Carmela Calandra

The Role of Oxidative Damage in the Pathogenesis and Progression of Alzheimer’s Disease and Vascular Dementia

Oxidative stress (OS) has been demonstrated to be involved in the pathogenesis of the two major types of dementia: Alzheimers disease (AD) and vascular dementia (VaD). Evidence of OS and OS-related damage in AD is largely reported in the literature. Moreover, OS is not only linked to VaD, but also to all its risk factors. Several researches have been conducted in order to investigate whether antioxidant therapy exerts a role in the prevention and treatment of AD and VaD. Another research field is that pertaining to the heat shock proteins (Hsps), that has provided promising findings. However, the role of OS antioxidant defence system and more generally stress responses is very complex. Hence, research on this topic should be improved in order to reach further knowledge and discover new therapeutic strategies to face a disorder with such a high burden which is dementia.

Sleep disorders and depression: brief review of the literature, case report, and nonpharmacologic interventions for depression

Sleep disorders are so frequently associated with depression that, in the absence of sleep complaints, a diagnosis of depression should be made with caution. Insomnia, in particular, may occur in 60%–80% of depressed patients. Depressive symptoms are important risk factors for insomnia, and depression is considered an important comorbid condition in patients with chronic insomnia of any etiology. In addition, some drugs commonly prescribed for the treatment of depression may worsen insomnia and impair full recovery from the illness. The aim of this paper is to review briefly and discuss the following topics: common sleep disturbances during depression (in particular pavor nocturnus, nightmares, hypersomnia, and insomnia); circadian sleep disturbances; and treatment of depression by manipulation of the sleep-wake rhythm (chronotherapy, light therapy, cycles of sleep, and manipulation of the sleep-wake rhythm itself). Finally, we present a case report of a 65-year-old Caucasian woman suffering from insomnia associated with depression who was successfully treated with sleep deprivation.

Borderline Personality Disorder and Depression: An Update

To review the literature related to recent temperamental and biological findings on borderline personality disorder (BPD) and major depression, the close link between the two disorders, and the latest therapeutical findings on BPD, focusing on the conditions of co-morbidity between depression and BPD. The National Institutes of Health’s PubMed database was used to identify indexed studies on BPD, depression and the co-morbidity between the two. Only studies published between 2000 and 2011 were assessed. Similar temperamental features have been demonstrated in BPD and depression. The strong link between the two disorders seems to be widely recognized by scientific community. Psychotherapy and new antipsychotics are the topics of current major interest of research. The therapeutic targets in the case of co-morbidity are BPD features associated with depressive symptoms, thus influencing prognosis. A global assessment is, in fact, fundamental for a successful therapy for the treatment of the several aspects of a complex psychopathological phenomenon.

Accelerated Aging in Major Depression: The Role of Nitro-Oxidative Stress

Nitro-oxidative stress (NOS) plays a fundamental role in aging, as well as in the pathogenesis of neurodegenerative disorders, and major depression (MD). The latter is a very frequent psychiatric illness characterized by accelerated aging, neurodegeneration, high comorbidity with age-related disorders, and premature mortality; all of these conditions find an explanation in an altered redox homeostasis. If aging, neurodegeneration, and major depression share a common biological base in their pathophysiology, common therapeutic tools could be investigated for the prevention and treatment of these disorders. As an example, antidepressants have been demonstrated to present neuroprotective and anti-inflammatory properties and to stimulate neurogenesis. In parallel, antioxidants that stimulate the antioxidant defense systems and interact with the monoaminergic system show an antidepressant-like activity. Further research on this topic could lead, in the near future, to the expansion of the therapeutic possibilities for the treatment of NOS-related disorders.

Haloperidol augmentation of fluvoxamine in skin picking disorder: a case report.

IntroductionCompulsive skin picking, being part of the broader category of impulse control disorders, is considered a residual diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. It is characterized by excessive scratching or picking of normal skin, or skin with minor surface irregularities, and occurs in 2% of patients attending dermatology clinics. Despite the clinical relevance of this disorder, no clear guidelines are available yet; clinical management is, therefore, compromised and the day-to-day clinical practice is burdened by difficulties. Studies on selective serotonin reuptake inhibitors and anti-epileptic drugs have provided limited results. The association between anti-depressants and anti-epileptics has been found to be beneficial in some impulse control disorders, but in skin picking no previous studies have been conducted on this pharmacological approach. There are very few reports on the efficacy of anti-psychotics in skin picking.Case presentationThe therapeutic path described in this case report produced good results for a 59-year-old Caucasian woman. The first therapeutic approach, with fluvoxamine and oxcarbazepine was partially effective; then, the suspension of oxcarbazepine and haloperidol augmentation of fluvoxamine were adopted. After 10 weeks, a significant improvement of the disease was observed: the clinical picture and the associated symptoms were nearly solved.ConclusionsTo the best of our knowledge, this is the first article reporting the association of fluvoxamine and haloperidol in skin picking disorder. It might be useful to perform further research regarding the treatment of skin picking disorder: in clinical practice, several variables might limit the choice of certain drugs. Therefore, it would be useful for the clinician to be aware of other therapeutic options.

Autonomic nervous system and lipid metabolism: findings in anxious-depressive spectrum and eating disorders

ObjectiveTo correlate lipid metabolism and autonomic dysfunction with anxious-depressive spectrum and eating disorders. To propose the lipid index (LI) as a new possible biomarker.Methods95 patients and 60 controls were enrolled from the University Psychiatry Unit of Catania and from general practitioners (GPs). The patients were divided into four pathological groups: Anxiety, Depression, Anxious-Depressive Disorder and Eating Disorders [Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision (DSM-IV-TR) official/appendix criteria]. The levels of the cholesterol, triglycerides and apolipoproteins A and B were determined. The LI, for each subject, was obtained through a mathematical operation on the values of the cholesterol and triglycerides levels compared with the maximum cut-off of the general population. The autonomic functioning was tested with Ewing battery tests. Particularly, the correlation between heart rate variability (HRV) and lipid metabolism has been investigated.ResultsPathological and control groups, compared among each other, presented some peculiarities in the lipid metabolism and the autonomic dysfunction scores. In addition, a statistically significant correlation has been found between HRV and lipid metabolism.ConclusionsLipid metabolism and autonomic functioning seem to be related to the discussed psychiatric disorders. LI, in addition, could represent a new possible biomarker to be considered.

Gsk3 Signalling and Redox Status in Bipolar Disorder: Evidence from Lithium Efficacy

Objective. To discuss the link between glycogen synthase kinase-3 (GSK3) and the main biological alterations demonstrated in bipolar disorder (BD), with special attention to the redox status and the evidence supporting the efficacy of lithium (a GSK3 inhibitor) in the treatment of BD. Methods. A literature research on the discussed topics, using Pubmed and Google Scholar, has been conducted. Moreover, a manual selection of interesting references from the identified articles has been performed. Results. The main biological alterations of BD, pertaining to inflammation, oxidative stress, membrane ion channels, and circadian system, seem to be intertwined. The dysfunction of the GSK3 signalling pathway is involved in all the aforementioned “biological causes” of BD. In a complex scenario, it can be seen as the common denominator linking them all. Lithium inhibition of GSK3 could, at least in part, explain its positive effect on these biological dysfunctions and its superiority in terms of clinical efficacy. Conclusions. Deepening the knowledge on the molecular bases of BD is fundamental to identifying the biochemical pathways that must be targeted in order to provide patients with increasingly effective therapeutic tools against an invalidating disorder such as BD.

Prevalence of depression and its relationship with work characteristics in a sample of public workers

Occupation is a fundamental right, enabling social interaction and financial support for the individual. However, it is an undeniable source of stress, with consequences for physical and mental health. The prevalence of depression and somatic complaints were assessed in 1,013 public workers using the Beck Depression Inventory and a questionnaire investigating for the presence of somatic problems designed by the research team. The results were related to demographic characteristics, history of previous depressive episodes, work schedule (day work, night and day rotating shift work, day rotating shift work), and duration of current work schedule. There were more cases of moderate depression in the day rotating shift workers (84%) than in those working at night (83%). More women had mild or moderate depression than men (22% and 4% versus 10% and 3%, respectively). Severe depression was found only in men. Nearly 10% of depressed individuals reported previous depressive episodes. A link between depression and somatic complaints was also found. In particular, 59% of depressed subjects reported gastrointestinal complaints and 41% did not (P<0.001). In conclusion, the occurrence of depressive symptoms could be facilitated by occupation. A history of depressive symptoms should not be neglected, given the risk of recurrence. Somatic complaints could represent a “wake-up call” regarding depression. Global assessment and effective support are fundamental for promotion of a better quality of life in the at-risk category of workers.

Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: results and lessons of an underpowered randomised clinical trial

BackgroundAs lithium treatment might be effective in reducing the risk of deliberate self-harm (DSH) in adult patients with unipolar affective disorders, we designed a pragmatic randomised trial to assess its efficacy in more than 200 patients with treatment-resistant depression. However, we randomised 56 patients only. The aim of this report is therefore twofold: first, to disseminate the results of this underpowered study which may be incorporated into future meta-analytical reviews; second, to analyse some critical aspects of the study which might explain failure to reach the target sample size.MethodsWe carried out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode were allocated to add lithium to usual care (intervention arm) versus usual care alone (control arm). Suicide completion and acts of DSH during the 12 months of follow-up constituted the composite primary outcome.ResultsOf 58 patients screened for inclusion, 29 were allocated to lithium plus usual care and 27 were assigned to usual care without lithium. Six patients in the lithium plus usual care group and seven in the usual care group committed acts of DSH during the follow-up phase. The survival probability did not differ between the two treatment arms (Chi2 = 0.17, p =0.676). With regard to changes in the severity of depressive symptomatology from baseline to endpoint, no significant differences were detected.ConclusionsThe present study failed to achieve the minimum sample size needed to detect a clinically meaningful difference between the two treatment arms. Consequently, the finding that lithium, in addition to usual care, did not exert a positive effect in terms of reduction of DSH after 12 months of follow-up is likely due to the lack of sufficient statistical power to detect a difference, if a difference existed. The dissemination of the results of this underpowered study will inform future meta-analytical reviews on lithium and suicide-related outcomes.Trial registrationClinicalTrials.gov identifier: NCT00927550

Clinical features and imaging findings in a case of Capgras syndrome

Capgras syndrome consists of the delusional belief that a person or persons have been replaced by doubles or impostors. It can occur in the context of both psychiatric and organic illness, and seems to be related to lesions of the bifrontal and right limbic and temporal regions. Indeed, magnetic resonance imaging has revealed brain lesions in patients suffering from Capgras syndrome. This case study reports the findings of a thorough diagnostic evaluation in a woman suffering from Capgras syndrome and presenting with the following clinical peculiarities: obsessive modality of presentation of the delusional ideation, intrusiveness of such ideation (that even disturbed her sleep), as well as a sense of alienation and utter disgust towards the double. These characteristics bring to mind the typical aspects of obsessive-compulsive disorder. Neuroanatomic investigation, through magnetic resonance imaging, performed on this patient showed alteration of the bilateral semioval centers, which are brain regions associated with the emotion of disgust and often show alterations in subjects suffering from obsessive-compulsive disorder. Hence, neuroimaging allows researchers to put forward the hypothesis of a common neuroanatomic basis for Capgras syndrome and obsessive-compulsive disorder, at least for cases in which the delusional ideation is associated with deep feelings of disgust and presents with a certain pervasiveness.