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The British Journal of General Practice... Jun 2024Early Intervention in Psychosis (EIP) services offer treatment to people experiencing a first episode of psychosis. Service users may be referred from primary care and...
BACKGROUND
Early Intervention in Psychosis (EIP) services offer treatment to people experiencing a first episode of psychosis. Service users may be referred from primary care and discharged directly back at the end of their time in an EIP service.
AIM
To explore the role of primary care in supporting EIP service users (SUs) and to understand how to improve collaboration between primary and specialist care.
METHOD
Qualitative study comprising semi-structured interviews with SUs, carers, healthcare professionals (HCPs), managers, and commissioners. Interviews were conducted either online or by telephone. Thematic analysis was carried out using principles of constant comparison. Patient and public involvement were key to all stages, including data analysis.
RESULTS
In total, 55 interviews were conducted with SUs ( = 13), carers ( = 10), and GPs, EIP HCPs, managers, and commissioners ( = 33). GPs reported difficulties in referring people into EIP services and little contact with SUs while in EIP services, even about physical health. GPs suggested they were not included in planning discharge from EIP to primary care. SUs and carers reported that transition from EIP can lead to uncertainty, distress, and exacerbation of symptoms. GPs reported only being made aware of patients on or after discharge, with no contact for 3 years. GPs described difficulty managing complex medication regimes, and barriers to re-referral to mental health services.
CONCLUSION
GPs have a key role in supporting people within EIP services, specifically monitoring and managing physical health. Inclusion of GPs in planning discharge from EIP services is vital.
Topics: Humans; Primary Health Care; Psychotic Disorders; Qualitative Research; Early Medical Intervention; Referral and Consultation; Male; Female; Mental Health Services; Attitude of Health Personnel; Adult; Caregivers
PubMed: 38902097
DOI: 10.3399/bjgp24X737541 -
The British Journal of General Practice... Jun 2024It is estimated 20-70% of those living with a dementia diagnosis experience dementia-related psychosis (D-RP). D-RP results in decreased quality of life, increased carer...
BACKGROUND
It is estimated 20-70% of those living with a dementia diagnosis experience dementia-related psychosis (D-RP). D-RP results in decreased quality of life, increased carer burden, increased rapid cognitive decline, increased need for primary care support, and earlier care/nursing home admission, all which come at a considerable cost to the NHS. Antipsychotic medications prescribed by primary care services are typically used as treatment but have short-term efficacy and dangerous side effects. Effective management with the use of non-pharmacological interventions could safely improve the quality of life of those living with dementia, as well as reduce burden on primary care services and GPs.
AIM
To evaluate the effectiveness of non-pharmacological interventions in the management of D-RP. Studies that measure the effect of non-pharmacological interventions on patient or caregiver quality of life or determine the cost-effectiveness and safety of non-pharmacological interventions against antipsychotic medications will also be included.
METHOD
A global systematic literature review was conducted in Medline, Embase, PsychInfo, CINAHL, Web of Science, and CENTRAL. Included studies were analysed using meta-analysis and narrative synthesis. The protocol is registered with PROSPERO (ID: CRD42022294750).
RESULTS
Data extraction of 18 included papers revealed 4 interventions to show evidence of efficacy in improving D-RP in older adults. Person-centred care, robot pets, cognitive rehabilitation, and music therapy significantly decreased psychosis in care homes and in participants living at home. These results are discussed, and implications noted.
CONCLUSION
Future RCTs should focus on specifically improving D-RP, as this was not the primary aim for many interventions.
Topics: Humans; Dementia; Psychotic Disorders; Quality of Life; Caregivers; Primary Health Care; Antipsychotic Agents; Cost-Benefit Analysis
PubMed: 38902088
DOI: 10.3399/bjgp24X737445 -
Progress in Neuro-psychopharmacology &... Jun 2024Schizophrenia is a prevalent mental disorder, leading to severe disability. Currently, the absence of objective biomarkers hinders effective diagnosis. This study was...
BACKGROUND
Schizophrenia is a prevalent mental disorder, leading to severe disability. Currently, the absence of objective biomarkers hinders effective diagnosis. This study was conducted to explore the aberrant spontaneous brain activity and investigate the potential of abnormal brain indices as diagnostic biomarkers employing machine learning methods.
METHODS
A total of sixty-one schizophrenia patients and seventy demographically matched healthy controls were enrolled in this study. The static indices of resting-state functional magnetic resonance imaging (rs-fMRI) including amplitude of low frequency fluctuations (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), and degree centrality (DC) were calculated to evaluate spontaneous brain activity. Subsequently, a sliding-window method was then used to conduct temporal dynamic analysis. The comparison of static and dynamic rs-fMRI indices between the patient and control groups was conducted using a two-sample t-test. Finally, the machine learning analysis was applied to estimate the diagnostic value of abnormal indices of brain activity.
RESULTS
Schizophrenia patients exhibited a significant increase ALFF value in inferior frontal gyrus, alongside significant decreases in fALFF values observed in left postcentral gyrus and right cerebellum posterior lobe. Pervasive aberrations in ReHo indices were observed among schizophrenia patients, particularly in frontal lobe and cerebellum. A noteworthy reduction in voxel-wise concordance of dynamic indices was observed across gray matter regions encompassing the bilateral frontal, parietal, occipital, temporal, and insular cortices. The classification analysis achieved the highest values for area under curve at 0.87 and accuracy at 81.28% when applying linear support vector machine and leveraging a combination of abnormal static and dynamic indices in the specified brain regions as features.
CONCLUSIONS
The static and dynamic indices of brain activity exhibited as potential neuroimaging biomarkers for the diagnosis of schizophrenia.
PubMed: 38901758
DOI: 10.1016/j.pnpbp.2024.111066 -
Journal of Clinical PsychopharmacologyDeutetrabenazine is approved for adults with tardive dyskinesia (TD). Data based on underlying psychiatric condition and baseline dopamine receptor antagonist (DRA) use...
Deutetrabenazine Provides Long-Term Benefit for Tardive Dyskinesia Regardless of Underlying Condition and Dopamine Receptor Antagonist Use: A Post Hoc Analysis of the 3-Year, Open-Label Extension Study.
BACKGROUND
Deutetrabenazine is approved for adults with tardive dyskinesia (TD). Data based on underlying psychiatric condition and baseline dopamine receptor antagonist (DRA) use are limited.
METHODS
Patients with TD who completed parent studies ARM-TD or AIM-TD were eligible for the 3-year, open-label extension study (RIM-TD; NCT02198794). In RIM-TD, deutetrabenazine was titrated based on dyskinesia control and tolerability. In this post hoc analysis of RIM-TD, total motor Abnormal Involuntary Movement Scale (AIMS) score and adverse events (AEs) were analyzed by underlying condition and DRA use at parent study baseline.
RESULTS
Of 343 patients enrolled in RIM-TD, 336 were included in the analysis by underlying condition, and 337 were included in the analysis by DRA use. One hundred eighty-nine of 205 (92%) patients with psychotic disorders (schizophrenia/schizoaffective disorder) and 65 of 131 (50%) with mood and other disorders (depression/bipolar disorder/other) were receiving a DRA. Mean (SE) deutetrabenazine doses at week 145 were 40.4 (1.13), 38.5 (1.21), 39.9 (1.00), and 38.5 (1.48) mg/d for patients with psychotic disorders, those with mood and other disorders, and those receiving DRAs or not, respectively. Mean (SD) changes in total motor AIMS score from this study baseline to week 145 were -6.3 (4.53), -7.1 (4.92), -6.1 (4.42), and -7.5 (5.19). Exposure-adjusted incidence rates (number of AEs/patient-years) of AEs were similar across groups: any (1.02, 1.71, 1.08, 1.97), serious (0.10, 0.12, 0.10, 0.12), and leading to discontinuation (0.07, 0.05, 0.06, 0.05).
CONCLUSIONS
Long-term deutetrabenazine provided clinically meaningful improvements in TD-related movements, with a favorable benefit-risk profile, regardless of underlying condition or DRA use.
Topics: Humans; Tardive Dyskinesia; Male; Female; Tetrabenazine; Middle Aged; Adult; Dopamine Antagonists; Psychotic Disorders; Aged; Antipsychotic Agents; Schizophrenia; Treatment Outcome
PubMed: 38901008
DOI: 10.1097/JCP.0000000000001885 -
Journal of Clinical PsychopharmacologyPsychotic bipolar depression (PBD) is a prevalent yet understudied psychiatric illness, and there are no specific guidelines or Food and Drug Administration-approved... (Review)
Review
BACKGROUND
Psychotic bipolar depression (PBD) is a prevalent yet understudied psychiatric illness, and there are no specific guidelines or Food and Drug Administration-approved medications for its treatment. Recent studies suggest that some antipsychotics and mood stabilizers may be effective in managing bipolar depression; however, their effectiveness for PBD remains unclear. Given the urgent need for more focused research for managing PBD, we conducted a literature review to summarize the existing literature on PBD.
METHODS
We conducted an electronic literature search from the 1960s to 2023, utilizing PubMed, MEDLINE, EMBASE, and Google, and selected studies based on their relevance to PBD.
FINDINGS
PBD is a complex disorder, with 50%-75% of patients with bipolar disorder exhibiting psychotic features. This likelihood increases among those with a history of psychotic mania. Treatment guidelines often recommend a combination of mood stabilizers, antipsychotics, or electroconvulsive therapy, but they do not specify a first-line treatment. PBD symptoms can be masked by mixed high mood and energy feelings, potentially delaying diagnosis and treatment while increasing suicide risk. Limited research has evaluated outcomes of various treatments for PBD, and despite the lack of evidence for superior efficacy, in clinical practice, antipsychotics are frequently prescribed. Notably, combining an antipsychotic with selective noradrenaline reuptake inhibitors or tricyclic antidepressants may be effective, but including a mood stabilizer is necessary.
CONCLUSION
PBD poses a significant challenge in mental health due to its severity and the lack of consensus on optimal treatment approaches. There is a critical need for more dedicated clinical trials and research to answer key questions about the effective treatment of acute PBD, ideal follow-up care, traits of responders to different therapies, and decision models for subsequent treatments.
Topics: Humans; Bipolar Disorder; Antipsychotic Agents; Electroconvulsive Therapy; Antimanic Agents; Antidepressive Agents; Drug Therapy, Combination; Psychotic Disorders
PubMed: 38901001
DOI: 10.1097/JCP.0000000000001879 -
BMC Psychiatry Jun 2024Psychotic disorders have long been considered neurodevelopmental disorders where excessive synaptic pruning and cortical volume loss are central to disease pathology. We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Psychotic disorders have long been considered neurodevelopmental disorders where excessive synaptic pruning and cortical volume loss are central to disease pathology. We conducted a systematic review of the literature to identify neuroimaging studies specifically examining synaptic density across the psychosis spectrum.
METHODS
PRISMA guidelines on reporting were followed. We systematically searched MEDLINE, Embase, APA PsycINFO, Web of Science and The Cochrane Library from inception to December 8, 2023, and included all original peer-reviewed articles or completed clinical neuroimaging studies of any modality measuring synaptic density in participants with a diagnosis of psychosis spectrum disorder as well as individuals with psychosis-risk states. The NIH quality assessment tool for observational cohort and cross-sectional studies was used for the risk of bias assessment.
RESULTS
Five studies (k = 5) met inclusion criteria, comprising n = 128 adults (psychotic disorder; n = 61 and healthy volunteers; n = 67 and specifically measuring synaptic density via positron emission tomography (PET) imaging of the synaptic vesicle glycoprotein 2 A (SV2A). Three studies were included in our primary meta-analysis sharing the same outcome measure of SV2A binding, volume of distribution (V). Regional SV2A V was reduced in psychotic disorder participants in comparison to healthy volunteers, including the occipital lobe (Mean Difference (MD)= -2.17; 95% CI: -3.36 to -0.98; P < 0.001 ), temporal lobe (MD: -2.03; 95% CI: -3.19 to -0.88; P < 0.001 ), parietal lobe (MD:-1.61; 95% CI: -2.85 to -0.37; P = 0.01), anterior cingulate cortex (MD= -1.47; 95% CI: -2.45 to -0.49; P = 0.003), frontal cortex (MD: -1.16; 95% CI: -2.18 to -0.15; P = 0.02), amygdala (MD: -1.36; 95% CI: -2.20 to -0.52, p = 0.002), thalamus (MD:-1.46; 95% CI:-2.46 to -0.46, p = 0.004) and hippocampus (MD= -0.96; 95% CI: -1.59 to -0.33; P = 0.003).
CONCLUSIONS
Preliminary studies provide in vivo evidence for reduced synaptic density in psychotic disorders. However, replication of findings in larger samples is required prior to definitive conclusions being drawn.
PROSPERO
CRD42022359018.
Topics: Humans; Psychotic Disorders; Neuroimaging; Synapses; Positron-Emission Tomography; Brain; Nerve Tissue Proteins; Membrane Glycoproteins
PubMed: 38898401
DOI: 10.1186/s12888-024-05788-y -
Psychiatry Research Jun 2024The impact of traumatic brain injury (TBI) on subsequent risk of schizophrenia (SCZ) or bipolar disorder (BD) remains contested. Possible genetic and environmental...
The impact of traumatic brain injury (TBI) on subsequent risk of schizophrenia (SCZ) or bipolar disorder (BD) remains contested. Possible genetic and environmental confounding effects have also been understudied. Therefore, we aim to investigate the impact of TBI on the risk of SCZ and BD and whether the effect varies by injury severity, age at injury, and sex. We identified 4,184 SCZ and 18,681 BD cases born between 1973 and 1998 in the Swedish National Registers. Case-control samples matched (1:5) on birth year, sex, and birthplace were created along with a family design study, with cases matched to non-case full siblings. TBI was associated with higher risk of SCZ and BD (IRR=1.33 for SCZ, IRR=1.78 for BD). The association remained significant in the sibling comparison study. Moderate or severe TBI was associated with higher risk for both SCZ and BD compared to mild TBI. Older age at injury was associated with higher risk of SCZ and BD, and the effect of TBI was stronger in women than men. Findings indicate that TBI is a risk factor for both SCZ and BD with differential impact by age, severity and sex and that this association cannot be explained by familial confounding alone.
PubMed: 38896929
DOI: 10.1016/j.psychres.2024.115990 -
BioRxiv : the Preprint Server For... Jun 2024Haloperidol is used to manage psychotic symptoms in several neurological disorders through mechanisms that involve antagonism of dopamine D2 receptors that are highly...
Haloperidol is used to manage psychotic symptoms in several neurological disorders through mechanisms that involve antagonism of dopamine D2 receptors that are highly expressed in the striatum. Significant side effects of haloperidol, known as extrapyramidal symptoms, lead to motor deficits similar to those seen in Parkinson's disease and present a major challenge in clinical settings. The underlying molecular mechanisms responsible for these side effects remain poorly understood. Parkinson's disease-associated LRRK2 kinase has an important role in striatal physiology and a known link to dopamine D2 receptor signaling. Here, we systematically explore convergent signaling of haloperidol and LRRK2 through pharmacological or genetic inhibition of LRRK2 kinase, as well as knock-in mouse models expressing pathogenic mutant LRRK2 with increased kinase activity. Behavioral assays show that LRRK2 kinase inhibition ameliorates haloperidol-induced motor changes in mice. A combination of electrophysiological and anatomical approaches reveals that LRRK2 kinase inhibition interferes with haloperidol-induced changes, specifically in striatal neurons of the indirect pathway. Proteomic studies and targeted intracellular pathway analyses demonstrate that haloperidol induces a similar pattern of intracellular signaling as increased LRRK2 kinase activity. Our study suggests that LRRK2 kinase plays a key role in striatal dopamine D2 receptor signaling underlying the undesirable motor side effects of haloperidol. This work opens up new therapeutic avenues for dopamine-related disorders, such as psychosis, also furthering our understanding of Parkinson's disease pathophysiology.
PubMed: 38895420
DOI: 10.1101/2024.06.06.597594 -
Frontiers in Psychiatry 2024Psychotic symptoms are among the most debilitating and challenging presentations of severe psychiatric diseases, such as schizophrenia, schizoaffective, and bipolar...
UNLABELLED
Psychotic symptoms are among the most debilitating and challenging presentations of severe psychiatric diseases, such as schizophrenia, schizoaffective, and bipolar disorder. A pathophysiological understanding of intrinsic brain activity underlying psychosis is crucial to improve diagnosis and treatment. While a potential continuum along the psychotic spectrum has been recently described in neuroimaging studies, especially for what concerns absolute and relative amplitude of low-frequency fluctuations (ALFF and fALFF), these efforts have given heterogeneous results. A transdiagnostic meta-analysis of ALFF/fALFF in patients with psychosis compared to healthy controls is currently lacking. Therefore, in this pre-registered systematic review and meta-analysis PubMed, Scopus, and Embase were searched for articles comparing ALFF/fALFF between psychotic patients and healthy controls. A quantitative synthesis of differences in (f)ALFF between patients along the psychotic spectrum and healthy controls was performed with Seed-based d Mapping, adjusting for age, sex, duration of illness, clinical severity. All results were corrected for multiple comparisons by Family-Wise Error rates. While lower ALFF and fALFF were detected in patients with psychosis in comparison to controls, no specific finding survived correction for multiple comparisons. Lack of this correction might explain the discordant findings highlighted in previous literature. Other potential explanations include methodological issues, such as the lack of standardization in pre-processing or analytical procedures among studies. Future research on ALFF/fALFF differences for patients with psychosis should prioritize the replicability of individual studies.
SYSTEMATIC REVIEW REGISTRATION
https://osf.io/, identifier (ycqpz).
PubMed: 38895037
DOI: 10.3389/fpsyt.2024.1378439 -
Frontiers in Psychiatry 2024Depressive episodes with psychotic symptoms are prevalent among the older adults, emphasizing the need to differentiate them from dementia with Lewy bodies (DLB), in...
Depressive episodes with psychotic symptoms are prevalent among the older adults, emphasizing the need to differentiate them from dementia with Lewy bodies (DLB), in which depressive and psychotic symptoms commonly coexist. In contrast, psychotic symptoms occur more frequently in depressive episodes of bipolar disorder (BD) than in major depressive disorder (MDD). Although MDD is a significant risk factor for dementia, studies exploring the relationship between BD and dementia are lacking. This report details the case of a 74-year-old female who experienced severe psychotic depression that led to suicide attempts during a long-term course of young-onset BD. Ultimately, she was diagnosed with DLB based on her neurocognitive symptoms and results of the neuroimaging examination. She had experienced multiple relapses in the past, predominantly characterized by depressive episodes in her old age. Notably, she had never undergone lithium treatment, which is known for its potential efficacy in preventing relapse and dementia. Recent systematic reviews and meta-analyses have suggested that patients with BD have a higher risk of dementia than the general population, and that lithium usage is associated with a reduced risk. Moreover, patients with BD have been suggested to have an elevated risk of developing Parkinson's disease (PD), and the pathophysiological relationship between BD and PD may be attributed to dopamine dysregulation resulting from multiple relapses. Future research is imperative to identify strategies for preventing dementia in patients with BD and to develop interventions for the comorbidities of BD and DLB.
PubMed: 38895028
DOI: 10.3389/fpsyt.2024.1409027