporal (long segment) and frontoparietal (anterior segment) connections of the arcuate fasciculus are left and right lateralized, respectively, and remain lateralized throughout adolescence and early adulthood. In contrast, temporoparietal (posterior segment) connections are right lateralized in childhood, but become progressively bilateral during adolescence. Preliminary twin analysis suggested that lateralization of the arcuate fasciculus is a heterogeneous process that depends on the interplay between genetic and environment factors specific to each segment. Tracts that exhibit higher age effects later in life (i.e., posterior segment) appear to be influenced more by specific environmental factors.

Interaction between effects of genes coding for dopamine and glutamate transmission on striatal and parahippocampal function.

The genes for the dopamine transporter (DAT) and the D-Amino acid oxidase activator (DAOA or G72) have been independently implicated in the risk for schizophrenia and in bipolar disorder and/or their related intermediate phenotypes. DAT and G72 respectively modulate central dopamine and glutamate transmission, the two systems most robustly implicated in these disorders. Contemporary studies have demonstrated that elevated dopamine function is associated with glutamatergic dysfunction in psychotic disorders. Using functional magnetic resonance imaging we examined whether there was an interaction between the effects of genes that influence dopamine and glutamate transmission (DAT and G72) on regional brain activation during verbal fluency, which is known to be abnormal in psychosis, in 80 healthy volunteers. Significant interactions between the effects of G72 and DAT polymorphisms on activation were evident in the striatum, parahippocampal gyrus, and supramarginal/angular gyri bilaterally, the right insula, in the right pre-/postcentral and the left posterior cingulate/retrosplenial gyri (P < 0.05, FDR-corrected across the whole brain). This provides evidence that interactions between the dopamine and the glutamate system, thought to be altered in psychosis, have an impact in executive processing which can be modulated by common genetic variation.

Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder.

Studies of the major psychoses, schizophrenia (SZ) and bipolar disorder (BD), have traditionally focused on genetic and environmental risk factors, although more recent work has highlighted an additional role for epigenetic processes in mediating susceptibility. Since monozygotic (MZ) twins share a common DNA sequence, their study represents an ideal design for investigating the contribution of epigenetic factors to disease etiology. We performed a genome-wide analysis of DNA methylation on peripheral blood DNA samples obtained from a unique sample of MZ twin pairs discordant for major psychosis. Numerous loci demonstrated disease-associated DNA methylation differences between twins discordant for SZ and BD individually, and together as a combined major psychosis group. Pathway analysis of our top loci highlighted a significant enrichment of epigenetic changes in biological networks and pathways directly relevant to psychiatric disorder and neurodevelopment. The top psychosis-associated, differentially methylated region, significantly hypomethylated in affected twins, was located in the promoter of ST6GALNAC1 overlapping a previously reported rare genomic duplication observed in SZ. The mean DNA methylation difference at this locus was 6%, but there was considerable heterogeneity between families, with some twin pairs showing a 20% difference in methylation. We subsequently assessed this region in an independent sample of postmortem brain tissue from affected individuals and controls, finding marked hypomethylation (>25%) in a subset of psychosis patients. Overall, our data provide further evidence to support a role for DNA methylation differences in mediating phenotypic differences between MZ twins and in the etiology of both SZ and BD.

Stroop-test interference in bipolar disorder.

We analysed Stroop (neuropsychological screening test) measures of response inhibition in 18 twin pairs discordant for bipolar I disorder compared with 17 healthy control pairs, as well as 40 singletons with bipolar disorder with psychotic features and a family history of psychosis, 46 of their first-degree relatives without bipolar disorder or psychosis and 48 controls. In both studies, individuals with bipolar disorder showed Stroop deficits and their first-degree relatives showed intact performance. In the twin patients, an interference score was associated with depressive symptoms. Having a first-degree relative with bipolar disorder, even a familial, psychotic form, did not confer risk for enhanced susceptibility to interference in our studies.