Major Depression as a Disorder of the Narrative Self: A Qualitative Study.

INTRODUCTION: Abnormal self-experiences are a common feature of major depression despite their absence from current diagnostic manuals. Current diagnostic criteria leave us with an impoverished conception of depressive disorders, and they fail to exploit the diverse experiential alterations that might be useful for understanding and diagnosing patients, and last but not least for explaining the aetiology of these disorders. Although some phenomenological descriptions of abnormal self-experiences in major depression are available, further research is needed to validate these through detailed clinical interviews. METHODS: To characterize these phenomena in more detail and to verify and consolidate previous accounts, we conducted a qualitative study using the Consensual Qualitative Research method. RESULTS: Our findings identified three categories of abnormal self-experiences: (1) impossibility to project oneself forward, (2) not recognizing one's self, and (3) losing control on one's self. CONCLUSION: Before delving into these results, we briefly described how the self is conceptualized in phenomenological psychopathology and explored in the literature on the self-experience in major depression. After discussing our results in the light of recent and contemporary phenomenological literature, we suggest that the inability to recognize otherness as part of oneself - which is the core of depressive experiences - ends in specific symptoms of depersonalization that differ from schizophrenic ones. We conclude that the self-experience, and in particular narrative identity, is central to the development and maintenance of depression.

Case report and systematic review of cerebellar vermis alterations in psychosis.

INTRODUCTION: Cerebellar alterations, including both volumetric changes in the cerebellar vermis and dysfunctions of the corticocerebellar connections, have been documented in psychotic disorders. Starting from the clinical observation of a bipolar patient with cerebellar hypoplasia, the purpose of this review is to summarize the data in the literature about the association between hypoplasia of the cerebellar vermis and psychotic disorders [schizophrenia (SCZ) and bipolar disorder (BD)]. METHODS: A bibliographic search on PubMed has been conducted, and 18 articles were finally included in the review: five used patients with BD, 12 patients with SCZ and one subject at psychotic risk. RESULTS: For SCZ patients and subjects at psychotic risk, the results of most of the reviewed studies seem to suggest a gray matter volume reduction coupled with an increase in white matter volumes in the cerebellar vermis, compared to healthy controls. Instead, the results of the studies on BD patients are more heterogeneous with evidence showing a reduction, no difference or even an increase in cerebellar vermis volume compared to healthy controls. CONCLUSIONS: From the results of the reviewed studies, a possible correlation emerged between cerebellar vermis hypoplasia and psychotic disorders, especially SCZ, ultimately supporting the hypothesis of psychotic disorders as neurodevelopmental disorders.

Does the comorbidity of borderline personality disorder affect the response to treatment in bipolar patients?

Bipolar disorder (BD) is a highly prevalent condition whose response to pharmacological treatment is associated with a number of factors including psychiatric comorbidity. Borderline personality disorder (BPD) shares clinical symptoms and biological vulnerability with BD and the two conditions are frequently comorbid, thus representing a clinical challenge. The purpose of the present review is to summarize the data related to treatment response in bipolar patients with comorbid BPD. According to systematic review process, a literature search was performed on the PubMed, Embase, PsycInfo, Isi Web of Knowledge, Medscape, and Cochrane Library databases. Peer-reviewed articles until December 2022 were eligible for inclusion. Comorbidity with BPD seems to be associated with a more difficult clinical stabilization in bipolar patients, often requiring poly-therapy or a longer duration of hospitalization. However, three studies, assessing the effectiveness of mood stabilizers in bipolar patients, did not demonstrate a prominent influence of BPD comorbidity in achieving clinical response. The most frequently administered pharmacological treatments in the selected studies include mood stabilizers and atypical antipsychotics. The presence of comorbid BPD in bipolar patients may hamper treatment effectiveness. Future studies, comparing different treatments and with larger samples, are needed to confirm the results critically summarized in the present review.

Affective Permeability: On Hysteria and Atmospheres.

BACKGROUND: Phenomenological literature has recently given much attention to the concept of atmosphere, which is the pre-individual affective tonality of the intersubjective space. The importance of atmospheres in psychopathology has been described for various disorders, but little is known about the interaction with hysteria. The aim of the present paper was to describe the psychopathology of hysteria from the angle of the phenomenon of atmosphere, focussing on the hysterical person's peculiar "affective permeability". SUMMARY: Hysterical people have difficulty defining themselves autonomously. As compensation, they adopt models transposed from the external environment such as social gender stereotypes or are influenced by the gaze and desire of others. They also possess a special sensitivity in perceiving the affectivity present in a given social situation, by which they are easily impressed and influenced. Their sensibility to environmental affectivity may allow them to take centre stage, assuming the postures and behaviours that others desire and that they sense by "sniffing" the atmosphere in which the encounter is immersed. Thus, a paradox may take place: sensibility is not mere passivity in hysteria but may become a tool for "riding" the emotional atmosphere and manipulating it. KEY MESSAGES: Affective permeability to environmental atmospheres and manipulation of the environment are the two sides of the same coin. This overlap of passive impressionability and active manoeuvring is necessary to be grasped in the clinical encounter with hysterical persons not to be submerged by their theatricality, that is, by the hyper-intensive expressivity of their feelings and behaviours.

The lived experience of depression: a bottom-up review co-written by experts by experience and academics.

We provide here the first bottom-up review of the lived experience of depression, co-written by experts by experience and academics. First-person accounts within and outside the medical field were screened and discussed in collaborative workshops involving numerous individuals with lived experience of depression, family members and carers, representing a global network of organizations. The material was enriched by phenomenologically informed perspectives and shared with all collaborators in a cloud-based system. The subjective world of depression was characterized by an altered experience of emotions and body (feeling overwhelmed by negative emotions, unable to experience positive emotions, stuck in a heavy aching body drained of energy, detached from the mind, the body and the world); an altered experience of the self (losing sense of purpose and existential hope, mismatch between the past and the depressed self, feeling painfully incarcerated, losing control over one's thoughts, losing the capacity to act on the world; feeling numb, empty, non-existent, dead, and dreaming of death as a possible escape route); and an altered experience of time (experiencing an alteration of vital biorhythms, an overwhelming past, a stagnation of the present, and the impossibility of the future). The experience of depression in the social and cultural context was characterized by altered interpersonal experiences (struggling with communication, feeling loneliness and estrangement, perceiving stigma and stereotypes), and varied across different cultures, ethnic or racial minorities, and genders. The subjective perception of recovery varied (feeling contrasting attitudes towards recovery, recognizing recovery as a journey, recognizing one's vulnerability and the need for professional help), as did the experience of receiving pharmacotherapy, psychotherapy, and social as well as physical health interventions. These findings can inform clinical practice, research and education. This journey in the lived experience of depression can also help us to understand the nature of our own emotions and feelings, what is to believe in something, what is to hope, and what is to be a living human being.

Are There Any Differences in Clinical and Biochemical Variables between Bipolar Patients with or without Lifetime Psychotic Symptoms?

INTRODUCTION: Psychotic symptoms occur in more than half of patients affected by Bipolar Disorder (BD) and are associated with an unfavorable course of the disorder. The objective of this study is to identify the differences in the clinical and biochemical parameters between bipolar patients with or without psychotic symptoms. METHODS: A total of 665 inpatients were recruited. Demographic, clinical, and biochemical data related to the first day of hospitalization were obtained via a screening of the clinical charts and intranet hospital applications. The two groups identified via the lifetime presence of psychotic symptoms were compared using t tests for quantitative variables and χ2 tests for qualitative ones; binary logistic regression models were subsequently performed. RESULTS: Patients with psychotic BD (compared to non-psychotic ones) showed a longer duration of hospitalization (p < 0.001), higher Young Mania Rating Scale scores (p < 0.001), lower Global Assessment of Functioning scores (p = 0.002), a less frequent history of lifetime suicide attempts (p = 0.019), less achievement of remission during the current hospitalization (p = 0.028), and a higher Neutrophile to Lymphocyte Ratio (NLR) (p = 0.006), but lower total cholesterol (p = 0.018) and triglycerides (p = 0.013). CONCLUSIONS: Patients with psychotic BD have a different clinical and biochemical profile compared to their counterparts, characterized by more clinical severity, fewer metabolic alterations, and a higher grade of inflammation. Further multi-center studies have to confirm the results of this present study.

Phenomenology of psychiatric emergencies.

Introduction: Psychiatric urgency is defined as a situation of serious mental suffering and behavioral alteration, which promptly requires adequate treatment; we talk about emergency when the condition can be life-threating. Even if until now neglected by phenomenological psychopathology, the emergency issue faces a clinical management challenge in which the phenomenological method becomes fundamental. The purpose of this manuscript is then to explore the phenomenological perspective of psychiatric emergencies. The manuscript is organized into four sections: the first deals with the encounter in clinical phenomenology, the second with the life-word of the crisis, the third with the atmosphere of emergency; finally, a final section on the importance of the phenomenological method for the clinician. The encounter in clinical phenomenology: The centrality of the encounter in clinical phenomenology cannot be stressed enough. It is not just the encounter between doctor and patient, but also and above all the encounter between two men, between two subjects. And it is in the affective space between them, in the intersubjectivity and intercorporeality of their encounter, that the transformative power of understanding emerges and reverberates from both sides. The approach to the other must be respectful, along the lines of the ethics of approximation, it must recognize the other as other and not overwrite it with one's own prejudices. Otherwise, if clinicians are not sufficiently trained in the encounter, the risk is to get stuck in the anguish of the instant, to be absorbed by it, to become its tools. It is precisely the atmosphere of the emergency room that is full of expectations, haste, anxiety, which actually hinders the possibility of encountering. Instead, this possibility must be recovered, because the encounter is the founding aspect of every clinical interview, of every diagnostic suspicion, of every therapeutic resolution. The life-word of the crisis: Seizing the encounter in its immediacy and in its totality, through the atmosphere that characterizes it, means for the clinician to position himself not outside the crisis, in an observational position in front of the patient, but to position himself next to him, to immerse himself in his life-world. Only then will the explosiveness of his symptoms appear to us not only as a symptomatic cascade to be contained and extinguished, but as the expression of a life-world in crisis. To use Ey's terminology, the madness of an instant must be placed within the madness of a lifetime. The patho-gnostic structures of the psychiatrist must tune into the structures of the life-world of the crisis, with the perspective of giving meaning, of helping the subject to re-inscribe the crisis within his history, and to overcome it. The atmosphere of emergency: The experience of emergency is in fact detached from daily life of our being-in-the-world, both from the clinician's side and from that of the patient, who loses himself in this pathically charged and tense atmosphere and needs someone to walk alongside him to find the reins of his world. The context of the emergency room puts the clinician in the position of applying Strauss's sympathetic perception of the world, made up of atmospheres, sensations, profiles, and not of eidetic knowledge. The concept of atmosphere, inaugurated by Tellenbach and taken up in recent years by several authors, appears fundamental in understanding the amalgam of emotional tension, haste and immersiveness that characterizes the emergency room environment. An atmosphere that can become oppressive, if not thematized, and that can lead the clinician to defend himself in the haste and superficiality of the intervention. The phenomenological method: Psychiatric crisis is always a situation in which we are thrown, perhaps to the highest degree, and the unfolding of references between the self and the world and between the self and the others becomes an essential skill. Even in the absence of an adequate setting, in the intersection between several pressures, the phenomenological method retains its panoramic gaze intact. We define it panoramic because it does not aim only at the observation and description of the present phenomena, which are generally characterized by violence, anguish, chaos. It is through the suspension of the epochè that the clinician can distance himself from the oppressive atmosphere of the crisis and grasp the coordinates of the patient's life-world. Only with this attitude does an authentic encounter become possible even in the difficult situation of emergency, paving the way for the challenge of care.

Which clinical factors and biochemical parameters are associated with late-life major depression?

INTRODUCTION: Late-life major depression (MD) is a frequent and high-cost psychiatric disorder. Our purpose was to detect clinical and biological factors possibly associated with this condition to better prevent and treat it. METHODS: We recruited 343 patients, consecutively admitted for a Major Depressive Episode to the inpatient clinic of Policlinico of Milan and ASST Monza, Italy. A large set of clinical and biochemical variables was collected from clinical charts. Univariate analyses were performed both dividing the sample into two groups (age < or ≥65) and considering age as a continuous quantitative variable. Regression analyses were then performed considering as independent variables only those statistically significant at univariate analyses. RESULTS: Patients aged ≥ 65 resulted in having longer duration of illness, shorter duration of last antidepressant therapy, higher number of antidepressants assumed in the past, higher frequency of treatment-resistant depression, higher frequency of overweight/obesity and diabetes. As for biochemical parameters, patients ≥ 65 showed lower total plasmatic proteins and albumin, higher uric acid and creatinine. CONCLUSIONS: These preliminary results suggest less effectiveness of antidepressants, more susceptibility to metabolic disorders and poor nutritional status in patients with late-life depression; such aspects may consequently be taken into consideration for a proper therapeutic approach. KEY POINTSDepression in late life seems to be associated with poorer response to antidepressants;Clinicians should prefer compounds with minimal pharmacokinetic interactions and less risk of side effects including metabolic ones;The poor nutritional status and the higher risk of metabolic disorders in older patients points out the importance of proper diet and healthy lifestyle in this group of subjects;Further studies are needed to confirm the results of this research.

Gender differences in clinical and biochemical parameters among patients hospitalized for schizophrenia: towards precision medicine.

BACKGROUND: The scientific literature shows some gender differences in the clinical course of schizophrenia. The aim of this study is to identify gender differences in clinical and biochemical parameters in subjects affected by schizophrenia. This would allow for the implementation of individualized treatment strategies. METHODS: We examined a large set of clinical and biochemical parameters. Data were obtained from clinical charts and blood analyses from a sample of 555 schizophrenia patients consecutively admitted for exacerbation of symptoms to the inpatient clinic of Fondazione IRCCS Policlinico (Milan) or ASST Monza in Italy from 2008 to 2021. Univariate analyses, binary logistic regression, and a final logistic regression model were performed with gender as dependent variable. RESULTS: The final logistic regression models showed that male patients (compared to females) were more prone to lifetime substance use disorders (p = 0.010). However, they also had higher GAF (global functioning) mean scores (p < 0.001) at the time of hospitalization. Univariate analyses showed that male patients (with respect to females) had an earlier age at onset (p < 0.001), a more frequent family history of multiple psychiatric disorders (p = 0.045), were more often smokers (p < 0.001), had a more frequent comorbidity with at least one psychiatric disorder (p = 0.001), and less often suffered from hypothyroidism (p = 0.011). In addition, men had higher levels of albumin (p < 0.001) and bilirubin (t = 2.139, p = 0.033), but lower levels of total cholesterol (t = 3.755, p < 0.001). CONCLUSIONS: Our analyses indicate a less severe clinical profile in female patients. This is evident especially in the early years of the disorder, as suggested by less comorbidity with psychiatric disorders or later age at onset; this is consistent with the related literature. In contrast, female patients seem to be more vulnerable to metabolic alterations as demonstrated by more frequent hypercholesterolemia and thyroid dysfunction. Further studies are needed to confirm these results in the framework of precision medicine.

Which factors are associated with duration of untreated illness in borderline personality disorder?

AIM: Borderline personality disorder (BPD) is a prevalent condition associated with high rates of hospitalizations. The purpose of this manuscript was to detect the factors associated with duration of untreated illness (DUI) in BPD. METHODS: Through chart review, we identified 152 patients followed up by community psychiatry services in Milan and Monza, Italy. The association between DUI and socioeconomic and clinical variables was examined using Pearson correlation and analyses of variances. The statistically significant variables from univariate analyses were then inserted in regression models. RESULTS: A longer DUI was associated with several variables (substance misuse after the onset of BPD, older age, earlier age at onset, longer duration of illness), but these results were not maintained in the regression analyses. CONCLUSIONS: In conclusion, DUI does not seem to be significantly associated with specific clinical aspects of BPD, or significantly modify the course and outcome of the disorder. Studies with larger samples have to confirm these preliminary findings.

The Body in Question in the Existence of Hysteric Persons: A Phenomenological Perspective.

The concept of hysteria, although apparently surpassed by contemporary nosographic classifications, continues to be talked about. Following Charbonneau's attempt to de-feminize and de-sexualize hysteria, clinical phenomenology can offer a perspective which, freed from stigma and prejudices through the suspension of judgement, allows us to understand hysteria not as a diagnostic category but as an existential position. In this sense, hysteria would be based on a hypo-sufficiency of the embodied self, which is not perceived as solid and continuous and needs external confirmations of its adequacy. According to the optical-coenaesthetic disproportion hypothesis, the hypo-sufficiency of the embodied self originates from the difficulty of experiencing one's body from the first-person perspective and from the consequent use of the gaze of others as a prosthesis to achieve a sense of selfhood and identity. Hysteric persons develop a mode of access to their corporeality mediated by visual representations - hence the theatricalization, centrality, and seductiveness of hysteric persons' behaviour. We suggest to call "figural body" the visual apprehension of one's body which tries to compensate for the weakness of coenaesthetic apprehension of the lived body. Over time, the figural body ends up superimposing itself on the immediate experience of the lived body. Placing itself on a representative register, this image conveys not only individual ghosts but also cultural aspects, social prejudices, gender stereotypes. Thus, the attempt to experience one's own body with the mediation of the other's gaze becomes an involuntary and unaware throwing of oneself into the meshes of representation that are necessarily alienating for the person. Hysterical persons remain stuck in their inability to access an experience of their body that is not figurative, alienating themselves in representations which always come from outside.

Which Clinical and Demographic Factors are Related to Incarceration in Male Patients With Antisocial Personality Disorder?

Antisocial Personality Disorder (APD) is a condition largely represented in detention centers where can reach a prevalence of 60% in male prisoners. The objective of this study is to identify the clinical and demographic factors that differentiate subjects with APD and hosted in penitentiary with respect to those are treated in outpatient psychiatric clinics. We recruited 65 male patients affected by APD, whose 26 were followed up in community mental health services and 39 were serving their sentence in a detention center located in Monza. Socio-demographic and clinical data were obtained through a review of the clinical charts, and interviews with patients or their relatives (if available). We performed descriptive analyses on the total sample, then we compared the two groups identified by the type of setting (outpatient clinic vs. penitentiary) by independent sample t tests (quantitative variables) or χ2 tests (qualitative ones). For qualitative variables odds ratios (ORs) were also calculated. Outpatients with APD (with respect to those hosted in the detention center) resulted: to be older (p = .02), to be less likely married (p = .01), to have more pre-onset psychiatric comorbidity (p = .05), to have more pre-onset substance poly-misuse (p = .01), to have more previous psychiatric hospitalizations (p < .01), and to be less likely to have received lifetime psychotherapy (p < .01). Globally, the results of this study show how the presence of psychiatric comorbidity or substance abuse (with the probable access to psychiatric services) before the onset of APD prevents imprisonment. This aspect is even more surprising when we consider that the two groups of patients show no differences in the frequency of crimes. Future research will have to confirm if early mental health care can really limit the access to penitentiary of subjects affected by APD.

Which Clinical and Biochemical Parameters Are Associated with Lifetime Suicide Attempts in Bipolar Disorder?

INTRODUCTION: Bipolar Disorder (BD) is a disabling condition with suicidal behavior as one of the most common adverse outcomes. The purpose of the present research is to investigate the relationship between lifetime suicide attempts and the clinical factors/biochemical parameters in a large sample of bipolar patients. METHODS: A total of 561 patients, consecutively hospitalized for BD in Milan and Monza (Italy), were recruited. Data about the demographic and clinical variables, as well as the values of blood analyses, were collected. The groups identified according to the presence/absence of lifetime suicide attempts were compared using univariate analyses. Then, three preliminary binary logistic regressions and a final logistic regression model were performed to identify the clinical and biochemical parameters associated with lifetime suicide attempts in BD. RESULTS: Lifetime suicide attempts in BD were predicted by a longer duration of untreated illness (DUI) (p = 0.005), absence of lifetime psychotic symptoms (p = 0.025), presence of poly-substance use disorders (p = 0.033), comorbidity with obesity (p = 0.022), a last mood episode of manic polarity (p = 0.044), and lower bilirubin serum levels (p = 0.002); higher total cholesterol serum levels showed a trend toward statistical significance (p = 0.058). CONCLUSIONS: BD patients with lifetime suicide attempts present unfavorable clinical features. Some specific biochemical characteristics of bipolar patients may represent potential markers of suicidal behavior and need to be better investigated to identify new targets of treatment in the framework of personalized medicine. These preliminary findings have to be confirmed by further studies in different clinical settings.

Decomposition: Partition as an Escape from Decay - A Gestalt of the Obsessive Life-World.

According to phenomenological literature, the life-world of the obsessive subject is characterized by its claustrophobic closure, the attempt to stop the flow of time, and the inability to accept the formlessness hidden behind the form. The obsessive obstinately tries to build defences against what he cannot tolerate of reality and this effort causes loss of spontaneity in the pre-reflective dimension of existence, resulting in the thought process being oversaturated and ending up by blocking action. Our proposal is to unpack the phenomenon of partition in the obsessive's world, analysing the similarities and differences with the schizophrenic life-world. In fact, although the mechanization and the predominance of a reflective dimension are similar in these psychopathological typologies, these phenomena are based on completely different foundations: the ontological question in the case of the schizophrenic subject, while the ontic question in the case of the obsessive subject. By decomposing reality, the obsessive tries to stem the dimension of the formless, which is hidden under the representative order of things which he cannot tolerate. Understanding the hyper-rationalizing tendency of obsessive thought offers important clinical implications by providing shareable insights into psychotherapeutic development.

Is there an association between inflammatory/anti-oxidant markers and the presence of psychotic symptoms or severity of illness in mood and psychotic disorders? A multi-centric study on a drug-free sample.

The immune and antioxidant systems are intimately connected and their role in the etiology of major psychiatric disorders is currently under study. The aim of this study was to evaluate the potential associations between inflammatory/antioxidant peripheral markers and presence of psychotic symptoms or severity of illness in patients affected by major psychiatric disorders. One hundred and twenty-six drug-free patients were included. A blood sample was collected to measure total/B/T lymphocytes and plasma levels of albumin, total bilirubin, uric acid, C-reactive protein, and vitamins A and E. Severity of illness was assessed using psychometric scales. Groups of patients divided according to diagnosis were compared in terms of measured markers using multivariate analyses of variance (MANOVAs). Linear and logistic regression analyses were performed to investigate the potential association between markers and severity of illness or presence/absence of psychotic symptoms. Albumin plasma levels were higher in patients with substance-induced psychotic disorder (SIPD) than subjects affected by schizophrenia (F â€‹= â€‹4.923; p â€‹= â€‹0.003). Lower vitamin E (OR â€‹= â€‹0.81; p â€‹= â€‹0.014) and T lymphocyte (OR â€‹= â€‹0.99; p â€‹= â€‹0.048) plasma levels were predictive of lifetime psychotic symptoms. Lower vitamin A levels were associated with higher Montgomery-Åsberg Depression Rating Scale scores (ߠ​= â€‹-24.26; p â€‹= â€‹0.029), independent of diagnosis. Patients with SIPD may be less vulnerable to oxidative stress. The severity of depressive symptoms, inversely associated with vitamin A plasma levels, is likely to be modulated by the degree of inflammation. Patients presenting with lifetime psychotic symptoms may be more vulnerable to oxidative stress and may have a higher activation of humoral immunity.

Gender differences in clinical and biochemical parameters of patients consecutively hospitalized for unipolar depression.

Major Depressive Disorder (MDD) is a medical illness twice as common in women than in men lifetime. Purpose of this study is to identify gender differences in clinical and biochemical parameters in subjects affected by MDD to implement individualized treatment strategies. We recruited 234 patients (112 males and 122 females) consecutively hospitalized for MDD in Milan (Italy). Data were obtained through a screening of the clinical charts and blood analyses. Univariate analyses, binary logistic regressions and a final logistic regression model were performed. The final logistic regression model showed that female patients (compared to males) had lower plasmatic levels of hemoglobin (p = 0.020) and uric acid (p = 0.002), higher levels of cholesterol (p < 0.001), had been treated with a lower number of antidepressants (p = 0.011), presented lower red blood cells (p < 0.001) and showed more frequently comorbidity with hypothyroidism (p = 0.036). Univariate analyses identified also that women had an earlier age at onset (p = 0.043), were less likely to have comorbidity with diabetes (p = 0.002) and were less frequently treated with a psychiatric polytherapy (p < 0.001). Finally, female patients had achieved more frequently remission in the last depressive episode (p = 0.001) and were more likely to have family history for psychiatric disorders (p < 0.001) than males. Female patients globally have a better response to treatments, but they seem to be more vulnerable to specific metabolic abnormalities as showed by more frequent hypercholesterolemia and lower plasma levels of uric acid. These results have to be confirmed by further studies.

Clinical and Biological Factors Are Associated with Treatment-Resistant Depression.

BACKGROUND: Treatment-resistant depression (TRD) is a debilitating condition associated with unmet clinical needs. Few studies have explored clinical characteristics and serum biomarkers associated with TRD. AIMS: We investigated whether there were differences in clinical and biochemical variables between patients affected by TRD than those without. METHODS: We recruited 343 patients (165 males and 178 females) consecutively hospitalized for MDD to the inpatient clinics affiliated to the Fondazione IRCCS Policlinico, Milan, Italy (n = 234), and ASST Monza, Italy (n = 109). Data were obtained through a screening of the clinical charts and blood analyses conducted during the hospitalization. RESULTS: TRD versus non-TRD patients resulted to be older (p = 0.001), to have a longer duration of illness (p < 0.001), to be more currently treated with a psychiatric poly-therapy (p < 0.001), to have currently more severe depressive symptoms as showed by the Hamilton Depression Rating Scale (HAM-D) scores (p = 0.016), to have lower bilirubin plasma levels (p < 0.001). In addition, more lifetime suicide attempts (p = 0.035), more antidepressant treatments before the current episode (p < 0.001), and a lower neutrophil to lymphocyte ratio at borderline statistically significant level (p = 0.060) were all associated with the TRD group. CONCLUSION: We identified candidate biomarkers associated with TRD such as bilirubin plasma levels and NLR, to be confirmed by further studies. Moreover, TRD seems to be associated with unfavorable clinical factors such as a predisposition to suicidal behaviors. Future research should replicate these results to provide robust data in support of the identification of new targets of treatment and implementation of prevention strategies for TRD.

Transition Between Sensitive Delusion of Reference and Mood Disorder: A Case Report.

The Sensitive Delusion of Reference is a clinical entity described by Ernst Kretschmer and never integrated into mainstream nosographic systems. It represents the possibility of developing psychosis starting from a personality characterized by sensitivity, scrupulousness, and fear of judgment of others. The presentation of the following clinical case highlights how the overlap between this clinical entity and mood disorders leads to characteristic psychopathology, which has not been sufficiently detailed. In particular, the delusions, which always starts from the idea of reference and the shame in the face of the judgment of others, takes on characteristics of guilt during the depressive phases and persecutory themes during the activation phases. This clinical observation, which obviously needs to be confirmed on a larger scale, encourages a renewed interest in the concept of Kretschmer's Sensitive Delusion of Reference and creates the possibility of intersecting multiple psychopathological levels, for a more complete perspective on the individual case.

Psychomotor Agitation Non-responsive to Treatment: A Case Report of Phenibut Withdrawal Syndrome.

Background and Objectives: Phenibut (4-amino-3-phenyl-butyric acid), acting as a GABA-B receptor agonist, has a beneficial effect on anxiety. Although its medical use is not approved in western countries, it can be easily obtained worldwide via the Internet, so it spread as a substance of abuse. In recent years, some case reports have, therefore, highlighted episodes of acute toxicity or withdrawal, but it is still a largely unknown phenomenon. Methods: In this case report, a 50-year-old woman was admitted to the emergency room with psychomotor agitation, psychotic symptoms, and insomnia, and was non-responsive to treatment. She was hospitalized at the psychiatry ward for 25 days and gave her consent for the publication of the present case report. Results: The suspicion of phenibut withdrawal allowed to establish the appropriate management, leading to the restitutio ad integrum of the psychopathological case. Conclusions: In the face of an incoercible psychomotor agitation case, the knowledge of the so-called novel psychoactive substances allows for more appropriate clinical management of intoxication and withdrawal syndromes. This is a scientifically significant report as it provides therapeutic and outcome data concerning a syndrome that is still quite unfamiliar.

Case Report: The Association Between Chromosomal Anomalies and Cluster A Personality Disorders: The Case of Two Siblings With 16p11.2 Deletion and a Review of the Literature.

Although several studies have shown the correlation between chromosomal rearrangements and the risk of developing psychotic disorders, such as schizophrenia, little attention has been given to identifying the genetic basis of pre-disposing personality so far. In this regard, a limited but significant number of studies seem to indicate an association between chromosomal anomalies and cluster A personality disorders (CAPD). Starting from the clinical description of two brothers affected by familial 16p11 deletion syndrome (OMIM #611913), both sharing cluster A and C personality traits, the aim of the present study is to critically review the literature regarding the correlation between chromosomal rearrangements and CAPD. A bibliographic search on PubMed has been conducted, and eight studies were finally included in our review. Most of the studies highlight the presence of schizotypal personality disorder in the 22q11.2 deletion syndrome, whose evolutionary course toward psychotic pictures is well-known. One study also identified a paranoid personality disorder in a patient with a deletion on chromosome 7q21.3. No studies have so far identified the presence of paranoid personality disorder in 16p11 deletion, as in the case of the two siblings we report, while its association with psychosis and autism is already known. Although further epidemiologic studies on broader populations are indicated, our observations might pave the way for the definition of new diagnostic subgroups of CAPD and psychotic disorders, in order to implement the clinical management of such complex conditions.