Antipsychotic treatment effects and structural MRI brain changes in schizophrenia.

BACKGROUND: Progressive brain structural MRI changes are described in schizophrenia and have been ascribed to both illness progression and antipsychotic treatment. We investigated treatment effects, in terms of total cumulative antipsychotic dose, efficacy and tolerability, on brain structural changes over the first 24 months of treatment in schizophrenia. METHODS: A prospective, 24-month, single-site cohort study in 99 minimally treated patients with first-episode schizophrenia, schizophreniform and schizoaffective disorder, and 98 matched healthy controls. We treated the patients according to a fixed protocol with flupenthixol decanoate, a long-acting injectable antipsychotic. We assessed psychopathology, cognition, extrapyramidal symptoms and BMI, and acquired MRI scans at months 0, 12 and 24. We selected global cortical thickness, white matter volume and basal ganglia volume as the regions of interest. RESULTS: The only significant group × time interaction was for basal ganglia volumes. However, patients, but not controls, displayed cortical thickness reductions and increases in white matter and basal ganglia volumes. Cortical thickness reductions were unrelated to treatment. White matter volume increases were associated with lower cumulative antipsychotic dose, greater improvements in psychopathology and cognition, and more extrapyramidal symptoms. Basal ganglia volume increases were associated with greater improvements in psychopathology, greater increases in BMI and more extrapyramidal symptoms. CONCLUSIONS: We provide evidence for plasticity in white matter and basal ganglia associated with antipsychotic treatment in schizophrenia, most likely linked to the dopamine blocking actions of these agents. Cortical changes may be more closely related to the neurodevelopmental, non-dopaminergic aspects of the illness.

Cognitive insight is associated with perceived body weight in overweight and obese adults.

BACKGROUND: Accurate perception of body weight is necessary for individuals with a high body mass index (BMI) to initiate strategies to improve their health status. Furthermore, identifying factors that influence accurate body weight perception can assist in designing appropriate educational and weight management programs. We therefore aimed to investigate whether levels of cognitive functioning and insight influence the ability to correctly judge body weight. METHODS: One hundred and eighty four overweight and obese adults who participated in a cross- sectional case-control study and were controls in the aforementioned study were included. The study was conducted in Cape Town, South Africa. Demographic, weight-related, neuropsychiatric, neurocognitive and cognitive insight measures were administered. Regression analysis was conducted to determine the factors associated with correct weight perception. RESULTS: The final regression model explained 52.3% of variation in accurate perception of body weight and was significant (p ≤ 0. 001). The model correctly classified 79.3% of individuals who were able to correctly and incorrectly judge their weight. Adults with higher BMI, and lower self-certainty, those who reported that they had gained weight in the previous year and those who were told by a healthcare professional to lose or maintain a healthy weight were more likely to correctly judge their weight. CONCLUSION: Some aspects of cognitive insight (self-certainty) but not cognitive functioning were associated with perception of body weight in this sample. Awareness of recent weight changes, higher BMI and advice from of health care professionals were also significantly associated with perception of body weight, while demographic variables were not. Understanding the factors that contribute to the correct perception of weight is important in identifying appropriate health interventions that may address the burden of associated non-communicable diseases in overweight and obese individuals.

Associations of premorbid adjustment with type and timing of childhood trauma in first-episode schizophrenia spectrum disorders.

BACKGROUND: Childhood trauma may contribute to poorer premorbid social and academic adjustment which may be a risk factor for schizophrenia. AIM: We explored the relationship between premorbid adjustment and childhood trauma, timing of childhood trauma's moderating role as well as the association of clinical and treatment-related confounders with premorbid adjustment. SETTING: We conducted a secondary analysis in 111 patients with first-episode schizophrenia (FES) disorders that formed part of two parent studies, EONKCS study (n =73) and the Shared Roots study (n =38). METHODS: Type of childhood trauma was assessed with the Childhood Trauma Questionnaire, short-form and premorbid adjustment using the Premorbid Adjustment Scale. Timing of childhood trauma was assessed using the Life Events Checklist and life events timeline. Linear regression analyses were used to assess the moderating effect of timing of childhood trauma. Clinical and treatment-related confounders were entered into sequential hierarchical regression models to identify independent predictors of premorbid adjustment across key life stages. RESULTS: Childhood physical neglect was associated with poorer premorbid academic functioning during childhood and early adolescence, and poorer premorbid social functioning during early and late adolescence. By hierarchical regression modelling (r 2 = 0.13), higher physical neglect subscale scores (p = 0.011) independently predicted poorer premorbid social adjustment during early adolescence. Timing of childhood trauma did not moderate the relationship between childhood trauma and premorbid functioning. CONCLUSION: In patients with FES, childhood physical neglect may contribute to poorer premorbid social functioning during early adolescence. This may provide us with an opportunity to identify and treat at-risk individuals earlier.

Rate and predictors of non-response to first-line antipsychotic treatment in first-episode schizophrenia.

OBJECTIVE: The goals of this study were to (i) estimate the rate of non-response to first-line treatment in first-episode schizophrenia, (ii) evaluate other outcomes associated with symptom non-response and (iii) identify demographic, baseline clinical and early treatment response predictors of non-response. METHODS: This was a single-site, longitudinal cohort study assessing the effects of treatment with flupenthixol decanoate according to a standardised protocol over 12 months in patients with schizophrenia, schizophreniform and schizo-affective disorders. RESULTS: Of 126 patients who received at least one dose of study medication, 84 (67%) completed the study. Fifteen (12%) met our predefined criteria for non-response. Non-responders were younger and at baseline had more prominent disorganised symptoms, poorer social and occupational functioning, poorer quality of life for psychological, social and environmental domains, more prominent neurological soft signs (NSS) and lower body mass index. At endpoint, the non-responders were characterised by higher levels of symptomatology in all domains, poorer functional outcome, poorer quality of life and greater cognitive impairments. They also had more prominent NSS and lower body mass index. The strongest predictors of non-response were more prominent baseline NSS and poor early (7 weeks) treatment response. CONCLUSIONS: Results are consistent with a lower rate of refractoriness to treatment in first-episode schizophrenia compared with multi-episode samples.

The invisibility of informal interpreting in mental health care in South Africa: notes towards a contextual understanding.

Despite South Africa's constitutional commitment to equality, represented by 11 official languages and the promotion of South African Sign Language, many users of the public health system receive treatment from people who cannot speak their language, and there are no formal interpreting services. This is a legacy of service provision from the apartheid era, and interpreting is currently undertaken by nurses, cleaners, security guards, and family members of patients, amongst others. We provide a preliminary outline of proximal and distal issues which may bear upon this situation. Changing understandings of the nature of careers in the health field, international trends in mental health theory and practice toward crude biologism, and ongoing patterns of social exclusion and stigma all contribute not only to a continuing state of compromised linguistic access to mental health care, but also to processes of rendering invisible the actual work of care in the mental health field.

A clinician-monitored 'PTSD Coach' intervention: findings from two pilot feasibility and acceptability studies in a resource-constrained setting.

Background: The high prevalence of trauma exposure and consequent post-traumatic stress disorder (PTSD) is well documented in low- and middle-income countries, and most individuals with PTSD have limited access to treatment in these settings. Freely available internet-based interventions, such as PTSD Coach (web-based and mobile application), can help to address this gap and improve access to and efficiency of care. Objective: We conducted two pilot studies to evaluate the feasibility, acceptability, and preliminary effectiveness of PTSD Coach in a South African resource-constrained context. Method: Pilot 1: Participants with PTSD (n = 10) were randomized to counsellor-supported PTSD Coach Online (PCO) or enhanced treatment as usual. Pilot 2: Participants (n = 10) were randomized to counsellor-supported PTSD Coach Mobile App or self-managed PTSD Coach Mobile App. Feasibility and acceptability were assessed by comparing attrition rates (loss to follow-up), reviewing participant and counsellor feedback contained in fieldnotes, and analysing data on the 'Perceived helpfulness of the PTSD Coach App' (Pilot 2). PTSD symptom severity was assessed with the Clinician Administered PTSD Scale for DSM-5 (CAPS-5), changes between treatment and control groups were compared, the reliable change index (RCI) was calculated, and clinically significant changes were determined. Results: Three participants in Pilot 1 and two participants in Pilot 2 were lost to follow-up. Fieldnotes indicated that PTSD Coach Mobile App addressed identified computer literacy challenges in Pilot 1 (PCO); and a shorter duration of intervention (from 8 to 4 weeks) was associated with less attrition. The RCI indicated that four participants in Pilot 1 and eight participants in Pilot 2 experienced significant improvement in PTSD symptom severity. Conclusions: The preliminary results suggest that both platforms can alleviate PTSD symptoms, and that the involvement of volunteer counsellors is beneficial. The use of PTSD Coach Mobile App may be more feasible than the online version (PCO) in our setting. HIGHLIGHTS Research on supported PTSD Coach interventions is limited in resource-constrained settings.Both volunteer counsellor-supported PTSD Coach Online and the PTSD Coach Mobile App showed preliminary reliable and clinically significant changes.The use of PTSD Coach Mobile App seems more feasible than the volunteer counsellor-supported PTSD Coach Online.

Antecedentes: La alta prevalencia de exposición a trauma y el consecuente trastorno de estrés postraumático (TEPT) están bien documentadas en países de bajos y medianos ingresos y la mayoría de los individuos con TEPT tiene acceso limitado a los tratamientos necesarios en estos entornos. Las intervenciones basadas en internet de acceso gratuito, como el 'PTSD Coach', nombre de la aplicación en inglés (disponible vía aplicación móvil y a través de la web), pueden ayudar a abordar esta brecha y mejorar el acceso y la eficiencia de la atención. Condujimos dos estudios piloto para evaluar la viabilidad, aceptabilidad y preliminarmente la efectividad del 'PTSD Coach' en un contexto con recursos limitados de Sudáfrica.Metodología: Piloto 1: Los participantes con TEPT (n = 10) fueron asignados al azar al 'PTSD Coach' en modalidad online (PCO en sus siglas en inglés) apoyado por un consejero o al tratamiento habitual mejorado. Piloto 2: Los participantes (n = 10) fueron asignados al azar al 'PTSD Coach' en modalidad de aplicación móvil apoyado por un consejero o a la aplicación móvil 'PTSD Coach' de manera auto-gestionada. La viabilidad y aceptabilidad se evaluaron comparando las tasas de deserción (perdida durante el seguimiento), revisando los comentarios de retroalimentación dados por los participantes y consejeros, los cuales se encontraban contenidos en las notas de campo, y analizando los datos en la 'Utilidad percibida de la aplicación PTSD Coach' (Piloto 2). La gravedad de los síntomas del TEPT se evaluaron con la Escala de TEPT Administrada por el Clínico (CAPS-5), donde se compararon los cambios entre los grupos de tratamiento y control, el índice de cambio confiable fue calculado y el cambio clínicamente significativo fue determinado.Resultados: En el Piloto 1 se perdieron en el seguimiento tres participantes y en el Piloto 2 se perdieron en el seguimiento dos participantes. Las notas de campo indicaron que la aplicación móvil del 'PTSD Coach' abordó los desafíos de la alfabetización informática en el Piloto 1 (PCO); y una intervención de duración más breve (de ocho a cuatro semanas) se asoció con menos deserción. En el Piloto 1 el RCI indicó que cuatro participantes experimentaron una mejoría significativa en la gravedad de los síntomas del TEPT, mientras que ocho indicaron una mejoría significativa en la gravedad de los síntomas del TEPT en el Piloto 2.Conclusiones: Los resultados preliminares sugieren que ambas plataformas pueden aliviar los síntomas de TEPT y que la participación de un consejero voluntario es beneficiosa. La aplicación móvil 'PTSD Coach' puede ser más factible que la versión en línea (PCO) en nuestro medio.

The association between hair cortisol levels, inflammation and cognitive functioning in females.

Glucocorticoids and inflammatory markers can influence cognitive function. Hair cortisol concentrations (HCC) reflect longer-term hypothalamic pituitary adrenal (HPA) axis function and combined with immune markers can provide insights into how HPA-axis and immune pathways interact to influence cognition. We examined the association between HCC and high sensitivity c-reactive protein (hsCRP) levels, as well as the interaction between HCC and hsCRP, and cognitive function in a sample of 153 females, aged between 18 and 79 years, from a cross-sectional case-control study (SHARED ROOTS), conducted in Cape Town, South Africa from May 2014 until June 2017. We examined whether HCC and hsCRP levels were associated with performance on neurocognitive tests in both unadjusted and adjusted linear regression models. HCC demonstrated a significant inverse association with verbal working memory in both unadjusted (p = 0.010) and adjusted (p = 0.016) analyses. There were significant interactions between HCC and hsCRP on verbal intelligence (p = 0.016), language (p = 0.023) and executive function (p = 0.008) scores, such that at low HCC hsCRP levels were positively associated with language (p = 0.020) and executive function (p = 0.006) scores and at high HCC hsCRP levels were inversely associated with verbal intelligence (p = 0.034) scores. Though the results did not survive correction for multiple comparisons, they suggest stress-related neuroendocrine effects on working memory impairment. Furthermore, under physiological conditions and low long-term HCC, there may be positive effects of peripheral inflammatory markers on cognitive performance, whereas there may be detrimental effects when the HPA-axis is dysregulated as reflected by high long-term cortisol output.

Differences in white matter microstructure in first-episode schizophrenia spectrum disorders vs healthy volunteers and their association with cognition.

OBJECTIVE: Both cognitive impairment and alterations in white matter tissue microstructure are well recognised in schizophrenia. We investigated whether differences in white matter microstructure underpin cognitive impairments in patients with first-episode schizophrenia spectrum disorders when controlling for multiple confounding factors. METHODS: We employed a cross-sectional study design and compared fractional anisotropy (FA) between individuals diagnosed with first- episode schizophrenia spectrum disorders (FES) (n = 68) and matched healthy controls (n = 120). We conducted multiple analyses of covariance (ANCOVAs) to compare the mean FA values for patients and controls across 27 white matter tracts. We conducted exploratory correlation analyses to determine if white matter tract differences were associated with global cognitive impairment as well as deficits across seven cognitive domains. RESULTS: We found widespread reductions in FA in patients compared to controls, after controlling for confounding variables, such as age, biological sex, education, substances, and childhood adversities. We found a significant positive correlation between the attention/vigilance domain and the splenium of the corpus collosum and external capsule after correction for multiple comparisons. In the control group we found no significant correlations between FA and cognition. CONCLUSION: Our findings provide a neurobiological basis for attentional cognitive deficits in schizophrenia, highlighting a potential role for the splenium of the corpus collosum and external capsule.

When roles within interpreter-mediated psychiatric consultations speak louder than words.

In South Africa, clinicians working in public psychiatric hospitals are mainly fluent in English and Afrikaans, while the majority of patients are not proficient in these languages. Due to a lack of professional interpreting services, informal, ad hoc interpreters are commonly employed in public psychiatric hospitals. We collected data on language practices in public psychiatric care in South Africa, and provide a detailed account of what happens when bilingual health care workers and cleaners haphazardly take on the additional role of interpreter. Data were collected during 2010 at a public psychiatric hospital in the Western Cape, South Africa. Thirteen interpreter-mediated psychiatric consultations were video-recorded, and 18 audio-recorded semi-structured interviews were conducted with the interpreters and clinicians who participated in the interpreter-mediated psychiatric consultations. Patients were proficient in isiXhosa (one of the 11 official languages of South Africa), the clinicians (all registrars) were first language English or Afrikaans speakers, while the health care workers (nurses and social workers) and cleaners were fluent in both the patients' and clinician's language. Our findings suggest that interpreters took on the following four roles during the interpreter-mediated psychiatric consultations: regulating turn-taking, cultural broker, gatekeeper and advocate. Our findings suggest that, despite interpreters and clinicians having the patient's best interests at heart, it is the patient's voice that becomes lost while the clinician and interpreter negotiate the roles played by each party.

The course and concomitants of depression in first-episode schizophrenia spectrum disorders: A 24-month longitudinal study.

Depressive symptoms are common in schizophrenia and have been associated with both favourable and unfavourable outcomes. We studied the longitudinal course of depressive symptoms and explored their temporal relationships with other manifestations of the illness and its treatment. This longitudinal cohort study included 126 antipsychotic naïve or only briefly treated patients with first-episode schizophrenia spectrum disorders treated with a long-acting antipsychotic over 24 months. Depressive symptoms were assessed at three monthly intervals using the Calgary Depression Scale for Schizophrenia and changes over time were assessed using linear mixed-effect models for continuous repeated measures. Depressive symptoms were most prominent at baseline with highly significant reductions during the first three months of treatment and maintenance of improvement thereafter. Most improvement occurred with antipsychotic treatment alone, with few patients requiring additional antidepressants. We also found that depressive symptoms were associated with positive symptoms, better insight and poorer quality of life, but not with negative symptoms, extrapyramidal symptoms, substance use or cumulative antipsychotic dose.There were few differences between patients who met criteria for depression during the acute phase of treatment and those in the post-acute phase.

Cannabis use and clinical outcome in people with first-episode schizophrenia spectrum disorders over 24 months of treatment.

Cannabis use is associated with an unfavourable course of illness in schizophrenia, although several factors may confound this association. In this longitudinal study, we explored the influence of cannabis use on baseline symptom severity and treatment outcomes in 98 patients with first-episode schizophrenia spectrum disorders treated with a long acting injectable antipsychotic over 24 months. Using mixed models for repeated measures, we compared visit-wise changes in psychopathology, social and occupational functioning and quality of life between recent/current cannabis users (n=45) and non-users (n=53). There were no significant group by time interactions for any of our outcomes, and with the exception of poorer functionality in cannabis users at baseline, no significant differences in these domains at baseline or month 24. Also, remission rates were similar. However, more cannabis users met our operationally defined relapse criteria compared to non-users, and more frequent cannabis use over the course of treatment, as assessed by positive urine toxicology testing, predicted relapse. Our results suggest that cannabis users do not have poorer treatment response than non-users in terms of symptom reduction over the 24 months of treatment. However, dose-related risk of relapse remains with ongoing cannabis use, possibly by directly reducing the threshold for psychotic breakthrough.

The association between resilience and psychosocial functioning in schizophrenia: A systematic review and meta-analysis.

The exploration of resilience in schizophrenia is recent and poorly understood. Literature suggests that exploration of the construct will help with the understanding of not only risk but also protective factors in individuals living with psychosis. We performed a systematic review and meta-analysis with the primary aim of synthesizing the evidence of an existing relationship between resilience and schizophrenia-spectrum disorders (SSD). We searched electronic databases for relevant articles that evaluated resilience and psychosocial functioning in participants with schizophrenia-spectrum disorders. Sixteen studies were deemed eligible for review. We also conducted a random-effects meta-analysis to explore resilience levels of study participants. Our findings highlight lower levels of resilience in SSD cohorts and poorer psychosocial functioning among those with low levels of resilience. Evidence also suggests that the presence of resilience in individuals with schizophrenia-spectrum disorders is associated with improved psychosocial functioning.

Ad hoc interpreters in South African psychiatric services: service provider perspectives.

Background: Language and communication lie at the heart of good quality mental health care and are a vital, yet complex, part of the diagnostic and treatment process. In South African mental health care, ad hoc interpreting arrangements are the status quo. However, these can cause both clinician and patient shame and distress.Objective: Though this issue has been researched from the point of view of informal interpreters, relatively little is known about psychiatrists' experiences of working with ad hoc interpreters. This study is part of an attempt to bridge that gap.Methods: We made use of a cross-sectional qualitative interview design. We interviewed seven psychiatrists working at a psychiatric hospital in the Western Cape of South Africa. Data were analysed manually using thematic analysis.Results:Five main themes can be identified from the data: miscommunication and other difficulties associated with the language barrier; the language barrier between clinicians and patients and a need for language services; participants' views on interpreting; the role of age, culture and gender; and the use of trained and untrained interpreters and using staff as interpreters.Conclusions: Psychiatrists experience numerous difficulties in conducting their work due to the language barrier. This has an impact on their ability to provide adequate mental health care to patients. There is a need for better language services to ensure that everyone that seeks mental health care can receive the same level of care. Currently, one's ability to speak a certain language will have a significant impact on the quality of care received.

The association between childhood trauma and treatment outcomes in schizophrenia spectrum disorders.

Childhood trauma exposure has been associated with poorer treatment outcomes in schizophrenia. Most studies to date have been conducted in naturalistic settings in which the outcome may have been mediated by factors such as poor adherence and substance abuse. We compared the effects of high vs low childhood trauma exposure on the treatment response over 24 months in 78 patients with first-episode schizophrenia spectrum disorders who received standardised treatment with a long acting injectable antipsychotic. Compared to the low childhood trauma group (n = 37), the high childhood trauma group (n = 41) received higher doses of antipsychotic medication and were less likely to achieve remission. When age, sex and cannabis use were controlled for, patients with high levels of childhood trauma had a slower treatment response for positive and disorganized symptom domains, although differences did not differ significantly at 24 months. While there were no differences in functional outcomes, self-rated quality of life was the domain that most clearly differentiated the high and low childhood trauma groups. High childhood trauma exposure was associated with lower quality of life scores at baseline, a lesser degree of improvement with treatment, and lower quality of life scores at 24 months.

Early recovery in the first 24 months of treatment in first-episode schizophrenia-spectrum disorders.

Studies assessing the treatment outcomes in first-episode schizophrenia have reported mixed results. While symptom improvement is frequently robust, when other domains are considered outcomes are generally poorer. We explored response trajectories, rates and predictors of recovery in the domains of core psychopathology, clinician-rated social and occupational functioning and patient-rated quality of life over 24 months of treatment in 98 patients with first-episode schizophrenia spectrum disorders who were treated with a long-acting antipsychotic medication. There was robust improvement in core psychopathology (effect size d = 3.36) and functionality (d = 1.78), with most improvement occurring within the first six months of treatment. In contrast, improvement in subjective quality of life was less marked (d = 0.37) and slower, only reaching significance after 12 months of treatment. Symptom remission was achieved by 70% of patients and over half met our criteria for functional remission and good quality of life. However, only 29% met the full criteria for recovery. Patients who met the recovery criteria had better premorbid adjustment, were less likely to be of mixed ethnicity and substance use emerged as the only modifiable predictor of recovery. Only 9% of our sample achieved both functional remission and good quality of life despite not being in symptom remission. We found high rates of symptom remission, functional remission and good quality of life in patients, although relatively few achieved recovery by meeting all three of the outcome criteria. Symptom remission is not a necessary prerequisite for functional remission and good quality of life, although few non-remitters achieve other recovery criteria.

Childhood trauma and hippocampal subfield volumes in first-episode schizophrenia and healthy controls.

Childhood trauma and schizophrenia are both associated with neuroanatomical abnormalities in the hippocampus, a stress-sensitive structure vulnerable to developmental insults. However, few studies have evaluated the effects of childhood trauma exposure on hippocampal morphometry in minimally treated first-episode schizophrenia patients. Here we aim to investigate the associations of childhood trauma with hippocampal subfield volumes in a cohort of antipsychotic-naive or minimally treated first-episode schizophrenia spectrum disorder patients and matched controls. 79 patients with first-episode schizophrenia spectrum disorder and 82 matched controls completed the childhood trauma questionnaire and underwent MRI assessment. Hippocampal subfields were reconstructed using FreeSurfer 6.0. We considered inter-correlations between the various subfields, by entering them as dependent variables into a multivariate analysis of co-variance (MANCOVA), modeling for interactions between diagnosis, childhood trauma total score and gender while controlling for substance use, scanner sequence and age. MANCOVA revealed a significant interaction between sex, childhood trauma total scores and diagnosis across hippocampal sub-regions (p = 0.012). Bonferroni corrected post-hoc analysis revealed a significant sex*diagnosis*childhood trauma score interaction for the hippocampal fissure (F(1,161) = 9.485,p = .002). Hippocampal fissure size showed a positive relationship with CA structures as well as whole hippocampal size in the larger sample. Findings from the present study suggest that childhood trauma exposure exerts illness-specific effects on hippocampal structures in female patients with first-episode schizophrenia, consistent with increased stress sensitivity in this group.

The 2019 Schizophrenia International Research Society Conference, 10-14 April, Orlando, Florida: A summary of topics and trends.

The Schizophrenia International Research Society (SIRS) recently held its first North American congress, which took place in Orlando, Florida from 10-14 April 2019. The overall theme of this year's congress was United in Progress - with the aim of cultivating a collaborative effort towards advancing the field of schizophrenia research. Student travel awardees provided reports of the oral sessions and concurrent symposia that took place during the congress. A collection of these reports is summarized and presented below and highlights the main themes and topics that emerged during the congress. In summary, the congress covered a broad range of topics relevant to the field of psychiatry today.

Childhood Trauma Associated White Matter Abnormalities in First-Episode Schizophrenia.

Schizophrenia is associated with brain connection irregularities within and between brain regions. Childhood trauma increases the risk of schizophrenia suggesting that the relationships between childhood trauma and brain connectivity requires further investigation. Here, we examine the relationship between childhood trauma (as measured by the Childhood Trauma Questionnaire) and fractional anisotropy (FA) in 54 minimally treated first-episode schizophrenia (FES) patients and 51 community matched controls. Patients who experienced high levels of trauma had significantly lower FA in the inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), and inferior fronto-occipital fasciculus (IFOF) compared with controls who experienced high levels of childhood trauma. A history of childhood sexual abuse in patients was associated with lower FA in the IFOF, ILF, SLF, and forceps major compared with patients without a history of sexual abuse. However, patients who had experienced childhood emotional neglect had higher FA in the right SLF compared to patients with low levels of emotional neglect. Our findings highlight altered cortico-limbic circuitry in FES patients compared with controls and differential effects of childhood emotional neglect and sexual abuse on white matter in patients. Although stress-related white matter (WM) pathways appear to be involved in both schizophrenia and otherwise healthy controls previously exposed to childhood trauma, the pattern of disruption of WM integrity in FES patients appears to be distinct.

Changes in insight over the first 24 months of treatment in schizophrenia spectrum disorders.

BACKGROUND: While insight in schizophrenia improves with treatment, significant impairments often persist. The degree of persistence is not well characterised. AIMS: We assessed patient and clinician-rated changes in insight in acutely ill, minimally treated first-episode schizophrenia spectrum disorder patients over 24 months of standardised treatment with a depot antipsychotic. METHOD: This single arm open label longitudinal cohort study included 105 participants with first-episode schizophrenia, schizophreniform or schizoaffective disorder. Insight was assessed at months 0, 6, 12 and 24 using the patient-rated Birchwood Insight Scale (BIS) and clinician-rated global insight item of the Positive and Negative Syndrome Scale (PANSS). Changes in insight over time were assessed using linear mixed-effect models for continuous repeated measures. Relationships between insight and psychopathology, functionality, cognition and quality of life were assessed with regression models. RESULTS: There was significant improvement over time for the PANSS insight item (p < 0.0001). However, the only significant improvement for the BIS was with the Need for Treatment subscale (p = 0.01). There were no significant improvements noted for the Symptom Attribution (p = 0.7) and Illness Awareness (p = 0.2) subscales, as well as the BIS Total score (p = 0.6). Apart from depressive symptoms at baseline, there were no significant predictors of patient-rated insight. CONCLUSIONS: Clinicians should note that, even when treatment is assured and response is favourable, fundamental impairments in patient-rated insight persist.

Efficacy and safety profile of paliperidone palmitate injections in the management of patients with schizophrenia: an evidence-based review.

The course of schizophrenia is characterized by multiple relapses, incomplete remission of symptoms, enduring cognitive deficits, and social and occupational functional impairments. Nonadherence to antipsychotic medication is a major determinant of this poor outcome. Long-acting injectable antipsychotics were developed specifically to address the nonadherence problem and are increasingly considered as an early treatment option, in an attempt to prevent accruing morbidity. This review focuses on paliperidone palmitate, the long-acting injectable (LAI) formulation of paliperidone. After considering the pharmacology of paliperidone palmitate, we review the randomized controlled trials, as well as pertinent observational, pragmatic studies for paliperidone once-monthly injections in schizophrenia. Finally, we review the recently introduced 3-monthly formulation of paliperidone palmitate. Taken together, the studies indicate that paliperidone palmitate (PP) has good efficacy compared with placebo and comparable with other antipsychotics including risperidone. The tolerability profile of PP is similar to that of risperidone, with the most important side effects being prolactin elevation, weight gain, and extrapyramidal symptoms. Advantages of PP include the extensive research database and clinical experience with paliperidone and its parent compound risperidone, the availability of different LAI formulations (once-monthly, 3-monthly, and perhaps even longer acting formulations in future), and the novel dose initiation procedure that provides rapid onset of action without the need for oral antipsychotic supplementation.