Case Report: Long-Acting Oral Cariprazine.

Introduction: Cariprazine is a third-generation antipsychotic, approved for the treatment of schizophrenia and bipolar disorder and used off-label for schizoaffective disorder and treatment-resistant depression. Cariprazine is a partial agonist at dopamine receptors D2 and D3 and serotonin receptor 5HT1A and an antagonist at serotonin receptors 5HT2B and 5HT2A. It is metabolized by CYP3A4 in desmetyl-cariprazine and didesmethyl-cariprazine, both active metabolites with a half-life of 1-2 days and 2-3 weeks, respectively. Case Report: Here we show the cases of 3 outpatients diagnosed with bipolar I disorder (two patients) and schizoaffective disorder (one patients) and characterized by low adherence to treatment, satisfactory cognitive and personal functioning and average disease severity to whom we administered cariprazine as a monotherapy, on a two-times a week schedule (i.e., every 72-96 h). We evaluated response to treatment and disease remission according to conventional definitions, using rating scales BPRS, PANSS and BDI-II. Two-times a week treatment was set either after a disease relapse (one patient), after a sustained remission obtained with daily administration of cariprazine (one patient) or since our first evaluation (one patient). After 4 weeks of treatment all three patients satisfied criteria for response to treatment and remission, a result that was sustained for 8 (in one patients) and 12 months (in other two patients) and still ongoing. Discussion: Reported results support our hypothesis that long half-lives of cariprazine and its metabolites provide an adequate therapeutic response with a two-times a week administration. In selected patients, cariprazine administered as a "oral long-acting" seems effective in treating acute episodes of illness and in sustaining remission, combining advantages of oral and long-acting injectable antipsychotics concerning therapeutic alliance.

Duloxetine in panic disorder with somatic gastric pain.

PANIC DISORDER IS THE MOST COMMON TYPE OF ANXIETY DISORDER, AND ITS MOST COMMON EXPRESSION IS PANIC ATTACKS CHARACTERIZED WITH SUDDEN ATTACKS OF ANXIETY WITH NUMEROUS SYMPTOMS, INCLUDING PALPITATIONS, TACHYCARDIA, TACHYPNEA, NAUSEA, AND VERTIGO: ie, cardiovascular, gastroenterologic, respiratory, and neuro-otologic symptoms. In clinical practice, panic disorder manifests with isolated gastroenteric or cardiovascular symptoms, requiring additional clinical visits after psychiatric intervention. The first-line treatment for anxiety disorders, and in particular for panic disorder, is the selective serotonin reuptake inhibitors. However, these drugs can have adverse effects, including sexual dysfunction, increased bodyweight, and abnormal bleeding, that may be problematic for some patients. Here we report the case of a 29-year-old Caucasian woman affected by panic disorder with agoraphobia who was referred to our clinic for recurrent gastroenteric panic symptoms. The patient reported improvement in her anxiety symptoms and panic attacks while on a selective serotonin reuptake inhibitor, but not in her gastric somatic problems, so the decision was taken to start her on duloxetine, a serotonin-norepinephrine reuptake inhibitor. After 6 months of treatment, the patient achieved complete remission of her gastric and panic-related symptoms, and was able to stop triple gastric therapy. Other authors have hypothesized and confirmed that duloxetine has greater initial noradrenergic effects than venlafaxine and is effective in patients with panic disorder. This case report underscores the possibility of tailoring therapeutic strategies for the gastroenteric expression of panic disorder.

[Approach to bipolar spectrum and subthreshold mood disorders]. / Lo spettro bipolare e le manifestazioni sottosoglia dell'umore.

In the last decades the concept of bipolar disorder was subjected to many revisions. The complexity in diagnosing mood disorders, on the other hand, stems from the problem to delineate the boundary of these morbid conditions. The current nosographic approach is limited by the lack of attention given to the natural course and to the longitudinal and family characteristics of patients suffering of mood disorders. Considering these limits, some authors developed different nosographic models to include other atypical, non-standardized characteristics of mood disorders. However, regardless of the efforts made so far, a gap in classification still remains, putting restrictions in the clinical and neurobiological range of activities.

Distinguishing affective depersonalization from anhedonia in major depression and bipolar disorder.

BACKGROUND: Affective depersonalization has received limited attention in the literature, although its conceptualization may have implications in terms of identification of clinical endophenotypes of mood disorders. Thus, this study aims to test the hypothesis that anhedonia and affective depersonalization represent 2 distinct psychopathological dimensions and to investigate their clinical correlates in patients with major depressive disorder (MDD) and bipolar disorder (BD). METHODS: Using a data pool of 258 patients with mood and anxiety disorders, an item response theory-based factor analysis approach was carried out on 16 items derived from 2 clinical instruments developed in the Spectrum Project (the Structured Clinical Interview for Mood Spectrum and the Structured Clinical Interview for Derealization-Depersonalization Spectrum). Clinical correlates of these psychometrically derived dimensions were subsequently investigated in patients with BD or MDD. RESULTS: Using an item response theory-based factor analysis, a 2-factor solution was identified, accounting overall for the 47.0% of the variance. Patients with BD showed statistically significant higher affective depersonalization factor scores than those with MDD (Z = 2.215, P = .027), whereas there was no between-groups difference in anhedonia scores (Z = 0.825 P = .411). In patients with BD, age of onset of the disease correlated with affective depersonalization factor scores (rho = -0.330, P = .001) but not with anhedonia factor scores (rho = -0.097, P = .361). CONCLUSIONS: Affective depersonalization and anhedonia seem to be 2 distinct psychopathological dimensions, although closely related, bearing the opportunity to identify patients with a specific profile for a better clinical and neurobiological definition.

The spontaneous Ala147Thr amino acid substitution within the translocator protein influences pregnenolone production in lymphomonocytes of healthy individuals.

The de novo production of steroids and neurosteroids begins in mitochondria by the conversion of cholesterol to pregnenolone through cytochrome P450 side-chain cleavage (CYP11A1) enzymatic activity. The C-terminal amino acid domain of the translocator protein (TSPO) has been demonstrated to bind cholesterol, thereby determining its mitochondrial translocation. The goal of the present study was to investigate the effect of the Ala147Thr single-nucleotide polymorphism localized in this TSPO region on pregnenolone production in healthy volunteers. Pregnenolone production was evaluated in a peripheral cell model, represented by circulating lymphomonocytes. First, CYP11A1 expression, both at mRNA and protein level, was demonstrated. Pregnenolone production varied among genotype groups. Comparison of pregnenolone mean values revealed that Thr147 homozygous or heterozygous individuals had significantly lower pregnenolone levels compared with Ala147 homozygous individuals. These findings suggested a dominant effect of the minor allelic variant Thr147 to produce this first metabolite of the steroidogenesis pathway. Interestingly, Ala147 homozygous individuals exhibited significant higher levels of circulating cholesterol-rich low-density lipoproteins with respect to heterozygous individuals. In conclusion, our results demonstrate that the Ala147Thr spontaneous amino acid substitution within TSPO is able to affect pregnenolone production; this should encourage further studies to investigate its potential role in polygenic dyslipidemias.

Clinical correlates of depersonalization symptoms in patients with bipolar disorder.

BACKGROUND: Prevalence and clinical correlates of dissociative symptoms in general, and depersonalization (DP) in particular, in patients with mood disorders have received limited attention in the literature. Nevertheless, the identification of these symptoms may have important implications in terms of a better definition of clinical endophenotypes. Thus, this study aimed at investigating frequency and clinical correlates of dissociative symptoms, with special attention to DP symptoms, in patients with bipolar disorder (BD) looking specifically at differences between BD-I and BD-II and the comorbidity with panic disorder. METHODS: The study sample included 91 adult patients with BD (BD-I=43; BD-II=48) assessed with the Semi-structured Clinical Interview for Temperament (TEMPS-I), the Dissociative Experiences Scale (DES) and the Structured Clinical Interview for Depersonalization-Derealization Spectrum (SCI-DER). RESULTS: There was no difference in lifetime dissociative experiences or DP symptoms between BD-I and BD-II patients. There was no difference in relation to temperament characteristics. Lifetime DP symptoms, as assessed with the SCI-DER, were associated to an early onset of the BD (beta=-0.436, t=-4.572, p<0.001). Derealization symptoms correlated with panic disorder comorbidity (OR=1.22; 95%CI=1.03-1.46, Wald=5.177, p=0.023). CONCLUSIONS: Our study suggests that lifetime DP symptoms are correlated with an early onset of the BD and derealization symptoms with panic disorder comorbidity, bearing the opportunity to identify patients with a specific profile for a better clinical and neurobiological definition.

Different temperament and character dimensions correlate with panic disorder comorbidity in bipolar disorder and unipolar depression.

BACKGROUND: This study aimed to investigate temperament and character correlates of panic disorder (PD) comorbidity in euthymic patients with bipolar disorder (BD) or unipolar depression (UD). METHODS: Temperament and character were assessed using the Temperament and Character Inventory Revised (TCI-R) in 181 patients (70 patients with BD-I, 51 patients with BD-II and 60 with UD) in a euthymic state for at least 2 months. RESULTS: PD was diagnosed in 14.3% of BD-I patients, 31.4% of BD-II and 40% of UD. BD patients with PD, when compared with BD patients without PD, had higher scores on harm avoidance (OR=1.04; 95% CI=1.02-1.07; p=0.002). Patients with UD and PD, when compared to patients with UD without PD, had higher scores on social acceptance (OR=1.27; 95% CI=1.08-1.49; p=0.004). CONCLUSION: Different temperament and character dimensions correlated with PD comorbidity in BD and UD patients, suggesting different underlying pathophysiological mechanisms.

Validity and reliability of the Structured Clinical Interview for Depersonalization-Derealization Spectrum (SCI-DER).

This study evaluates the validity and reliability of a new instrument developed to assess symptoms of depresonalization: the Structured Clinical Interview for the Depersonalization-Derealization Spectrum (SCI-DER). The instrument is based on a spectrum model that emphasizes soft-signs, sub-threshold syndromes as well as clinical and subsyndromal manifestations. Items of the interview include, in addition to DSM-IV criteria for depersonalization, a number of features derived from clinical experience and from a review of phenomenological descriptions. Study participants included 258 consecutive patients with mood and anxiety disorders, 16.7% bipolar I disorder, 18.6% bipolar II disorder, 32.9% major depression, 22.1% panic disorder, 4.7% obsessive compulsive disorder, and 1.5% generalized anxiety disorder; 2.7% patients were also diagnosed with depersonalization disorder. A comparison group of 42 unselected controls was enrolled at the same site. The SCI-DER showed excellent reliability and good concurrent validity with the Dissociative Experiences Scale. It significantly discriminated subjects with any diagnosis of mood and anxiety disorders from controls and subjects with depersonalization disorder from controls. The hypothesized structure of the instrument was confirmed empirically.