A pilot study of resilience and severity of depressive symptoms in patients with psoriasis.

Background: Patients with psoriasis show an increased prevalence of depressive symptoms that worsen disease outcomes. This study investigated the effect of resilience and other sociodemographic/clinical variables on depressive symptoms' severity in patients with psoriasis. Methods: This study included 58 psoriasis patients consecutively enrolled during the 14 months of the study. We evaluated psoriasis severity using the Psoriasis Area and Severity Index, Body Surface Area, and Physician Global Assessment. The psychometric assessment included the Resilience Scale and the Beck Depression Inventory-II (BDI-II). We divided participants into two subgroups based on the optimal BDI-II cut-off score (Group A: BDI-II ≤17; Group B: BDI-II >17). A stepwise regression analysis explored whether the variation in the BDI-II score could be predicted by a linear combination of sociodemographic and clinical variables. Results: Psoriasis patients with more severe depressive symptoms (Group B patients) showed lower resilience levels than Group A patients (p <0.001). Moreover, depressive symptoms correlated only with resilience levels (p <0.001), with a negative correlation. The stepwise regression analysis revealed that resilience explained 37.1 % of the variance in BDI-II scores, whereas resilience, gender, and comorbidity with other physical illnesses combined explained 51.3 % of the variance. Conclusion: Resilience may alleviate depressive symptoms in psoriasis patients. This study underscores the importance of resilience-building interventions for these patients. HIPPOKRATIA 2022, 26 (4):131-137.

Gut microbiome and adaptive immunity in schizophrenia.

Over the past few years, immunopathogenesis has emerged as one of the most compelling aetiopathological models of schizophrenia (SCZ), suggesting a chronic, immune-based, low-grade inflammatory background of this devastating disorder.1,2 Mounting evidence points towards a prominent role of the adaptive immune system in SCZ, suggesting alterations in defense mechanisms, such as altered T-cell function and a shift towards B-cell immunity.3 Immune cells have the ability to infiltrate the brain and mediate a neuroimmune cross-talk through activation of microglia, production of proinflammatory cytokines and reactive oxygen species, leading to neuroinflammation, as mediator of neuroprogressive and neurodegenerative changes in SCZ.4 Antipsychotic drugs, commonly used to treat SCZ, are also known to affect the adaptive immune system, interfering with the differentiation and function of immune cells, towards their normalization in response to treatment. Adaptive immunity is principally founded on T-cell and B-cell populations, but also includes the host microbiome. The gastrointestinal microbiota is a complex ecosystem with a great organism diversity and refined genomic structure that resides in the intestinal tract and has a central position in human health and disease.5 Neuroimmune dysregulation, relying of the highly sensitive and fine-tuned equilibrium between microbiome and adaptive immunity, can tip the scales towards neuroinflammation and disruption of higher-order brain networks.4,6,7 During the last decade, the human microbiome and the microbiota-gut-brain (MGB)-axis have become a novel epicentre in mental health research as a potentially vital new determinant in the field of neuroimmunoregulation, brain development, emotions, cognition and behaviour.7 The MGB-axis represents a bidirectional, key communication pathway between the immune system and the brain, thus partly also mediating the regulation of cognitive and emotional processing. An imbalanced human microbiome might greatly influence proper neuroimmune reactions and neurodevelopment with long-lasting effects and could thus play a pivotal role in the susceptibility and aetiology of psychiatric illness. Recent research offers first evidence that patients with SCZ show marked disturbances of gut bacterial taxa composition with a decreased microbiome diversity index, party associated with specific SCZ phenotype, symptom severity and treatment response.8,9 As the elegant education of the adaptive immune compartment depends on the colonization niche, antigen type and metabolic property of different gut microbes, T-cell differentiation as well as a continuous diversification of B-cell repertoire is expressed through microbiome-related, antigen-specific receptors that define a unique clonotype.10 However, there is only sparse evidence on the precise role of the microbiome on the programming of T- and B-cells in the underlying neurobiological pathways of SCZ and even less findings on the association of molecular T- and B-cell receptor repertoire signature and microbiome clonal landscape with specific phenotypical features of the disease.11 The latest conceptual advances in immunology urge an integrative re-evaluation of previous immunological findings in SCZ through modern approaches. High-throughput, next-generation sequencing (NGS) represents a powerful singlecell transcriptomic tool to profile the whole clonal landscape of T and B cells and human microbiome. NGS thus offers a unique opportunity for in-depth characterization of cellular and molecular signatures of adaptive immune receptor repertoires and microbiome taxonomy in SCZ and investigation of their intersection as a relevant pathway of disease progression and phenotype differentiation. SCZ patients are likely to show a diverging host-microbiome immune homeostasis with disease-specific clonotypes of adaptive immune receptor repertoires associated with altered microbiome taxonomy and molecular signature differences, which, in turn, may be related to distinct symptomatic phenotypes and neurocognitive patterns. Such sophisticated immuno-bioinformatic analyses may transform our understanding of SCZ by identification of novel neuroimmune pathways, offering us clinically accessible symptomatic and diagnostic biomarkers important for personalized medicine implications.12 An increased understanding and better characterization of immuno-phenotypes in SCZ will better guide the development of novel immune-based treatments in this severe disease and pave the way for possible prevention options through implementation of antibody engineering, vaccine design, and cellular immunotherapy.

Understanding of Faux Pas in patients with schizophrenia.

Theory of Mind (ToM) refers to our ability to attribute mental states such as beliefs, intentions and desires to other, allowing us to explain, manipulate and predict others' behavior. ToM abilities of patients with schizophrenia were repeatedly found to be deficient. Our purpose in undertaking the present study was to explore ToM deficits in patients with schizophrenia, using a task of an affective aspect of ToM abilities, namely, "Faux Pas" Test (FPT). The FPT requires a "cognitive" ToM ability (i.e., knowing that the person who insults the other has not realized that she/he should not do that) and a more "affective" component (i.e., empathizing for the person who received the insulting utterance). We assessed 40 inpatients with schizophrenia (32 men) and 30 healthy participants (24 men), matching on age, level of education and sex ratio. All patients met DSM-IV criteria for schizophrenia. Four written scenarios containing a faux pas (unintentionally insulting or hurtful statements given a particular context) were presented to each examinee. The participants read each scenario and responded to a series of 4 questions: "Did anyone say something she/he should not have said?" (faux pas detection); "Why shouldn't she/he have said it?" (appreciation of potential negative impact on others); "Why do you think she/he said it?" (appreciation of speaker's lack of consideration); "How do you think the other person might have felt?" (awareness of other's emotional reaction). Patients with schizophrenia performed more poorly than healthy participants across all conditions: detection of FP [U=366.5, p=0.001], reasons should not have made FP [U=215.5, p<0.001], reasons for making FP [t(65)=4.294, p<0.001], and empathy [U=372, p=0.001]. Only the third condition (reasons for making FP) was significantly correlated with the age at first diagnosis (r=0.462, =0.004) and with ratings of positive symptoms (r=-0.391, p=0.017) and with symptoms of general psychopathology (r=-0.339, p=0.040). The present study further supports previous findings of patients with schizophrenia difficulties in theory of mind, as it was measured through a faux pas which also assess, apart from the understanding of a person' s mental state, the understanding of a person's emotional state, after having received an unintentional insult. The inability of patients with schizophrenia to empathize and therefore detect a faux pas may cause serious problems in their everyday communication with others. Appropriate cognitive interventions may help patients to avoid unintentionally hurting other people's emotions, thus improving their interpersonal relationships.

Early intervention services in Greece: Time to focus on people at high risk.

Over the last twenty years, a lot of early intervention services operate worldwide with the aim of offering assistance and promoting the early diagnosis and management, not only of people who experience a first episode of psychosis but also of individuals that are at high risk of developing psychosis. The early intervention services that operate in other countries have been reviewed in correlation with the current status of early intervention services for psychosis in Greece. Early intervention services were first established in Australia, and now hundreds of similar programs exist in Europe, North America and Asia. Furthermore, early intervention services incorporate teams that engage people who have an at risk mental state (ARMS), and are at high risk of developing psychosis. The first clinical service for individuals at high risk for psychosis was established in Melbourne in 1995, and an increasing number of similar services have since emerged worldwide. One of the largest of these is OASIS (Outreach and Support in South London). The first early intervention service was developed during the December 2007, in a rural catchment region of north-western Greece, in Ioannina. After the establishment of Ioannina Early Intervention Service, there was a growing interest of the Greek psychiatric community in the issues of early detection and prevention of psychotic disorders which led to the development of early psychosis units in other regions of Greece, like Athens, Thessaloniki and Patras. However, this field remains neglected in Greece, since in the absence of funding for such early detection services, there are only a few programs that operate mainly on a voluntary basis. Moreover, specialized mental health services for people at high risk for psychosis that have significant clinical benefits and are also cost effective, do not exist in the majority of Greek services. Greece and other countries in a similar condition need to understand the significance of untreated or poorly treated psychotic disorders that affect a lot of young people in late adolescence and early adult life. Focusing on people at high risk of developing psychosis will promote public health and will help not only to prevent the onset of psychotic disorders but to enhance their prognosis as well.

[Psychotic episode due to Hashimoto's thyroiditis].

Thyroid hormones are crucial in adult brain metabolic activity. As a result, abnormal thyroid gland function and in particular hypofunction, might cause principally depression and neurocognitive dysfunction. Psychosis, presented mainly with thought disorders and perceptual disturbances, is a much rarer manifestation of hypothyreoidism. A correlation between hypothyreoidism and psychosis has been described since 1888, especially in cases of advanced hypothyreoidism. A few years later (1949), Asher first added the terminology "myxedema madness" to the literature. Psychotic symptoms typically appear after the onset of physical symptoms, usually with a delay of months or years. The case of a female patient who presented a psychotic episode as a first manifestation of hypothyroidism will be described. NE, a 48 yearold female patient, was admitted for the first time to an inpatient mental health care unit due to delusions of persecution and reference, as well as auditory hallucinations that appeared a few weeks ago. After the patient admission, routine laboratory examination was conducted. In order to relieve the patient from her sense of discomfort and while awaiting laboratory results, olanzapine, 5 mg/day, was administered. Neurological examination and cranial computed tomography scan were unremarkable. Hormonal laboratory tests though revealed severe low thyroid hormone levels. Thyroid antibody testing certified Hashimoto's thyroiditis. Olanzapine was discontinued and the patient received thyroid hormone substitution, levothyroxine 75 µg/day, instead. The patient was discharged showing a significant improvement of psychotic symptoms after a 12-day hospitalization. A month later the patient was reevaluated. She had fully recovered from the psychotic episode. A year later, the patient continues to remain free from psychiatric symptoms, while thyroid hormone levels have been restored within normal range. The patient continues receiving only thyroid hormone substitution therapy with levothyroxine. Cases of acute psychosis associated with low levels of thyroid hormones in the context of primary hypothyreoidism have been repeatedly reported. The present case report emphasizes the importance of hypothyroidism exclusion as a secondary cause of psychosis. Thyroid disease treatment ameliorates psychotic disorder symptoms and recovers patients' mental condition.

Controlled shifting of attention in schizophrenia and bipolar disorder through a dichotic listening paradigm.

The dichotic listening (DL) task was developed originally to examine bottom-up or "automatic" information processing. More recently, however, it has been used as a tool in the study of top-down or "controlled" information processing. This has been done by including forced-choice conditions, wherein the examinee is required to focus attention on one or the other ear. It has been widely utilized with patients with schizophrenia, who exhibit rather severe deficits in managing their attention, but not with other patient groups, such as patients with bipolar disorder. In the present study, we examined potential performance similarities in the DL listening task. In total, the sample consisted of 38 patients with schizophrenia, 20 patients with psychotic bipolar disorder and 35 healthy individuals, who performed a DL task with verbal stimuli once at the beginning of their hospitalization and again on the last day before discharge. Our findings indicated that both patient groups showed similarly diminished performance when compared to healthy participants at both times of administration. Symptom improvement between the two evaluations did not significantly influence performance in the DL task. In conclusion, impaired automated and controlled information processing appears to be a common deficit in both schizophrenia and bipolar disorder.

Semantic priming in remitted patients with bipolar disorder.

BACKGROUND AND OBJECTIVES: Semantic priming disturbances are increasingly recognized as a feature of schizophrenia, and increased priming has been suggested to constitute a "cognitive correlate" of positive formal thought disorder (FTD). The present study aimed to investigate semantic priming in patients with bipolar disorder (BD). METHODS: A primed lexical decision task with strongly related (STR), weakly related (WR), or unrelated (UR) prime-target pairs (SOA = 250 ms) was administered to fourteen remitted patients with BD and twelve control subjects matched on key demographic variables. FTD was measured by means of the Scale for Thought, Language and Communication (TLC). RESULTS: Control subjects showed a robust (59.6 ms) and statistically significant priming effect for STR words, while priming for UR words was non-significant. In patients there was no evidence of priming in either condition. In patients, there were no significant correlations between priming magnitude and TLC scores. However, the only patient with a positive score on the TLC disorganization factor exhibited evidence of hyperpriming. LIMITATIONS: The present patient sample exhibited very low TLC scores, and no direct comparison to patients with schizophrenia was possible. CONCLUSIONS: The finding of decreased priming in patients with BD raises the possibility that semantic processing abnormalities in BD are of a different nature than those encountered in schizophrenia. Due to the small size and very low TLC scores of the present patient sample, no definite conclusions can be drawn as to the relationship of formal thought disorder and semantic processing abnormalities in BD.

Insights into theory of mind in schizophrenia: the impact of cognitive impairment.

The ability to mentalize and attribute beliefs, intentions and desires to others has been found by the vast majority of studies to be impaired in patients with schizophrenia. However, it is not yet clear if this deficit in Theory of Mind (ToM) is independent of their also well established deficits in basic cognitive functioning. In the present study, we sought to clarify the above relationship by exploring patients' ToM impairment after controlling for their putative cognitive deficits. We examined 36 patients with schizophrenia and 30 healthy matched controls on first and second order tasks of ToM and on commonly used neuropsychological tests. Patients performed poorly on ToM tasks even after controlling for their cognitive deficits, particularly on second order ToM. The present findings contribute to the understanding of the mechanism of ToM, suggesting that ToM deficits are core characteristics in schizophrenia and relatively independent of patients' cognitive impairment.

Do age and education contribute to performance on the clock drawing test? Normative data for the Greek population.

Our purpose in undertaking the present study was to develop norms for the Greek population for the Clock Drawing Test (CDT), using a systematic scoring procedure, and to explore the influence of demographic factors on the performance of healthy individuals. We administered the CDT to 223 healthy adults and scored it according to the method of Freedman et al. (1994). In 136 of the participants, we also measured global cognitive status with the Mini-Mental State Examination. We found that both age and level of education contributed to CDT performance. Interestingly, CDT performance was relatively consistent across the ages between 14-59 years, showing a marked decline after 60 and another decline after 70. Therefore, we concluded that CDT performance is relatively resistant to the effects of age for those below 60 years old. We present preliminary normative data for the Greek population stratified by age and level of education. Further research should include more extensive sampling of elderly participants (>60 years old) with varying levels of education, in order to establish more reliable norms for the elderly.

[The PLACEBO effect: Definition, theories of action, ethical considerations].

The placebo effect (from latin placere=to please), i.e. the nonspecific psychological therapeutic effects of a substance or procedure, remains one of the biggest challenges encountered by modern medicine, as a therapeutic means with unquestionable and yet unappreciated, global and yet uncontrollable, efficacy. The history of medicine largely intersects the history of placebo effect, as the first scientifically proven non-placebo drug only appeared in the 17th century. Today, placebos have themselves become an object of investigations aiming to clarify the mechanisms of mind-body interactions. Moreover, placebos occupy an important place as methodological tools in modern medical research; randomized double-blind, placebo-controlled studies have been established as the golden standard in the evaluation of new therapies. However, the use of placebos raises a number of important ethical issues, as it comes in contrast to the two most basic principles of medicine, beneficence and autonomy. Therefore, the use of placebos in clinical research should always include measures that ensure minimization of any risk associated with delay of active treatment, as well as preser vation of the patients' interests. In clinical practice, physicians should be aware of psychological dimensions of treatment, of the meaning that the patient ascribes to it, as well as of the influence of the doctor-patient relationship, so that they can use these beneficial nonspecific (i.e. placebo) effects of treatment in the best interest of their patients.

Treatment of Huntington's disease with galantamine.

We present the case of a patient with Huntington's disease and psychosis, whose motor and psychiatric symptoms improved after administration of galantamine, an acetylcholinesterase inhibitor.

Schizophrenic-like symptoms in a patient with thrombo-angiitis obliterans (Winiwarter-Buerger's disease).

In this article a case of schizophrenic-like symptoms in a patient with thrombo-angiitis obliterans (TAO) is presented. His CT and MRI findings indicated a diffuse ischemia in the white matter, suggestive of TAO, not of focal lesions. The patient, except for age, did not have other risk factors for other cerebrovascular diseases. Psychotic symptoms may be the result of cerebral TAO, via deep and periventricular white matter lesions.