Multi-Site Statistical Mapping of Along-Tract Microstructural Abnormalities in Bipolar Disorder with Diffusion MRI Tractometry.

Investigating alterations in brain circuitry associated with bipolar disorder (BD) may offer a valuable approach to discover brain biomarkers for genetic and interventional studies of the disorder and related mental illnesses. Some diffusion MRI studies report evidence of microstructural abnormalities in white matter regions of interest, but we lack a fine-scale spatial mapping of brain microstructural differences along tracts in BD. We also lack large-scale studies that integrate tractometry data from multiple sites, as larger datasets can greatly enhance power to detect subtle effects and assess whether effects replicate across larger international datasets. In this multisite diffusion MRI study, we used BUndle ANalytics (BUAN, Chandio 2020), a recently developed analytic approach for tractography, to extract, map, and visualize profiles of microstructural abnormalities on 3D models of fiber tracts in 148 participants with BD and 259 healthy controls from 6 independent scan sites. Modeling site differences as random effects, we investigated along-tract white matter (WM) microstructural differences between diagnostic groups. QQ plots showed that group differences were gradually enhanced as more sites were added. Using the BUAN pipeline, BD was associated with lower mean fractional anisotropy (FA) in fronto-limbic, interhemispheric, and posterior pathways; higher FA was also noted in posterior bundles, relative to controls. By integrating tractography and anatomical information, BUAN effectively captures unique effects along white matter (WM) tracts, providing valuable insights into anatomical variations that may assist in the classification of diseases.

Smartphone-based interventions in bipolar disorder: Systematic review and meta-analyses of efficacy. A position paper from the International Society for Bipolar Disorders (ISBD) Big Data Task Force.

BACKGROUND: The clinical effects of smartphone-based interventions for bipolar disorder (BD) have yet to be established. OBJECTIVES: To examine the efficacy of smartphone-based interventions in BD and how the included studies reported user-engagement indicators. METHODS: We conducted a systematic search on January 24, 2022, in PubMed, Scopus, Embase, APA PsycINFO, and Web of Science. We used random-effects meta-analysis to calculate the standardized difference (Hedges' g) in pre-post change scores between smartphone intervention and control conditions. The study was pre-registered with PROSPERO (CRD42021226668). RESULTS: The literature search identified 6034 studies. Thirteen articles fulfilled the selection criteria. We included seven RCTs and performed meta-analyses comparing the pre-post change in depressive and (hypo)manic symptom severity, functioning, quality of life, and perceived stress between smartphone interventions and control conditions. There was significant heterogeneity among studies and no meta-analysis reached statistical significance. Results were also inconclusive regarding affective relapses and psychiatric readmissions. All studies reported positive user-engagement indicators. CONCLUSION: We did not find evidence to support that smartphone interventions may reduce the severity of depressive or manic symptoms in BD. The high heterogeneity of studies supports the need for expert consensus to establish ideally how studies should be designed and the use of more sensitive outcomes, such as affective relapses and psychiatric hospitalizations, as well as the quantification of mood instability. The ISBD Big Data Task Force provides preliminary recommendations to reduce the heterogeneity and achieve more valid evidence in the field.

Applicability, potential and limitations of TSPO PET imaging as a clinical immunopsychiatry biomarker.

PURPOSE: TSPO PET imaging may hold promise as a single-step diagnostic work-up for clinical immunopsychiatry. This review paper on the clinical applicability of TSPO PET for primary psychiatric disorders discusses if and why TSPO PET imaging might become the first clinical immunopsychiatry biomarker and the investment prerequisites and scientific advancements needed to accommodate this transition from bench to bedside. METHODS: We conducted a systematic search of the literature to identify clinical studies of TSPO PET imaging in patients with primary psychiatric disorders. We included both original case-control studies as well as longitudinal cohort studies of patients with a primary psychiatric diagnosis. RESULTS: Thirty-one original studies met our inclusion criteria. In the field of immunopsychiatry, TSPO PET has until now mostly been studied in schizophrenia and related psychotic disorders, and to a lesser extent in mood disorders and neurodevelopmental disorders. Quantitative TSPO PET appears most promising as a predictive biomarker for the transdiagnostic identification of subgroups or disease stages that could benefit from immunological treatments, or as a prognostic biomarker forecasting patients' illness course. Current scanning protocols are still too unreliable, impractical and invasive for clinical use in symptomatic psychiatric patients. CONCLUSION: TSPO PET imaging in its present form does not yet offer a sufficiently attractive cost-benefit ratio to become a clinical immunopsychiatry biomarker. Its translation to psychiatric clinical practice will depend on the prioritising of longitudinal research and the establishment of a uniform protocol rendering clinically meaningful TSPO uptake quantification at the shortest possible scan duration without arterial cannulation.

Stability of chronotype over a 7-year follow-up period and its association with severity of depressive and anxiety symptoms.

BACKGROUND: Chronotype is an individual's preferred timing of sleep and activity, and is often referred to as a later chronotype (or evening-type) or an earlier chronotype (or morning-type). Having an evening chronotype is associated with more severe depressive and anxiety symptoms. Based on these findings it is has been suggested that chronotype is a stable construct associated with vulnerability to develop depressive or anxiety disorders. To examine this, we test the stability of chronotype over 7 years, and its longitudinal association with the change in severity of depressive and anxiety symptoms. METHODS: Data of 1,417 participants with a depressive and/or anxiety disorder diagnosis and healthy controls assessed at the 2 and 9-year follow-up waves of the Netherlands Study of depression and anxiety were used. Chronotype was assessed with the Munich chronotype questionnaire. Severity of depressive and anxiety symptoms were assessed with the inventory of depressive symptomatology and Beck anxiety inventory. RESULTS: Chronotype was found to be moderately stable (r = 0.53) and on average advanced (i.e., became earlier) with 10.8 min over 7 years (p < .001). Controlling for possible confounders, a decrease in severity of depressive symptoms was associated with an advance in chronotype (B = 0.008, p = .003). A change in severity of anxiety symptoms was not associated with a change in chronotype. CONCLUSION: Chronotype was found to be a stable, trait-like construct with only a minor level advance over a period of 7 years. The change in chronotype was associated with a change in severity of depressive, but not anxiety, symptoms.

Tinnitus in vascular conflict of the eighth cranial nerve: a surgical pathophysiological approach to ABR changes.

Some forms of tinnitus are associated with a blood vessel being in close contact with the auditory nerve near its entrance into the brainstem. The outcome of operations for tinnitus, moving the blood vessel off the nerve (microvascular decompression operations, MVD) is less successful than microvascular decompression operations for other vascular conflict syndromes (hemifacial spasm, HFS, and trigeminal neuralgia, TGN). No generally accepted criteria exist for the selection of candidates for MVD for tinnitus. A pathophysiological approach for interpreting auditory brainstem response (ABR) changes is proposed as a basis for selection of tinnitus patients for the MVD operation. We followed changes in the ABR and the tinnitus in 78 patients with unilateral tinnitus, who had indications of having vascular conflicts of the eighth nerve. In 18 of these patients a blood vessel was removed of the auditory nerve and in 9 of these a correlation could be made between preoperative and postoperative clinical changes and ABR changes. In this retrospective study we found abnormalities in the amplitude of peak II and the interpeak latency (IPL) I-III of the ABR that were related to the duration of their tinnitus and its intensity. While no ABR changes could be detected during the first 2 years, after that period a decrease of the amplitude of peak II occurred, and a prolongation the IPL of peak I-III occurred in patients whose peak II had disappeared. The rate of IPL I-III increase slows down after 10 years. IPL I-III prolongation correlates with ipsilateral hearing loss at tinnitus frequency and worsens in time. This correlates with a worsening of the tinnitus associated with the worsening of the IPL I-III. Tinnitus frequency correlates to the frequency of maximal hearing loss and the more the hearing loss at tinnitus frequency the worse the tinnitus. Postoperative improvement of tinnitus correlated with postoperative improvement of peak II and postoperative improvement of hearing loss at the tinnitus frequency correlated with postoperative IPL I-III improvement. It is concluded that interpreting ABRs from a pathophysiological point of view can be beneficial for surgeons performing MVDs for tinnitus, especially with regard to timing of the surgery and interpretation of symptom presentation.