Machine Learning and Pharmacogenomics at the Time of Precision Psychiatry.

Traditional medicine and biomedical sciences are reaching a turning point because of the constantly growing impact and volume of Big Data. Machine Learning (ML) techniques and related algorithms play a central role as diagnostic, prognostic, and decision-making tools in this field. Another promising area becoming part of everyday clinical practice is personalized therapy and pharmacogenomics. Applying ML to pharmacogenomics opens new frontiers to tailored therapeutical strategies to help clinicians choose drugs with the best response and fewer side effects, operating with genetic information and combining it with the clinical profile. This systematic review aims to draw up the state-of-the-art ML applied to pharmacogenomics in psychiatry. Our research yielded fourteen papers; most were published in the last three years. The sample comprises 9,180 patients diagnosed with mood disorders, psychoses, or autism spectrum disorders. Prediction of drug response and prediction of side effects are the most frequently considered domains with the supervised ML technique, which first requires training and then testing. The random forest is the most used algorithm; it comprises several decision trees, reduces the training set's overfitting, and makes precise predictions. ML proved effective and reliable, especially when genetic and biodemographic information were integrated into the algorithm. Even though ML and pharmacogenomics are not part of everyday clinical practice yet, they will gain a unique role in the next future in improving personalized treatments in psychiatry.

Building a neurocognitive profile of suicidal risk in severe mental disorders.

BACKGROUND: Research on the influence of neurocognitive factors on suicide risk, regardless of the diagnosis, is inconsistent. Recently, suicide risk studies propose applying a trans-diagnostic framework in line with the launch of the Research Domain Criteria Cognitive Systems model. In the present study, we highlight the extent of cognitive impairment using a standardized battery in a psychiatric sample stratified for different degrees of suicidal risk. We also differentiate in our sample various neurocognitive profiles associated with different levels of risk. MATERIALS AND METHODS: We divided a sample of 106 subjects into three groups stratified by suicide risk level: Suicide Attempt (SA), Suicidal Ideation (SI), Patient Controls (PC) and Healthy Controls (HC). We conducted a multivariate Analysis of Variance (MANOVA) for each cognitive domain measured through the standardized battery MATRICS Consensus Cognitive Battery (MCCB). RESULTS: We found that the group of patients performed worse than the group of healthy controls on most domains; social cognition was impaired in the suicide risk groups compared both to HC and PC. Patients in the SA group performed worse than those in the SI group. CONCLUSION: Social cognition impairment may play a crucial role in suicidality among individuals diagnosed with serious mental illness as it is involved in both SI and SA; noteworthy, it is more compromised in the SA group fitting as a marker of risk severity.

Grey Matter Volume Reductions of the Left Hippocampus and Amygdala in PTSD: A Coordinate-Based Meta-Analysis of Magnetic Resonance Imaging Studies.

INTRODUCTION: In recent years, research on posttraumatic stress disorder (PTSD) focused on the description of different biological correlates of illness. Morphological changes of different brain regions were involved in PTSD neurophysiopathology, being related to trauma or considered a resilience biomarker. In this meta-analysis, we aimed to investigate the grey matter changes reported in magnetic resonance imaging (MRI) studies on patients who have developed PTSD compared to exposed subjects who did not show a clinical PTSD onset. METHODS: We meta-analysed eight peer-reviewed MRI studies conducted on trauma-exposed patients and reported results corrected for false positives. We then conducted global and intergroup comparisons from neuroimaging data of two cohorts of included subjects. The included studies were conducted on 250 subjects, including 122 patients with PTSD and 128 non-PTSD subjects exposed to trauma. RESULTS: Applying a family-wise error correction, PTSD subjects compared to trauma-exposed non-PTSD individuals showed a significant volume reduction of a large left-sided grey matter cluster extended from the parahippocampal gyrus to the uncus, including the amygdala. CONCLUSIONS: These volumetric reductions are a major structural correlate of PTSD and can be related to the expression of symptoms. Future studies might consider these and other neural PTSD correlates, which may lead to the development of clinical applications for affected patients.

Neural functional correlates of hypnosis and hypnoanalgesia: Role of the cingulate cortex.

Hypnosis is a hetero-induced or self-induced altered state of consciousness that involves focused attention and reduced peripheral awareness. It is determined by response to suggestions and can be used in the management of various clinical conditions. Nowadays there is growing attention to the neurobiological correlates of hypnosis because of its future clinical applications. The greater attention is due to the wide range of applications that might stem from its knowledge. Functional neuroimaging studies show that hypnosis affects attention by modulating the activation of the anterior cingulate cortex and other brain areas, modifying the conflict monitoring and cognitive control. During hypnoanalgesia, several changes in brain functions occur in all the areas of the pain network, and other brain areas. Among these, the anterior cingulate cortex is significantly involved in modulating the activity of pain circuits under hypnosis, both in the affective, sensory-cognitive, and behavioral aspects. The study of the functionality of the cingulate cortices, mainly the anterior and medial portions, appears to be crucial for better understanding the hypnotic phenomena, related to both the neurocognitive and somatosensory aspects.

The Impact of the COVID-19 Pandemic on Postpartum Maternal Mental Health.

OBJECTIVES: There are reports of mental health worsening during the COVID-19 pandemic. We aimed to assess whether this occurred in women who were pregnant at baseline (late 2019) and unaware of the pandemic, and who delivered after the implementation of COVID-19 restrictions and threat (March-April 2020). To compare the pandemic period with the pre-pandemic, we capitalized on a retrospective 2014-2015 perinatal sample which had had affective symptoms assessed. METHODS: The COVID sample were administered the Postnatal Depression Scale (EPDS), Zung Self-Rating Anxiety Scale (SAS), Hypomania Checklist-32 (HCL-32), Pittsburgh Sleep Quality Index (PSQI), and Perceived Stress Scale (PSS) at T0 (pregnancy) and T1 (post-delivery). The Non-COVID sample had completed EPDS and HCL-32 at the same timepoints. RESULTS: The COVID sample included 72 women, aged 21-46 years (mean = 33.25 years ± 4.69), and the Non-COVID sample included 68 perinatal women, aged 21-46 years (mean = 34.01 years ± 4.68). Our study showed greater levels of mild depression in T1 among the COVID sample compared to the Non-COVID sample. No significant differences in terms of major depression and suicidal ideation were found. The levels of hypomania were significantly different between the two groups at T1, with the COVID sample scoring higher than the Non-COVID sample. This may be related to the high levels of perceived stress we found during the postpartum evaluation in the COVID sample. LIMITATIONS: There was a relatively small sample size. CONCLUSIONS: New mothers responded to the pandemic with less mental health impairment than expected, differently from the general population. Women delivering amidst the pandemic did not differ in depressive and anxiety symptoms from their pre-pandemic scores and from pre-pandemic women. Because stress responses have high energy costs, it is optimal for maternal animals to minimize such high metabolic costs during motherhood. Evidence suggests that reproductive experience alters the female brain in adaptive ways. This maternal brain plasticity facilitates a higher purpose, the continuation of the species. This may point to the recruitment of motherhood-related resources, for potentially overcoming the effects of the pandemic on mental health.

Current Clinical Psychopharmacology in Borderline Personality Disorder.

BACKGROUND: Patients with Borderline Personality Disorder (BPD) manifest affective and behavioral symptoms causing personal distress, relationship difficulties, and reduced quality of life with global functioning impairment, mainly when the disease takes an unfavorable course. A substantial amount of healthcare costs is dedicated to addressing these issues. Many BPD patients receive medications, mostly those who do not respond to psychological interventions. OBJECTIVE: Our aim was to assess the efficacy of the most used strategies of pharmacological interventions in BPD with a comprehensive overview of the field. METHODS: We searched the PubMed database for papers focused on the most used psychotropic drugs for BPD. We included randomized controlled trials and open studies in adult patients with BPD, focusing on the efficacy and tolerability of single classes of drugs with respect to specific clinical presentations that may occur during the course of BPD. RESULTS: Specific second-generation antipsychotics (SGAs) or serotonergic antidepressants can be effective for different core symptoms of BPD, mainly including mood symptoms, anxiety, and impulse dyscontrol. Some atypical antipsychotics can also be effective for psychotic and dissociative symptoms. Specific antiepileptics can be useful in some cases in treating different BPD symptoms, mainly including mood instability, impulsiveness, and anger. CONCLUSION: No medication is currently approved for BPD, and clinicians should carefully assess the benefits and risks of drug treatment. Further studies are needed to identify specific personalized treatment strategies, also considering the clinical heterogeneity and possible comorbidities of BPD.

The COVID-19 Outbreak and Subjects With Mental Disorders Who Presented to an Italian Psychiatric Emergency Department.

ABSTRACT: We performed a retrospective study from January to May 2020 to establish the sociodemographic and clinical characteristics of patients with mental health problems who arrived at an Italian emergency department during the COVID-19 outbreak. We divided the sample into two groups taking as a watershed March 11, when the World Health Organization announced COVID-19 outbreak as a pandemic. Chi-square/t-tests, adjusted p values (Bonferroni method), and regression analysis were performed. Patients who arrived at the emergency department during the lockdown decreased by 56%; showed greater active suicidal ideation, more tension, and more severe psychopathological state; were living alone more frequently; and were taking home treatment mainly based on second-generation antipsychotics. According to our study, it seems that patients with mental disorders have consulted psychiatric services less frequently during the pandemic, but the economic, health, and social distress may be linked with an increase in suicidal risk and the severity of the psychopathological state.

Relationship between aberrant salience and positive emotion misrecognition in acute relapse of schizophrenia.

INTRODUCTION: Aberrant salience is the incorrect assignment of salience or significance to innocuous stimuli, and been hypothesized to be a central mechanism in the development of psychosis. In addition to aberrant salience, social-cognitive models of psychosis suggest that the way people process information about the self is important in all stages of psychosis. The aim of the present study is to explore the relationship between aberrant salience and emotion processing in schizophrenia patients with psychotic relapse. METHODS: A sample of 42 patients with relapse was recruited. Aberrant salience was measured with the Aberrant Salience Inventory (ASI). Assessment of social cognition was carried out using the Facial Emotion Identification Test (FEIT). Partial correlations were controlled for possible confounding variables. RESULTS: The ASI factors "increase in meaning" and "heightened cognition" positively correlated with impaired recognition of positive emotions, and ASI total score inversely correlated to time to response to task. Most of incorrect answers corresponded to misclassification of positive emotions. CONCLUSION: Our findings show that there is evidence for a relationship between aberrant salience and emotion processing during a psychotic episode; we propose that aberrant salience and alterations in emotion processing trigger the loss of modulating feedback from the external world to produce a self-referential mental state.

The Complex Relationship Among Formal Thought Disorders, Neurocognition, and Functioning in Nonacutely Ill Schizophrenia Patients.

The aims of the present study were to 1) evaluate clinical differences between patients suffering from schizophrenia (SZ) with mild versus moderate/severe formal thought disorder (FTD); 2) explore relationships between dimensions of FTD, neuropsychological domains, and global functioning; and 3) compare clinical dimensions of FTD in early and late SZ. One hundred thirty-six individuals with schizophrenia were recruited and evaluated during a nonacute phase of illness. FTD was assessed with the Thought, Language, and Communication Scale. Partial correlations, t-tests, and stepwise regression were undertaken to address the study aims. Patients with moderate/severe FTD performed worse than those with mild FTD for processing speed, reasoning and problem solving, and social cognition, and demonstrated poorer global functioning. Early SZ did not differ from late SZ in terms of negative FTD and difficulty in abstract thinking (DAT). Negative FTD was correlated with reasoning and problem solving; DAT was correlated with social cognition. All clinical dimensions of FTD, regardless of neurocognitive impairment, accounted for a significant amount of variance in global functioning. FTD predicted global functioning, regardless of neurocognitive factors. Due to their stability in different phases of the course of the disease and their strong relationship with other core variables, Neg-FTD and DAT should be investigated as an intermediate phenotype of the illness.