Response to electroconvulsive therapy in elderly patients with late-onset bipolar disorder: The impact of cerebral small vessel disease.

OBJECTIVES: Cerebral Small Vessel Disease (CSVD) is a chronic, progressive vascular disorder that confers increased vulnerability to psychiatric syndromes, including late-life mood disorders. In this study, we investigated the impact of CSVD on electroconvulsive therapy (ECT) outcomes in patients with late-onset bipolar disorder (BD). METHODS: A sample of 54 non-demented elderly patients (≥60 years) with late-onset BD and treatment-resistant major depression, mixed state, or catatonia who underwent bilateral ECT were included in this naturalistic observational study. A diagnosis of CSVD was established based on brain neuroimaging performed before ECT. All patients were evaluated before and after ECT using the Brief Psychiatric Rating Scale (BPRS), the Hamilton Rating Scale for Depression (HAM-D), and the Clinical Global Impression scale (CGI). RESULTS: Of the total sample, 19 patients were diagnosed with CSVD (35.2%). No significant differences were observed at baseline between patients with and without CSVD. Overall, a response was obtained in 66%-68.5% of patients, with remission in 56.2%. No significant differences in ECT outcomes were found between those with and without CSVD, and both groups exhibited substantial improvements in symptom severity following ECT. CONCLUSIONS: The outcome of ECT in late-onset BD was not influenced by the presence of CSVD. This finding aligns with previous research on unipolar depression. Accordingly, ECT should be considered for elderly patients with late-onset BD, regardless of the presence of CSVD.

Development of a self-report screening instrument for emotional dysregulation: the Reactivity, Intensity, Polarity and Stability questionnaire, screening version (RIPoSt-SV).

BACKGROUND: Emotional dysregulation (ED) refers to the inability to manage emotional experiences or expressions hindering goal-oriented behavior. Moderate impairment on at least two domains among temper control, affective lability, and emotional over-reactivity has been proposed to identify ED in adults with attention-deficit/hyperactivity disorder (ADHD). No screening measure designed for use in diverse psychiatric samples exists. We aimed to develop a self-report screening tool for ED based on the 40-item version of the Reactivity, Intensity, Polarity, and Stability questionnaire (RIPoSt-40). METHODS: 150 adult outpatients with non-psychotic conditions were enrolled between February and July 2023 at the Second Psychiatry Unit of Pisa University Hospital. Clinically significant ED (CSED) was defined based on the previously suggested approach for ADHD. Differences between patients with and without CSED were tested. To develop our screening instrument, a decision tree algorithm was trained by hyperparameter tuning through 5-fold cross-validation in 120 subjects and tested on the remaining 30. RESULTS: 75 subjects met criteria for CSED (50 %). CSED was associated with lower age and higher prevalence of psychiatric conditions, including minor mood disorders, ADHD, cannabis use disorders, and eating disorders. We identified a decision tree consisting of six items from RIPoSt-40 that effectively detected CSED, with accuracy, sensitivity, specificity, positive and negative predictive values of 80 % or higher in both the training and testing sets. LIMITATIONS: Tertiary-level; no consensus on criteria; sample size. CONCLUSION: The screening version of the Reactivity, Intensity, Polarity, and Stability questionnaire (RIPoSt-SV) demonstrates promise as a valuable tool for ED screening in clinical settings.

Pseudodementia in Patients with Unipolar and Bipolar Disorders: A Case Series and Literature Review.

Even though pseudodementia has been historically linked to depression, other psychiatric conditions may cause reversible cognitive alterations. The purpose of this study is to improve our understanding of pseudodementia occurring throughout the entire bipolar spectrum. A systematic review was conducted according to PRISMA guidelines. PubMed, Scopus, and Web of Science databases were searched up to March 2023. Fifteen articles on patients with pseudodementia and bipolar disorder (BD), mania, hypomania, or mixed depression have been included. Moreover, seven female patients with mood disorders diagnosed with pseudodementia have been described. According to our research, pseudodementia in patients with BD mostly occurs during a depressive episode. However, pseudodementia has also been observed in the context of manic and mixed states. Psychomotor and psychotic symptoms were commonly associated. The most typical cognitive impairments were disorientation, inattention, and short-term memory deficits. Alterations in neuroimaging were frequently observed. Electroconvulsive therapy and lithium, either alone or in combination with antipsychotics, resulted in the most widely used therapies. Cognitive decline may occur in a substantial proportion of patients. Since pseudodementia can manifest along the entire mood spectrum, it should be taken into consideration as a possible diagnosis in BD patients showing cognitive deficits during manic, mixed, and depressive states.

The impact of mild behavioral impairment on the prognosis of geriatric depression: preliminary results.

Our study aimed to examine how the presence of Mild Behavioral Impairment (MBI) symptoms influenced the outcome of late-life depression (LLD). Twenty-nine elderly (≥ 60 years) depressive patients, including eleven (37.9%) with MBI, were recruited and followed-up on average for 33.41 ±â€…8.24 weeks. Psychiatric symptoms severity and global functioning were assessed, respectively, using the Brief Psychiatric Rating Scale (BPRS) and the Global Assessment of Functioning (GAF) scale. BPRS total score significantly decreased from baseline to follow-up (P < 0.001, d = 1.33). The presence of MBI had no significant effect on mood and cognitive symptoms improvement. On the contrary, while a significant increase in GAF score was observed in patients without MBI (P = 0.001, d = 1.01), no significant improvement of global functioning was detected in those with MBI (P = 0.154, d = 0.34) after 6-month follow-up. The presence of MBI in patients with LLD may negatively affect long-term outcome, slowing or preventing functional improvement.

Type 2 diabetes mellitus is associated with manic morbidity in elderly patients with mood disorders.

The association between mood disorders, especially bipolar disorder (BD), and metabolic disorders, is long known. However, to which extent metabolic disorders affect the course of mood disorders in late life is still open to inquiring. To assess the impact of type 2 diabetes mellitus (T2DM) on late-life mood disorders a retrospective chart review was performed. Elderly depressive patients (≥ 65 years) diagnosed with Major Depressive Disorder (N = 57) or BD (N = 43) and followed up for at least 18 months were included and subdivided according to the presence of T2DM comorbidity. Vascular encephalopathy (39.1% vs. 15.6%, P  = 0.021) and neurocognitive disorders (21.7% vs. 5.2%, P  = 0.028), were more frequently reported in patients with T2DM than in those without. Patients with T2DM showed a greater percentage of follow-up time in manic episodes (r = -0.23, P  = 0.020) and a higher rate of manic episode(s) during follow-up (21.7% vs. 5.2%, P  = 0.028) than those without. When restricting longitudinal analyses to patients with bipolar spectrum disorders, results were confirmed. In line with the well-known connection between BD and metabolic disorders, our data support an association between T2DM and unfavorable course of illness in the elderly with BD.

Revisiting stimulant use for emotional dysregulation in attention-deficit/hyperactivity disorder (ADHD).

INTRODUCTION: Emotional dysregulation (ED) symptoms are present in a considerable portion of patients with attention-deficit/hyperactivity disorder (ADHD). In recent years, an increasing number of studies investigated the effects of stimulant medications on ED in patients with ADHD. AREAS COVERED: A narrative review of the literature on stimulant treatment for ED is provided, including controlled and observational clinical studies conducted on pediatric and adult samples and neurobiological investigations. Positive effects of stimulants on irritability have been demonstrated in children. Comorbidity with disruptive behavior disorders (DBD) and disruptive mood dysregulation disorder does not prevent stimulant effectiveness. Methylphenidate has also been found to reduce temper problems, affective instability, and emotional over-reactivity in adults with ADHD, although with variable effect sizes. A variety of adverse emotional effects have been reported, especially at high doses and in special populations. However, several possible confounders of treatment-emergent ED have been highlighted. Finally, according to neuroimaging studies, stimulants may mitigate emotional processing anomalies associated with ADHD. EXPERT OPINION: The findings are consistent with models including ED within the core features of ADHD. Stimulant treatment should be prioritized over antipsychotics in ADHD-DBD. It remains to be elucidated whether other medications may be more effective in specific populations with ADHD and/or ED.

Mild Behavioral Impairment in Psychogeriatric Patients: Clinical Features and Psychopathology Severity.

The Mild Behavioral Impairment (MBI) concept was developed to determine whether late-onset persistent neuropsychiatric symptoms (NPSs) may be early manifestations of cognitive decline. Our study aims to investigate the prevalence and differentiating features of MBI with respect to major neurocognitive disorders (MNDs) and primary psychiatric disorders (PPDs). A total of 144 elderly patients who were referred to our psychogeriatric outpatient service were recruited. The severity of mental illness was evaluated by means of the Clinical Global Impression Severity scale, the severity of psychopathology was evaluated by means of the Brief Psychiatric Rating Scale (BPRS), and overall functioning was evaluated by means of the Global Assessment of Functioning scale. The sample included 73 (50.6%) patients with PPDs, 40 (27.8%) patients with MBI, and 31 (21.5%) patients with MNDs. Patients with MNDs reported the greatest severity of mental illness, the highest BPRS Total, Psychosis, Activation, and Negative Symptom scores, and the lowest functioning. Patients with MBI and PPDs had comparable levels of severity of mental illness and overall functioning, but MBI patients reported higher BPRS Total and Negative Symptom scores than PPD patients. Patients with MBI frequently reported specific clinical features, including a higher severity of apathy and motor retardation. These features merit further investigation since they may help the differential diagnosis between MBI and PPDs.

Could Temperamental Features Modulate Participation in Clinical Trials?

The prodromal stages of Alzheimer's disease (AD) are the primary focus of research aimed at slowing disease progression. This study explores the influence of affective temperament on the motivation of people with mild cognitive impairment (MCI) and subjective cognitive decline (SCD) to participate in clinical trials. One hundred four subjects with MCI and SCD were screened for participation in pharmacological and non-pharmacological trials. Affective temperament was assessed based on the Temperament Evaluation of the Memphis, Pisa, Paris and San Diego (TEMPS) scale. Demographic variables and temperament subscales scores were compared between MCI and SCD patients and among patients participating in the pharmacological trial, the non-pharmacological trial and refusing participation. Twenty-one subjects consented to participate in the pharmacological trial, seventy consented to the non-pharmacological trial and thirteen refused to participate in any trial. Patients with SCD had greater education and more depressive temperamental traits than those with MCI. While older age, higher education and anxious temperament were negatively associated with participation in the pharmacological trial, irritable temperamental positively predicted pharmacological trial participation. In conclusion, temperamental features may affect the willingness of patients with MCI and SCD to take part in clinical trials and, especially, the choice to participate in pharmacological studies.

Bipolar Disorder and Manic-Like Symptoms in Alzheimer's, Vascular and Frontotemporal Dementia: A Systematic Review.

BACKGROUND: An increased risk of manic episodes has been reported in patients with neurodegenerative disorders, but the clinical features of bipolar disorder (BD) in different subtypes of dementia have not been thoroughly investigated. OBJECTIVES: The main aim of this study is to systematically review clinical and therapeutic evidence about manic syndromes in patients with Alzheimer's disease (AD), vascular dementia (VaD), and frontotemporal dementia (FTD). Since manic-mixed episodes have been associated to negative outcomes in patients with dementia and often require medical intervention, we also critically summarized selected studies with relevance for the treatment of mania in patients with cognitive decline. METHODS: A systematic review of the literature was conducted according to PRISMA guidelines. PubMed, Scopus, and Web of Science databases were searched up to February 2022. Sixty-one articles on patients with AD, VaD, or FTD and BD or (hypo) mania have been included. RESULTS: Manic symptoms seem to be associated to disease progression in AD, have a greatly variable temporal relationship with cognitive decline in VaD, and frequently coincide with or precede cognitive impairment in FTD. Overall, mood stabilizers, and electroconvulsive therapy may be the most effective treatments, while the benefits of short-term treatment with antipsychotic agents must be balanced with the associated risks. Importantly, low-dose lithium salts may exert neuroprotective activity in patients with AD. CONCLUSION: Prevalence, course, and characteristics of manic syndromes in patients with dementia may be differentially affected by the nature of the underlying neurodegenerative conditions.

Psychiatric Symptoms in Patients with Cerebral Endometriosis: A Case Report and Literature Review.

Endometriosis is a systemic medical condition characterized by endometrial tissue that is abnormally implanted in extrauterine sites, including the central nervous system. In this article, we reported the case of a patient with presumed cerebral endometriosis who was diagnosed with bipolar disorder and panic disorder and systematically reviewed the literature for previously reported neuropsychiatric symptoms in patients with cerebral and cerebellar endometriosis. The PubMed, Scopus, and Web of Science bibliographic databases were searched according to the PRISMA guidelines. Seven previous case reports were found and described. While neurological disturbances dominated the clinical picture in the cases retrieved from the literature, our patient represented the first case to show both neurological and psychiatric manifestations. Atypical features of bipolar disorder including chronic mood instability, mixed episodes, and excitatory interepisodic symptoms were highlighted. During the neuropsychological evaluation, a dysexecutive profile consistent with frontal lobe pathology was evidenced. We hypothesized that the course and features of the illness were largely influenced by the presence of documented brain lesions compatible with endometrial implants, especially in the frontal region. Accordingly, patients with endometriosis who exhibit neurological as well as mental symptoms should be investigated for cerebral lesions.

Risk of conversion to bipolar disorder in patients with late-onset major depression.

To evaluate the impact of age at onset on late-life depression course and on risk of conversion to bipolar disorder (BD). A retrospective chart review of 100 elderly patients (age ≥ 65 years) diagnosed with a moderate-to-severe depressive episode and followed up for at least 18 months was conducted. Among patients affected by major depressive disorder ( N = 57), follow-up morbidity differences between those with typical onset depression (TOD) (<60 years) and those with late-onset depression (LOD) (≥60 years) were investigated using Wilcoxon rank-sum test and Cox proportional hazard model. Patients belonging to the LOD group had a significantly lower percentage of follow-up time spent with depressive symptoms compared with patients with TOD ( r = 0.36; P = 0.006), but significantly more time spent with (hypo)manic episodes ( r = -0.31; P = 0.021). Moreover, LOD was significantly associated with a faster conversion to BD (hazard ratio = 3.05; P = 0.037). Depression first emerging in late life may represent an unstable condition with a high risk to convert to BD. Given the potential clinical implications, further studies on the course of LOD are required.

Bipolar Spectrum disorders in Parkinson's disease: a systematic evaluation.

OBJECTIVE: Psychiatric disorders are very common in patients affected by Parkinson's disease (PD). However, comorbidity with Bipolar Spectrum disorders is understudied. The aim of this study is to explore the clinical correlates of PD associated with Bipolar Spectrum disorders. METHODS: One hundred PD patients were screened for psychiatric comorbidities, cognitive profile, motor, and non-motor symptoms. The sample was divided into three groups: PD-patients with Bipolar Spectrum disorders (bipolar disorder type I, type II, and spontaneous or induced hypomania; N = 32), PD-patients with others psychiatric comorbidities (N = 39), PD-patients without psychiatric comorbidities (N = 29). Clinical features were compared among the groups using analysis of variance and chi-square test. A logistic regression was performed to evaluate the association between Bipolar Spectrum disorders and early onset of PD (≤50 years) controlling for lifetime antipsychotic use. RESULTS: In comparison with PD patients with and without other psychiatric comorbidity, subjects affected by Bipolar Spectrum disorders were younger, showed more frequently an early onset PD, reported more involuntary movements and a higher rate of impulse control disorders and compulsive behaviors. No differences were observed in indexes of exposure to dopamine agonist treatments. The early onset of PD was predicted by Bipolar Spectrum comorbidity, independently from lifetime antipsychotic use. CONCLUSION: Bipolar Spectrum disorders are common in early onset PD. The presence of bipolar comorbidity could identify a particular subtype of PD, showing higher rates of neurological and psychiatric complications and deserving further investigation.

Prevalence and Clinical Correlates of Comorbid Anxiety and Panic Disorders in Patients with Parkinson's Disease.

Mood and anxiety disorders are the most common neuropsychiatric syndromes associated with Parkinson's disease (PD). The aim of our study was to estimate the prevalence of lifetime and current anxiety disorders in patients with Parkinson's Disease (PD), to explore possible distinctive neurological and psychiatric features associated with such comorbidity. One hundred patients were consecutively recruited at the Movement Disorders Section of the Neurological Outpatient Clinic of the University of Pisa. According to the MINI-Plus 5.0.0, 41 subjects were diagnosed with lifetime anxiety disorder (22 with panic disorder) and 26 were diagnosed with current anxiety disorders. Patients with anxiety disorders were more frequently characterized by psychiatric symptoms preceding PD, lifetime major depression and antidepressant treatments. They showed more anxious temperamental traits and scored higher at Parkinson Anxiety Scale (PAS) and persistent anxiety subscale. Current anxiety disorders were associated with more severe psychopathology, depressive symptomatology, and avoidant behavior. Among anxiety subtypes, patients with lifetime panic disorder showed higher rates of psychiatric symptoms before PD, lifetime unipolar depression, current psychiatric treatment, and a more severe psychopathology. Given the overall high impact of anxiety on patients' quality of life, clinicians should not underestimate the extent of different anxiety dimensions in PD.

Plasma redox and inflammatory patterns during major depressive episodes: a cross-sectional investigation in elderly patients with mood disorders.

BACKGROUND: While both depression and aging have been associated with oxidative stress and impaired immune response, little is known about redox patterns in elderly depressed subjects. This study investigates the relationship between redox/inflammatory patterns and depression in a sample of elderly adults. METHODS: The plasma levels of the advanced products of protein oxidation (AOPP), catalase (CAT), ferric reducing antioxidant power (FRAP), glutathione transferase (GST), interleukin 6 (IL-6), superoxide dismutase (SOD), total thiols (TT), and uric acid (UA) were evaluated in 30 patients with mood disorders with a current depressive episode (depressed patients, DP) as well as in 30 healthy controls (HC) aged 65 years and over. Subjects were assessed with the Hamilton Depression Rating Scale (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), the Geriatric Depression Rating Scale (GDS), the Scale for Suicide Ideation (SSI), the Reason for Living Inventory (RFL), the Activities of Daily Living (ADL), and the Instrumental Activity of Daily Living (IADL). RESULTS: DP showed higher levels than HC of AOPP and IL-6, while displaying lower levels of FRAP, TT, and CAT. In the DP group, specific correlations were found among biochemical parameters. SOD, FRAP, UA, and TT levels were also significantly related to psychometric scale scores. CONCLUSION: Specific alterations of redox systems are detectable among elderly DP.

Adult attention-deficit hyperactivity disorder and clinical correlates of delayed sleep phase disorder.

The purpose of the study was to assess the prevalence and clinical correlates of Delayed Sleep Phase Disorder (DSPD) in adults with Attention-Deficit/Hyperactivity Disorder. Participants were 102 adults (Female= 27), aged 18-65 (mean age= 28.2 years), with ADHD diagnosed in adulthood. ADHD and DSPD diagnosis were made according to DSM-5 criteria. Assessing instruments included the Morningness-Eveningness Questionnaire, the brief Temperament Evaluation of Memphis, Pisa, Paris and San Diego Questionnaire, the Barratt Impulsiveness Scale, the Reactivity Intensity Polarity Stability Questionnaire-40 and the World Health Organization Disability Assessment Schedule 2.0. Epidemiological and Clinical features were compared in patients with and without DSPD. 34 out of 102 patients were classified as having a Delayed Sleep Phase Disorder. As expected, DSPD patients reported a more frequent evening chronotype. In the multivariate logistic regression analysis, Delayed Sleep Phase Disorder was significantly associated with young age, cannabis use, cyclothymic temperamental traits and severe global impairment. An early diagnosis with a proper treatment targeted to both disorders may be fundamental in order to improve the overall functioning and the outcome of adult ADHD patients.

Mild Behavioral Impairment: presentation of the diagnostic criteria and the Italian version of the MBI-Checklist.

Neuropsychiatric symptoms (NPS) are common in the prodromal stage of dementia and can precede the onset of cognitive impairment. The presence of NPS in cognitively normal patients or in patients with Mild Cognitive Impairment (MCI) is associated with an increased risk of progression along the neurodegenerative process. The need to identify, in the early stages of the disease, the population at risk of cognitive decline has led to the formulation of the concept of Mild Behavioral Impairment (MBI). This neurobehavioral syndrome is characterized by late-onset sustained psychiatric symptoms, in patients without cognitive deficits or in those with MCI, identifying a condition associated with an increased probability of conversion into dementia. MBI represents the neurobehavioral axis of pre-dementia risk states, as a complement to the neurocognitive axis of MCI. For some, MBI may be the initial manifestation of neurodegenerative disease, observed before cognitive impairment is apparent. The Mild Behavioral Impairment-Checklist (MBI-C) was developed on the basis of the MBI diagnostic criteria, established by the International Society to Advance Alzheimer's Research and Treatment (ISTAART). The MBI-C allows to identify, in a standardized way, patients with MBI and to follow the course of their neurodegenerative disease. This article describes the creation of the MBI-C scale and presents its Italian version.