A 52-week prophylactic randomised control trial of omega-3 polyunsaturated fatty acids in bipolar disorder.

OBJECTIVES: Previous work suggests supplementation with omega-3 polyunsaturated fatty acids (PUFAs) may improve mood symptoms in bipolar disorder (BD) although findings remain unclear. In this study, we assess the efficacy of omega-3 PUFA administration for prophylaxis in BD using a clinical trial design over 52-weeks (ClinicalTrials.gov Identifier: NCT04210804). METHODS: Individuals with BD (n = 80) were randomised to receive placebo (n = 40) or 1 g eicosapentaenoic acid (EPA) plus 1 g docosahexaenoic acid (DHA; n = 40) adjunctively for 52-weeks. The primary outcome measure comprised the number of mood episode relapses including hospital admissions and medication changes experienced. Secondary outcome measures included time to first mood episode relapse and change in psychometric measures of depression and elation (Hamilton Depression Rating Scale and Young Mania Rating Scale). RESULTS: No significant differences in the number of mood episode relapses (U = 490.00, p = 0.14) or the number of individuals requiring admission to hospital (χ2  = 0.67, p = 0.41) or medication adjustment in the omega-3 PUFA compared to the placebo group were noted. Time to relapse was not significantly different between groups (Log Rank χ2  = 0.41, p = 0.52). Change in Young Manic Rating Scale (F(3.12, 152.86) = 2.71, p = 0.05) was significantly different between treatment groups over 12-months, with scores at 9-months and 12-months significantly lower than those at 3-months in the omega-3 group and not in the placebo group. Change in Hamilton Depression Rating Scale, Global Clinical Impression and Global Assessment of Functioning were not different between groups. CONCLUSIONS: Despite a minor reduction in hypomania scores in the omega-3 PUFA group compared to placebo, we find little evidence that the supplementation of omega-3-PUFAs exhibits prophylactic benefit in BD.

Neuroanatomical Dysconnectivity Underlying Cognitive Deficits in Bipolar Disorder.

BACKGROUND: Graph theory applied to brain networks is an emerging approach to understanding the brain's topological associations with human cognitive ability. Despite well-documented cognitive impairments in bipolar disorder (BD) and recent reports of altered anatomical network organization, the association between connectivity and cognitive impairments in BD remains unclear. METHODS: We examined the role of anatomical network connectivity derived from T1- and diffusion-weighted magnetic resonance imaging in impaired cognitive performance in individuals with BD (n = 32) compared with healthy control individuals (n = 38). Fractional anisotropy- and number of streamlines-weighted anatomical brain networks were generated by mapping constrained spherical deconvolution-reconstructed white matter among 86 cortical/subcortical bilateral brain regions delineated in the individual's own coordinate space. Intelligence and executive function were investigated as distributed functions using measures of global, rich-club, and interhemispheric connectivity, while memory and social cognition were examined in relation to subnetwork connectivity. RESULTS: Lower executive functioning related to higher global clustering coefficient in participants with BD, and lower IQ performance may present with a differential relationship between global and interhemispheric efficiency in individuals with BD relative to control individuals. Spatial recognition memory accuracy and response times were similar between diagnostic groups and associated with basal ganglia and thalamus interconnectivity and connectivity within extended anatomical subnetworks in all participants. No anatomical subnetworks related to episodic memory, short-term memory, or social cognition generally or differently in BD. CONCLUSIONS: Results demonstrate selective influence of subnetwork patterns of connectivity in underlying cognitive performance generally and abnormal global topology underlying discrete cognitive impairments in BD.

Bipolar Disorder and Gender Are Associated with Frontolimbic and Basal Ganglia Dysconnectivity: A Study of Topological Variance Using Network Analysis.

Well-established structural abnormalities, mostly involving the limbic system, have been associated with disorders of emotion regulation. Understanding the arrangement and connections of these regions with other functionally specialized cortico-subcortical subnetworks is key to understanding how the human brain's architecture underpins abnormalities of mood and emotion. We investigated topological patterns in bipolar disorder (BD) with the anatomically improved precision conferred by combining subject-specific parcellation/segmentation with nontensor-based tractograms derived using a high-angular resolution diffusion-weighted approach. Connectivity matrices were constructed using 34 cortical and 9 subcortical bilateral nodes (Desikan-Killiany), and edges that were weighted by fractional anisotropy and streamline count derived from deterministic tractography using constrained spherical deconvolution. Whole-brain and rich-club connectivity alongside a permutation-based statistical approach was used to investigate topological variance in predominantly euthymic BD relative to healthy volunteers. BP patients (n = 40) demonstrated impairments across whole-brain topological arrangements (density, degree, and efficiency), and a dysconnected subnetwork involving limbic and basal ganglia relative to controls (n = 45). Increased rich-club connectivity was most evident in females with BD, with frontolimbic and parieto-occipital nodes not members of BD rich-club. Increased centrality in females relative to males was driven by basal ganglia and fronto-temporo-limbic nodes. Our subject-specific cortico-subcortical nontensor-based connectome map presents a neuroanatomical model of BD dysconnectivity that differentially involves communication within and between emotion-regulatory and reward-related subsystems. Moreover, the female brain positions more dependence on nodes belonging to these two differently specialized subsystems for communication relative to males, which may confer increased susceptibility to processes dependent on integration of emotion and reward-related information.

The Arcuate Fasciculus Network and Verbal Deficits in Psychosis.

BACKGROUND: Verbal learning (VL) and fluency (VF) are prominent cognitive deficits in psychosis, of which the precise neuroanatomical contributions are not fully understood. We investigated the arcuate fasciculus (AF) and its associated cortical regions to identify structural abnormalities contributing to these verbal impairments in early stages of psychotic illness. METHODS: Twenty-six individuals with recent-onset psychosis and 27 healthy controls underwent cognitive testing (MATRICS Consensus Cognitive Battery) and structural/diffusion-weighted MRI. Bilaterally, AF anisotropy and cortical thickness, surface area and volume of seven cortical regions were investigated in relation to VL and VF performance in both groups. RESULTS: Reduced right superior temporal gyrus surface area and volume related to better VF in controls. In psychosis, greater right pars opercularis volume and reduced left lateralization of this region related to better VL, while greater right long AF fractional anisotropy and right pars orbitalis volume related to better VF, these findings not present in controls. Psychosis had reduced right pars orbitalis thickness compared to controls. CONCLUSION: Anatomical substrates for normal processing of VL and VF appear altered in recent-onset psychosis. A possible aberrant role of the right hemisphere arcuate fasciculus and fronto-temporal cortical regions in psychosis may contribute to deficits in VL and VF.

Clozapine-induced hypersalivation: an estimate of prevalence, severity and impact on quality of life.

OBJECTIVES: The objective of this study was to evaluate the prevalence and severity of clozapine-induced hypersalivation, and assess the impact hypersalivation has on global functioning. METHODS: Participants attending a dedicated clozapine clinic were invited to undertake a structured interview regarding their experiences of clozapine-induced hypersalivation. Two psychometric instruments to measure hypersalivation, the Nocturnal Hypersalivation Rating Scale and the Drooling Severity and Frequency Scale were used. RESULTS: Clozapine-induced hypersalivation was experienced by 92% of participants, with nocturnal hypersalivation more prevalent compared to daytime hypersalivation (85% versus 48%). Daytime drooling was severe in 18% of cases and was present on a frequent or constant basis for 20% of individuals. Hypersalivation had at least a moderate impact on the quality of life of 15% of study participants. CONCLUSIONS: Clozapine-induced hypersalivation is the most prevalent adverse effect experienced by patients treated with clozapine and negatively impacts on quality of life, particularly if daytime drooling is present. The development of further strategies to ameliorate this adverse effect is required given the demonstrated lack of success to date in managing this condition.

Cognitive course in first-episode psychosis and clinical correlates: A 4 year longitudinal study using the MATRICS Consensus Cognitive Battery.

While cognitive impairments are prevalent in first-episode psychosis, the course of these deficits is not fully understood. Most deficits appear to remain stable, however there is uncertainty regarding the trajectory of specific cognitive domains after illness onset. This study investigates the longitudinal course of cognitive deficits four years after a first-episode of psychosis and the relationship of performance with clinical course and response to treatment. Twenty three individuals with psychotic illness, matched with 21 healthy volunteers, were assessed using the MATRICS Consensus Cognitive Battery at illness onset and 4 years later. We also investigated the relationship between cognitive deficits and quality of life and clinical indices. Verbal learning and two measures of processing speed had marked poorer trajectory over four years compared to the remaining cognitive domains. Processing speed performance was found to contribute to the cognitive deficits in psychosis. Poorer clinical outcome was associated with greater deficits at illness onset in reasoning and problem solving and social cognition. Cognitive deficits did not predict quality of life at follow-up, nor did diagnosis subtype differentiate cognitive performance. In conclusion, an initial psychotic episode may be associated with an additional cost on verbal learning and two measures of processing speed over a time spanning at least four years. Moreover, processing speed, which has been manipulated through intervention in previous studies, may represent a viable therapeutic target. Finally, cognition at illness onset may have a predictive capability of illness course.

Childhood trauma levels in individuals attending adult mental health services: An evaluation of clinical records and structured measurement of childhood trauma.

Despite an increased awareness regarding the prevalence and impact of childhood trauma, especially childhood sexual abuse (CSA), few studies examine the clinical reporting of such childhood experiences. This study compared the prevalence of childhood trauma recorded in individual's clinical notes to those ascertained with a structured validated questionnaire, examined which forms of childhood trauma were less likely to be reported to the treating mental health team and established which demographic or clinical factors were associated with reporting of childhood trauma. The prevalence of childhood trauma was ascertained using both the Childhood Trauma Questionnaire (CTQ) and a lifetime retrospective clinical note review in 129 individuals attending a general adult mental health service. Individuals were evaluated for the presence of mental health disorders, impulsivity, symptom severity and disability. Using the CTQ, childhood trauma was noted in 77% of individuals and recorded in 38% of individual's clinical notes (p<0.001). The greatest differences between CTQ reporting and clinical note documentation were noted for emotional neglect (62% versus 13.2%), physical neglect (48.1% versus 5.4%) and CSA (24.8% versus 8.5%). Childhood trauma was associated with increased psychopathology and greater symptom severity, and was particularly prevalent for individuals with personality disorders. This study demonstrated high rates of childhood trauma amongst adults attending a general adult mental health service. Furthermore, we demonstrated high rates of either non-enquiry from mental health professionals and/or high rates of non-documentation of childhood trauma by mental health professionals. Given the disparity between reporting of childhood trauma in clinical notes and findings with the CTQ, the use of a standardised questionnaire for the assessment of childhood trauma should be considered when performing a comprehensive mental health history.

A case of paliperidone-palmitate-induced tardive dyskinesia.

OBJECTIVES: This is one of the first cases reported in the literature of paliperidone-palmitate-induced prolonged dyskinesia. METHOD: Case report. RESULTS: We report the case of a 49-year-old woman with paranoid schizophrenia who developed orofacial dyskinesia some 4 months after the commencement of paliperidone long-acting injection. CONCLUSION: This case serves as a clinical reminder that dyskinesia can occur with all antipsychotic medications.

Patient satisfaction with psychiatric outpatient care in a university hospital setting.

OBJECTIVES: To measure patient satisfaction with psychiatric outpatient care in a university hospital setting. We wished to ascertain whether there was an association between increased patient satisfaction and background factors such as demographic details, diagnosis and patient preference for outpatient treatment in a hospital or a community setting. METHODS: We conducted a cross-sectional survey of individuals' satisfaction levels with their outpatient treatment. Outpatients were invited to complete the Client Satisfaction Questionnaire-8 (CSQ-8), a well validated self-report instrument, along with some additional questions on their attitudes to the service. RESULTS: One hundred and sixty-two respondents had a mean total CSQ-8 score of 26.7 (s.d. = 4.6) indicating a moderate to high level of satisfaction with outpatient care. Ninety percent of patients were satisfied with their psychiatric outpatient care. There were no significant sociodemographic or clinical associations with satisfaction levels identified. Sixty one percent of patients were in favour of retaining outpatient care in the university hospital. CONCLUSIONS: This study demonstrates high satisfaction levels with psychiatric outpatient care in a university hospital setting. The majority of patients expressed a preference for maintaining outpatient care in the general hospital setting, rather than transferring to a stand-alone mental health facility in a suburban setting.

Quinacrine induced mood disturbance--the unmasking of bipolar affective disorder.

The authors report the case of a 20-year-old man who presented with a de novo episode of hypomania subsequent to the initiation of quinacrine for treatment resistant giardiasis. The hypomanic episode commenced some 20 days after the successful completion of a week long course of quinacrine 100 mg three times daily. The hypomanic episode was treated with olanzapine 10 mg daily. Two months subsequent to this, the patient developed a moderate depressive episode which was treated with escitalopram and olanzapine. One month after the resolution of the depressive episode, he once again presented with a hypomanic episode. The recurring episodes of discrete mood disturbance all occurred within 5 months of the commencement of quinacrine in an individual with no personal history of affective disorders.

Delayed Onset of Neuropsychiatric Effects Associated with Montelukast.

Montelukast (a leukotriene receptor antagonist) is a commonly prescribed medication used in the management of asthma in both children and adults. It has been associated with a possible increased risk of various neuropsychiatric events in post-marketing analyses of clinical trial data and surveillance studies. When establishing a link between a medication and side effects, it is usual to establish and enquire whether there is a chronological relationship between the commencement of the medication and the onset of the symptoms. We report a case where a number of unusual neuropsychiatric events were reported several years after commencement of montelukast in a young boy who may have a genetic predisposition and a likely psychological trigger. There was complete resolution of these symptoms upon the withdrawal of montelukast.