It is hypothesized that factors associated with bipolar disorder could, uer defined conditions, produce adaptive behaviors. The aim is to verify whether a genetic feature associated with bipolar disorder can be found in people without bipolar disorder but with hyperactivity/exploration traits. Healthy old adults (N = 40) recruited for a previous study on exercise were subdivided using a previously validated tool into those with and without hyperactivity/exploration traits and compared with a group of old patients with bipolar disorder (N = 21). The genetic variant RS1006737 of CACNA1C was analyzed using blood samples, DNA extraction, real-time PCR, FRET probes, and SANGER method sequencing. People with hyperactivity/exploration traits and without bipolar disorder were like people with bipolar disorder regarding the frequency of the genetic variant (OR = 0.79, CI95%: 0.21–2.95), but were different from people without either hyperactivity/exploration traits and bipolar disorder (OR = 4.75, CI95%: 1.19–18.91). The combined group of people with hyperactivity/exploration traits without bipolar disorder plus people with bipolar disorder had a higher frequency of the variant than people without either hyperactivity/exploration traits or bipolar disorder (OR = 4.25, CI95%: 1.24–14.4). To consider the genetic profile of bipolar disorder not an aberrant condition opens the way to a new approach in which the adaptive potential would be a central point in psychosocial treatment in addition to drug therapy. Future research can confirm the results of our study.

Background: Studies performed to assess the relevance of duration of untreated psychosis (DUP) as a predictor of long-term outcome (i.e. follow-ups of ten years or more) are somewhat limited. The aim of this study was to evaluate the potential association between DUP and very long-term outcome (16-33 yrs) of schizophrenia by means of a retrospective design. Methods: Retrospective data obtained from clinical records were collected regarding DUP and outcome variables (number of hospitalizations; number of attempted suicides; course of illness; GAF scores at last observation) for a cohort of 80 outpatients (52 Males, 28 Females, mean age 51.0+/-11.58 years) affected by schizophrenia according to DSMIVTR attending a university community mental health centre. Results: Mean duration of follow up was 25.2 +/- 8.68 years; mean duration of untreated psychosis was 49.00 months (range 1-312 mo), with no significant difference according to gender. Patients with a shorter DUP (=/< 1 year) displayed more frequent “favourable” courses of illness (28.9% vs 8.6%) (p = 0.025), more frequent cases with limited (=/< 3) number of hospital admissions (85.7% vs 62.1%) (p = 0.047) and a better functioning (mean GAF score = 50.32+/-16.49 vs 40.26+/-9.60, p = 0.002); regression analyses confirmed that shorter DUP independently predicted a more positive outcome in terms of number of hospital admissions, course of illness, functioning (GAF scores). Conclusion: A shorter DUP appears to act as a significant predictor of better outcome in schizophrenia even in the very long-term.

The aim of this paper is to verify if people with a positive score on the Mood Disorder Questionnaire (MDQ) without comorbidity of mood disorders showed a worse level of Health-related Quality of life (HRQol) compared to a control-matched sample of MDQ negatives, identifying a specific syndrome. This is a case-control study based on a database from a community survey. Cases: MDQ-positive without mood disorders; Controls: MDQ negatives matched by sex, age, and psychiatric diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria. Tools: MDQ, the Advanced Neuropsychiatric Tools and Assessment Schedule (ANTAS) semi-structured interview for psychiatric diagnosis, and the Health Survey Short Form (SF-12) for measuring HRQol. People scoring positive on the MDQ without a diagnosis of mood disorders showed significantly lower scores on the SF-12 compared to people of the same age and of the same sex with an equal diagnosis of psychiatric disorders not related to mood disorders (35.21 ± 6.30 vs. 41.48 ± 3.39, p < 0.0001). In the debate whether a positive score on the MDQ selects an area of “malaise” due to the presence of disorders differing from Bipolar Disorders, or if a positive score on the MDQ may be considered a “subthreshold” form of bipolar disorder in people who may later develop bipolar disorder, a third hypothesis can be advanced, i.e., that a positive score on the MDQ identifies a specific “Dysregulation of Mood, Energy, and Social Rhythms Syndrome” (DYMERS), characterized by a considerable amount of suffering and not attributable to other disorders, and which might represent a trigger for the previously mentioned disorders with which a positive score on the MDQ is associated, probably including, in severe conditions, bipolar disorder.

Background: Cognitive impairment is a frequent consequence of bipolar disorder (BD) that is difficult to prevent and treat. In addition, the quality of the preliminary evidence on the treatment of BD through Cognitive Remediation (CR) with traditional methods is poor. This study aims to evaluate the feasibility of a CR intervention with fully immersive Virtual Reality (VR) as an additional treatment for BD and offers preliminary data on its efficacy. Methods: Feasibility randomized controlled cross-over clinical study, with experimental condition lasting three months, crossed between two groups. Experimental condition: CR fully immersive VR recovery-oriented program plus conventional care; Control condition: conventional care. The control group began the experimental condition after a three months period of conventional care (waiting list). After the randomization of 50 people with BD diagnosis, the final sample consists of 39 participants in the experimental condition and 25 in the control condition because of dropouts. Results: Acceptability and tolerability of the intervention were good. Compared to the waitlist group, the experimental group reported a significant improvement regarding cognitive functions (memory: p = 0.003; attention: p = 0.002, verbal fluency: p = 0.010, executive function: p = 0.003), depressive symptoms (p = 0.030), emotional awareness (p = 0.007) and biological rhythms (p = 0.029). Conclusions: The results are preliminary and cannot be considered exhaustive due to the small sample size. However, the evidence of efficacy, together with the good acceptability of the intervention, is of interest. These results suggest the need to conduct studies with larger samples that can confirm this data. Trial registration: ClinicalTrialsgov NCT05070065, registered in September 2021

This editorial explores the role of hyperactivity and social rhythm dysregulation in bipolar disorder (BD) and related syndromes. Social Rhythm Dysregulation Syndrome (DYMERS) is proposed as a common vulnerability across various disorders, including panic disorder (PD), attention deficit hyperactivity disorder, and post-traumatic stress disorder. A study conducted on a sample of elderly individuals participating in an active aging study investigated whether individuals with PD exhibit higher biological rhythm dysregulation compared to those without PD. The sample, consisting of 119 individuals, revealed that those with a lifetime PD diagnosis scored significantly higher on the dysregulation of biological rhythms scale compared to those without panic disorder. A higher prevalence of depressive episodes was found in individuals with PD at the time of the interview. Notably, a small sample of elderly individuals with panic disorder, voluntarily selected for a physical exercise trial, showed a significantly higher level of dysregulation of social rhythms compared to those without panic disorder. This study opens a debate on the accuracy of paper and pencil screening tests for bipolar disorders, especially regarding false positives in individuals with panic disorder. Our hypothesis is that DYMERS could be a shared vulnerability substrate for various disorders, serving as a basis for bipolar onset in the presence of a hyperactivity profile, even with genetic features. The data collected from older adults suggest that social rhythm dysregulation is a typical feature of PD, regardless of the coexistence of a depressive episode. While the study has limitations due to a small sample size, the findings warrant careful analysis and suggest the need for larger-scale replication studies. If confirmed, the dysregulation of rhythms and its association with depressive disorders highlight a significant area of vulnerability for serious psychopathological disorders, emphasizing the importance of extending research to younger populations.

Bipolar disorder (BD) is a relevant public health issue, therefore accurate screening tools could be useful. The objective of this study is to verify the accuracy of the Mood Disorder Questionnaire (MDQ) and genetic risk as screeners, and their comparison in terms of reliability. Older adults (N = 61, ≥60 years) received a clinical psychiatric evaluation, the MDQ, and were evaluated according to the presence of the genetic variant RS1006737 of CACNA1C. MDQ+ versus the diagnosis of BD as a gold standard shows a sensitivity of 0.286 (Cl 95% 0.14–0.39); a specificity of 0.925 (Cl 95% 0.85–0.08); a predictive positive value (PPV) of 0.667 (Cl 95% 0.33–0.91); and a predictive negative value (PNV) of 0.702 (Cl 95% 0.65–0.75). The positivity for the variant RS1006737 of the CACNA1C against the diagnosis of BD as a gold standard shows a sensitivity of 0.750 (Cl 95% 0.55–0.90); a specificity of 0.375 (Cl 95% 0.28–0.45); a PPV of 0.375 (Cl 95% 0.28–0.45); and a PNV of 0.750 (Cl 95% 0.55–0.90). The reliability between the MDQ+ and positivity for the variant RS1006737 of the CACNA1C was very low (K = −0.048, Cl 95% −0.20–0.09). The study found that both the genetic and the paper and pencil test were quite accurate, but were not reliable in case finding. In fact, despite some validity, albeit specular (in the case of a positive genetic test, the probability of having the disorder is very high, whereas in the case of a negative score on the paper and pencil test, the probability of not having the disorder is very high), the unreliability of the two tests (i.e., they certainly do not measure the same underlying dimension) opens the door to the need for an interpretation and the possibility of a synergistic use for screening. From a heuristic perspective, which obviously requires all of the necessary verifications, this study seems to suggest the hypothesis that a condition of hyperactivation common to disorders and stress conditions, and identified by a positive score on the MDQ (which is common to BD, post-traumatic stress disorder (PTSD), and anxiety disorders and whose genetic basis has not yet been clarified) can trigger BD in people with a predisposition to hyperactivity (i.e., in people with the condition identified by the analyzed genetic variant).