Biological Psychiatry Research Articles (Page 1)

Expression of concern: “Adolescent nicotine abstinence increases anxiety and depressive-like behaviors, alcohol consumption, oxidative stress and inflammatory response accompanied by attenuated serotonergic/dopaminergic and cholinergic function in rats” [Progress in Neuro-Psychopharmacology & Biological Psychiatry, volume 141 (2025), 111464

Human neuroimaging and epigenetic research stand ready to advance biological psychiatry. Drawing on the concept of imaging genetics, the analysis of associations between human neuroimaging and epigenetic data provides an attractive framework for investigating multi-scale biological mechanisms linking the environment to psychiatric risk and protection. A basic assumption is that environmental stress causes epigenetic changes that lead to alterations in cellular ensembles, which in turn can be measured as changes in brain structure and function using human neuroimaging. However, unlike genotypes, epigenetics varies within individuals, between cell types, or over time, and thus caution is required when inferring the immediacy and directionality of observed associations. In this review, we discuss recent advances and challenges to this methodological framework. Future studies should address causal hypotheses and explain within-individual variance in psychopathology through sophisticated contextualization of observed associations and rigorous analyses of longitudinal data. These advances will be critical for developing a comprehensive understanding of the biological contributions to mental health risk and protection.

Therapeutic Shifts and Scientific Influence in Treatment-Resistant Depression Research: A Data-Driven Perspective

This Genomic Press Interview explores Dr. David R. Rubinow's transformative contributions to reproductive psychiatry through his journey from a major in philosophy and history to becoming a leading researcher. Rubinow fundamentally changed how we understand mood disorders linked to hormonal changes by discovering that women with conditions like premenstrual dysphoric disorder (PMDD), postpartum depression, and perimenopausal depression have normal hormone levels but respond differently to hormonal fluctuations, a concept he termed “differential sensitivity.” This breakthrough shifted treatment approaches from attempting to normalize hormones to targeting the abnormal responses themselves. His research directly contributed to the development of brexanolone (Zulresso), the first FDA-approved medication specifically for postpartum depression, which works through novel neurosteroid mechanisms rather than traditional antidepressant pathways. After 27 years at the National Institutes of Health (NIH), where he served as National Institute of Mental Health (NIMH) Clinical Director and founding Chief of the Behavioral Endocrinology Branch, Rubinow joined UNC-Chapel Hill in 2006 as Chair of Psychiatry, a position he held until 2019. During his tenure, he founded the UNC Center for Women's Mood Disorders, established the nation's first peripartum inpatient unit and first NIH-sponsored fellowship in women's mood disorders, and led the department to consistently top-10 national rankings in NIH funding. A member of the National Academy of Medicine since 2012, Rubinow has authored over 400 scientific publications and served as president of both the Society of Biological Psychiatry and the American College of Neuropsychopharmacology. The interview reveals how serendipity shaped his career trajectory, from an unexpected fellowship with Bob Post to leadership positions while maintaining parallel passions for music and woodworking. His philosophy of “bringing the chisel when sent for the hammer” reflects the thoughtful approach that has characterized his research. Rubinow's work has validated the experiences of millions of women whose hormone-related mood symptoms were previously dismissed, establishing reproductive psychiatry as a legitimate subspecialty with evidence-based treatments.

In this Genomic Press Interview, Professor Barbara Franke, a trailblazing molecular psychiatrist at Radboud University in Nijmegen, shares her extraordinary scientific journey from an inquisitive child fascinated by nature to becoming one of the world's most influential researchers in biological psychiatry. With over 500 peer-reviewed publications and recognition among the top 1% most cited scientists globally, Franke has helped to revolutionize our understanding of the genetic foundations of neurodevelopmental disorders, particularly ADHD. Bringing together international experts for interdisciplinary research, she founded and leads multiple international research consortia, including the International Multicentre persistent ADHD Collaboration (IMpACT) and the ECNP Network ADHD across the lifespan. Her pioneering work extends beyond gene identification to illuminating the biological pathways from genetic variations to altered behaviour, employing innovative complementary approaches including bioinformatics, brain imaging genetics, and experimental models using fruit flies and human induced pluripotent stem cells. An elected member of the Royal Netherlands Academy of Arts and Sciences, decorated Knight in the Order of the Netherlands Lion, and recipient of numerous prestigious awards, Franke's scientific contributions are matched by her passionate commitment to international collaboration and mentorship of the next generation of researchers. Her recent move into epigenetics research, investigating the interplay between heritable and environmental influences on psychiatric conditions, illustrates her unwavering determination to contribute to a new nosology in psychiatry that will ultimately improve diagnosis, treatment, and management for millions worldwide. Guided by the German proverb “Die Suppe wird nicht so heiß gegessen, wie sie gekocht wird” (“The soup is not eaten as hot as it is cooked”), Franke's balanced approach to life and science continues to inspire groundbreaking advances at the intersection of genetics, neuroscience, and psychiatry.

Psychosocial interventions are essential in the treatment of severe mental disorders, including Bipolar Disorder. These interventions aim to enhance patients' psychopathology, alongside pharmacological treatments, while also improving personal functioning and quality of life. We conducted a comprehensive review of available international guidelines concerning the treatment of Bipolar Disorder, specifically examining their recommendations on the efficacy and implementation of psychosocial interventions across different phases of the illness. The guidelines included in our review were from the National Institute for Health and Care Excellence (NICE), the Scottish Intercollegiate Guidelines Network (SIGN), the Royal Australian and New Zealand College of Psychiatrists (RANZCP), the American Psychiatric Association (APA), the Canadian Network for Mood and Anxiety Treatments (CANMAT), the International Society for Bipolar Disorders (ISBD), the British Association for Psychopharmacology (BAP), Bangladesh Association of Psychiatrists (BAP 2022), and the World Federation of Societies of Biological Psychiatry (WFSBP). The international guidelines endorse psychosocial interventions as supportive treatments in conjunction with pharmaceutical or psychotherapeutic approaches for Bipolar Disorder. Further research is needed to validate the suggested effectiveness of psychosocial interventions on the long-term outcomes of Bipolar Disorder.

Anorexia nervosa, bulimia nervosa and binge-eating disorder are severe mental illnesses and are often associated with mental comorbidities, such as depression, anxiety and obsessive-compulsive disorders. Psychotherapy is considered the primary method of treatment; however, in the clinical practice it is not uncommon to also use psychopharmacotherapy. The article considers international and national guidelines as well as the updated World Federation of Societies of Biological Psychiatry (WFSBP) guidelines to summarize the current evidence on psychopharmacotherapy of eating disorders. Anorexia nervosa: psychopharmacotherapy for anorexia nervosa should especially support weight gain. To date, there is no evidence for the efficacy of antidepressants for weight gain in anorexia nervosa. For antipsychotics, such as olanzapine in particular, the studies are heterogeneous, which is why off-label use in clinical practice is limited exclusively to individual cases. Bulimia nervosa: fluoxetine has been shown to be effective in reducing binge eating and compensatory behaviors. Fluoxetine is also the only medication approved in Germany for the treatment of an eating disorder. Binge-eating disorder: by far the greatest evidence exists for lisdexamfetamine. But this is not approved in Germany for the treatment of binge-eating disorder. In recent years the number of randomized controlled trials on psychopharmacotherapy for eating disorders has greatly increased. In Germany, fluoxetine is still the only approved drug for the treatment of bulimia nervosa; however, psychopharmacotherapy for eating disorders should always be embedded in atreatment plan with psychotherapy and nutritional management as well as appropriate medical monitoring. Overall, there is aneed for further research.

Depression significantly threatens human health. Purinergic receptors are reported to be associated with depression. However, there is no bibliometric research in this field have been published. To provide some reference for the further research in the field of purinergic receptors and depression utilizing bibliometric analysis. Relevant researches were retrieved from the Web of Science Core Collection database. The period of the search was from January 1, 2003 to December 31, 2023. The CiteSpace (6.2.R7) and VOSviewer (1.6.19) were applied to identify the main contributors of countries, authors, institutions, references and journals. Besides, we evaluate keywords to assess the hotspots and trends over the previous 2 decades. Totally, 247 articles were identified, showing an increasing trend over time. The most productive country, institution, and journal in this field are China, Harvard University, and Biological Psychiatry, respectively. Liang SD and Rodrigues, Ana Lucia S were the most prolific authors. Burnstock G ranked first among the cited authors. The cooperation among countries and disciplines is crucial. The P2X7 receptor provides promising prospects for treating depression and further studies are warranted to validate the scope and significance of depression therapeutic strategies. This study provides an overview of the worldwide research status and future trends in purinergic receptors and depression. P2X7 receptor is considered an appropriate target for the treatment of depression, as well as neurological diseases. It is implied that based on purinergic system, the future prospects for interventions aimed at depression treatment are promising, showing the way for both augmentation strategies and new drug treatments in the context of the pharmacology of depression.

BackgroundWhereas ketamine has displayed robust antidepressant effects in treatment-resistant depression (TRD) (Han et al., 2016), only 30-40% of patients with TRD respond to ketamine therapy (Wilkinson et al., 2018; Sakurai et al., 2020). Several postmortem studies have shown decreased myelination in patients with depression (Hamidi, Drevets and Price, 2004; Altshuler et al., 2010), and an animal study suggested that increased myelination may underlie the antidepressant effects of ketamine for TRD (Huang et al., 2023). Quantitative susceptibility mapping (QSM) is a magnetic resonance imaging technique for assessing magnetic susceptibility in brain tissues, which can examine the degrees of iron deposition and myelination (Harada et al., 2022). Several studies noted increased susceptibility in the subcortical regions of patinets with depression (Yao et al., 2017; Zhang et al., 2019; Duan et al., 2022; Wang et al., 2022). However, no study has examined the relationship between magnetic susceptibility and ketamine treatment efficacy in patients with TRD.Aims and ObjectionsTo evaluate whether pre-treatment subcortical susceptibility can predict clinical outcomes post-ketamine infusion, we conducted a post-hoc analysis of data from a placebo-controlled, double-blind, randomized clinical trial (DBRCT) followed by an open-label trial, where the efficacy of repeated ketamine infusion was examined in patients with TRD.MethodsIn this DBRCT, 34 patients with TRD were either treated with intravenous ketamine (0.5 mg/kg) or placebo, which were administered over 40 minutes, twice weekly for two weeks. After the DBRCT was completed, those allocated to the placebo group were enrolled in an open-label trial, in which the participants received the same ketamine treatment as in DBRCT. The primary outcome was the Montgomery-Å sberg Depression Rating Scale (MADRS) score difference between pre- and post- treatment. All participants underwent 3T MRI scans using a 32-channel head/neck coil with the following parameters: repetition time/first echo time = 44.0/3.6 ms, echo spacing = 5.91 ms, and number of echoes = 8. We measured magnetic susceptibility in the region of interest (ROI), including 10 subcortical structures defined by the ITK-SNAP software. Univariate regression analyses were performed to examine the association between susceptibility in each ROI before ketamine infusion and the change in MADRS total scores after treatment from baseline.ResultsAmong the 34 patients who participated in the original clinical trial, 13 (DBRCT, n=7; open-label phase, n=6) were included in this post-hoc analysis. The mean change in MADRS total score between ketamine treatment was -7.8 ± 6.3. Positive correlations between the baseline susceptibility in the left globus pallidus externa (GPe) (β = 152.8, p = 0.035), left globus pallidus interna (GPi) (β = 153.2, p = 0.042), left substantia nigra (SN) (β = 142.3, p = 0.017) and right SN (β = 131.5, p = 0.031), and the change in MADRS total scores following the treatment.Discussion and ConclusionThe baseline myelination measured by QSM in the left GPe, left GPi, and bilateral SN may predict a favorable response to ketamine treatment in patients with TRD.ReferencesAltshuler, L. L. et al. (2010), “Amygdala astrocyte reduction in subjects with major depressive disorder but not bipolar disorder,” Bipolar Disorders, 12(5), pp. 541–549.Duan, X. et al. (2022), “Quantitative Susceptibility Mapping of Brain Iron Deposition in Patients With Recurrent Depression,” Psychiatry Investigation, 19(8), pp. 668–675.Hamidi, M., Drevets, W. C., and Price, J. L. (2004), “Glial reduction in amygdala in major depressive disorder is due to oligodendrocytes,” Biological Psychiatry, 55(6), pp. 563–569.Han, Y. et al. (2016), “Efficacy of ketamine in the rapid treatment of major depressive disorder: a meta- analysis of randomized, double-blind, placebo-controlled studies,” Neuropsychiatric Disease and Treatment, 12, pp. 2859–2867.Harada, T. et al. (2022), “Quantitative Susceptibility Mapping: Basic Methods and Clinical Applications,” Radiographics: A Review, a Publication of the Radiological Society of North America, Inc., 42(4), pp. 1161–1176.Huang, C. et al. (2023), “Myelin-associated oligodendrocytic basic protein-dependent myelin repair confers the long-lasting antidepressant effect of ketamine." Molecular psychiatry. doi: 10.1038/s41380-023-02288-5.Sakurai, H. et al. (2020), “Long-term outcome in outpatients with depression treated with acute and maintenance intravenous ketamine: A retrospective chart review,” Journal of Affective Disorders, 276, pp. 660–666.Wang, F. et al. (2022), “Alterations in brain iron deposition with progression of late-life depression measured by magnetic resonance imaging (MRI)-based quantitative susceptibility mapping,” Quantitative imaging in medicine and surgery, 12(7), pp. 3873–3888.Wilkinson, S. T. et al. (2018), “Acute and Longer-Term Outcomes Using Ketamine as a Clinical Treatment at the Yale Psychiatric Hospital,” The Journal of Clinical Psychiatry, 79(4). doi: 10.4088/JCP.17m11731. Yao, S. et al. (2017), “Quantitative Susceptibility Mapping Reveals an Association between Brain Iron Load and Depression Severity,” Frontiers in Human Neuroscience, 11, p. 442.Zhang, W. et al. (2019), “Brain Iron Deposits in Thalamus Is an Independent Factor for Depressive Symptoms Based on Quantitative Susceptibility Mapping in an Older Adults Community Population,” Frontiers in Psychiatry / Frontiers Research Foundation, 10, p. 734.

BackgroundIntermittent theta-burst stimulation (iTBS), as an updated form of repetitive transcranial magnetic stimulation (rTMS), was effective in treating treatment-resistant depression (TRD)1,2,3. 10-Hz rTMS at left prefrontal cortex (PFC) was reported to have antidepressant effects by modulating the activities in bilateral frontal-cingulo-temporal circuit2. Although both 10-Hz rTMS and iTBS were found to be effective, iTBS (80% motor threshold, 1800 pulses) acted differently by modulating the activities in midline structures, such as cingulate cortex and precuneus. Although the clinical effects were not enhanced compared to single session of iTBS treatment per day, we recently reported that 2 uninterrupted sessions of iTBS were also effective4. However, it remains elusive whether accelerated protocols (i.e., two uninterrupted sessions per day: prolonged iTBS x 2, piTBS*2) may also be effective through modulation in the midline structures.MethodsPatients with antidepressant-resistant major depressive disorder were randomly assigned and to the piTBS*2 group, rTMS*2 group (10Hz, 120% motor threshold, 3000pulses/session, 2 sessions/day), and sham treatment group. Before and after the trials, 18F-FDG PET was applied and depression severity by 17-item Hamilton Depression Rating Scale (HDRS- 17) was evaluated.ResultsHDRS-17 scores decreased significantly in all three groups. Voxel-based analysis revealed that the piTBS*2 group showed increased activities after treatment in the midline structures including anterior and middle cingulate cortex and precuneus. By contrast, rTMS increased the bilateral frontal and temporal lobe activities.ConclusionAccelerated iTBS modulated the metabolism in the midline structures, but the direction of modulation is opposite to the findings reported in the singles-session iTBS protocol. Findings in the rTMS*2 group were similarr with past studies. Our results suggested that neural mechanisms of iTBS was not linear and dose-dependent.ReferencesCheng-Ta Li* et al. Efficacy of Prefrontal Theta-Burst Stimulation in Refractory Depression: A Randomized Sham-Controlled Study. Brain, 2014 Jul;137(Pt 7):2088-98. Cheng-Ta Li* et al. Effects of prefrontal theta-burst stimulation on brain function in treatment-resistant depression. Brain Stimulation. 2018;11(5):1054-1062.Cheng-Ta Li* et al. Antidepressant Efficacy of Prolonged Intermittent Theta Burst Stimulation Monotherapy for Recurrent Depression and Comparison of Methods for Coil Positioning: A Randomized, Double-Blind, Sham-controlled Study. Biological Psychiatry, Mar. 2020Cheng-Ta Li* et al. The longer, the better ? Longer left-sided prolonged intermittent theta burst stimulation in patients with major depressive disorder. Asian J Psychiatry. 2023

BackgroundThe depressive phase of bipolar disorder lasts longer than the manic phase and poses the highest risk due to its negative impact on quality of life and mental health, and peak in suicide attempts. Unfortunately, current therapies for bipolar disorder are far more efficacious in mania than depression, suggesting an urgent need for new and improved therapies for bipolar depression. The literature suggests the chronic presence of low-grade peripheral and central inflammation is a key pathophysiology of depression. In particular, Angiotensin II Type I receptor (AT1R) of the renin-angiotensin system appears to play a critical role in activating the relevant stress, oxidative stress and inflammatory pathways (see Vian et al., 2017, for review). In support of this, cutting-edge genomic studies (e.g. Kidnapillai et al., 2020), findings from animal models of bipolar disorder (e.g. Luo et al., 2020), independent large-scale epidemiological studies (e.g. Johansen et al., 2012) and a meta-analysis (Brownstein et al., 2018) have collectively nominated agents that reduce AT1R activity as a potential novel therapy for depression. Thus, our team designed clinical trials using candesartan, a common anti-hypertensive medication and AT1R blocker, to target this major unmet need in depression.Aims & ObjectivesThe clinical trials aim to investigate the efficacy of adjunctive candesartan versus placebo for the treatment of major depression in unipolar and bipolar disorder. To achieve this aim, two separate trials are run in parallel for participants with either bipolar disorder or major depressive disorder. The two streams are: The Candesartan Adjunctive Bipolar Depression Trial (CADET-BD) and The Candesartan Adjunctive Major Depression Trial (CADET-UD). These trials are the first study of this agent in bipolar and major depressive disorder and will provide important proof-of-principle of the role of the angiotensin system in mood regulation. The primary outcome will measure if candesartan is superior to placebo in reducing depressive symptoms. The secondary outcomes will measure weather candesartan is superior to placebo in reducing anxiety symptoms, inflammatory biomarkers, and improving quality of life, social and work function and cognition.MethodFunded by National Health and Medical Research Council (NHMRC) and Medical Research Future Fund (MRFF), the CADET trials are both 16-week multi-site double-blind randomized placebo-controlled trials and will aim to recruit 240 participants each (i.e. bipolar depression and unipolar depression). The trials are being conducted at five sites in Australia and each site is equipped with a team of Research Assistants and Principal Investigators to assess participants for inclusion (e.g. moderate to severe depression indexed by a depression rating scale score of 20 or higher), exclusion (e.g. a diagnosis of another psychotic disorder assessed using the SCID-5-RV) and withdrawal criteria, and conduct participant interviews. The participant will first attend the screen visit, followed by six visits within the 16 weeks, either in-person or via telehealth. The participants will complete different sets of tasks at each visit (Figure 1).Results, Discussion & ConclusionThe trials are double-blinded and currently recruiting participants. The results, discussion and conclusion will be available once the recruitment is complete.ReferencesBrownstein, D.J., Salagre, E., Kö hler, C., Stubbs, B., Vian, J., Pereira, C., Chavarria, V., Karmakar, C., Turner, A., Quevedo, J. and Carvalho, A.F., 2018. Blockade of the angiotensin system improves mental health domain of quality of life: A meta-analysis of randomized clinical trials. Australian &New Zealand Journal of Psychiatry, 52(1), pp.24-38.Kidnapillai, S., Bortolasci, C.C., Udawela, M., Panizzutti, B., Spolding, B., Connor, T., Sanigorski, A., Dean, O.M., Crowley, T., Jamain, S. and Gray, L., 2020. The use of a gene expression signature and connectivity map to repurpose drugs for bipolar disorder. The World Journal of Biological Psychiatry, 21(10), pp.775- 783.Luo, H., Wu, P.F., Cao, Y., Jin, M., Shen, T.T., Wang, J., Huang, J.G., Han, Q.Q., He, J.G., Deng, S.L. and Ni, L., 2020. Angiotensin-converting enzyme inhibitor rapidly ameliorates depressive-type behaviors via bradykinin-dependent activation of mammalian target of rapamycin complex 1. Biological Psychiatry, 88 (5), pp.415-425.Johansen, A., Holmen, J., Stewart, R. and Bjerkeset, O., 2012. Anxiety and depression symptoms in arterial hypertension: the influence of antihypertensive treatment. The HUNT study, Norway. European journal of epidemiology, 27, pp.63-72.Vian, J., Pereira, C., Chavarria, V., Kö hler, C., Stubbs, B., Quevedo, J., Kim, S.W., Carvalho, A.F., Berk, M. and Fernandes, B.S., 2017. The renin– angiotensin system: a possible new target for depression. BMC medicine, 15, pp.1-13.

BackgroundThe intersection of HIV/AIDS, substance use disorders, and depression represents a complex and pressing challenge within the realm of healthcare and clinical psychiatry (Berger-Greenstein et al., 2007). While significant progress has been made in the management of HIV/AIDS and in understanding the physiological and psychosocial aspects of substance use and depression, the co-occurrence of these conditions in HIV-positive individuals poses unique and multifaceted difficulties (Medeiros et al., 2020). Addressing these psychopharmacological challenges is essential to provide comprehensive and effective care for HIV/AIDS patients with a history of substance use experiencing depression.Aims & ObjectivesTo provide insights into the complexities of medication management for the HIV patients, considering their unique clinical needs and potential interactions between psychopharmaceuticals and antiretroviral therapies (ART).MethodWe present a case report with a discussion using relevant literature.ResultsA 38-year-old male patient living with HIV/AIDS, had a history of multiple drug use disorder (opioid, methamphetamine, and benzodiazepine). The patient reported severe depressive symptoms with psychotic features, all of which significantly impaired his quality of life. He was prescribed ART (tenofovir, lamivudine, and abacavir) and psychopharmacological treatment (quetiapine to address his cravings, sertraline as his antidepressant, aripiprazole as an adjuvant for the antidepressant, and clonazepam). Efforts were made to simplify his drug regimen, but the patient's cravings increased when quetiapine was discontinued, and his depression worsened despite increasing the dose of sertraline when aripiprazole was stopped. Clozapine was introduced to replace quetiapine and aripiprazole, and the patient's condition improved. Fortunately, there is no interaction between ART and the other medications used.Discussion & ConclusionExisting studies have reported a high prevalence of HIV/AIDS patients experiencing substance use and depression problems, with one report even noting a percentage as high as 73% (Berger-Greenstein et al., 2007). Treating this population is exceptionally challenging due to the influence of psychosocial support, neurocognitive functioning, drug interactions, and medication side effects (Medeiros et al., 2020; Millar et al., 2017)). The use of clozapine in the treatment of depression in HIV patients is a subject of ongoing research and clinical discussion. Depression in individuals with HIV/AIDS can be complex and multifactorial, often related to a combination of medical, psychological, and social factors. The use of clozapine or other atypical antipsychotics for depression in HIV patients may be considered in specific situations, especially when depression is treatment-resistant and accompanied by psychotic features (Ranjan and Meltzer, 1996). Furthermore, clozapine is also deemed effective in reducing cravings in patients with substance use disorder (Teixeira et al., 2022; Brunette et al., 2006). However, this decision should be made by a healthcare provider experienced in treating psychiatric conditions in the context of HIV/AIDS. Treatment decisions should be based on a thorough assessment of the individual's specific case and should consider factors such as co-occurring substance use disorders, other medications the patient may be taking, and potential interactions with ART.ReferencesBerger-Greenstein, J. A., Cuevas, C. A., Brady, S. M., Trezza, G., Richardson, M. A., & Keane, T. M. (2007). Major depression in patients with HIV/AIDS and substance abuse. AIDS Patient Care and STDs, 21(12), 942-955.Medeiros, G. C., Smith, F. A., Trivedi, M. H., & Beach, S. R. (2020). Depressive disorders in HIV/AIDS: A clinically focused narrative review. Harvard Review of Psychiatry, 28(3), 146-158.Millar, B. M., Starks, T. J., Gurung, S., & Parsons, J. T. (2017). The Impact of Comorbidities, Depression, and Substance Use Problems on Quality of Life Among Older Adults Living With HIV. AIDS and Behavior, 21(6), 1684-1690.Ranjan, R., & Meltzer, H. Y. (1996). Acute and long-term effectiveness of clozapine in treatment- resistant psychotic depression. Biological Psychiatry, 40(4), 253-258.Teixeira, J., Alexandre, S., Cunha, C., Raposo, F., Costa, J. P. (2022). Impact of clozapine as the mainstay therapeutic approach to schizophrenia and substance use disorder: A retrospective inpatient analysis. Psychiatry Research Communications, 2(3), 100056. ISSN 2772-5987.Brunette, M. F., Drake, R. E., Xie, H., McHugo, G. J., & Green, A. I. (2006). Clozapine use and relapses of substance use disorder among patients with co-occurring schizophrenia and substance use disorders. Schizophrenia bulletin, 32(4), 637–643.

BackgroundSex-specific differences in brain morphology [1] and specifically gray matter (GM) volume [2, 3], density (GMD) and microstructure (GMM) [4] were shown in several neuroimaging studies. Sex steroids were suggested to have a significant impact on these sex-dependent GM characteristics [5, 6]. Given the accurate monitoring of peripheral sex steroid levels in transgender individuals receiving gender-affirming hormone therapy (GHT), the effect of sex hormones on structural alterations of the brain can be reliably quantified in these cohorts via magnetic resonance imaging (MRI) technologies [7].Aims & ObjectivesHere, we investigated the effects of long-term GHT on GMD and GMM.Methods20 cisgender women (CW), 11 cisgender men (CM), 20 transgender women (TW) and 10 transgender men (TM) underwent two MRI sessions, once before GHT initiation and once after 4.5 months of treatment. GM changes determined by diffusion weighted imaging (DWI) metrics for GMM and voxel based morphometry (VBM) for GMD were estimated using repeated measures ANOVA. Plasma levels of luteinizing hormone, follicle-stimulating hormone, progesterone, estradiol, testosterone, sex hormone binding globulin and dehydroepiandrosterone sulfate were assessed via blood draw right before or after each MRI session and added to the models as covariates.ResultsSignificant time-by-group interaction effects on both GMD and GMM were found. An overlap of GMM- and GMD-specific changes was found in the fusiform gyrus, rolandic operculum, inferior occipital cortex, middle and anterior cingulum, bilateral insula, cerebellum and the lingual gyrus (post-hoc tests: p FWE+Bonferroni <0.025). After GHT, an increase in GMD was found in the fusiform gyrus, cerebellum and lingual gyrus for TM compared to both cisgender groups. In contrast, TW showed a GMD-decrease in the rolandic operculum, insula, posterior cingulum, cerebellum and lingual gyrus when compared to CM and CW. The opposite interaction effects were found in mean diffusivity (MD; an index for GMM) of the fusiform and lingual gyrus for TM compared to both cisgender groups. An MD-increase in the insula was found for TW when compared to CM and CW.Discussion & ConclusionThese results provide further evidence for a reliable influence of GHT on structural GM characteristics following an interregional pattern.References1) Cosgrove, K.P., C.M. Mazure, and J.K. Staley, Evolving knowledge of sex differences in brain structure, function, and chemistry. Biological psychiatry, 2007. 62(8): p. 847-855.2) Lotze, M., et al., Novel findings from 2,838 adult brains on sex differences in gray matter brain volume. Scientific reports, 2019. 9(1): p. 1671.3) Luders, E., et al., Why Sex Matters: Brain Size Independent Differences in Gray Matter Distributions between Men and Women. The Journal of Neuroscience, 2009. 29(45): p. 14265-14270.4) Gennatas, E.D., et al., Age-related effects and sex differences in gray matter density, volume, mass, and cortical thickness from childhood to young adulthood. Journal of Neuroscience, 2017. 37(20): p. 5065-5073.5) Koolschijn, P.C.M., J.S. Peper, and E.A. Crone, The influence of sex steroids on structural brain maturation in adolescence. PloS one, 2014. 9(1): p. e83929.6) Witte, A.V., et al., Regional sex differences in grey matter volume are associated with sex hormones in the young adult human brain. Neuroimage, 2010. 49(2): p. 1205-1212.7) Kranz, G.S., et al., Gender-affirming hormone treatment - A unique approach to study the effects of sex hormones on brain structure and function. Cortex, 2020. 129: p. 68-79.

BackgroundSocial anxiety disorder (SAD) is one of the most common psychiatric disorders in Japan, with teenagers being the most common age of onset, although the recently published Japanese guidelines for SAD 1 are intended for adults and not for children and adolescents.Aims & ObjectivesReview placebo-controlled drug trials for SAD in children and adolescents. Method Placebo-controlled trials in children and adolescents with SAD published from April 1986 to August 2023 were reviewed and summarized.ResultsThere were one randomized placebo-controlled trial (RCT) of paroxetine 2, one of venlafaxine 3, and one of fluoxetine plus psychotherapy versus placebo 4 in children and adolescents. There have been no further RCTs in child and adolescent subjects reported since the earlier National Institute for Health and Care Excellence (NICE) clinical guidelines reviewed them in 20135. The three RCTs showed efficacy with mild to moderate effect sizes compared to placebo in the treatment of SAD, but all agents had significantly more side effects, including gastrointestinal symptoms, compared to placebo. In addition, for paroxetine and venlafaxine, suicidal ideation, which was not reported with placebo, was reported in the actual drug group. Psychotherapy was more effective than fluoxetine. Other than RCTs, one open- label study each of sertraline 6 and escitalopram 7 have been reported. Open trials have also shown efficacy, but severe side effects have been reported: tremor, nausea, headache, insomnia, and restlessness.Discussion & ConclusionA network meta-analysis of anxiety disorder treatment in children and adolescents8 has shown that serotonin reuptake inhibitors (SSRIs) are the only class of drugs that are superior to placebo in both anxiety reduction and treatment response rate. However, the high dropout rates due to activation and gastrointestinal symptoms, as well as the high incidence of suicidal ideation, should be treated cautiously. NICE clinical guidelines state that drugs should not be routinely offered for the treatment of social anxiety disorder in children and adolescents due to the high risk of side effects. On the other hand, others argue that SSRIs can be considered in the initial phase of treatment for anxiety if the anxiety is severe or causing significant functional impairment, or if the child does not benefit from psychotherapy9. The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines point out that the increased risk of suicide and self-harm with antidepressants for major depressive disorder may not apply to anxiety disorders and suggest that medication should be reserved for patients who do not respond to psychotherapy10. In any case, careful observation will be required when considering prescriptions. Although evidence is insufficient, SSRIs and serotonin noradrenaline reuptake inhibitors, which have been shown to be effective in adults with SAD, may also be effective in children and adolescents with SAD. Further RCTs are warranted to establish the medication's efficacy and tolerability.

ABSTRACT This article reconsiders the role of aesthetic experience in Gregory Bateson’s work, reading Bateson’s accounts of the double bind and “the external pathways of the mind” alongside developments in brain-centered biological psychiatry. The article discusses Bateson’s response to these modernizing developments before examining one of his aesthetic engagements in detail. Noting that Bateson quotes the same line from Wordsworth’s much-maligned narrative poem Peter Bell twice, in two essays published in consecutive years and both later included in Steps to an Ecology of Mind, the author argues that Wordsworth’s Peter Bell becomes a counterexample for Bateson, a figure who stands opposed to the form of ecological thought that Bateson develops in his writings in the late 1960s and 1970s. Bateson suggests, with Wordsworth, that such a figure can be taught and that his indifference and insensibility need not be abiding or untreatable. But what would treatment or teaching mean in this context? Returning to Wordsworth’s poem with Bateson’s work in mind can help us answer this question and appreciate the implications of Bateson’s thought for contemporary aesthetic theory.

A pioneering force in psychiatric neuroscience, Dr. Kerry Ressler divides his time between serving as Chief Scientific Officer at McLean Hospital, Professor of Psychiatry at Harvard Medical School, and translational neuroscientist. Drawing from both molecular biology and human genetics, he has fundamentally changed how we understand fear and anxiety in the brain, especially through his innovative research on the amygdala. Throughout his remarkable career, which includes over 500 published papers, he has uncovered critical insights into the genetic and epigenetic basis of post-traumatic stress disorder (PTSD) and related anxiety disorders. His expertise has earned him membership in the National Academy of Medicine and a term as president of the Society for Biological Psychiatry. Dr. Ressler co-directs the Psychiatric Genomics Consortium PTSD Workgroup and founded the Grady Trauma Project in Atlanta before joining McLean Hospital. This Genomic Press Interview offers an intimate look at the path and perspectives of a scientist who has shaped modern psychiatric research and treatment.

French Society for Biological Psychiatry and Neuropsychopharmacology (AFPBN) guidelines for the management of patients with partially responsive depression and treatment-resistant depression: Update 2024

Attention Deficit Hyperactivity Disorder (ADHD) has traditionally been understood as a condition primarily associated with childhood. However, growing evidence indicates that ADHD persists into adulthood, manifesting in various ways. Despite its prevalence and significant impact on daily life, adult ADHD has been considerably underestimated and underdiagnosed, resulting in a substantial burden for affected individuals, as well as their families and social environment. This comprehensive review aims to explore the complexity of ADHD in adulthood by addressing its etiology, definition, clinical presentation, risk factors, common comorbidities, evaluation methods, and neuropsychological aspects, alongside both pharmacotherapeutic and non-pharmacotherapeutic approaches for treatment. Additionally, the implications for diagnosis and treatment are examined, emphasizing the need for a thorough understanding of this condition. Through this document, the Argentine Association of Biological Psychiatry (Asociación Argentina de Psiquiatría Biológica, AAPB) not only seeks to compile and analyze the evidence on adult ADHD but also to provide a practical guide for healthcare professionals treating this disorder. The ultimate goal of this article is to contribute to the development of effective strategies for the evaluation and management of ADHD, ultimately improving the quality of life for patients.

The concept of clinical-high risk (CHR) for schizophrenia implies the possibility of identifying a potential predisposition to future schizophrenia manifestation. An important goal of biological psychiatry is conducting research aimed at understanding the neurophysiological mechanisms of this condition. In this study, saccade characteristics of patients at CHR for schizophrenia (n = 15) and healthy participants (n = 15), as well as parameters of their slow negative potentials in the one-second interval preceding the signal to perform a saccade in a “memory-guided saccades/antisaccades” paradigm were analyzed. 12 participants from the CHR group also underwent magnetic resonance imaging (MRI) for subsequent comparison with the control group selected from the laboratory database. Saccade latencies and error rates were higher in the CHR group. There were also found lateral differences in CHR, but not in the control group. However, no between-group differences were observed in studied electrophysiological and MRI parameters. The obtained results may be interpreted as indirect signs of impairments in executive control, interhemispheric asymmetry and connectivity in the CHR group, although further studies are required to determine the possibility of using slow negative potentials parameters as clinical markers.

Even though psychopharmacology has made substantial progress in many areas of psychiatry since the discovery of antipsychotics and antidepressants in the 1950s, the evidence base for pharmacological treatments in the field of eating disorders has been lagging. The World Federation of Societies of Biological Psychiatry guidelines update 2023 on the pharmacological treatment of eating disorders provides a comprehensive summary of pharmacological studies and recommendations for anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), avoidant restrictive food intake disorder, pica and rumination disorder. However, there are very few studies in adolescents, implying that evidence-based recommendations in this population are difficult to make. Gender-specific aspects have also been addressed in the guidelines update, such as the small number of male patients included in pharmacological studies in AN and BN. Furthermore, the guidelines recommend against the treatment of female AN patients with testosterone, mention that topiramate for the treatment of BN and BED is contraindicated during pregnancy and that fluoxetine and its metabolite norfluoxetine inhibit the metabolism of the anti-breast cancer prodrug tamoxifen to its active metabolite endoxifen.