Lo studio della risposta neurobiologica ai trattamenti con rTMS e tDCS, revisione della letteratura, presentazione di un progetto sperimentale e dati preliminari.

La depressione maggiore rappresenta un disturbo dell’umore altamente invalidante; compromette le capacità funzionali dell’individuo, e, secondo stime della WHO è tra le principali cause di disabilità a livello mondiale. Si tratta di un disturbo ricorrente e dagli elevati costi sociali che ha trovato nel neuroimaging un valido strumento di ricerca delle sue basi fisiopatologiche, fino a poco tempo fa in larga parte sconosciute (Pandya, Altinay, Malone, & Anand, 2012). Studi dell’attività cerebrale in vivo hanno mostrato alterazioni di attivazione e di connettività cerebrale in numerose (e variabili) aree cerebrali, sottolineando l’estrema complessità del disturbo depressivo. L’utilizzo della risonanza magnetica funzionale (fMRI) nello studio di questa patologia psichiatrica pone le basi per una futura discriminazione in endofenotipi e relative terapie personalizzate (Hasler & Northoff, 2011). Il mio progetto di tesi muove dall’incontro tra neuroscienze e psichiatria: presenta uno studio fMRI su pazienti depressi per identificare una differenza significativa di connettività tra pazienti e gruppo di controllo. Questo risultato è stato poi scelto come metodo d’indagine dei correlati funzionali di due nuovi strumenti terapeutici qui presentati: stimolazione magnetica transcranica (rTMS) e stimolazione transcranica a corrente diretta (tDCS). La rTMS e la tDCS rappresentano una nuova prospettiva terapeutica, di dimostrata efficacia, nel trattamento della depressione farmaco-resistente (Connolly, Helmer, Cristancho, Cristancho, & O'Reardon, 2012), definita come forma depressiva che non risponde ad almeno due cicli con antidepressivi di differenti classi farmacologiche. Lo sviluppo di questo protocollo di ricerca si pone l’obiettivo di identificare i correlati neurobiologici dell’efficacia di queste due nuove strumentazioni terapeutiche

PENGARUH MOTIVASI, PERSEPSI DAN SIKAP TERHADAP KEPUTUSAN PEMBELIAN PADA KONSUMEN MUSLIM (STUDI KASUS KFC CABANG JAMTOS JAMBI)

Skripsi ini bertujuan untuk mengungkap pengaruh motivasi, persepsi dan sikap terhadap keputusan pembelian pada konsumen muslim (study kasus KFC Cabang Jamtos Jambi) Skripsi ini menggunakan pendekatan kuantitatif dengan metode analisis statistik regresi berganda secara parsial dan secara simultan dengan sampel berjumlah 100 konsumen KFC Cabang Jamtos Jambi. Penelitian yang dilakukan diperoleh hasil dan kesimpulan sebagai berikut: Secara parsial variabel independen Motivasi Konsumen (X1), Persepsi Konsumen (X2) dan Sikap Konsumen (X3) berpengaruh terhadap Keputusan Pembelian (Y). Hasil penghitungan secara parsial (uji T) variabel independen Motivasi Konsumen (X1), Persepsi Konsumen (X2) dan Sikap Konsumen (X3) berpengaruh terhadap Keputusan Pembelian (Y). Karena hasil penghitungan nilai T hitung lebih besar dari T tabel yaitu Motivasi Konsumen (X1) 4.187 > 1.984 dan nilai signifikansi 0.000 > 0.05. Persepsi Konsumen (X2) 5.073 > 1.984 dan signifikansi 0.000 > 0.05. Sikap Konsumen (X3) 3.883 > 1.984 signifikansi 0.000 > 0.05, maka Ho ditolak dan Ha diterima. Secara simultan (uji F) menjukkan bahwa F hitung ( 165.546) > F tabel (2.70) dan nilai signifikan (0.000) > (2.70), maka Ho ditolak dan Ha diterima artinya bahwa ada secara bersama-sama atau simultan berpengaruh terhadap Keputusan Pembelian Pengaruh Motivasi, Persepsi dan Sikap Pada Konsumen Muslim. Dan variabel yang paling dominan mempengaruhi keputusan pembelian pada konsumen muslim adalah Persepsi Konsumen

Trait and state effects of Substance Use Disorder on brain structure in ADHD patients

Several studies separately investigated the neurobiology of Attention Deficit Hyperactivity Disorder (ADHD) and Substance Use Disorder (SUD), showing overlapping morphological abnormalities and suggesting shared pathophysiological mechanisms. Little is known about the combined effect of ADHD and SUD on brain morphology and it is unclear to what extent family history (trait) and/or substance non-medical use (state) effects explain the observed overlap. Our aim was to examine the effects of (i) SUD family history (FH) and (ii) substance non-medical use on brain structure in ADHD population and controls. (iii) We also explored if FH density could have different impact on brain morphology. (i) We investigated SUD trait effects on prefrontal cortical thickness (CT) and subcortical volumes (SCV) in ADHD patients and controls with and without FH (ADHD-FH+: n=139; ADHD-FH-: n=86; controls-FH+: n=60; controls-FH-: n=74). (ii) Then, we tested SUD state effects by comparing FH-matched ADHD patients with and without substance non-medical use and controls (ADHD+SNM, ADHD-only and controls, n=68 per group.(iii) Furthermore, we explored whether FH effects were more pronounced in subjects with SUD in both parents (n=63) compared to subjects with one SUD parent (n=105) and without FH (n=160.(i) Trait analysis revealed that there was no main FH effect on prefrontal CT, while the finding of a bigger putamen in FH+ did not survive after correction for multiple comparisons. (ii) In state analyisis, ADHD+SM showed decreased CT in inferior frontal gyrus (IFG) compared to controls, while no difference was found between ADHD-only and ADHD+SM or controls. We did not find any effect of substance use on subcortical volumes. (iii) Subjects with SUD in both parents showed decreased thickness of IFG and volume of nucleus accumbens (NAcc), compared to those with one SUD parent and those without FH. Substance misuse in ADHD might result in smaller IFG, which is in line with findings in SUD-literature. Greater SUD FH density suggests premorbid alterations in inhibitory control and reward networks. Future studies should investigate the potential role of these regions in term of treatment and prevention strategies

Lack of Resilience Is Related to Stress-Related Sleep Reactivity, Hyperarousal, and Emotion Dysregulation in Insomnia Disorder

STUDY OBJECTIVES: According to the diathesis-stress model of insomnia, insomnia may develop in vulnerable individuals in response to stress. Resilience is a psychobiological factor that determines an individual\u27s capacity to adapt successfully to stressful events and low resilience increases vulnerability for development of mental disorders. The aim was to explore resilience in subjects with insomnia and its relationship with the factors that contribute to its development and perpetuation. METHODS: The study consisted of 58 subjects with Insomnia Disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and 38 good sleepers. Resilience Scale for Adults (RSA), Ford Insomnia Response to Stress Test (FIRST), Pre-sleep Arousal Scale (PSAS), and Difficulties in Emotion Regulation Scale (DERS) were administered while taking into account psychiatric symptoms. Differences in means between groups were assessed using t test or Mann-Whitney U/Wilcoxon test. Linear/multivariable regression analyses and mediation analyses were performed. RESULTS: Subjects with insomnia (24 females, mean age 49 ± 2.1 years) had lower RSA and higher FIRST, DERS, and PSAS scores than good sleepers (22 females, mean age 47.2 ± 1.2 years). After controlling for anxiety/depressive symptoms, low resilience correlated with high stress-related sleep reactivity (P = .004), pre-sleep cognitive hyperarousal (P = .01) and emotion dysregulation (P = .01). Emotion dysregulation mediated the relationship between low resilience and cognitive hyperarousal (Z = 2.06, P = .03). CONCLUSIONS: Subjects with insomnia showed low resilience, which was related to high stress-related sleep reactivity, emotional dysregulation, and hyperarousal. If resilience helps to minimize the extent of pathogenesis in the developmental process, an early identification of vulnerable candidates should be useful for preventing insomnia development and maintenance. COMMENTARY: A commentary on this article appears in this issue on page 709

Stress-related sleep reactivity is associated with insomnia, psychopathology and suicidality in pregnant women: preliminary results

INTRODUCTION: Depression and anxiety symptoms are commonly experienced by women during pregnancy and may have negative consequences on mothers and newborns. Deterioration of sleep quality throughout pregnancy increases insomnia, which may lead to adverse outcomes including increased psychopathology in the perinatal period. Thus, identifying women at high risk of developing insomnia may have important clinical implications on maternal-fetal outcomes. Stress-related sleep reactivity is a well-established risk factor for future insomnia, depression, and anxiety in general adult samples. However, little is known of sleep reactivity and its relations to sleep and mood pathology in pregnancy. Therefore, we explored sleep reactivity in pregnant women and its relations to prenatal symptoms of insomnia, depression, anxiety, and suicidality. METHOD: Sixty-two pregnant women (mean age 33.6 ± 3 years, 20.6 ± 0.6 weeks of pregnancy) were evaluated during their routine visit at the Gynecological Unit of the University of Pisa, Italy, using the Insomnia Severity Index (ISI) for insomnia symptoms, the Ford Insomnia Response to Stress Test for sleep reactivity (FIRST), Edinburgh Postnatal Depression Scale (EPDS) for depressive symptoms, and the Zung Self Rating Anxiety Scale (SAS) for anxiety symptoms. Item #10 of the EPDS was used to assess for suicidality. Differences in means between women with high vs low stress-related sleep reactivity were calculated using t-test or Mann-Whitney U/Wilcoxon test. Linear/multiple regression analyses have been performed to study associations between variables. RESULTS: Pregnant women with high stress-related sleep reactivity, relative to those with low reactivity, reported greater symptoms of insomnia (t = 6.5, 0.004) as well as higher rates of depression (62.0% vs 6.1%, p \u3c 0.001), anxiety (55.1% vs 15.1%, p = 0.030), and suicidality (17.2% vs 3.0%, p = 0.025). Multivariate models revealed sleep reactivity to correlate independently with symptoms of insomnia, depression, and anxiety, when controlling for comorbid symptoms. CONCLUSIONS: In mid-pregnancy, women with high sleep reactivity report elevated symptoms of insomnia, depression, and anxiety, and are more likely to endorse suicidal ideation. As a prognostic marker of future insomnia and psychiatric illness, early detection of high prenatal sleep reactivity holds potential to prevent the development of sleep and mood pathology during pregnancy, thereby potentially improving maternal and child outcomes

Comparison of digital PCR systems for the analysis of liquid biopsy samples of patients affected by lung and colorectal cancer

Background and aims: Highly sensitive technologies are available for the molecular characterization of solid tumors, including digital PCR (dPCR). Liquid biopsy, based on the analysis of cell-free DNA (cfDNA), is often used to assess EGFR or RAS alterations in lung and colorectal cancers. Our study aimed to compare the results of two different dPCR platforms for the detection of mutations in cfDNA. Methods: Plasma samples from lung and colorectal cancer patients collected as per routine procedures have been tested. cfDNA Was extracted from plasma, and samples were screened on the droplet digital PCR (ddPCR, BioRad) and solid dPCR QIAcuity (Qiagen). Results: A total of 42 samples were analyzed, obtained from 20 Non-Small Cell Lung Cancer (NSCLC) patients carrying an EGFR or a KRAS mutation on tissue at diagnosis, and from 22 samples of colorectal cancer (CRC) patients, 10 of which presenting a KRAS mutation. EGFR mutation detection was 58.8% for ddPCR and 100% for dPCR (κ = 0.54; 95% CI, 0.37-0.71), compared to tissue results. The detection rate for RAS mutations was 72.7% for ddPCR and 86.4% for dPCR (κ = 0.34; 95% CI, 0.01-0.68), compared to tissue results. Conclusions: This study showed moderate agreement between dPCR and ddPCR. Sampling effect or threshold settings may potentially explain the differences in the cfDNA data between the two different platforms