Personalized Medicine in Psychiatry最新文献

Substance use disorders (SUDs) are common among individuals with schizophrenia and negatively affect the clinical course of the illness. Despite the high prevalence and significant impact on outcomes, the etiology of SUDs in individuals with schizophrenia remains poorly understood. A better understanding of the etiology, shared mechanisms, temporal evolution, and complex interplay between pathophysiologies will provide the foundation for rational development of targeted therapeutics. We review the literature on the prevalence, etiology, biomarkers, and treatment for individuals with comorbid SUDs and schizophrenia. Substance use is associated with increased risk of subsequent development of schizophrenia. However, the directionality of the relationship between substance use and schizophrenia remains unclear. While several SUDs are associated with increased psychotic symptoms, others are correlated with less severe psychopathology. Individuals with schizophrenia who have more severe symptoms are more likely to have a SUD. There is evidence for shared genetic risk for SUDs and schizophrenia. Comorbid SUDs and schizophrenia share abnormalities in the mesolimbic dopamine system, affecting drug reward, sensitization, and craving. Neuroimaging studies have identified molecular, structural, and functional pathophysiology in co-occurring schizophrenia and SUDs. Neuroinflammation may also represent a shared pathophysiology between SUDs and schizophrenia. While treatments for SUDs exist, they are generally less effective and underutilized for individuals with schizophrenia. Future research is essential to understand the underlying etiology of SUDs in schizophrenia. We propose that neuromodulatory experiments can establish this etiology and identify therapeutic targets. Longitudinal studies across multiple modalities (i.e. neuroimaging, serum, genetics) may help to identify risk factors and biomarkers.

Objectives

This study investigated the perceived impact of the COVID-19 pandemic on youth with chronic tic disorders (CTD) and/or obsessive–compulsive disorder (OCD) based on subjective reports, objective measures, and parental feedback. This study also sought to investigate whether and how these reported experiences differed based on the presence of underlying tic and/or OCD spectrum diagnoses.

Methods

Children with CTD, OCD, and Tics + OCD and their parents were recruited to complete an online survey from July 2020 through April 2021. Forty-eight responses were received; child respondents had a median age of 12 years.

Results

On average, youth reported that the pandemic negatively impacted them in several domains, particularly after-school activities, relationships with friends, and social/community gatherings. Despite the small sample size, youth with OCD appeared to experience a greater negative impact compared to other subgroups. Median screen use in this sample was 3–8 hours a day, and youth who reported > 8 hours on weekends trended towards increased depressive symptoms.

Conclusion

Consistent with the physician-authors’ clinical experiences, youth with CTD, OCD, and Tics + OCD and their parents reported a subjective negative impact of the pandemic on various symptoms and psychosocial domains. Going forward, if another lockdown loomed, it would be valuable to stay attuned to these vulnerable youth, particularly those with OCD symptoms, and consider providing support in specific psychosocial domains, such as relationship with peers and home life.

Psychiatry awaits new biomarkers to guide diagnosis and treatment, but identifying, testing, and applying valid technologies will be an extended process, likely requiring years of development. Meanwhile, numerous features of illness and proven techniques for gathering key information on individual patients are underutilized. Such information includes: Details of current presentation and history, including treatments and outcomes; other medical history, including treatments and outcomes; general health and habits; family history of relevant illnesses; and the personal and social context of each patient’s life and illness. Rarely is enough time allotted or resources made available to obtain all this information. However, these data can be obtained by system modifications including: Offloading some work from the treating psychiatrist to allow more time for discussion, data gathering, and relationship building with the patient; using standardized tools and procedures, such as electronic assessment and tracking tools, to gather and share information; improving means to obtain information from other sources, such as other informants, colleagues treating the patient, and the medical record; and providing easily accessible assessment and treatment guidelines containing evidence-based expert-consensus techniques for matching treatment to individual presentation and circumstances. These approaches can be implemented, by means detailed in the text. Briefly, providing more personalized care requires some shifts in funding, some changes in staffing and communication, and some improvements in electronic data gathering, sharing, and searching. In the service of care, it is incumbent on all involved agencies, institutions, and practices to make these changes in the immediate future.

Background

There is growing evidence suggesting a connection between gut dysbiosis and the development of psychiatric disorders. A number of studies have shown that probiotics contribute to symptom reduction in major depressive disorder, but very few such studies have been conducted on bipolar disorder. The present study is a systematic review of such studies.

Methods

Systematic review following PRISMA guidelines of studies published in the past ten years which involve the use of probiotics in patients with bipolar disorder.

Results

Of 4717 articles screened, 5 were included in this review [n = 193]. Collectively, the studies measured the effects of probiotics on the symptoms of bipolar disorder as well as rehospitalization rates.

Conclusion

Despite the limited number of studies done on this topic, there is evidence that probiotics improve symptoms of bipolar disorder, particularly manic symptoms, with no significant negative effects.

Major Depressive Disorder (MDD) and Obsessive-Compulsive Disorder (OCD) are common and potentially incapacitating conditions. Even when recognized and adequately treated, in over a third of patients with these conditions the response to first-line pharmacological and psychotherapeutic measures is not satisfactory. After more assertive measures including pharmacological augmentation (and in the case of depression, transcranial magnetic stimulation, electroconvulsive therapy, or treatment with ketamine or esketamine), a significant number of individuals remain severely symptomatic. In these persons, different ablation and deep-brain stimulation (DBS) psychosurgical techniques have been employed. However, apart from the cost and potential morbidity associated with surgery, on average only about half of patients show adequate response, which limits the widespread application of these potentially life-saving interventions. Possible reasons are considered for the wide variation in outcomes across different series of patients with MDD or OCD exposed to ablative or DBS psychosurgery, including interindividual anatomical and etiological variability. Low-intensity focused ultrasound (LIFU) is an emerging technique that holds promise in its ability to achieve anatomically circumscribed, noninvasive, and reversible neuromodulation of deep brain structures. A possible role for LIFU in the personalized presurgical definition of neuromodulation targets in the individual patient is discussed, including a proposed roadmap for clinical trials addressed at testing whether this technique can help to improve psychosurgical outcomes.

Background

Therapeutic options for bipolar disorder vary based on individual presentation and phase of illness. In addition to well documented disparities in diagnosis, racial and gender differences in treatment complicate efforts to provide effective individualized treatment to patients with bipolar disorder. The present work was undertaken to identify the persistence of racial and gender disparities across diverse community and national populations and to compare treatment disparities in bipolar disorder with those observed for schizophrenia.

Methods

Commonly prescribed treatments for bipolar disorder and schizophrenia were quantified using information gathered from the All of Us Research Program and de-identified electronic health records at the University of Mississippi Medical Center.

Results

Black patients with bipolar disorder, in comparison to white patients, had significantly less utilization of lithium, lamotrigine, and antidepressants, but greater utilization of haloperidol and other first-generation antipsychotics. Disparities in antipsychotic use were reduced in patients with schizophrenia compared to those with a bipolar diagnosis.

Conclusions

The disparities enumerated here have real world clinical implications. Black patients with bipolar disorder have less utilization of lithium, the gold standard mood stabilization treatment. Further community-guided research to better understand the origins of these disparities and clinical trials to evaluate non-antipsychotic mood stabilization treatment for bipolar disorder across populations is warranted.

Background

Neuromodulation of brain circuits important for affect, behavior, and cognition may decrease the symptomatology and functional impairment of military veterans suffering from posttraumatic stress disorder (PTSD). Cranial electrotherapy stimulation (CES) techniques, such as Alpha-Stim®, have demonstrated preliminary benefit for symptoms that commonly co-occur with PTSD, such as pain, anxiety, depression, and insomnia. However, CES has not yet been specifically tested as a treatment for PTSD. The objective of this open-label pilot study was to examine feasibility, safety, and preliminary efficacy of Alpha-Stim® for treatment of PTSD.

Methods

Open-label Alpha-Stim® was administered to nine veterans who were diagnosed with PTSD via structured interview (Clinician-Administered PTSD Scale for DSM-5 [CAPS-5]) and were taking at least one psychotropic medication. Treatment consisted of 20 CES sessions administered at home over 40 days. Effects on PTSD symptoms, functioning, depression symptoms, pain, anxiety symptoms, and insomnia were assessed at baseline and every week of treatment for four weeks. Effects on PTSD symptoms, depression symptoms, and pain were assessed one month and three months post-treatment.

Results

Seven patients (78%) successfully completed treatment. There were no adverse events. Following four weeks of Alpha-Stim® treatment, PTSD symptoms decreased by 38%, depression symptoms decreased by 52%, insomnia decreased by 34%, and pain decreased by 11%. Significant improvements in PTSD and depression, but not pain, persisted at one-month and three-months posttreatment. Presumptive loss of diagnosis rates (i.e., PTSD Checklist for DSM-5 total score below 33) immediately following treatment and one and three months later were 43%, 33%, and 29%, respectively.

Conclusions

Alpha-Stim® showed an excellent safety profile with no adverse effects. The results suggest preliminary efficacy for improving PTSD symptoms as well as concomitant depression symptoms, insomnia, and pain. Limitations of this pilot study include the open-label, uncontrolled design and small sample size. These results support additional larger, randomized controlled trials of Alpha-Stim® for veterans with PTSD.

Suicide is a devastating complication of psychiatric disorders characterized by despair, hopelessness, and overwhelming mental distress or pain. Non-suicidal self-injury (NSSI), suicide ideation (SI) and suicide attempts (SA) all fall under the umbrella of suicide behaviour (SB). Several biopsychological theories describe SB as an attempt to relieve mental pain. They comment on the role of tolerance-habituation to the rewarding effects of SB-induced emotional regulation, as well as increasing physical or somatic pain tolerance, both of which contribute to the escalating patterns of repetitive SB. The endocannabinoid system (ECS) is involved in a wide range of homeostatic and neuromodulatory functions including appetite/feeding, sleep, motor control, pain perception, cognition, mood/affect, and reward processing. The downregulation of endocannabinoid signalling has major implications for affective disorders, pain disorders, and substance use disorders. SB can be seen as a manifestation of these disorders and has also been linked to ECS dysfunction. Drawing from both animal and human studies, we aim to understand repetitive SB as an endocannabinoid-mediated pain and reward disorder. We hypothesize that mental distress triggers the first incidence of NSSI or SB, from which patients derive stress-induced endocannabinoid-mediated analgesia. As patients become increasingly tolerant to this mechanism of analgesia, SB escalates to override increasing mental distress. This hypothesis calls for more research on endocannabinoid-based therapies to prevent the progression from NSSI or SI to fatal SA.