Antonio Del Casale

Periventricular white matter hyperintensities as predictors of suicide attempts in bipolar disorders and unipolar depression

The aim of this study was to evaluate whether deep white matter hyperintensities (DWMH) and periventricular white matter hyperintensities (PVH) are associated with suicidal behavior in patients with major affective disorders. Subjects were 99 consecutively admitted inpatients (42 men; 57 women; mean age: 46.5 years [SD=15.2; Min./Max.=19/79]) with a diagnosis of major affective disorder (bipolar disorder type I, bipolar disorder type-II and unipolar major depressive disorder). 44.4% of the participants had made at least one previous suicide attempt. T2-weighted brain magnetic resonance images were rated for the presence and extension of WMH using the modified Fazekas scale. Patients were interviewed for clinical data on average 5 days after admission. Bivariate analyses, corrected for multiple-testing, and logistic regression analysis were used to test the association between suicide attempts and clinical variables. Attempters and nonattempters differed only in the presence of PVH--the former were more likely to have PVH. The logistic regression indicated that the presence of PVH was robustly associated with suicidal behaviors after controlling for age (OR: 8.08). In conclusion, neuroimaging measures may be markers of risk for suicidal attempts in patients with major affective disorders.

Improving adherence in mood disorders: the struggle against relapse, recurrence and suicide risk

Medication nonadherence is a major obstacle to translating treatment efficacy from research settings into effectiveness in clinical practice for patients with affective disorders. Adherence to beneficial drug therapy is associated with lower mortality compared with poor adherence. Reduced adherence is associated with increased suicide risk, especially when lithium is discontinued. The aim of this paper is to review the prevalence, predictors and methods for improving medication adherence in unipolar and bipolar affective disorders. Studies were identified through Medline and PsycInfo searches of English language publications between 1976 and 2009. This was supplemented by a hand search and the inclusion of selected descriptive articles on good clinical practice. Estimates of medication nonadherence for unipolar and bipolar disorders range from 10 to 60% (median: 40%). This prevalence has not changed significantly with the introduction of new medications. There is evidence that attitudes and beliefs are at least as important as side effects in predicting adherence. The limited number of empirical studies on reducing nonadherence indicate that, if recognized, the problem may be overcome. Clinical data highlight the importance of extended courses of medication in improving the long-term prognosis of patients with affective disorders.

Duloxetine in acute major depression: review of comparisons to placebo and standard antidepressants using dissimilar methods

Randomized controlled trials (RCTs) of duloxetine (DLX), an inhibitor of both norepinephrine and serotonin transporters (SNRI), have tested its efficacy in acute major depressive disorder (MDD) versus placebo (PBO) or standard serotonin‐reuptake inhibitors (SRIs) and require review, comparing analytical methods.

Substance Abuse, Temperament and Suicide Risk: Evidence from a Case-Control Study

ABSTRACT The aim of the current study was to evaluate differences between two matched groups of psychiatric outpatients (those with and those without substance abuse) on clinical variables that previous research has suggested may be associated with substance abuse comorbidity. The sample consisted of 31 consecutively admitted psychiatric outpatients (16 men and 15 women) with substance use comorbidity; controls were 31 outpatients without substance use comorbidity who were matched for sex and age. The patients completed the Mini International Neuropsychiatric Interview, the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-autoquestionnaire version, the Symptom Checklist-90-Revised, the Gotland Male Depression Scale, and the Beck Hopelessness Scale. As a group, the substance abusers had a different temperament profile (higher dysthymic/cyclothymic/anxiety and irritability and lower hyperthymic traits), a higher hopelessness, global psychopathology severity, impulsivity/aggression, and suicide risk (higher lifetime suicide ideation and suicide attempts), and were more frequently depressed. However, few differences were significant and almost all were of small magnitude. Furthermore, bipolar disorders type II were overrepresented in the abuser group compared to the control group (45% vs. 22%, respectively).

Efficacy of Add-On Deep Transcranial Magnetic Stimulation in Comorbid Alcohol Dependence and Dysthymic Disorder: Three Case Reports

BACKGROUND Craving for alcohol is associated with abnormal activation in the dorsolateral prefrontal cortex. Deep transcranial magnetic stimulation (dTMS) has shown promise in the treatment of depression. There are few treatment options for treatment-resistant dysthymic disorder comorbid with alcohol use disorder. OBJECTIVE To investigate the possible anticraving efficacy of bilateral dorsolateral prefrontal cortex high-frequency dTMS in 3 patients with comorbid long-term DSM-IV-TR dysthymic disorder and alcohol use disorder. METHOD Three patients with alcohol use disorder with dysthymic disorder in their detoxification phase (abstaining for > 1 month) underwent twenty 20-minute sessions of 20 Hz dTMS over the dorsolateral prefrontal cortex over 28 days between 2011 and 2012. Alcohol craving was rated with the Obsessive Compulsive Drinking Scale and depressive symptoms with the Hamilton Depression Rating Scale. RESULTS All 3 patients responded unsatisfactorily to initial intravenous antidepressant and antianxiety combinations but responded after 10 dTMS sessions, improving on both anxiety-depressive symptoms and craving. This improvement enabled us to reduce antidepressant dosages after dTMS cycle completion. DISCUSSION High-frequency bilateral dorsolateral prefrontal cortex dTMS with left prevalence was found to produce significant anticraving effects in alcohol use disorder comorbid with dysthymic disorder. The potential of dTMS for reducing craving in patients with substance use disorder deserves to be further investigated.

Surviving the suicides of significant others: a case study.

Psychological pain has been reported to be major contributing factor for completed suicide, and classical suicidology based its wisdom on this construct. In this paper we report the case of a patient whose family experienced a high number of suicides apparently due to an escalation of psychological pain in the family members after the successive suicides. We also briefly discuss the problem of helping survivors after the suicide of loved one.

Anabolic-androgenic steroid use and psychopathology in athletes. A systematic review.

The use of anabolic-androgenic steroids (AASs) by professional and recreational athletes is increasing worldwide. The underlying motivations are mainly performance enhancement and body image improvement. AAS abuse and dependence, which are specifically classified and coded by the DSM-5, are not uncommon. AAS-using athletes are frequently present with psychiatric symptoms and disorders, mainly somatoform and eating, but also mood, and schizophrenia-related disorders. Some psychiatric disorders are typical of athletes, like muscle dysmorphia. This raises the issue of whether AAS use causes these disorders in athletes, by determining neuroadaptive changes in the reward neural circuit or by exacerbating stress vulnerability, or rather these are athletes with premorbid abnormal personalities or a history of psychiatric disorders who are attracted to AAS use, prompted by the desire to improve their appearance and control their weights. This may predispose to eating disorders, but AASs also show mood destabilizing effects, with longterm use inducing depression and short-term hypomania; withdrawal/discontinuation may be accompanied by depression. The effects of AASs on anxiety behavior are unclear and studies are inconsistent. AASs are also linked to psychotic behavior. The psychological characteristics that could prompt athletes to use AASs have not been elucidated.

Neurodevelopment in Schizophrenia: The Role of the Wnt Pathways

Objectives. To review the role of Wnt pathways in the neurodevelopment of schizophrenia. Methods: Systematic PubMed search, using as keywords all the terms related to the Wnt pathways and crossing them with each of the following areas: normal neurodevelopment and physiology, neurodevelopmental theory of schizophrenia, schizophrenia, and antipsychotic drug action. Results: Neurodevelopmental, behavioural, genetic, and psychopharmacological data point to the possible involvement of Wnt systems, especially the canonical pathway, in the pathophysiology of schizophrenia and in the mechanism of antipsychotic drug action. The molecules most consistently found to be associated with abnormalities or in antipsychotic drug action are Akt1, glycogen synthase kinase3beta, and beta-catenin. However, the extent to which they contribute to the pathophysiology of schizophrenia or to antipsychotic action remains to be established. Conclusions: The study of the involvement of Wnt pathway abnormalities in schizophrenia may help in understanding this multifaceted clinical entity; the development of Wnt-related pharmacological targets must await the collection of more data.

The wnt pathway in mood disorders

Objectives: To review the evidence of the involvement of the Wnt signalling pathway in mood disorders and in the action of drugs used to treat these disorders. Methods: We performed a careful PubMed search using as keywords all possible terms relevant to the Wnt pathway and crossing them with each of four areas, i.e., developmental effects, behavioural effects, mood disorders, and drugs used in their treatment. Papers were selected on the basis of their content and their data used for discussion. Results: Neurodevelopmental and behavioural data point to the possibility of involvement of the Wnt pathway in the pathophysiology of mood disorders. Clinical and post-mortem data are not sufficient to corroborate a definite role for Wnt alterations in any mood disorder. Combining genetic and pharmacological data, we may state that glycogen synthase kinase is the key molecule in bipolar disorder, as it is connected with many other signalling pathways that were shown to be involved in mood disorders, while Wnt molecules in the hippocampus appear to be mainly involved in depressive disorders. Conclusions: Altered Wnt signalling may play a role in the pathophysiology of mood disorders, although not a central one. It is premature to draw conclusions regarding the possible usefulness of Wnt manipulations in the treatment of mood disorders.

Structural brain alterations in bipolar disorder II: a combined voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) study.

BACKGROUND Brain structural changes have been described in bipolar disorder (BP), but usually studies focused on both I and II subtypes indiscriminately and investigated changes in either brain volume or white matter (WM) integrity. We used combined voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) analysis to track changes in the grey matter (GM) and WM in the brains of patients affected by BPII, as compared to healthy controls. METHODS Using VBM and DTI, we scanned 20 DSM-IV-TR BPII patients in their euthymic phase and 21 healthy, age- and gender-matched volunteers with no psychiatric history. RESULTS VBM showed decreases in GM of BPII patients, compared to controls, which were diffuse in nature and most prominent in the right middle frontal gyrus and in the right superior temporal gurus. DTI showed significant and widespread FA reduction in BPII patients in all major WM tracts, including cortico-cortical association tracts. LIMITATIONS The small sample size limits the generalisability of our findings. CONCLUSIONS Reduced GM volumes and WM integrity changes in BPII patients are not prominent like those previously reported in bipolar disorder type-I and involve cortical structures and their related association tracts.