Daniela Caldirola

Villa San Benedetto Hospital, Albese con Cassano, Lombardy, Italy

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Publications (65)239.48 Total impact

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    ABSTRACT: Background: Two different polymorphisms (TPH2 G-703T and 5-HTTLPR) involved in the serotonergic pathway have been reported to play a role, both alone and in interaction with the environment, in early and adult emotion regulation. As most of these studies are cross-sectional, we know little about the impact of these polymorphisms over time, particularly during adolescence. Methods: Because we were interested in the effects of these polymorphisms and environment (i.e., family structure) at different time-points on the emotional dysregulation profile, we performed a path analysis model in a general adolescent population sample of a five-year follow-up study. Results: We found a high stability of Dysregulation Profile problems independently from the examined allelic variants. We also found that early family structure directly influences the levels of dysregulation problems in early adolescence, both alone and in interaction with TPH2, suggesting the presence of a gene-environment interaction effect. Furthermore, we found that in adolescents homozygous for the TPH2 G allele, the effect of the early family structure remains active during late adolescence, albeit mediated by earlier emotional problems. Limitations: The high attrition rate, the use of only one source on behavioral problems of adolescents, and the focus on a single polymorphism in the investigated genes could limit the generalizability of the present results. Conclusions: These results suggest that early family structure could play a significant role in the development and maintenance of emotional and behavioral problems not only in early adolescence but also in late-adolescence, although this effect was mediated and moderated by behavioral and genetic variables.
    Journal of Affective Disorders 11/2015; 190. DOI:10.1016/j.jad.2015.10.057 · 3.38 Impact Factor
  • Alessandra Alciati · Daniela Caldirola · Diego Foschi · Giampaolo Perna ·

    Journal of Loss and Trauma 08/2015; DOI:10.1080/15325024.2015.1075796 · 1.03 Impact Factor
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    ABSTRACT: Adverse events during childhood, including loss of a parent, are related to a higher risk of adult obesity. We investigated whether childhood parental loss is related to adult rapid weight gain through exposition to a later loss event. We assessed the mediation effect of recent loss and non-loss events on the association between childhood loss and rapid weight gain in 138 individuals seeking bariatric surgery. Our results showed that recent loss events mediate the effect of childhood parental loss on rapid weight gain (0.790; p < .001), suggesting the need for specific programs to prevent and treat obesity in individuals with multiple losses. © The Author(s) 2015.
    Journal of Health Psychology 08/2015; DOI:10.1177/1359105315595451 · 1.88 Impact Factor
  • Daniela Caldirola · Giampaolo Perna ·

    Pharmacogenomics 06/2015; 16(8):1-4. DOI:10.2217/pgs.15.66 · 3.22 Impact Factor
  • Giampaolo Perna · Koen Schruers · Alessandra Alciati · Daniela Caldirola ·
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    ABSTRACT: Introduction: Panic disorder (PD) is a common disabling anxiety disorder associated with relevant social costs. Effective anti-panic medications exist but have several drawbacks. From a clinical perspective, there is still a strong unmet need for more effective, faster acting and more tolerable therapeutic treatments. Areas covered: The authors review the available results on novel mechanism-based anti-panic drugs that are under investigation in animal studies up to Phase II studies. The preclinical studies investigated include: the modulators of the glutamate/orexin/cannabinoid systems, corticotrophin-releasing factor 1 (CRF1)/arginine vasopressine V₁B/angiotensin II receptor antagonists and neuropeptide S. The Phase I/II studies investigated include: the modulators of the glutamate system, isoxazoline derivative, translocator protein (18 kDa) ligands and CRF1/neurokinin receptor antagonists. Expert opinion: There has been little progress in recent times. However, glutamate- and orexin-related molecular targets may represent very promising opportunities for treating panic attacks. Very preliminary findings suggest that the antagonists of CRF1 and A-II receptors may have anti-panic properties. However, new medications for PD are far from being implemented in clinical use. The reasons are multiple, including: the heterogeneity of the disorder, the translational validity of animal models and the insufficient use of biomarkers in preclinical/clinical studies. Nevertheless, biomarker-based strategies, pharmacogenomics, 'personalized psychiatry' and the NIH's Research Domain Criteria approach could help to remove those obstacles limiting drug development.
    Expert Opinion on Investigational Drugs 12/2014; 24(4):1-15. DOI:10.1517/13543784.2014.996286 · 5.53 Impact Factor
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    ABSTRACT: Objectives: There is evidence of baseline respiratory abnormalities in panic disorder (PD), but whether they are specific to PD remains unclear. To investigate this issue, we meta-analyzed results from studies comparing baseline respiratory and hematic variables between subjects with PD and subjects with other anxiety disorders. Methods: A literature search in bibliographic databases was performed. Fixed-effects models were applied. Several moderator analyses and publication bias diagnostics were performed. Results: We found: (1) significantly lower mean end-tidal partial pressure of CO(2) (et-pCO(2)) in subjects with PD than in those with social phobia (SP) or generalized anxiety disorder (GAD), and (2) higher mean respiratory rate, lower venous et-pCO(2) and HCO(3)(-) concentration in subjects with PD than in those with SP. No publication bias was found. Conclusions: Subjects with PD show a condition of baseline hyperventilation when compared to subjects with SP or GAD. Hematic variables suggest that the hyperventilation may be chronic. These results support the idea that baseline respiratory abnormalities are specific to PD pathophysiology. Further studies are needed to clarify whether these abnormalities are related to a malfunction of the respiratory system or to specific cognitive/emotional/behavioral factors in this population.
    Neuropsychobiology 09/2014; 70(1):52-60. DOI:10.1159/000364830 · 2.26 Impact Factor
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    ABSTRACT: In nonclinical samples, childhood trauma (CT) has been found to negatively affect temperament/character traits. In major depressive disorder (MDD) and bipolar disorder (BD), abnormal personality traits have been found to impair clinical course/treatment outcome. Although a link between CT and MDD/BD is firmly established, no previous studies explored the relationship between CT and temperament/character in these populations. We investigated this issue in a preliminary sample of inpatients with MDD (n = 29) or BD (n = 50). We assessed CT (sexual/physical/emotional abuse, physical/emotional neglect) (Childhood Trauma Questionnaire), personality traits (Temperament and Character Inventory-Revised version), and illness severity (Brief Psychiatric Rating Scale). We found significant (p < 0.01) associations between emotional neglect, emotional abuse, physical neglect, and low self-directedness (SD). Potential underlying mechanisms are discussed. Because low SD has been previously associated with illness severity and poor outcome, the relationship between CT and low SD might partly explain the well-known negative impact of CT on course and outcome of MDD/BD.
    Journal of Nervous & Mental Disease 09/2014; 202(9):695-698. DOI:10.1097/NMD.0000000000000186 · 1.69 Impact Factor
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    Giampaolo Perna · Giuseppe Guerriero · Paolo Brambilla · Daniela Caldirola ·
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    ABSTRACT: One of the most influential theories has conceived unexpected panic attack (PA) as a primal defensive reaction to threat within the internal milieu of the body. This theory is based on findings suggesting the involvement of dysfunctional respiratory regulation and/or abnormally sensitive central neural network of carbon dioxide (CO2)/hydrogen ion (H+) chemoreception in PA. Thus, unexpected PA may be related to phylogenetically older brain structures, including the brainstem areas, which process basic functions related to the organism's internal milieu. The brainstem represents a crucial area for the regulation of homeostatic functions, including chemoreception and cardio-respiratory control. In addition, the midbrain dorsal periaqueductal gray may be involved in the unconditioned defense reactions to proximal threats, including internal physical stimuli. Our aim was to specifically consider the potential involvement of the brainstem in panic disorder (PD) by a comprehensive review of the available neuroimaging studies. Available data are limited and potentially affected by several limitations. However, preliminary evidence of a role of the brainstem in PD can be found and, secondly, the brainstem serotonergic system seems to be involved in panic modulation with indications of altered both serotonergic receptors and 5-HT transporter bindings. In conclusion, our review suggests that the brainstem may be involved in psychopathology of PD and supports the relevant role of subcortical serotonergic system in panic pathogenesis.
    CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) 06/2014; 13(6). DOI:10.2174/1871527313666140612112923 · 2.63 Impact Factor
  • Giampaolo Perna · Erika Sangiorgio · Tatiana Torti · Daniela Caldirola ·
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    ABSTRACT: Generalized Anxiety Disorder (GAD) is an anxiety disorder characterized by a state of chronic and excessive anxiety and apprehension for potential negative occurrences. GAD symptoms include hypervigilance, negative anticipation, tension, intolerance of uncertainty and exaggerated worry for a period of at least 6 months. Neuroimaging studies showed that the peculiar features of the anxious experience are related to specific neural structures. This network mainly consists of limbic (e.g. the amygdala), and paralimbic regions (e.g. insula, hippocampus, cingulate cortex, prefrontal cortex), which are involved in vigilance and aversive anticipation processes. In healthy subjects these areas correctly integrate autonomic, sensory, and cognitive information, to create an accurate perception, evaluation and regulation of the internal and external stimuli. However, in individuals with GAD the anatomic and functional connections within this system appear to be disrupted, and this may lead to the pathology. Finally, a neural pattern similar to that observed in GAD patients has been also observed in individuals characterized by an anxious temperament, suggesting that common neuroanatomical structures might be involved both in GAD and anxious temperament.
    New Perspectives on Generalized Anxiety Disorder, Edited by Riccardo Guglielmo, Luigi Janiri, Gino Pozzi, 01/2014: chapter Neuroimaging in Generalized Anxiety Disorder: pages 55-68; Nova Science Publishers., ISBN: 978-1-62948-036-7
  • M. Grassi · D. Caldirola · G. Guerriero · D. Prestia · B. Dal Santo · G. Perna ·

    European Psychiatry 12/2013; 28:1. DOI:10.1016/S0924-9338(13)77050-0 · 3.44 Impact Factor
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    ABSTRACT: This study aimed to investigate 1) the relationship between subjective perception of quality of life (QoL) and clinician-rated levels of psychosocial functioning and 2) the relationship of these indicators with neuropsychological performances, in a sample of 117 subjects with mood and anxiety disorders hospitalized for a 4-week psychiatric rehabilitation program. At the beginning of the hospitalization, QoL and clinician-rated functioning were respectively measured by the World Health Organization Quality of Life Assessment-Brief Form (WHOQOL-BREF) and the Global Assessment of Functioning (GAF) scale, and subjects were administered a neuropsychological battery evaluating verbal and visual memory, working memory, attention, visual-constructive ability, language fluency and comprehension. We did not find any association between WHOQOL-BREF and GAF scores and between cognitive impairment and lower QoL or clinician-rated functioning. Our results suggest that 1) the individuals' condition encompasses different dimensions that are not fully captured by using only clinician-rated or self-administered evaluations; 2) the GAF scale seems unable to indicate the cognitive impairments of our subjects and the WHOQOL-BREF does not appear to be influenced by these deficits. Overall, our findings suggest the need of simultaneously use of multiple assessment tools, including objective evaluations of functioning and different measures of QoL, in order to obtain a more complete clinical picture of the patients. This may allow to identify more specific targets of therapeutic interventions and more reliable measures of outcome.
    Comprehensive psychiatry 12/2013; 55(4). DOI:10.1016/j.comppsych.2013.12.007 · 2.25 Impact Factor
  • Enrica Di Rosa · Daniela Caldirola · Achille Motta · Giampaolo Perna ·
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    ABSTRACT: Objective: Urgency, urinary incontinence and bowel disturbances are distressing side effects that have been observed during treatment with risperidone and other antipsychotics probably due to the receptor affinity profile. This occurrence can lead to poor compliance and therefore impair clinical outcome. Method: We report the case of a 50 year-old lady, who experienced urinary incontinence and diarrhoea, when switching from oral to injectable risperidone, which ceased when discontinuing the drug. Results and conclusions It should be taken into account that some side effects can be revealed when switching from oral to depot formulations due to non-compliance to orals; nevertheless dose-dependent mechanisms and individual metabolic variability must be considered when observing idiosyncratic reactions to drugs.
    Acta Neuropsychiatrica 04/2013; 25(02). DOI:10.1111/acn.12008 · 0.80 Impact Factor
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    ABSTRACT: To investigate the effects of cigarette smoking on neuropsychological performance in patients with mood disorders. One hundred depressed patients with DSM-IV-TR-defined major depressive disorder (n = 61) or bipolar disorder (n = 39), hospitalized for a 4-week psychiatric rehabilitation program, were included. Forty-five were active regular smokers, and 55 were nonsmokers who had never smoked in their lifetime. At the beginning and the end of the hospitalization, patients were administered a comprehensive neuropsychological battery (evaluation of verbal and visual memory, working memory, attention, visual-constructive ability, language fluency, and comprehension) as primary outcome measures and psychometric scales (evaluation of depression and illness severity). Smoking status was assessed by personal interviews. Investigators were blind to the results of neuropsychological tests and to the smoking status of the patients. Data were collected from February 2011 to January 2012. At the beginning of the hospitalization, smokers showed significantly better performance in verbal memory, language fluency, and working memory (all P values < .01) than nonsmokers. No interaction between smoking and diagnosis was found. At the end of the hospitalization, the whole group of patients significantly improved in several cognitive domains, with smokers maintaining significantly better performance in verbal memory, language fluency, and working memory (all P values < .01) than nonsmokers. Our preliminary results indicate a better performance by smokers in verbal memory and working memory domains than by nonsmokers, suggesting that a cognitive enhancement may be associated with nicotine use in depressed patients with MDD or bipolar disorder. Smoking may be a form of cognitive self-medication mediating the association between smoking and mood disorders. Further studies with larger samples are needed.
    The Journal of Clinical Psychiatry 02/2013; 74(2):e130-6. DOI:10.4088/JCP.12m07985 · 5.50 Impact Factor
  • G. Perna · A. Citterio · E. Di Rosa · A. Motta · M. Grassi · D. Caldirola ·
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    ABSTRACT: In patients with Schizophrenia an association between smoking and improvement in cognitive deficits was found. Patients with Major Depressive Disorder (MDD) and Bipolar Disorder (BD) have shown a high prevalence of smoking habit and cognitive deficits but only a few studies have investigated the effect of smoking on their cognitive functions.Objectives To study the effect of nicotine assumption on cognitive function in MDD and BD.Methods50 inpatients with MDD and 50 with BD (Major Depressive Episode) underwent a neuropsychological test battery (Anna Pesenti test, Attentive Matrices, Rey-Osterrieth Complex Figure, Phonemic/Semantic Fluency tests, Token test) at the beginning of their hospitalization. Smoking habit (current, lifetime) was investigated by specific questionnaires. Factorial ANOVA models were applied, with cognitive test scores as dependent variables and smoking (smoker/non-smoker) and diagnosis (MDD/BD) as factors.ResultsSmokers showed significantly better performance in verbal memory (p < 0.001) and fluency tests (phonemic p = 0.012; semantic p = 0.023) than non-smokers. Significant and positive correlations were found between the scores of these tests and the number of cigarettes smoked in the 24 hours before, while no associations with the years of smoking habit were found. No effects of diagnosis or interaction between smoking and diagnosis on the cognitive performance were found.Conclusions Animal models show that nicotine can increase the monoamine levels in brain areas involved in memory and language functions. Our results suggest that the positive effect of smoking on cognitive functions may contribute to increase the smoking habit in patients with Mood Disorders as a self-medication strategy.
    European Psychiatry 12/2012; 27:1. DOI:10.1016/S0924-9338(12)74687-4 · 3.44 Impact Factor
  • D. Caldirola · R. Teggi · E. di Rosa · A. Motta · M. Grassi · G. Perna ·
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    ABSTRACT: A connection between balance system dysfunction and Agoraphobia (AG) in Panic Disorder (PD) has been found. Balance control of many patients with PD and AG rely mainly on visual cues (visual dependence) and moving visual stimuli in their peripheral visual field induce postural instability and anxiety. These features may maintain agoraphobic symptoms after standard treatments.Objectives To study whether balance rehabilitation with moving peripheral visual stimuli would benefit patients with PD and AG not fully responders to standard treatments.Methods Six patients with PD and AG were included. Inclusion criteria: 1) panic-phobic symptoms despite adequate treatments (SSRIs for at least 3 months; cognitive behavioral therapy) and 2) balance dysfunction with instability during peripheral visual stimuli (posturography with and without peripheral visual stimulation).The patients went through 10 sessions (3 sessions/week) of balance rehabilitation: static and dynamic exercises, with movements of eyes and head, during projection of peripheral visual stimuli (video-films, 32 times-accelerated, on large lateral screens). Descriptive and non-parametric analyses were applied.ResultsAfter rehabilitation, the patients showed significant improvement both in panic-phobic symptoms (specific psychometric scale scores) (p < 0.05) and in balance performance (post-rehabilitation posturography with and without peripheral visual stimulation) (p < 0.05).Conclusions Balance rehabilitation with peripheral visual stimuli may increase the efficacy of standard treatments in patients with PD and AG and visual-balance dysfunction. Mechanisms of physical and emotional habituation to environmental destabilizing stimuli may be involved. Further larger and controlled studies are warranted.
    European Psychiatry 12/2012; 27:1. DOI:10.1016/S0924-9338(12)74288-8 · 3.44 Impact Factor
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    ABSTRACT: BACKGROUND: The presence of abnormalities in baseline respiratory function of subjects with panic disorder (PD) is expected according to PD respiratory theories. We aimed to meta-analyze results from studies comparing baseline respiratory and hematic parameters related to respiration between subjects with PD and controls. METHODS: A literature research in bibliographic databases was performed. Fixed-effects models were applied for all parameters while random-effects models only when suitable (at least 10 independent studies). Several moderator analyses and publication bias diagnostics were performed. RESULTS: We found significantly higher mean minute ventilation and lower et-pCO(2) in subjects with PD than controls. Moreover we also found evidences of reduced HCO(3)(-) and PO(4)(-) hematic concentrations, higher indexes of respiratory variability/irregularity and higher rate of sighs and apneas. Evidence of heterogeneity was partly explained by moderator analyses. No relevant publication bias was found. LIMITATIONS: Several shortcomings affected the included studies, such as over-inclusive recruitment criteria, samples unbalanced for socio-demographic characteristics, lack of statistical details and small number of studies available for several parameters. DISCUSSION: Our results support the idea of abnormalities in respiratory function of subjects with PD. Compared to controls, they showed baseline hyperventilation; the results from hematic parameters suggest that hyperventilation may be chronic and not simply caused by their high anxiety levels during respiratory assessment. Evidences of higher variability and irregularity in respiratory patterns of subjects with PD were also found. It is unclear to what extent the higher rate of sighs and apneas may explain the other baseline respiratory abnormalities found in PD.
    Journal of Affective Disorders 10/2012; 146(2). DOI:10.1016/j.jad.2012.08.034 · 3.38 Impact Factor
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    ABSTRACT: Adult patients with panic disorder (PD) show high levels of harm avoidance and anxiety sensitivity. Peculiar temperament profiles and high anxiety sensitivity have been proposed as developmental risk factors for PD in adult age. Since familial-genetic influences play a role both in PD and in anxiety sensitivity and temperament profiles, this study aims to investigate the possible association between family history of PD and peculiar temperament-character profiles or high anxiety sensitivity in offspring of patients with PD. Thirty-four children of patients with PD with/without agoraphobia and 30 children of healthy subjects were compared. Temperament and character dimensions and anxiety sensitivity levels of children were obtained by the Junior Temperament and Character Inventory and the Childhood Anxiety Sensitivity Index. Children of patients with PD and children of healthy subjects differed neither in temperament and character dimensions nor in anxiety sensitivity levels. Our results show that family history of PD is not associated with peculiar temperament and character profiles or high anxiety sensitivity in children, suggesting that these factors may not be early expressions of familial vulnerability to PD. Since the sample is small and the study has a cross-sectional design, longitudinal studies in larger samples are warranted to confirm these findings and to clarify the role of anxiety sensitivity and temperament-character dimensions in the development of PD.
    Psychopathology 07/2012; 45(5):300-4. DOI:10.1159/000335072 · 2.08 Impact Factor
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    Roberto Teggi · Daniela Caldirola · Giampaolo Perna · Mario Bussi ·

    Up to Date on Tinnitus, 12/2011; , ISBN: 978-953-307-655-3
  • Giampaolo Perna · Giuseppe Guerriero · Daniela Caldirola ·
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    ABSTRACT: INTRODUCTION: Panic disorder (PD) is a common anxiety disorder impairing strongly quality of life with high social costs. Effective anti-panic medications exist but a substantial proportion of patients do not fully respond, the available drugs have several side effects and most medications have a delayed onset of their therapeutic effect. Thus, further advances are needed. AREAS COVERED: We review available data on emerging drugs for the treatment of PD including those in development, such as metabotropic glutamate II receptor agonists, D-cycloserine and levetiracetam, and new compounds with potential efficacy that may be relevant for future developments, such as modulators of cholinergic and orexin systems. EXPERT OPINION: To date, the pharmacological research on PD appears to be relatively limited and probably still needs more time before making available new advances beyond the currently used medications. Many reasons may explain these difficulties, including the heterogeneity of the disorder, the incomplete understanding of its underlying pathophysiological mechanisms and difficulties in the selection of appropriate animal models in preclinical studies. Defining biomarkers and endophenotypes in PD may offer advantages in both understanding the pathophysiology of the disorder and selecting appropriate targets and outcomes for planning future pharmacological research.
    Expert Opinion on Emerging Drugs 12/2011; 16(4):631-45. DOI:10.1517/14728214.2011.628313 · 3.06 Impact Factor
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    ABSTRACT: To investigate the possible influence of psychological variables on cardiorespiratory responses and perceived exertion of patients with Panic Disorder (PD) during a submaximal exercise test. Ten outpatients with PD and 10 matched healthy subjects walked up on a treadmill slope at a speed of 4 km/h in order to reach 65% of their maximum heart rate. Cardiorespiratory variables were continuously recorded. Before the exercise, the state and trait anxiety (State-Trait Anxiety Inventory scores), fear of physical sensations (Body Sensation Questionnaire scores), and fear of autonomic arousal (Anxiety Sensitivity Index scores) were assessed; during the exercise, levels of anxiety (VAS-A) and exertion (Borg Scale CR 10) were measured. Compared to controls, patients reached earlier the target HR and the ventilatory threshold, showed lower oxygen consumption, higher HR and lower within-subject standard deviations of HR (a measure of cardiac variability). Exertion was also higher, and there was a significant correlation between breathing frequency, tidal volume and HR. No significant associations were found between cardiorespiratory response, perceived exertion, and psychological variables in patients with PD. Although patients with PD presented poor cardiorespiratory fitness and were required to spend more effort during physical exercise, this did not appear to be related to the psychological variables considered. Further studies with larger groups are warranted.
    Revista Brasileira de Psiquiatria 12/2011; 33(4):385-9. DOI:10.1590/S1516-44462011000400013 · 1.77 Impact Factor

Publication Stats

947 Citations
239.48 Total Impact Points


  • 2011-2014
    • Villa San Benedetto Hospital
      Albese con Cassano, Lombardy, Italy
  • 2001-2009
    • Università Vita-Salute San Raffaele
      • Faculty of Psychology
      Milano, Lombardy, Italy
  • 1992-2002
    • University of Milan
      Milano, Lombardy, Italy