Psychedelics and the 'inner healer': Myth or mechanism?

BACKGROUND: Reference to an intrinsic healing mechanism or an 'inner healer' is commonplace amongst psychedelic drug-using cultures. The 'inner healer' refers to the belief that psychedelic compounds, plants or concoctions have an intrinsically regenerative action on the mind and brain, analogous to intrinsic healing mechanisms within the physical body, for example, after sickness or injury. AIMS: Here, we sought to test and critique this idea by devising a single subjective rating item pertaining to perceived 'inner healing' effects. METHODS: The item was issued to 59 patients after a single high (25 mg, n = 30) or 'placebo' (1 mg, n = 29) dose of psilocybin in a double-blind randomised controlled trial of psilocybin for depression. RESULTS: Inner healer scores were higher after the high versus placebo dose of psilocybin (t = 3.88, p < 0.001). Within the high-dose sub-sample only, inner healer scores predicted improved depressive symptomatology at 2 weeks post-dosing. CONCLUSIONS: The principle of activating inner healing mechanisms via psychedelics is scientifically nascent; however, this study takes a positivist and pragmatic step forward, asking whether it warrants further examination.

Music as an Intervention to Improve the Hemodynamic Response of Ketamine in Depression: A Randomized Clinical Trial.

This randomized clinical trial explores whether music improves the hemodynamic response of ketamine among patients with treatment-resistant depression in Canada.

The Montreal model: an integrative biomedical-psychedelic approach to ketamine for severe treatment-resistant depression.

Background: Subanesthetic ketamine has accumulated meta-analytic evidence for rapid antidepressant effects in treatment-resistant depression (TRD), resulting in both excitement and debate. Many unanswered questions surround ketamine's mechanisms of action and its integration into real-world psychiatric care, resulting in diverse utilizations that variously resemble electroconvulsive therapy, conventional antidepressants, or serotonergic psychedelics. There is thus an unmet need for clinical approaches to ketamine that are tailored to its unique therapeutic properties. Methods: This article presents the Montreal model, a comprehensive biopsychosocial approach to ketamine for severe TRD refined over 6 years in public healthcare settings. To contextualize its development, we review the evidence for ketamine as a biomedical and as a psychedelic treatment of depression, emphasizing each perspectives' strengths, weaknesses, and distinct methods of utilization. We then describe the key clinical experiences and research findings that shaped the model's various components, which are presented in detail. Results: The Montreal model, as implemented in a recent randomized clinical trial, aims to synergistically pair ketamine infusions with conventional and psychedelic biopsychosocial care. Ketamine is broadly conceptualized as a brief intervention that can produce windows of opportunity for enhanced psychiatric care, as well as powerful occasions for psychological growth. The model combines structured psychiatric care and concomitant psychotherapy with six ketamine infusions, administered with psychedelic-inspired nonpharmacological adjuncts including rolling preparative and integrative psychological support. Discussion: Our integrative model aims to bridge the biomedical-psychedelic divide to offer a feasible, flexible, and standardized approach to ketamine for TRD. Our learnings from developing and implementing this psychedelic-inspired model for severe, real-world patients in two academic hospitals may offer valuable insights for the ongoing roll-out of a range of psychedelic therapies. Further research is needed to assess the Montreal model's effectiveness and hypothesized psychological mechanisms.

Indigenous Voices in Psychedelic Therapy: Experiential Learnings from a Community-Based Group Psychedelic Therapy Program.

Novel and traditional psychedelic medicines are attracting interest as potential treatments of mental illness. Before psychedelic therapies can be made available in culturally safe and effective ways to diverse peoples, the field must grapple with the complex legacies of colonialism and ongoing clashes between biomedical and Indigenous Ways of Knowing. This article presents results of a pilot program offering group-based therapy augmented by three sessions of ketamine at a psychedelic dose, for a group of Indigenous participants. This unique project was undertaken in partnership between Roots to Thrive and the Snuneymuxw First Nation to assess this approach's effectiveness and safety for Indigenous peoples. Thematic analysis of qualitative interviews and anonymous feedback received throughout the program from eight participants and two Elders provided rich information on participant motivations, perceived barriers, appreciated and beneficial aspects of the program, and the psychedelic experiences, as well as important directions for further improvement. In addition to challenges, participants attributed significant benefits to the program while highlighting the importance of the involvement of Indigenous team members, the incorporation of traditional approaches to healing, and the cultivation of open and authentic relationships between group participants and facilitators. We discuss important lessons learned and the essential work of reconciliation in, and beyond, psychedelic therapies.

Intravenous ketamine for benzodiazepine deprescription and withdrawal management in treatment-resistant depression: a preliminary report.

We present the first evidence that sub-anesthetic ketamine infusions for treatment resistant depression (TRD) may facilitate deprescription of long-term benzodiazepine/z-drugs (BZDRs). Long-term BZDR prescriptions are potentially harmful yet common, partly because of challenging withdrawal symptoms. Few pharmacological interventions have evidence for facilitating BZDR discontinuation, and none in patients actively suffering from TRD. In this ambi-directional cohort study, discontinuation of long-term (>6 month) BZDRs was attempted in 22 patients with severe unipolar or bipolar TRD receiving a course of six subanesthetic ketamine infusions over four weeks. We investigated the rates of successful BZDRs deprescription, trajectories of acute psychological withdrawal symptoms, and subsequent BZDRs abstinence during a mean follow-up of 1 year (primary outcome). Clinically significant deteriorations in depression, anxiety, sleep, and/or suicidality during the acute BZDR discontinuation phase were measured by repeated standardized scales and analyzed by latent growth curve models and percent correct classification analysis. Of the 22 eligible patients, all enrolled in this study and 91% (20/22) successfully discontinued all BZDRs by the end of the 4-week intervention, confirmed by urinary analyses. Less than 25% of discontinuers experienced any significant worsening of anxiety, depression, sleep difficulties, or suicidality during treatment. During follow-up (mean [range] duration, 12 [3-24] months), 64% (14/22) of patients remained abstinent from any BZDRs. These preliminary results suggest that ketamine infusions for TRD may facilitate the deprescription of BZDRs, even in patients with active depressive symptoms and significant comorbidity. Further investigation is warranted into this potential novel application of ketamine.

Imprinting: expanding the extra-pharmacological model of psychedelic drug action to incorporate delayed influences of sets and settings.

Background: Psychedelic drug experiences are shaped by current-moment contextual factors, commonly categorized as internal (set) and external (setting). Potential influences of past environments, however, have received little attention. Aims: To investigate how previous environmental stimuli shaped the experiences of patients receiving ketamine for treatment-resistant depression (TRD), and develop the concept of "imprinting" to account for such time-lagged effects across diverse hallucinogenic drugs. Methods: Recordings of treatment sessions and phenomenological interviews from 26 participants of a clinical trial investigating serial intravenous ketamine infusions for TRD, conducted from January 2021 to August 2022, were retrospectively reviewed. A broad literature search was undertaken to identify potentially underrecognized examples of imprinting with both serotonergic and atypical psychedelics, as well as analogous cognitive processes and neural mechanisms. Results: In naturalistic single-subject experiments of a 28-year-old female and a 34-year-old male, subjective ketamine experiences were significantly altered by varying exposures to particular forms of digital media in the days preceding treatments. Higher levels of media exposure reduced the mystical/emotional qualities of subsequent psychedelic ketamine experiences, overpowering standard intention-setting practices and altering therapeutic outcomes. Qualitative data from 24 additional patients yielded eight further spontaneous reports of past environmental exposures manifesting as visual hallucinations during ketamine experiences. We identified similar examples of imprinting with diverse psychoactive drugs in past publications, including in the first-ever report of ketamine in human subjects, as well as analogous processes known to underly dreaming. Conclusions/interpretation: Past environmental exposures can significantly influence the phenomenology and therapeutic outcomes of psychedelic experiences, yet are underrecognized and understudied. To facilitate future research, we propose expanding the contextual model of psychedelic drug actions to incorporate imprinting, a novel concept that may aid clinicians, patients, and researchers to better understand psychedelic drug effects. Clinical trial registration: ClinicalTrials.gov, identifier NCT04701866.

Ketamine for depression: a potential role in requests for Medical Aid in Dying?

Medical Aid in Dying (MAiD) is the act of a healthcare provider ending a patient's life, at their request, due to unbearable suffering from a grievous and incurable disease. Access to MAiD has expanded in the last decade and, more recently, it has been made available for psychiatric illnesses in a few countries. Recent studies have found that such psychiatric requests are rapidly increasing and primarily involve mood disorders as the primary condition. Nevertheless, MAiD for psychiatric disorders is associated with significant controversy and debate, especially regarding the definition and determination of irremediability - that a given patient lacks any reasonable prospect for recovery. In this article, we report the case of a Canadian patient who was actively requesting Medical Assistance in Dying for severe and prolonged treatment-resistant depression until she experienced remarkable benefits from a course of intravenous ketamine infusions. To our knowledge, this is the first report of ketamine or any other intervention yielding remission in a patient who would have otherwise likely been eligible for MAiD for depression. We discuss implications for the evaluation of similar requests and, more specifically, why a trial of ketamine warrants consideration.

The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Report: Serotonergic Psychedelic Treatments for Major Depressive Disorder.

OBJECTIVE: Serotonergic psychedelics are re-emerging as potential novel treatments for several psychiatric disorders including major depressive disorder. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence and provide a consensus recommendation for the clinical use of psychedelic treatments for major depressive disorder. METHODS: A systematic review was conducted to identify contemporary clinical trials of serotonergic psychedelics for the treatment of major depressive disorder and cancer-related depression. Studies published between January 1990 and July 2021 were identified using combinations of search terms, inspection of bibliographies and review of other psychedelic reviews and consensus statements. The levels of evidence for efficacy were graded according to the Canadian Network for Mood and Anxiety Treatments criteria. RESULTS: Only psilocybin and ayahuasca have contemporary clinical trials evaluating antidepressant effects. Two pilot studies showed preliminary positive effects of single-dose ayahuasca for treatment-resistant depression (Level 3 evidence). Small randomized controlled trials of psilocybin combined with psychotherapy showed superiority to waitlist controls and comparable efficacy and safety to an active comparator (escitalopram with supportive psychotherapy) in major depressive disorder, with additional randomized controlled trials showing efficacy specifically in cancer-related depression (Level 3 evidence). There was only one open-label trial of psilocybin in treatment-resistant unipolar depression (Level 4 evidence). Small sample sizes and functional unblinding were major limitations in all studies. Adverse events associated with psychedelics, including psychological (e.g., psychotomimetic effects) and physical (e.g., nausea, emesis and headaches) effects, were generally transient. CONCLUSIONS: There is currently only low-level evidence to support the efficacy and safety of psychedelics for major depressive disorder. In Canada, as of 2022, psilocybin remains an experimental option that is only available through clinical trials or the special access program. As such, Canadian Network for Mood and Anxiety Treatments considers psilocybin an experimental treatment and recommends its use primarily within clinical trials, or, less commonly, through the special access program in rare, special circumstances.

Psychedelic medicine at a crossroads: Advancing an integrative approach to research and practice.

Psychedelics have been already used by human societies for more than 3000 years, mostly in religious and healing context. The renewed interest in the potential application of psychedelic compounds as novel therapeutics has led to promising preliminary evidence of clinical benefit in some psychiatric disorders. Despite these promising results, the potential for large-scale clinical application of these profoundly consciousness-altering substances, in isolation from the sociocultural contexts in which they were traditionally used, raises important concerns. These concerns stem from the recognition that the mechanisms of therapeutic action of psychedelics are not entirely dependent on neurobiology, but also on the psychological, social and spiritual processes for their efficacy. For these reasons, physicians or psychotherapists involved in psychedelic-assisted psychotherapy need training in ways to accompany patients through this experience to promote positive outcomes and address potential side effects. Psychedelic therapies may foster the emergence of a novel paradigm in psychiatry that integrates psychopharmacological, psychotherapeutic, and cultural interventions for patients with mental health issues.

Efficacy of ketamine intervention to decrease alcohol use, cravings, and withdrawal symptoms in adults with problematic alcohol use or alcohol use disorder: A systematic review and comprehensive analysis of mechanism of actions.

BACKGROUND: Alcohol use disorder is highly prevalent and has important economical, societal, psychiatric, and medical consequences. All currently approved therapeutic approaches targeting alcohol dependence have relatively modest effects and high relapse rates. Recent evidence suggests that ketamine may be an effective intervention to treat alcohol use disorder and alcoholic withdrawal. This systematic review aimed to assess the current level of evidence for this intervention. METHODS: This systematic review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered on the international database of systematic reviews PROSPERO. Medline(Ovid), CINAHL Complete(EBSCOhost), PsycINFO(Ovid), EBM Reviews(Ovid), EMBASE(Ovid), and Google Scholar were searched for studies using ketamine to treat harmful alcohol use, craving, or withdrawal states in humans. Studies of any methodology that evaluated ketamine in isolation or combination with other interventions were included. The risk of bias was assessed using specific Cochrane critical appraisal tools. RESULTS: Of 1922 abstracts identified, 8 full-text articles were eligible for inclusion, yielding a total sample size of 634 participants. Five studies investigated the impact of ketamine on alcohol use and/or cravings and/or withdrawal in outpatient settings. Three studies looked at the effect of adding ketamine to conventional treatment of withdrawal symptoms in participants admitted to intensive care unit for severe alcohol withdrawal. Results on primary outcomes were mixed within and across trials. CONCLUSIONS: Despite promising results, the current evidence does not permit definitive conclusions about the efficacy of ketamine in alcohol use disorders or withdrawal. Future studies are warranted.

Psychotropic Drugs and Adverse Kidney Effects: A Systematic Review of the Past Decade of Research.

BACKGROUND AND OBJECTIVE: Psychotropic drugs are a heterogenous group of treatments prescribed for many psychiatric disorders, often for long periods. Their effects on the kidney and its functioning are complex and a source of significant research and debate. This article aims to review recent evidence of the acute and chronic kidney adverse events of diverse psychotropes. METHODS: A systematic search of randomized controlled trials and large observational studies (n ≥ 100) reporting the effects of psychotropic drugs on the kidney was conducted. The MEDLINE, PsycInfo, and EMBASE databases from 2011 to 2021, inclusive, were broadly searched with few restrictions and no prespecified outcomes. Two or more independent reviewers assessed and summarized all eligible studies, including risks of bias and levels of evidence. RESULTS: In all, 1999 abstracts were screened for eligibility and 47 articles were included, which examined lithium (33), antiepileptics (10), antipsychotics (13), and antidepressants (9). No studies examining kidney adverse effects of other psychotropes, such as benzodiazepines, met inclusion criteria. Study populations were adult (8), geriatric (9), and mixed (30). Lithium was almost unanimously associated with (1) chronic kidney disease and (2) nephrogenic diabetes insipidus in methodologically diverse studies. The most supported risk factors for declining kidney functioning with lithium were advanced age, duration of lithium treatment, acute lithium toxicity, female sex, medications with known renal interactions, diabetes mellitus/hyperglycemia, and overall medical comorbidity. Supratherapeutic lithium concentrations are both the causes and consequences of acute kidney injury. Once significant chronic kidney disease has developed, four studies found that replacing lithium with other mood stabilizers does not slow progression, and the evolution to end-stage kidney disease is rare overall with modern practices. Compared to lithium, fewer studies examined antipsychotics and antiepileptics but found relatively less direct kidney harms. Antidepressants were not associated with acute or chronic kidney harms. CONCLUSIONS: Despite the heterogeneity of findings, owing to varying methodologies and research challenges, recent studies strongly suggest that lithium is associated with an increased risk of chronic kidney disease and nephrogenic diabetes insipidus, especially in older adults and long-term lithium users. Clinicians should balance the harms of lithium against its established benefits, and ensure adequate monitoring and management of comorbidities in all patients. Weaker evidence suggests that antiepileptics such as valproate and antipsychotics result in comparatively less harm to the kidney than lithium, but warrant monitoring because of multiple direct and indirect mechanisms for potential kidney adverse events. Antidepressants do not have clear kidney adverse effects and appear safe (though potentially less effective) in the setting of kidney disease. Other classes of psychotropic drugs have received little research interest. Further research is warranted, particularly into specific antiepileptics and antipsychotics, and careful attention should be paid to mitigating important sources of bias such as confounding by indication.

A Systematic Review of Telemedicine for Older Adults With Dementia During COVID-19: An Alternative to In-person Health Services?

Introduction: Older adults with dementia have been significantly at more risk for not receiving the care needed and for developing further mental health problems during COVID-19. Although the rise in telemedicine adoption in the healthcare system has made it possible for patients to connect with their healthcare providers virtually, little is known about its use and effects among older adults with dementia and their mental health. Objective: This systematic review aimed to explore the use, accessibility, and feasibility of telemedicine in older adults with dementia, as well as examine the potential mental health impacts of these technologies, through reviewing evidence from studies conducted during COVID-19. Methods: PubMed, Scopus, and Web of Science databases were searched with the following keywords: (COVID* OR SARS-CoV-2 OR Coronavirus) AND ("mental health" OR Depression OR Stress) AND (Dementia OR Multi-Infarct Dementia OR Vascular Dementia OR Frontotemporal Dementia) AND (elder OR Aging OR Aging OR Aged) AND (Telemedicine OR "Remote Consultation" OR telehealth OR technology). Results: A total of 7 articles from Asia, Europe, and the United States were included in this review. Throughout the studies cognitive and mental health assessments (e.g., MoCA, FAST, etc.) were performed. Despite the barriers, telemedicine was noted as a feasible approach to assist individuals with dementia in connecting with their service providers and family while reducing complications related to travel (e.g., difficulty moving, traffic, distance). Conclusions: Due to the COVID-19 pandemic, finding alternative ways to provide services to older adults with dementia through technology may continue to become more necessary as time goes on.

Low MoCA performances correlate with suicidal ideation in late-life depression.

Late-life depression remains an underdiagnosed clinical entity, mainly because the presence of cognitive impairment in the elderly leads clinicians to suspect dementia rather than depression. Our objective was to analyze the cognitive abilities of elderly depressed patients using the Montreal Cognitive Assessment (MoCA) in relation to the presence or absence of suicidal ideation. The MoCA, Beck Scale of Suicidal Ideation, Hamilton Anxiety Scale, and Hamilton Depression Scale were administered to 72 patients with a recent history of late life depression: 43 with suicidal ideation and 29 non-suicidal controls. The results show that suicidal patients demonstrated significantly worse performance on the MoCA total score and the delayed recall subtest in comparison to non-suicidal controls. In addition, after adjusting for age and depression, poorer performance on the MoCA total score correlated to the presence of suicidal ideation. We found that the MoCA total score is able to predict the presence of suicidal ideation in depressed elderly patients in a fair-to-good manner. As late-life depression is already established as a potential prodrome of dementia, longitudinal follow-up may determine whether depressed individuals with suicidal ideation are at higher risk of converting to dementia.

Adjunctive music improves the tolerability of intravenous ketamine for bipolar depression.

Intravenous ketamine is an effective treatment of bipolar depression. One of its most important side-effects is a transient altered state of consciousness commonly referred to as dissociation. These states can be anxiety-provoking, distressing and even treatment-limiting, warranting research into mitigation strategies. In this article, we present two cases that demonstrate the potential of adjunctive music to diminish the distress associated with ketamine-induced dissociation - though not necessarily its degree - in bipolar 1 disorder. Both patients suffering from severe depression underwent their first ketamine infusion without music and opted for music with subsequent infusions. They reported that music significantly improved the tolerance of their dissociative symptoms, thereby reducing distress and facilitating subsequent treatments. Both patients achieved remission from their highly treatment-resistant depressive episodes following six ketamine infusions. This is the first report of music's benefits on ketamine for bipolar 1 depression, though there is precedence in the scientific literature on 'psychedelics' where the use of music in combination with medication-induced altered states has been studied. The principles regarding music selection that have resulted from this paradigm may be applicable to the use of ketamine in unipolar and bipolar depression. The optimal use of music with ketamine warrants further research.

Childhood cognitive skill trajectories and suicide by mid-adulthood: an investigation of the 1958 British Birth Cohort.

BACKGROUND: Poor cognitive abilities and low intellectual quotient (IQ) are associated with an increased risk of suicide attempts and suicide mortality. However, knowledge of how this association develops across the life-course is limited. Our study aims to establish whether individuals who died by suicide by mid-adulthood are distinguishable by their child-to-adolescence cognitive trajectories. METHODS: Participants were from the 1958 British Birth Cohort and were assessed for academic performance at ages 7, 11, and 16 and intelligence at 11 years. Suicides occurring by September 2012 were identified from linked national death certificates. We compared mean mathematics and reading abilities and rate of change across 7-16 years for individuals who died by suicide v. those still alive, with and without adjustment for potential early-life confounding factors. Analyses were based on 14 505 participants. RESULTS: Fifty-five participants (48 males) had died by suicide by age 54 years. While males who died by suicide did not differ from participants still alive in reading scores at age 7 [effect size (g) = -0.04, p = 0.759], their reading scores had a less steep improvement up to age 16 compared to other participants. Adjustments for early-life confounding factors explained these differences. A similar pattern was observed for mathematics scores. There was no difference between individuals who died by suicide v. participants still alive on intelligence at 11 years. CONCLUSIONS: While no differences in tests of academic performance and IQ were observed, individuals who died by suicide had a less steep improvement in reading abilities over time compared to same-age peers.

Psychological pain and depression: it's hard to speak when it hurts.

OBJECTIVE: To investigate the neuropsychological features of depressed patients reporting high level of psychological pain. METHODS: Sixty-two inpatients were included and divided into two groups according to the level of psychological pain assessed by a Likert scale. Cognitive abilities were assessed using the Trail Making Test, the Stroop test, and Verbal Fluency Test (semantic and phonemic verbal fluency). Univariate and multivariate analyses were performed to determine neuropsychological factors associated with a high level of psychological pain. RESULTS: The median level of psychological pain was 8/10. High level of psychological pain was associated with poor phonemic verbal fluency performance in men (p = 0.009), but not in women, even after controlling for confounding factors (age, level of depression, anxiety). Groups did not differ on the Trail Making Test, the Stroop test, or the semantic verbal fluency measure. CONCLUSION: Psychological pain is a specific clinical entity that should be considered to be more significant than just a symptom of depression. High level of psychological pain appears to be associated with a deficit of phonemic verbal fluency in depressed men. This finding could help to target psychotherapeutic treatments and improve screening.Key pointsPatients with high psychological pain do not differ on the Trail Making Test, the Stroop Test or the Sematic Verbal Fluency Measure to patients with low psychological painHigh psychological pain is associated with a deficit in phonemic verbal fluency in depressed menFuture research should aim to clarify gender differences in psychological pain in participants with and without major depressive disorder, as well as explore the complex relationship between cognition and the different forms of pain (psychological, physical and psychosomatic).

Childhood-maltreatment subtypes in bipolar patients with suicidal behavior: systematic review and meta-analysis.

OBJECTIVE: Patients with bipolar disorders have a high risk of suicidal behavior. Childhood maltreatment is a well-established risk factor for suicidal behavior. The objective of this study was to examine the association between childhood-maltreatment subtypes and vulnerability to suicide attempts in bipolar disorder using the Childhood Trauma Questionnaire (CTQ). METHODS: A literature review was performed using the MEDLINE, Embase, and PsycINFO databases. Thirteen studies met the selection criteria. In the meta-analysis, the Childhood Trauma Questionnaire (CTQ) was used to assess a wide range of childhood maltreatment subtypes, which were analyzed by using a random-effects model to account for the likely variations of true effect sizes between the included studies. RESULTS: In the systematic review, 13 studies met the selection criteria. The CTQ was selected for the meta-analysis to increase the homogeneity of assessment and to encompass a wide range of childhood-maltreatment subtypes. The data were analyzed using a random-effects model. Compared to bipolar non-attempters, bipolar suicide attempters had experienced childhood maltreatment with a significantly higher frequency and had higher total CTQ scores (Hedges' g = -0.38, 95%CI -0.52 to -0.24, z = -5.27, p < 0.001) and CTQ sub-scores (sexual abuse: g = -0.39, 95%CI -0.52 to -0.26, z = -5.97; physical abuse: g = -0.26, 95%CI -0.39 to -0.13, z = -4.00; emotional abuse: g = -0.39, 95%CI -0.65 to -0.13, z = -2.97; physical neglect: g = -0.18, 95%CI -0.31 to -0.05, z = -2.79; emotional neglect: g = -0.27, 95%CI -0.43 to -0.11, z = -3.32). CONCLUSIONS: Childhood maltreatment, as assessed by the CTQ, may contribute to an increased risk of suicidal behavior among people with bipolar disorders. Recognizing maltreatment as an etiological risk factor is a crucial step toward furthering science-based preventive psychiatry.