Personalized Medicine in Psychiatry最新文献

Identifying objective and reliable markers to tailor diagnosis and treatment of psychiatric patients remains a challenge, as conditions like major depression, bipolar disorder, or schizophrenia are qualified by complex behavior observations or subjective self-reports instead of easily measurable somatic features. Recent progress in computer vision, speech processing and machine learning has enabled detailed and objective characterization of human behavior in social interactions. However, the application of these technologies to personalized psychiatry is limited due to the lack of sufficiently large corpora that combine multi-modal measurements with longitudinal assessments of patients covering more than a single disorder. To close this gap, we introduce Mephesto, a multi-centre, multi-disorder longitudinal corpus creation effort designed to develop and validate novel multi-modal markers for psychiatric conditions. Mephesto will consist of multi-modal audio-, video-, and physiological recordings as well as clinical assessments of psychiatric patients covering a six-week main study period as well as several follow-up recordings spread across twelve months. We outline the rationale and study protocol and introduce four cardinal use cases that will build the foundation of a new state of the art in personalized treatment strategies for psychiatric disorders.

Objective

Few instruments measuring life events over the course of bipolar disorder distinguish the valence of events or consider cumulative stress burden. In the current study, we used a valence-focused life event questionnaire to assess stress in the last 12 months in patients with bipolar I (n = 863) and bipolar II (n = 362) disorder.

Methods

Associations between recent stress and lifetime illness severity features were evaluated via linear and logistic regression, adjusting for age and gender. We additionally investigated the feasibility of quantifying recent stress burden by measuring methylation at a known bipolar susceptibility locus, SLC1A2 in a subset of bipolar I patients (n = 150) with or without comorbid substance use.

Results

Bipolar II patients endorsed higher total, negative, and positive stress burden than their bipolar I counterparts, but the latter displayed more significant stress-illness severity associations, notably to all forms of substance abuse (e.g., alcohol, nicotine, food, other drugs). Irrespective of bipolar subtype, negative stress burden was significantly associated with illness severity features. High versus low total stress predicted hypomethylation of the SLC1A2 promoter (p < 0.05).

Conclusion

Together, these findings reveal substantial differences in how bipolar subtypes experience and perceive stress. The observed degree of association between recent stress and substance abuse in bipolar I lend further support to the multidirectional effects of stress, affective episodes, and substance abuse on illness severity. Quantification of recent total stress using the methylation status of the SLC1A2 promoter is feasible, although a whole-methylome approach will likely prove more effective in disaggregating other environmental influences.

Objective

Repetitive negative thinking (RNT) is an important symptom in the development and maintenance of eating disorders (EDs). RNT Research on RNT’s effect on cognition in EDs is scarce. This investigation focused on associations between RNT and cognition in individuals with EDs.

Methods

Ruminative Response Scale (RRS) was used from Tulsa-1000 study (T-1000) data (eating disorders-ED, Major Depressive Disorder-MDD, and healthy subjects) who were propensity matched to examine associations with cognitive performance. RNT was examined across groups and we quantified the associations between scores for RNT, depression, executive function, and learning/memory from the T-1000 study. A linear regression analysis was conducted to determine predictors of disability.

Results

RNT was similar in ED and MDD participants, and more intense than in controls. RNT was significantly correlated with verbal learning/memory in the control (r = 0.514, p = 0.006) and ED groups (r = −0.447, p = 0.020), but this relationship had opposite slopes in either group. Increased RNT was associated with decreased verbal learning/memory ability in ED participants while in controls, increased RNT was associated with increased ability. Comorbid depression in the ED group acted as a potential moderator of the above relationship between RNT and EF. Among ED patients, depressive symptom severity was the best predictor of disability.

Discussion

The differential association of RNT with cognitive abilities in ED and MDD patients suggests depression is not a mediator of RNT-mediated cognitive dysfunction in EDs. This necessitates a better understanding of the mechanistic relationship between RNT and diverse types of cognitive functioning.

Background

Individuals experiencing socioeconomic deprivation consistently demonstrate poorer physical and mental health. Income alone is inadequate as a measure of socioeconomic status (SES); a better measure for assessing the deprivation status of individuals is needed.

Methods

The New Zealand Index of Socioeconomic Deprivation for Individuals, a validated, eight-item measure of deprivation, was modified to create the United States Index of Socioeconomic Deprivation for Individuals (USiDep). The questionnaire was administered to patients with major depressive disorder participating in two clinical trials. Spearman’s correlation coefficients evaluated associations between USiDep scores with income and other measures associated with deprivation.

Results

The USiDep was completed by 118 participants, demonstrating adequate internal consistency (Crohnbach’s alpha = 0.766) and strong item-total correlations. USiDep scores were moderately correlated with past-year personal income (Spearman’s rho = -0.362, p < .001) and several other measures related to deprivation, including body mass index, level of education, quality of life, severity of childhood traumatic events, self-reported physical health, and negative life events. Patients scoring 5 on the USiDep (the highest possible score, indicating greater deprivation) had significantly lower rates of remission after 12 weeks of treatment than those scoring ≤ 4 (1/12, 8.3% vs 40/98, 40.8%, respectively, p = .03), whereas the lowest income group showed no significant associations with outcomes.

Conclusion

The USiDep is a valid, brief questionnaire for assessing SES that has utility for clinical research and may serve as a predictor of treatment outcomes in clinical trials. Validation of the USiDep in healthy controls and other medically and psychiatrically ill populations is warranted.

Objective

Major depressive disorder is a common medical problem, frequently resistant to antidepressant treatments. We sought to describe functional connectivity correlates of response and non-response to rapid-acting antidepressants in patients with treatment-resistant depression.

Methods

We performed an MRI-based, BOLD functional connectivity analysis on three patients with treatment-resistant depression, with varying degrees of response to electroconvulsive therapy (ECT) or intravenous subanesthetic ketamine.

Results

Response to treatment was associated with an increase of positive correlations and increased connectivity of bilateral frontal, subcortical, right temporal and right occipital regions. Treatment nonresponse was associated with an increase in negative correlations between frontal lobes and their respective contra- and ipsilateral parietal and occipital lobes.

Conclusion

Response to rapid-acting treatments was associated in this case series to increased functional connectivity, especially in homologous regions of both hemispheres. If replicated in a bigger sample, this correlate of response can provide insights into mechanisms of rapid-acting antidepressant treatment response.

Background

Ecological momentary assessment (EMA) offers a highly valid strategy to assess everyday functioning in people with severe mental illness. Adherence is generally good, but several questions regarding the impact of study length, daily density of sampling, and symptom severity on adherence remain.

Methods

EMA adherence in two separate studies was examined. One sampled participants with schizophrenia (n = 106) and healthy controls (n = 76) 7 times per day for 7 days and the other sampled participants with schizophrenia (n = 104) and participants with bipolar illness (n = 76) 3 times per day for 30 days. Participants were asked where they were, who they were with, what they were doing and how they were feeling in both studies. The impact of rates of very early adherence on eventual adherence was investigated across the samples, and adherence rates were examined for associations with mood state and most common location when answering surveys.

Results

Median levels of adherence were over 80% across the samples, and the 10th percentile for adherence was approximately 45% of surveys answered. Early adherence predicted study-long adherence quite substantially in every sample. Mood states did not correlate with adherence in the patient samples and being home correlated with adherence in only the bipolar sample.

Implications: Adherence was quite high and was not correlated with the length of the study or the density of sampling per study day. There was a tendency for bipolar participants who were more commonly away from home to answer fewer surveys but overall adherence for the bipolar patients was quite high. These data suggest that early nonadherence is a potential predictor of eventual nonadherence and study noncompletion.

Psychotic disorders are morbid mental disorders that impair working memory. Theory suggests that longer duration of untreated psychosis (DUP) results in worse working memory. However, results from previous studies are contradictory, with no study having been conducted in children. This study aims at finding out the association between duration of untreated psychosis and working memory in children. This is a cross-sectional study with 45 subjects. DUP was collected from medical records whereas working memory was measured using digit span backward raw score. Average digit span backward scores of subjects was 3.7 ± 1.18. Analysis using Spearman test showed no significant association (p = 0.128) between DUP and working memory. In conclusion, there is no association between DUP and working memory in children, therefore we recommend that psychiatrists pay attention to working memory impairment in all pediatric patients with psychotic disorders, regardless of their DUP.

Present review focuses on the possible role of tryptophan (Trp) – kynurenine (Kyn) pathway in the mechanism(s) of COVID-19 associated psychiatric complications. SARS-CoV-2 infection, that causes COVID-19, triggers overproduction of interferon-gamma (IFNG), a pro-inflammatory cytokine. IFNG activates indoleamine 2,3-dioxygenase-1 (IDO), enzyme that catalyzes Trp conversion into Kyn, and enzymes of down-stream Kyn pathway that catalyze Kyn conversion into 3-hydroxykynurenine, kynurenic and anthranilic acids in brain and peripheral organs. We reviewed data on SARS-CoV-2 - IFNG – induced changes of peripheral Trp – Kyn pathway, considering their translational potential for personalized psychiatric care. Elevated blood levels of Trp – Kyn pathway metabolites were correlated with the severity of symptoms and predicted the negative outcomes in COVID-19 patients. Association of Trp – Kyn pathway up-regulation with psychiatric complication in non-COVID-19 patients suggests that activation of these pathways contribute to the mechanism(s) of COVID-19 associated psychiatric conditions as well. Increased risk of psychiatric complications in carriers of T (high producer) allele of polymorphic IFNG gene and elevation of serum levels of Kyn and its metabolites in interferon-alpha treated hepatitis C virus patients provides further support for such a suggestion. Assessment of blood levels of Kyn and its metabolites, and polymorphism of Trp – Kyn pathway genes might be developed into personalized biological markers predicting gender/aging dependent individual’s risk of psychiatric complications in COVID-19 patients. Up-regulation of IFNG and IDO is necessary for anti-viral protection. Therefore, inhibition of down-stream Kyn pathway should be considered as a new target for prevention/treatment of COVID-19 and COVID-19-associated psychiatric complications.