Gabriele Mandarelli

What every psychiatrist should know about PANDAS: a review

The term Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus infections (PANDAS) was coined by Swedo et al. in 1998 to describe a subset of childhood obsessive-compulsive disorders (OCD) and tic disorders triggered by group-A beta-hemolytic Streptococcus pyogenes infection. Like adult OCD, PANDAS is associated with basal ganglia dysfunction. Other putative pathogenetic mechanisms of PANDAS include molecular mimicry and autoimmune-mediated altered neuronal signaling, involving calcium-calmodulin dependent protein (CaM) kinase II activity. Nonetheless the contrasting results from numerous studies provide no consensus on whether PANDAS should be considered as a specific nosological entity or simply a useful research framework. Herein we discuss available data that could provide insight into pathophysiology of adult OCD, or might explain cases of treatment-resistance. We also review the latest research findings on diagnostic and treatment.

Fatal thromboembolism following physical restraint in a patient with schizophrenia

Fatal thromboembolism during physical restraint in patients suffering from psychotic disorders is a very rare occurrence. In the case we present here, the criteria used in forensic pathology for the age determination of venous thrombi are applied to a case of pulmonary embolism in a patient suffering from schizophrenia who died after physical restraint. The possible association between conventional antipsychotic drugs and deep venous thrombosis, followed by pulmonary embolism, in a man with no predisposing risk factors, as well as the question concerning the appropriateness of medical care, are discussed.

Neurological soft signs discriminate schizophrenia from bipolar disorder

Background. Although neurological soft signs have been consistently described in patients with schizophrenia, their diagnostic specificity is not well clarified. Methods. To test the hypothesis that neurological soft signs are specifically related to schizophrenia, we examined 305 subjects (patients with schizophrenia-spectrum disorder, n=167; patients with bipolar I disorder, n=88; controls, n=50). Neurological soft signs were assessed using the Neurological Evaluation Scale (NES). Multiple logistic regression analysis was used to compute the diagnostic predictive power of neurological soft signs. Results. Patients in the schizophrenia-spectrum disorder group were found to have significantly greater neurological impairment (NES total score=23.9, standard deviation [SD] 11.2) than those in the bipolar disorder group (NES total score=18.2, SD 7.6; p<0.001). Neurological functioning was closely associated with psychopathology (all p<0.001). The NES total score reliably distinguished patients with schizophrenia spectrum disorders from those with bipolar disorder in 68.7% of the cases (p<0.001). Moreover, a particular set of neurological soft signs showed specificity for the schizophrenia-spectrum disorder diagnostic group. Conclusions. Our findings suggest that schizophrenia and bipolar disorder can be distinguished in terms of neurological impairment. Furthermore, we recommend the utility of neurological soft signs as a useful, quantifiable, sensitive, and inexpensive tool for the diagnostic work-up of schizophrenia. (Journal of Psychiatric Practice 2014;20:147–153)

The safety of serotonin–noradrenaline reuptake inhibitors (SNRIs) in pregnancy and breastfeeding: a comprehensive review

The present study provides a comprehensive review of the existing literature on the safety of serotonin–noradrenaline reuptake inhibitors (SNRIs) in pregnancy and lactation.

Treatment decision-making capacity in non-consensual psychiatric treatment: a multicentre study

AIMS To evaluate treatment decision-making capacity (DMC) to consent to psychiatric treatment in involuntarily committed patients and to further investigate possible associations with clinical and socio-demographic characteristics of patients. METHODS 131 involuntarily hospitalised patients were recruited in three university hospitals. Mental capacity to consent to treatment was measured with the MacArthur Competence Assessment Tool for Treatment (MacCAT-T); psychiatric symptoms severity (Brief Psychiatric Rating Scale, BPRS-E) and cognitive functioning (Mini Mental State Examination, MMSE) were also assessed. RESULTS Mental capacity ratings for the 131 involuntarily hospitalised patients showed that patients affected by bipolar disorders (BD) scored generally better than those affected by schizophrenia spectrum disorders (SSD) in MacCAT-T appreciation (p < 0.05) and reasoning (p < 0.01). Positive symptoms were associated with poorer capacity to appreciate (r = -0.24; p < 0.01) and reason (r = -0.27; p < 0.01) about ones own treatment. Negative symptoms were associated with poorer understanding of treatment (r = -0.23; p < 0.01). Poorer cognitive functioning, as measured by MMSE, negatively affected MacCAT-T understanding in patients affected by SSD, but not in those affected by BD (SSD r = 0.37; p < 0.01; BD r = -0.01; p = 0.9). Poorer MacCAT-T reasoning was associated with more manic symptoms in the BD group of patients but not in the SSD group (BD r = -0.32; p < 0.05; SSD r = 0.03; p = 0.8). Twenty-two per cent (n = 29) of the 131 recruited patients showed high treatment DMC as defined by having scored higher than 75% of understanding, appreciating and reasoning MacCAT-T subscales maximum sores and 2 at expressing a choice. The remaining involuntarily hospitalised patients where considered to have low treatment DMC. Chi-squared disclosed that 32% of BD patients had high treatment DMC compared with 9% of SSD patients (p < 0.001). CONCLUSIONS Treatment DMC can be routinely assessed in non-consensual psychiatric settings by the MacCAT-T, as is the case of other clinical variables. Such approach can lead to the identification of patients with high treatment DMC, thus drawing attention to possible dichotomy between legal and clinical status.

The relationship between alexithymia and circulating cytokine levels in subjects undergoing upper endoscopy

Objective: Despite emerging evidence suggesting a link between alexithymia and immune function, previous studies yielded contrasting results. The proposed link between alexithymia and immune function remains controversial as does the role, in this relationship, of anxiety, depression and subjective stress. The aim of the study is to investigate the possible association between alexithymia and circulating levels of cytokines in subjects awaiting an upper endoscopy, a stressful procedure, controlling for anxiety levels, depression and subjective stress. Methods: Participants were recruited from among consecutive patients referred for routine diagnostic upper endoscopy. All participants completed the Toronto Alexithymia Scale (TAS-20), the Hospital Anxiety and Depression Scale, and the Stress-related Vulnerability Scale. Serum levels of IL-1β, IL-4, IL-6, IL-10, TNF-α and IFN-γ were measured by ELISA. Results: Of the 90 subjects initially approached, 68 completed the study. The TAS-20 identified 22 alexithymic and 36 non-alexithymic patients. ELISA detected significantly lower IL-4 and IL-6 concentrations in alexithymic than in non-alexithymic patients. According to multiple linear regression analysis, alexithymia predicted low IL-4 and IL-6 levels in the sample overall, independently of stress, anxiety, depression and other possible confounders. No between-group differences were found in serum levels of IFN-γ, IL-1β, and TNF-α. Conclusion: These findings argue against an isolated shift towards pro-inflammatory or anti-inflammatory mediators and suggest that circulating cytokine profiles differ in alexithymic and non-alexithymic subjects.

[Informed consent and neuromodulation techniques for psychiatric purposes: an introduction].

The aim of this review was to investigate informed consent-related issues concerning vagus nerve stimulation and deep brain stimulation in the treatment of psychiatric disorders. We searched the principal medical databases for studies concerning informed consent, as well as ethical and deontological issues in psychosurgery. Data were critically analysed. We also provided guidelines for the evaluation of accuracy of the informed consent in such treatments. Despite major deontological and ethical implications, there is substantial lack of information pertaining informed consent decision-making in psychiatric patients with an indication for psychosurgery. In clinical research studies, deep brain stimulation and vagus nerve stimulation have been mainly used in drug-resistant major depressive disorder, Tourette syndrome and obsessive-compulsive disorder. Existing data on efficacy and tolerability, as well as those studies indicating the risk for incapacity in drug-resistant severe mental disorders, suggest the need to achieve a better understanding of the capacity to consent to psychosurgery in patients affected by mental disorders. Informed consent decision-making in clinical trials of deep brain stimulation and vagus nerve stimulation in psychiatric patients is largely unknown and deserves further investigation.The aim of this review was to investigate informed consent-related issues concerning vagus nerve stimulation and deep brain stimulation in the treatment of psychiatric disorders. We searched the principal medical databases for studies concerning informed consent, as well as ethical and deontological issues in psychosurgery. Data were critically analysed. We also provided guidelines for the evaluation of accuracy of the informed consent in such treatments. Despite major deontological and ethical implications, there is substantial lack of information pertaining informed consent decision-making in psychiatric patients with an indication for psychosurgery. In clinical research studies, deep brain stimulation and vagus nerve stimulation have been mainly used in drug-resistant major depressive disorder, Tourette syndrome and obsessive-compulsive disorder. Existing data on efficacy and tolerability, as well as those studies indicating the risk for incapacity in drug-resistant severe mental disorders, suggest the need to achieve a better understanding of the capacity to consent to psychosurgery in patients affected by mental disorders. Informed consent decision-making in clinical trials of deep brain stimulation and vagus nerve stimulation in psychiatric patients is largely unknown and deserves further investigation.

Suicide of isolated inmates suffering from psychiatric disorders: when a preventive measure becomes punitive

We performed external autopsies and examinations on two inmates who had committed suicide by hanging themselves with their underwear and using the window bars of their cells as ligature points after they had been placed in solitary confinement. In one case, the inmate had even been deprived of her clothing (with the exception to her underwear). Underwear has been rarely described as a means for self-harm and, to the best of our knowledge, no previous study has focused on cases of prison suicides committed using this garment, even though it is available to every inmate. The two cases were very similar; both inmates were young, physically aggressive and in their first week at a new facility; both had been affected by mental disorders, had been prescribed psychotropic medications and had histories of psychiatric hospitalisation. In each case, the psychiatric evaluations had highlighted significant suicidal risk. We discuss these two cases in an attempt to describe the complexity of and contradictions within the management of suicidal inmates at correctional facilities. We aim to propose new strategies and emphasise the need to introduce evidence-based standardised protocols over inhumane, ineffective and simplistic punitive measures in the management of these individuals.

Informed Consent Decision-Making in Deep Brain Stimulation

Deep brain stimulation (DBS) has proved useful for several movement disorders (Parkinson’s disease, essential tremor, dystonia), in which first and/or second line pharmacological treatments were inefficacious. Initial evidence of DBS efficacy exists for refractory obsessive-compulsive disorder, treatment-resistant major depressive disorder, and impulse control disorders. Ethical concerns have been raised about the use of an invasive surgical approach involving the central nervous system in patients with possible impairment in cognitive functioning and decision-making capacity. Most of the disorders in which DBS has been used might present with alterations in memory, attention, and executive functioning, which may have an impact on the mental capacity to give informed consent to neurosurgery. Depression, anxiety, and compulsivity are also common in DBS candidate disorders, and could also be associated with an impaired capacity to consent to treatment or clinical research. Despite these issues, there is limited empirical knowledge on the decision-making levels of these patients. The possible informed consent issues of DBS will be discussed by focusing on the specific treatable diseases.

Free will, neuroscience, and choice: towards a decisional capacity model for insanity defense evaluations

Free will has often been considered central to criminal responsibility. Yet, the concept of free will is also difficult to define and operationalize, and, moreover, it is intensely debated. In particular, the very existence of free will has been denied based on recent neuroscience findings. This debate has significant implications on those fields in which the link between free will and behaviour is the main focus of interest, such as forensic psychiatry. In fact, a tension is often experienced between the centrality of the notion of free will on the one hand, and its controversial status on the other. This tension needs to be addressed, especially in forensic psychiatry, since it is relevant for actual assessments of legal insanity. In the present paper we will try to operationalize “free will” using a fourpartite decision-making capacity model, which can be used in forensic assessment of insanity. We will describe its advantages and application to guide mental insanity assessments. Whereas free will is often considered problematic from a neuroscience perspective, this model, we argue, is compatible with neuroscience; moreover, evaluations using this model can also be informed and strengthened by neuroscientific findings, for example regarding inhibitory control.