Psychiatry - Research Publications

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    Networks of inflammation, depression, and cognition in aging males and females.
    Chalmers, RA ; Cervin, M ; Choo, C ; Baune, BT ; Trollor, JN ; Numbers, K ; Sachdev, PS ; Brodaty, H ; Kochan, NA ; Medvedev, ON (Springer Science and Business Media LLC, 2022-10)
    BACKGROUND: Prioritizing the maintenance of healthy cognitive aging and personalizing preventive interventions to enhance their effectiveness is crucial as the global population ages. Systemic inflammation and depression in older people have been associated with decreased levels of cognition but results have been inconsistent. AIMS: To explore the interactive network of inflammation, depression and cognition by sex in older people. METHODS: We used novel network analysis to explore the unique associations between inflammatory biomarkers, depression, cognition, and somatic, genetic, and lifestyle risk factors in an older (aged 70-90 years), non-demented, community-dwelling sample from the longitudinal Sydney Memory and Aging Study (N = 916) at baseline and at a two-year follow-up. RESULTS: The networks of biomarkers, depression, cognition, and relevant covariates were significantly different between males and females. A stable negative link between depression and cognition was found in females only; a stable positive association between biomarker interleukin-6 and depression was found in females only; and a stable positive association between biomarker interleukin-8 and alcohol was found in females only. For both males and females, a stable, positive relationship was found between the presence of APOE-ε4 gene and biomarker C-reactive protein; between education and cognition; and between biomarker interleukin-6 and all other biomarkers. CONCLUSIONS: These findings suggest different psychophysiological mechanisms underlie the interactive network of biomarkers, depression and cognition in males and females that should be considered when designing personalized preventive interventions to maintain cognitively healthy aging.
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    [Vagus nerve stimulation for difficult to treat depression].
    Reif-Leonhard, C ; Reif, A ; Baune, BT ; Kavakbasi, E (Springer Science and Business Media LLC, 2022-09)
    INTRODUCTION: For the past 20 years vagus nerve stimulation (VNS) has been an approved invasive treatment option for treatment-resistant depression (TRD) across Europe. In contrast to more common treatments, such as ECT, knowledge about VNS is low both in the general population and among professionals. METHODS: In this narrative review, we provide a clinically and scientifically sound overview of VNS. Hypotheses on the mechanism of action as well as the current evidence base on efficacy are presented. Perioperative management, adverse event profile and follow-up including dose titration are described. A comparison of international guideline recommendations on VNS is also provided. Furthermore, we formulate criteria that are helpful in the selection of appropriate patients. RESULTS: Electrical impulses are transmitted afferently via the vagus nerve and stimulate a neuromodulatory cerebral network via different pathways. Many studies and case series demonstrated the efficacy of VNS as an adjuvant procedure for TRD. The effect occurs with a latency period of 3-12 months and possibly increases with the duration of VNS. If stimulation recommendations are followed, side effects are tolerable for most patients. CONCLUSION: The use of VNS is an approved, effective and well-tolerated long-term therapy for chronic and treatment-resistant depression. Further sham-controlled studies over a longer observational period are desirable to improve the evidence.
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    Predictive role of atrial fibrillation in cognitive decline: a systematic review and meta-analysis of 2.8 million individuals.
    Koh, YH ; Lew, LZW ; Franke, KB ; Elliott, AD ; Lau, DH ; Thiyagarajah, A ; Linz, D ; Arstall, M ; Tully, PJ ; Baune, BT ; Munawar, DA ; Mahajan, R (Oxford University Press (OUP), 2022-09-01)
    AIMS: To systematic review and meta-analyse the association and mechanistic links between atrial fibrillation (AF) and cognitive impairment. METHODS AND RESULTS: PubMed, EMBASE, and Cochrane Library were searched up to 27 March 2021 and yielded 4534 citations. After exclusions, 61 were analysed; 15 and 6 studies reported on the association of AF and cognitive impairment in the general population and post-stroke cohorts, respectively. Thirty-six studies reported on the neuro-pathological changes in patients with AF; of those, 13 reported on silent cerebral infarction (SCI) and 11 reported on cerebral microbleeds (CMB). Atrial fibrillation was associated with 39% increased risk of cognitive impairment in the general population [n = 15: 2 822 974 patients; hazard ratio = 1.39; 95% confidence interval (CI) 1.25-1.53, I2 = 90.3%; follow-up 3.8-25 years]. In the post-stroke cohort, AF was associated with a 2.70-fold increased risk of cognitive impairment [adjusted odds ratio (OR) 2.70; 95% CI 1.66-3.74, I2 = 0.0%; follow-up 0.25-3.78 years]. Atrial fibrillation was associated with cerebral small vessel disease, such as white matter hyperintensities and CMB (n = 8: 3698 patients; OR = 1.38; 95% CI 1.11-1.73, I2 = 0.0%), SCI (n = 13: 6188 patients; OR = 2.11; 95% CI 1.58-2.64, I2 = 0%), and decreased cerebral perfusion and cerebral volume even in the absence of clinical stroke. CONCLUSION: Atrial fibrillation is associated with increased risk of cognitive impairment. The association with cerebral small vessel disease and cerebral atrophy secondary to cardioembolism and cerebral hypoperfusion may suggest a plausible link in the absence of clinical stroke. PROSPERO CRD42018109185.
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    Corrigendum: Potential genetic overlap between insomnia and sleep symptoms in major depressive disorder: A polygenic risk score analysis.
    Melhuish Beaupre, LM ; Tiwari, AK ; Gonçalves, VF ; Zai, CC ; Marshe, VS ; Lewis, CM ; Martin, NG ; McIntosh, AM ; Adams, MJ ; Baune, BT ; Levinson, DF ; Boomsma, DI ; Penninx, BWJH ; Breen, G ; Hamilton, S ; Awasthi, S ; Ripke, S ; Jones, L ; Jones, I ; Byrne, EM ; Hickie, IB ; Potash, JP ; Shi, J ; Weissman, MM ; Milaneschi, Y ; Shyn, SI ; de Geus, EJC ; Willemsen, G ; Brown, GM ; Kennedy, JL ; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, (Frontiers Media SA, 2022)
    [This corrects the article DOI: 10.3389/fpsyt.2021.734077.].
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    Transdiagnostic Cognitive-Behavioral Therapy for Depression and Anxiety Disorders in Cardiovascular Disease Patients: Results From the CHAMPS Pilot-Feasibility Trial.
    Tully, PJ ; Turnbull, DA ; Horowitz, JD ; Beltrame, JF ; Baune, BT ; Sauer-Zavala, S ; Baumeister, H ; Bean, CG ; Pinto, RB ; Cosh, S ; Wittert, GA (Frontiers Media SA, 2022)
    Objective: The aim of the Cardiovascular Health in Anxiety and Mood Problems Study (CHAMPS) is to pilot the Unified Protocol (UP) for the transdiagnostic treatment of depression and anxiety disorders in patients recently hospitalized for cardiovascular diseases (CVDs) and evaluate the feasibility. Methods: The present study is a controlled, block randomized pragmatic pilot-feasibility trial incorporating qualitative interview data, comparing UP (n = 9) with enhanced usual care (EUC, n = 10). Eligible trial participants had a recent CVD-cause admission and were above the severity threshold for depression or anxiety denoted by Patient Health Questionnaire (PHQ-9) total scores ≥10 and/or Generalized Anxiety Disorder (GAD-7) total scores ≥7 respectively on two occasions, and met criteria for one or more depression or anxiety disorders determined by structured clinical interview. Study outcomes were analyzed as intention-to-treat using linear mixed models and qualitative interview data were analyzed with content analysis. Results: Quantitative and qualitative measured indicated acceptability of the transdiagnostic CBT intervention for CVD patients with depression or anxiety disorders. Satisfaction with UP was comparable to antidepressant therapy and higher than general physician counseling. However, there were difficulties recruiting participants with current disorders and distress on two occasions. The UP was associated with a reduction in total number of disorders determined by blinded raters. Linear mixed models indicated that a significantly greater reduction in anxiety symptoms was evident in the UP group by comparison to the EUC group (GAD-7, p between groups = 0.011; Overall Anxiety Severity and Impairment Scale, p between groups = 0.013). Results favored the UP group by comparison to EUC for change over 6 months on measures of physical quality of life and harmful alcohol use. There was no difference between the two groups on changes in depression symptoms (PHQ-9), stress, metacognitive worry beliefs, physical activity, or adherence. Discussion: In conclusion, this feasibility trial indicates acceptability of transdiagnostic CBT intervention for CVD patients with depression or anxiety disorders that is tempered by difficulties with recruitment. Larger trials are required to clarify the efficacy of transdiagnostic depression and anxiety disorder CBT in populations with CVDs and depressive or anxiety disorders. Clinical Trial Registration: https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12615000555550, identifier: ACTRN12615000555550.
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    Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients (vol 12, 278, 2022)
    Schubert, KO ; Thalamuthu, A ; Amare, AT ; Frank, J ; Streit, F ; Adl, M ; Akula, N ; Akiyama, K ; Ardau, R ; Arias, B ; Aubry, J-M ; Backlund, L ; Bhattacharjee, AK ; Bellivier, F ; Benabarre, A ; Bengesser, S ; Biernacka, JM ; Birner, A ; Marie-Claire, C ; Cearns, M ; Cervantes, P ; Chen, H-C ; Chillotti, C ; Cichon, S ; Clark, SR ; Cruceanu, C ; Czerski, PM ; Dalkner, N ; Dayer, A ; Degenhardt, F ; Del Zompo, M ; DePaulo, JR ; Etain, B ; Falkai, P ; Forstner, AJ ; Frisen, L ; Frye, MA ; Fullerton, JM ; Gard, S ; Garnham, JS ; Goes, FS ; Grigoroiu-Serbanescu, M ; Grof, P ; Hashimoto, R ; Hauser, J ; Heilbronner, U ; Herms, S ; Hoffmann, P ; Hou, L ; Hsu, Y-H ; Jamain, S ; Jimenez, E ; Kahn, J-P ; Kassem, L ; Kuo, P-H ; Kato, T ; Kelsoe, J ; Kittel-Schneider, S ; Ferensztajn-Rochowiak, E ; Konig, B ; Kusumi, I ; Laje, G ; Landen, M ; Lavebratt, C ; Leboyer, M ; Leckband, SG ; Maj, M ; Manchia, M ; Martinsson, L ; McCarthy, MJ ; McElroy, S ; Colom, F ; Mitjans, M ; Mondimore, FM ; Monteleone, P ; Nievergelt, CM ; Nothen, MM ; Novak, T ; O'Donovan, C ; Ozaki, N ; Osby, U ; Papiol, S ; Pfennig, A ; Pisanu, C ; Potash, JB ; Reif, A ; Reininghaus, E ; Rouleau, GA ; Rybakowski, JK ; Schalling, M ; Schofield, PR ; Schweizer, BW ; Severino, G ; Shekhtman, T ; Shilling, PD ; Shimoda, K ; Simhandl, C ; Slaney, CM ; Squassina, A ; Stamm, T ; Stopkova, P ; Tekola-Ayele, F ; Tortorella, A ; Turecki, G ; Veeh, J ; Vieta, E ; Witt, SH ; Roberts, G ; Zandi, PP ; Alda, M ; Bauer, M ; McMahon, FJ ; Mitchell, PB ; Schulze, TG ; Rietschel, M ; Baune, BT (SPRINGERNATURE, 2022-07-11)
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    Antidepressant prescribing patterns in Australia
    Malhi, GS ; Acar, M ; Kouhkamari, MH ; Chien, TH ; Juneja, P ; Siva, S ; Baune, BT (CAMBRIDGE UNIV PRESS, 2022-06-30)
    BACKGROUND: The Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders (MDcpg2015 and MDcpg2020) provide evidence-based and consensus-based recommendations for managing mood disorders. AIMS: We examined Australian real-world prescribing habits to determine whether management in clinical practice aligned with MDcpg2015 recommendations. METHOD: A retrospective analysis of a cohort of patients ≥16 years old who had been dispensed a Pharmaceutical Benefits Scheme (PBS)-listed antidepressant between July 2013 and June 2019 was conducted using Australian Commonwealth Department of Human Services PBS 10% sample data. RESULTS: Between July 2013 and June 2019, 239 944 patients in Australia commenced antidepressant treatment. Of these, 22% (52 694 patients) received a second treatment (a new class of treatment after a period of discontinuation or additional antipsychotic therapy) and 6% (15 741 patients) received a third treatment. Patients were initially prescribed primarily selective serotonin reuptake inhibitors (SSRIs; 52% of prescriptions) or tricyclic antidepressants (TCAs; 25%), even though TCAs are not recommended for first-line treatment. Fewer than one-quarter of patients were prescribed serotonin-noradrenaline reuptake inhibitors (13%) or other agents (10%). General practitioners (GPs) were more likely to initiate TCAs than psychiatrists (22% v. 7%).Once initiated, the overall median time patients remained on treatment was 4.5 months; this was highest with SSRIs (5.8 months) and lowest with TCAs (0.9 months). CONCLUSIONS: First-line prescribing broadly follows guidelines. GP and psychiatrist prescribing patterns differ, perhaps reflecting different patient groups and the need to tailor treatment to individuals. Future guidelines should aim to capture the different presentations and complexity of depression.
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    Systemic Inflammation Predicts Alzheimer Pathology in Community Samples without Dementia.
    Cherbuin, N ; Walsh, EI ; Leach, L ; Brüstle, A ; Burns, R ; Anstey, KJ ; Sachdev, PS ; Baune, BT (MDPI AG, 2022-05-26)
    Neuroinflammation and oxidative stress (OS) are implicated in the pathophysiology of Alzheimer's disease (AD). However, it is unclear at what stage of the disease process inflammation first becomes manifest. The aim of this study was to investigate the associations between specific plasma markers of inflammation and OS, tau, and Amyloid-β 38, 40, and 42 levels in cognitively unimpaired middle-age and older individuals. Associations between inflammatory states identified through principal component analysis and AD biomarkers were investigated in middle-age (52-56 years, n = 335, 52% female) and older-age (72-76 years, n = 351, 46% female) participants without dementia. In middle-age, a component reflecting variation in OS was most strongly associated with tau and to a lesser extent amyloid-β levels. In older-age, a similar component to that observed in middle-age was only associated with tau, while another component reflecting heightened inflammation independent of OS, was associated with all AD biomarkers. In middle and older-age, inflammation and OS states are associated with plasma AD biomarkers.
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    Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
    Blokland, GAM ; Grove, J ; Chen, C-Y ; Cotsapas, C ; Tobet, S ; Handa, R ; St Clair, D ; Lencz, T ; Mowry, BJ ; Periyasamy, S ; Cairns, MJ ; Tooney, PA ; Wu, JQ ; Kelly, B ; Kirov, G ; Sullivan, PF ; Corvin, A ; Riley, BP ; Esko, T ; Milani, L ; Jonsson, EG ; Palotie, A ; Ehrenreich, H ; Begemann, M ; Steixner-Kumar, A ; Sham, PC ; Iwata, N ; Weinberger, DR ; Gejman, P ; Sanders, AR ; Buxbaum, JD ; Rujescu, D ; Giegling, I ; Konte, B ; Hartmann, AM ; Bramon, E ; Murray, RM ; Pato, MT ; Lee, J ; Melle, I ; Molden, E ; Ophoff, RA ; McQuillin, A ; Bass, NJ ; Adolfsson, R ; Malhotra, AK ; Martin, NG ; Fullerton, JM ; Mitchell, PB ; Schofield, PR ; Forstner, AJ ; Degenhardt, F ; Schaupp, S ; Comes, AL ; Kogevinas, M ; Guzman-Parra, J ; Reif, A ; Streit, F ; Sirignano, L ; Cichon, S ; Grigoroiu-Serbanescu, M ; Hauser, J ; Lissowska, J ; Mayoral, F ; Muller-Myhsok, B ; Schulze, TG ; Nothen, MM ; Rietschel, M ; Kelsoe, J ; Leboyer, M ; Jamain, S ; Etain, B ; Bellivier, F ; Vincent, JB ; Alda, M ; O'Donovan, C ; Cervantes, P ; Biernacka, JM ; Frye, M ; McElroy, SL ; Scott, LJ ; Stahl, EA ; Landen, M ; Hamshere, ML ; Smeland, OB ; Djurovic, S ; Vaaler, AE ; Andreassen, OA ; Baune, BT ; Air, T ; Preisig, M ; Uher, R ; Levinson, DF ; Weissman, MM ; Potash, JB ; Shi, J ; Knowles, JA ; Perlis, RH ; Lucae, S ; Boomsma, D ; Penninx, BWJH ; Hottenga, J-J ; de Geus, EJC ; Willemsen, G ; Milaneschi, Y ; Tiemeier, H ; Grabe, HJ ; Teumer, A ; Van der Auwera, S ; Volker, U ; Hamilton, SP ; Magnusson, PKE ; Viktorin, A ; Mehta, D ; Mullins, N ; Adams, MJ ; Breen, G ; McIntosh, AM ; Lewis, CM ; Hougaard, DM ; Nordentoft, M ; Mors, O ; Mortensen, PB ; Werge, T ; Als, TD ; Borglum, AD ; Petryshen, TL ; Smoller, JW ; Goldstein, JM (ELSEVIER SCIENCE INC, 2021-11-29)
    BACKGROUND: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. METHODS: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. RESULTS: Across disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10-8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10-6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10-7; rs73033497, p = 8.8 × 10-7; rs7914279, p = 6.4 × 10-7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10-7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10-7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10-7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). CONCLUSIONS: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.
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