Enrico Massimetti

Plasma Brain-Derived Neurotrophic Factor in treatment-resistant depressed patients receiving electroconvulsive therapy

There is an increasing evidence that the Brain-Derived Neurotrophic Factor (BDNF) could be involved in the mode of action of antidepressants and, perhaps, of ECT. This study aimed to investigate whether the clinical course of medication-resistant depressed patients following a course of ECT might be associated with changes of plasma BDNF concentrations. Our findings showed that at T0 (baseline) plasma BDNF levels of patients were significantly lower than those of control subjects, and that at T2 (after ECT) were significantly increased in parallel with the decrease of the Hamilton Rating Scale for Depression (HRSD) total score. However, only remitter patients who showed higher baseline BDNF levels than non-remitters reached normalized BDNF levels after ECT. These findings would suggest the potential usefulness of baseline plasma BDNF levels as predictors of response to ECT in treatment-resistant depressed patients.

Adult Autism Subthreshold Spectrum (AdAS Spectrum): Validation of a questionnaire investigating subthreshold autism spectrum

AIM Increasing literature has shown the usefulness of a dimensional approach to autism. The present study aimed to determine the psychometric properties of the Adult Autism Subthreshold Spectrum (AdAS Spectrum), a new questionnaire specifically tailored to assess subthreshold forms of autism spectrum disorder (ASD) in adulthood. METHODS 102 adults endorsing at least one DSM-5 symptom criterion for ASD (ASDc), 143 adults diagnosed with a feeding and eating disorder (FED), and 160 subjects with no mental disorders (CTL), were recruited from 7 Italian University Departments of Psychiatry and administered the following: SCID-5, Autism-Spectrum Quotient (AQ), Ritvo Autism and Asperger Diagnostic Scale 14-item version (RAADS-14), and AdAS Spectrum. RESULTS The AdAS Spectrum demonstrated excellent internal consistency for the total score (Kuder-Richardsons coefficient=.964) as well as for five out of seven domains (all coefficients>.80) and sound test-retest reliability (ICC=.976). The total and domain AdAS Spectrum scores showed a moderate to strong (>.50) positive correlation with one another and with the AQ and RAADS-14 total scores. ASDc subjects reported significantly higher AdAS Spectrum total scores than both FED (p<.001) and CTL (p<.001), and significantly higher scores on the Childhood/adolescence, Verbal communication, Empathy, Inflexibility and adherence to routine, and Restricted interests and rumination domains (all p<.001) than FED, while on all domains compared to CTL. CTL displayed significantly lower total and domain scores than FED (all p<.001). A significant effect of gender emerged for the Hyper- and hyporeactivity to sensory input domain, with women showing higher scores than men (p=.003). A Diagnosis* Gender interaction was also found for the Verbal communication (p=.019) and Empathy (p=.023) domains. When splitting the ASDc in subjects with one symptom criterion (ASD1) and those with a ASD, and the FED in subjects with no ASD symptom criteria (FED0) and those with one ASD symptom criterion (FED1), a gradient of severity in AdAS Spectrum scores from CTL subjects to ASD patients, across FED0, ASD1, FED1 was shown. CONCLUSIONS The AdAS Spectrum showed excellent internal consistency and test-retest reliability and strong convergent validity with alternative dimensional measures of ASD. The questionnaire performed differently among the three diagnostic groups and enlightened some significant effects of gender in the expression of autistic traits.

Chronology of illness in dual diagnosis heroin addicts: The role of mood disorders.

BACKGROUND Recent celebrity deaths have been widely reported in the media and turned the public attention to the coexistence of mood, psychiatric and substance-abuse disorders. These tragic and untimely deaths motivated us to examine the scientific and clinical data, including our own work in this area. The self-medication hypothesis states that individuals with psychiatric illness tend to use heroin to alleviate their symptoms. This study examined the correlations between heroin use, mood and psychiatric disorders, and their chronology in the context of dual diagnosis. METHODS Out of 506 dual diagnosed heroin addicts, 362 patients were implicated in heroin abuse with an onset of at least one year prior to the associated mental disorder (HER-PR), and 144 patients were diagnosed of mental illness at least one year prior to the associated onset of heroin use disorder (MI-PR). The retrospective cross-sectional analysis of the two groups compared their demographic, clinical and diagnostic characteristics at univariate and multivariate levels. RESULTS Dual diagnosis heroin addicts whose heroin dependences existed one year prior to their diagnoses (HER-PR) reported more frequent somatic comorbidity (p≤0.001), less major problems at work (p=0.003), more legal problems (p=0.004) and more failed treatment for their heroin dependence (p<0.001) in the past. More than 2/3 reached the third stage of heroin addiction (p=<0.001). Their length of dependence was longer (p=0.004). HER-PR patients were diagnosed more frequently as affected by mood disorders and less frequently as affected by psychosis (p=0.004). At the multivariate level, HER-PR patients were characterized by having reached stage 3 of heroin dependence (OR=2.45), diagnosis of mood disorder (OR=2.25), unsuccessful treatment (OR=2.07) and low education (OR=1.79). LIMITATIONS The main limitation is its retrospective nature. Nonetheless, it does shed light on what needs to be done from a clinical and public health perspective and especially prevention. CONCLUSIONS The data emerging from this study, does not allow us to determine a causal relation between heroin use and mental illness onset. However, this data, even if requiring longitudinal studies, suggest that self-medication theory, in these patients, can be applied only for chronic psychoses, but should not be applied to patients with mood disorders using heroin.

Subthreshold autism spectrum disorder in patients with eating disorders

AIM Increasingly data suggest a possible overlap between psychopathological manifestations of eating disorders (EDs) and autism spectrum disorders (ASD). The aim of the present study was to assess the presence of subthreshold autism spectrum symptoms, by means of a recently validated instrument, in a sample of participants with EDs, particularly comparing participants with or without binge eating behaviours. METHODS 138 participants meeting DSM-5 criteria for EDs and 160 healthy control participants (HCs), were recruited at 3 Italian University Departments of Psychiatry and assessed by the SCID-5, the Adult Autism Subthreshold Spectrum (AdAS Spectrum) and the Eating Disorders Inventory, version 2 (EDI-2). ED participants included: 46 with restrictive anorexia (AN-R); 24 with binge-purging type of Anorexia Nervosa (AN-BP); 34 with Bulimia Nervosa (BN) and 34 with Binge Eating Disorder (BED). The sample was split in two groups: participants with binge eating behaviours (BEB), in which were included participants with AN-BP, BN and BED, and participants with restrictive behaviours (AN-R). RESULTS participants with EDs showed significantly higher AdAS Spectrum total scores than HCs. Moreover, EDs participants showed significantly higher scores on all AdAS Spectrum domains with the exception of Non verbal communication and Hyper-Hypo reactivity to sensory input for AN-BP participants, and Childhood/Adolescence domain for AN-BP and BED participants. Participants with AN-R scored significantly higher than participants with BEB on the AdAS Spectrum total score, and on the Inflexibility and adherence to routine and Restricted interest/rumination AdAS Spectrum domain scores. Significant correlations emerged between the Interpersonal distrust EDI-2 sub-scale and the Non verbal communication and the Restricted interest and rumination AdAS Spectrum domains; as well as between the Social insecurity EDI-2 sub-scale and the Inflexibility and adherence to routine and Restricted interest and rumination domains in participants with EDs. CONCLUSIONS Our data corroborate the presence of higher subthreshold autism spectrum symptoms among ED participants with respect to HCs, with particularly higher levels among restrictive participants. Relevant correlations between subthreshold autism spectrum symptoms and EDI-2 Subscale also emerged.

Impact of Mood Spectrum Spirituality and Mysticism Symptoms on Suicidality in Earthquake Survivors with PTSD

The aim of the present study was to explore the correlations between Spirituality/Mysticism/Psychoticism symptoms and suicidality in young adult survivors of the L’Aquila earthquake. The sample included 475 subjects recruited among high school seniors who had experienced the April 6, 2009, earthquake. Assessments included: Trauma and Loss Spectrum–Self Report and Mood Spectrum–Self Report (MOODS-SR). Mysticism/Spirituality dimension and suicidality were evaluated by means of some specific items of the MOOD-SR. The Spirituality/Mysticism/Psychoticism MOODS-SR factor score was significantly higher among subjects with PTSD diagnosis with respect to those without. Similarly, subjects with suicidal ideation, as well as those who committed a suicide attempt, reported significantly higher scores than those without.

Six-Month Outcome in Bipolar Spectrum Alcoholics Treated with Acamprosate after Detoxification: A Retrospective Study

Background: Glutamate system is modified by ethanol and contributes both to the euphoric and the dysphoric consequences of intoxication, but there is now growing evidence that the glutamatergic system also plays a central role in the neurobiology and treatment of mood disorders, including major depressive disorders and bipolar disorders. We speculate that, using acamprosate, patients with bipolar depression (BIP-A) can take advantage of the anti-glutamate effect of acamprosate to “survive” in treatment longer than peers suffering from non-bipolar depression (NBIP-A) after detoxification. Method: We retrospectively evaluated the efficacy of a long-term (six-month) acamprosate treatment, after alcohol detoxification, in 41 patients (19 males and 22 females), who could be classified as depressed alcoholics, while taking into account the presence/absence of bipolarity. Results: During the period of observation most NBIP-A patients relapsed, whereas a majority of BIP-A patients were still in treatment at the end of their period of observation. The cumulative proportion of ‘surviving’ patients was significantly higher in BIP-A patients, but this finding was not related to gender or to other demographic or clinically investigated characteristics. The treatment time effect was significant in both subgroups. The treatment time-group effect was significant (and significantly better) for bipolar patients on account of changes in the severity of their illness. Limitations: Retrospective methodology and the lack of DSM criteria in diagnosing bipolarity. Conclusions: Bipolarity seems to be correlated with the efficacy of acamprosate treatment in inducing patients to refrain from alcohol use after detoxification (while avoiding relapses) in depressed alcoholics. Placebo-controlled clinical trials are now warranted to check the validity of this hypothesis.

Predictors of recurrence during long-term treatment of bipolar I and II disorders. A 4 year prospective naturalistic study

BACKGROUND Despite the large number of treatments available for bipolar disorder (BD), more than one half of patients have a recurrence within 2 years, and over 90% experience at least one additional affective episode during their lifetime. METHODS The aim of this study was to test the impact of a number of demographic and clinical features on the risk to recurrence in a real- word representative sample of 266 outpatients with BD-I or II treated in a naturalistic setting during a 4-years-follow-up period. RESULTS We found that the number of episodes per year after study entry, compared to the number of episodes per year before study entry,significantly decreased and that about one third of patients had no recurrences during the observation period. The length of follow-up and the number of previous episodes, mainly depressive, predicted the risk of recurrence, while female gender, higher age at intake, and a higher frequency of past mixed episodes predicted a higher frequency of recurrences. LIMITATIONS The study had some limitations to consider: i.e. the risk of poor reliability of information on the previous course of illness or the naturalistic treatment during the follow-up. CONCLUSIONS Our study suggests that (a) an evidence-based long-term treatment, with regular follow-up visits could improve the course of disease and prognosis; (b) clinicians should carefully consider the presence of a high number of mixed episodes, to provide more targeted treatment strategies; (c) an appropriate use of antidepressants in selected patients did not worsen the course of illness.

Differentiating between the course of illness in bipolar 1 and chronic-psychotic heroin-dependent patients at their first agonist opioid treatment.

In an effort to inquiry the “self-medication hypothesis” in heroin-dependent patients suffering from chronic psychosis and bipolar disorder, a naturalistic comparative cohort study was designed with the aim of comparing, according to the presence of dual diagnosis, the clinical characteristics of heroin-dependent patients presenting for their first agonist opioid treatment. The main finding was that addictive (heroin) illness was more severe in bipolar 1 patients and less severe in chronic psychotic patients when compared with heroin-dependent patients without dual diagnoses. In the case of chronic psychotic patients, these differences do not allow us to exclude a therapeutic heroin use, at least at the beginning of their toxicomanic career, with limited progression of their addictive disease. This occurrence seems to be excluded for bipolar 1 heroin-dependent patients, who come to their first agonist opioid treatment with a more severe addictive disease.

P01-143 - Gender differences in the correlations between cortisol levels or DHEA-S/cortisol ratio and panic-agoraphobic dimensions in healthy subjects

Introduction A link between anxiety and disfunctions of the Hypotalamic-pituitary-adrenal (HPA) axis has been widely reported in both normal and pathological anxiety, but research findings are controversial. Objectives To explore gender differences in the relationships between cortisol and neurosteroids and subthreshold anxiety dimensions. Aims To investigate the possible correlations between serum cortisol and dehydroepiandrosterone sulphate (DHEA-S) levels, or DHEA-S/cortisol ratio, and the subthreshold panic dimensions in a sample of healthy subjects. Methods Forty-two Italian civilians, without current or lifetime psychiatry disorders, were recruited and assessed by means of the Structured Clinical Interview for DSM-IV (SCID-I/P) and a specific questionnaire, the so-called Panic Agoraphobic Spectrum-Self Report lifetime version (PAS-SR), for assessing subthreshold panic-agoraphobic dimensions. Results The results showed the presence of significant negative correlations between the cortisol levels and the total scores of the PAS-SR and of the following domains: separation sensitivity, panic like symptoms and medication/substance sensitivity. The PAS-SR total and the panic-like symptoms domain scores were related positively to the DHEAS/cortisol ratio. When the sample was distinguished in women and men, it turned out that this correlations were present only in women. Conclusions This findings would indicate that cortisol levels are related to subthreshold panic-agoraphobic symptoms, with a gender specificity. Therefore, further studies are needed to investigate those subthreshold conditions in order to indentify possible gender differences that may account for phenotypes at higher risk for psychiatric disorders.

Quality of Life, Depression, and Anxiety in Patients with Uveal Melanoma: A Review

The aim is to summarize current knowledge on both QoL and depressive/anxious symptoms in patients with UM, including studies on the effect on QoL and psychological status of genetic testing related to the risk of metastatic disease. A review from the last 25 years by using the databases “PsycInfo,” “Medline,” and “Science Direct” was performed. As a total result, eighteen papers were retrieved. Eight studies (44.4%) used a prospective design methodology: two were retrospective observations (11.1%), three were cross-sectional observational studies (16.6%), and three (16.6%) were naturalistic follow-up studies. One trial was conducted with a case-control design (5.5%), and one was a methodological paper (5.5%). The number of subjects included in the studies ranged widely, between 7 and 842 (mean: 152.1 ± 201.3), for a total of 2587 patients, 1306 males (50.5%) and 1281 females (49.5%). The mean age of subject enrolled was 61.3 ± 4.1 years. Twenty-six different scales, questionnaires, or interviews were utilized. No significant differences in QoL between radiotherapy and enucleation emerged. Genetic testing did not significantly affect QoL or psychological status.