Several etiologies can underlie the development of late-onset psychosis, defined by first psychotic episode after age 40 years. Late-onset psychosis is distressing to patients and caregivers, often difficult to diagnose and treat effectively, and associated with increased morbidity and mortality.

The literature was reviewed with searches in Pubmed, MEDLINE, and the Cochrane library. Search terms included “psychosis,” “delusions,” hallucinations,” “late onset,” “secondary psychoses,” “schizophrenia,” bipolar disorder,” “psychotic depression,” “delirium,” “dementia,” “Alzheimer’s,” “Lewy body,” “Parkinson’s, “vascular dementia,” and “frontotemporal dementia.” This overview covers the epidemiology, clinical features, neurobiology, and therapeutics of late-onset psychoses.

Late-onset schizophrenia, delusional disorder, and psychotic depression have unique clinical characteristics. The presentation of late-onset psychosis requires investigation for underlying etiologies of “secondary” psychosis, which include neurodegenerative, metabolic, infectious, inflammatory, nutritional, endocrine, and medication toxicity. In delirium, psychosis is common but controlled evidence is lacking to support psychotropic medication use. Delusions and hallucinations are common in Alzheimer’s disease, and hallucinations are common in Parkinson’s disease and Lewy body dementia. Psychosis in dementia is associated with increased agitation and a poor prognosis. Although commonly used, no medications are currently approved for treating psychosis in dementia patients in the USA and nonpharmacological interventions need consideration.

The plethora of possible causes of late-onset psychosis requires accurate diagnosis, estimation of prognosis, and cautious clinical management because older adults have greater susceptibility to the adverse effects of psychotropic medications, particularly antipsychotics. Research is warranted on developing and testing efficacious and safe treatments for late-onset psychotic disorders.

We aimed to investigate the association between very late-onset schizophrenia-like psychosis (VLOSLP), a schizophrenia spectrum disorder with an onset of ≥60 years, and Alzheimer’s disease (AD) using biomarkers.

Retrospective cross-sectional study.

Neuropsychology clinic of Osaka University Hospital in Japan.

Thirty-three participants were classified into three groups: eight AD biomarker-negative VLOSLP (VLOSLP−AD), nine AD biomarker-positive VLOSLP (VLOSLP+AD), and sixteen amnestic mild cognitive impairment due to AD without psychosis (aMCI−P+AD) participants.

Phosphorylated tau levels in the cerebrospinal fluid and 18F-Florbetapir positron emission tomography results were used as AD biomarkers. Several scales (e.g. the Mini-Mental State Examination (MMSE), Wechsler Memory Scale-Revised (WMS-R) Logical Memory (LM) I and II, and Neuropsychiatric Inventory (NPI)-plus) were conducted to assess clinical characteristics.

Those in both VLOSLP−AD and +AD groups scored higher than those in aMCI−P+AD in WMS-R LM I. On the other hand, VLOSLP+AD participants scored in between the other two groups in the WMS-R LM II, with only VLOSLP−AD participants scoring significantly higher than aMCI−P+AD participants. There were no significant differences in sex distribution and MMSE scores among the three groups or in the subtype of psychotic symptoms between VLOSLP−AD and +AD participants. Four VLOSLP−AD and five VLOSLP+AD participants harbored partition delusions. Delusion of theft was shown in two VLOSLP−AD patients and five VLOSLP+AD patients.

Some VLOSLP patients had AD pathology. Clinical characteristics were different between AD biomarker-positive and AD biomarker-negative VLOSLP, which may be helpful for detecting AD pathology in VLOSLP patients.

Delusional disorder (DD) is defined by the presence of one or more delusions, of at least one month’s duration, in the absence of prominent hallucinations or other symptoms of schizophrenia. Although functioning may not be markedly impaired, the delusion(s) or its ramifications may have a significant impact in the patient’s life. With a life-time prevalence of 0.18%, DD is still neglected in terms of approved treatment recommendations.

We present the case of a patient diagnosed with DD and discuss the treatment of DD according to current evidence.

Relevant clinical information was extracted from the patient’s clinical process. A non-systematic review was made in Pubmed database with the terms “Delusional Disorder” and “Treatment”.

Male, 76 years old, divorced, living alone, autonomous. First admitted at age 62 in our inpatient psychiatry ward for a persecutory delusion regarding his neighbors. He was discharged with the diagnosis of DD and started a follow-up in a mental health community team. He abandoned treatment and psychiatric consultation after 9 years. During 17 years he moved home more than 10 times due to a progressive dynamism of the delusion, leading to recent marked behavior changes towards his neighbors. He is again admitted in our inpatient psychiatry ward.

This case illustrates the impact that untreated DD can have on its patients. Although consensus using antipsychotics, there are still insufficient studies to make evidence-based recommendations to treat people with DD. Further research is needed in this sense.

No significant relationships.

Electroconvulsive therapy (ECT) is a medical treatment for those patients with high suicide risk or refractory psychiatric disorders. It is currently a safe technique, and its effectiveness has been widely demonstrated.

Presentation of a clinical case about a patient with drug-resistant delusional disorder and high suicide risk, who eventually received ECT treatment.

Bibliographic review including the latest articles in Pubmed about ECT procedure, effects and use.

We present a 45-year-old man, who visited different doctors several times by reporting he had the feeling of “having a brain tumor or a vascular disorder”, so he requested imaging tests (computed tomography and magnetic resonance). These tests were absolutely normal, but he kept thinking something was wrong, and eventually attempted suicide by hanging (his family founded him before it was too late). The patient was admitted to hospital, and started psychopharmacological treatment, with minimal response. He desperately insisted that he had “something inside his head”. At this point, it was proposed to start ECT, and the patient accepted. After 6 bilateral ECT sessions, he was visibly more relaxed and less worried, and he no longer presented autolytic ideation. He was still a little bit suspicious about the feeling of having a neurological disease. Currently, the patient runs a follow-up consultation.

Electroconvulsive therapy is a safe and effective technique for those patients with high suicide risk. It may be useful to perform imaging tests in certain cases, for detecting intracranial pressure, acute hemorrhage, tumors… A follow-up of these patients must be performed

No significant relationships.

Hypochondria is characterized by the presence, for 6 months or more, of a generalized and non-delusional concern with fear of having (or the idea that one has) a serious illness, based on the wrong interpretation of the symptoms. In somatic-type delusional disorder, the delusional idea is fixed, indisputable, and occurs intensely because the patient is fully convinced of the physical nature of the disorder.

To describe a clinical case and make a differential diagnosis of hypochondriac disorder vs somatic-type delusional disorder.

Case report: 61-year-old woman, after suffering from COVID-19, develops a hypochondriacal disorder vs. somatic delusional disorder, presenting anxiety-depressive symptoms and digestive somatic complaints, with a loss of 15 kg of weight. She made frequent visits to doctors and multiple complementary tests discarding organicity. She required involuntary hospital admission for 48 days, and pharmacological treatment with Venlafaxine 150 mg, Olanzapine 5mg, Mirtazapine 30mg and Alprazolam 1mg. The patient presented slow evolution during admission, with ups and downs and stagnation, meriting enteral nutrition due to refusal to ingest, given abdominal kinesthetic hallucinations and digestive evaluation (EDS) with a result of antral gastritis and negative H. pylori. In subsequent follow-ups after partial remission of symptoms, obsessive personality traits are glimpsed, although with better personal functioning.

The diagnosis at discharge was inconclusive, however the data points to a somatic-type delusional disorder.

The influence of COVID-19 as a triggering factor, social isolation and premorbid personality traits, influence the development of a Somatic Delusional Disorder vs Hypochondriac Disorder, regarding this case.

No significant relationships.

Ekbom syndrome is a clinical term for delusional parasitosis, a condition characterized by the belief that one’s skin is infested by invisible parasites. Despite having no medical evidence, patients strive to prove their illness and interpret different sensations and symptoms as infestation with parasites.

Our objective was to present a case report of a patient with Ekbom syndrome with detailed clinical information and treatment complications.

We included patient’s history, psychiatric evaluation, complete diagnostic work-up, therapy and follow-up.

A 60-years old female patient was admitted to her first hospital treatment in our psychiatric clinic. Upon admittance, she was extremely tense, preoccupied with the idea that bed bugs have infested her body. She showed extensive medical documentation, including numerous dermatologic reports regarding her condition, interpreting them in accordance with her delusions. In attempt to help herself and “release” the bugs, she harmed herself causing multiple skin lesions across her body and face. The treatment was complicated with secondary skin infections, ulcers, cellulitis and oedemas. Initial treatment with olanzapine was switched to risperidone due to side-effects (sedation, increase of appetite, weight gain). Gradually, with pharmacological treatment, psychoeducation and support, remission was achieved, but poor insight to her previous condition and psychiatric symptoms remained.

Ekbom syndrome presents a serious disorder that can be complicated with secondary somatic complications, often requiring involvement of different medical specialists. Moreover, lack of insight into the need for psychiatric treatment can lead to therapy discontinuation and relapse of symptoms.

No significant relationships.

Delusional idea disorders are a group of syndromes whose main or unique characteristic is the presence of consolidated delusional ideas that usually have a chronic character and do not fit into other diagnoses such as schizophrenia, affective disorder or other organic diseases. On the other hand, Charles Bonnet syndrome is an organ hallucinosis in whose context visual hallucinations may appear in patients with a visual deficit. Historically, it has been considered that the presence of another psychiatric condition is an exclusion criterion for the diagnosis of Charles Bonnet syndrome, although the presence of similar etiological and maintenance factors means that this situation of dignous exclusion must be reconsidered.

The objective of the present communication is to study the current state of the topics “delusional disorder” and “Charles Bonnet syndrome”. Another objective is to reconsider that the presence of previous or concurrent psychiatric pathology is an exclusion criterion for the diagnosis of Charles Bonnet syndrome..

A bibliographic review on “delusional ideas disorder” and “Charles Bonnet syndrome” has been carried out, as well as a discussion on the diagnostic and exclusion criteria, based on the etiopathogenic and maintenance factors.

Both in “delusional ideas disorder” and in “charles bonnet syndrome” advanced age, social isolation and deficiencies in sense organs constitute etiological factors that facilitate the appearance of these syndromes and make their treatment difficult.

Due to this, we consider that the appearance of another previous or present psychiatric illness should not be an exclusion criterion, both can appear in the same patient.

No significant relationships.

Delusional disorder (DD) is a psychotic disorder with an estimated prevalence of less than one percent,traditionally characterized by systematized delusional ideas with no cognitive deterioration.However, some studies have been reporting impairment of neurocognitive system (social cognition,learning and memory, expressive language,complex attention, executive function) that might have an impact functionality both in social and work domains..

This work aims to review clinical evidence on self-perceived functional impairment or disability in DD and to present two clinical cases evaluated at a psychiatric unit.

We report two clinical cases based on patients’ history and clinical data, and reviewed clinical records using PubMed® database with search terms of “Delusional Disorder”,“Cognition Impairment in Persistent DD”.

We present two clinical cases of patients who were admitted to psychiatric unit after developing psychotic symptoms namely persecutory delusions about neighbors.A persistent delusional disorder was established and antipsychotic treatment was initiated.The 74-years-old men presented deficits in executive and memory processes; ended up institutionalized after two months of being discharged.The 47-years-old woman, despite remaining as a lawyer, noticed a decrease in work capacity and so she ended up being responsible for less demanding cases.Cases of delusional disorder showed a poor performance in most cognitive tests and some of the cognitive deficits seem to affect functionality namely memory, expressive language and attention.

Although classical literature has not systematized an association between DD and personality deterioration,there are some evidences of loss of functionality and cognitive commitment in this disorder.This suggests the importance of cognitive interventions to improve functional prognosis in this clinical population.

No significant relationships.

States compatible with “Delusional disorder” have been described since the XIX century. Esquirol mentioned “irrational ideas and actions that would develop via logical and plausible arguments”; Kraepelin referred to the condition as “paranoia” and considered that hallucinations could not be present– unlike Bleuler, who considered them to be a possible feature. The criteria for delusional disorder have suffered several changes in the last centuries.

We aim to review the evolution of the criteria for delusional disorder across the editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM).

Review of DSM editions.

Criteria for the diagnosis of “paranoia” (DSM III) or “delusional disorder” (DSM III-IV.V) underwent several changes. In the first editions hallucinations could not be prominent (DSM-III-IIIR) and in the DSM IV, only tactile or olfactory hallucinations related to delusions could be present. In DSM-V hallucinations of other modalities related to the delusional theme can be present. Regarding delusional themes, the first edition of the DSM III regarded persecutory delusions only – which was changed in the DSM-III-R, with the inclusion of grandiose, jealous, erotomaniac, and somatic. Only in the DSM-V did the occurrence of bizarre delusions become possible in delusional disorder. Across the editions, there is a consensus about the absence of negative symptoms, absence of disorganized speech, and that the behavior is not odd aside from delusional content.

The most debatable symptoms across centuries in the classification of delusional disorders were: presence of hallucinations, the nature of the delusional content, and inclusion of bizarre delusions.

No significant relationships.

The influence of sexual hormones on mental disorders have been extensively reported. In fact, recent studies suggest that sex hormones may play a relevant role in the pathophysiology of psychosis, may be a precipitant when exogenously administered or even be used as a treatment agent of psychotic disorders.

To describe the case of a patient with a recent diagnosis of delusional disorder (DD) with an onset in the perimenopausal period.

Case report and narrative review focused on the impact of sexual hormones on depressive symptoms and alcohol use comorbidity during perimenopause in DD women by using PubMed database.

Case report: A 48-year-old woman diagnosed with DD. The clinical assessment of climacteric symptoms, as well as the gonadotropins (elevated levels of follicle-stimulating hormone -FSH- and luteinizing hormone -LH-) and estrogen levels monitoring (variations on 17-β-estradiol -E2-) enabled to link the endocrine changes with the onset and course of the psychiatric disorder. During the development of the disease, the patient also presented comorbid depressive symptoms and alcohol use disorder. Review: Estrogen depletion seems to increase the risk of psychosis, while scientific literature is not conclusive in establishing a definitive relationship between depressive symptoms and hormonal imbalance in DD. Alcohol use disorder is a common comorbidity in both perimenopausal women and patients with DD.

Multiaxial management of the case helped clinicians to achieve clinical stabilization. Sex differences as well as hormonal pattern disturbances should receive special attention due to the seminal implications in pharmacotherapy and clinical outcomes.

No significant relationships.

A delusion of parasitosis is defined as the fixed, false belief of infestation by invisible organisms or fibrous material of unknown origin. The differential diagnosis is true infection, substance use disorder, dementia or other neuropsychiatric disease.

Our goal was to characterize delusions of parasitosis, classically named Ekbom syndrome, among individuals attending our emergency department (ED).

Over a four-year period (2017-2020), we carried out a retrospective case-register study of patients with DSM-5 Ekbom syndrome attending an ED that provides mental health services to an area of nearly 450.000 inhabitants in Sabadell (Barcelona, Spain).

There were 13 eligible patients: 7 were diagnosed for the first time and 6 had multiple episodes. Female-to-male ratio was 1.6:1; average age was 56.9. The most common diagnosis was delusional disorder (n=5;8.5%), followed by schizophrenia (n=3;23.1%) and organic disorders (n=2;15.4%). Origin: Africa (n=5;38.5%), South-America (n=4;30.8%) and Spain (n=4;30.8%). Fifty percent showed poor treatment compliance. Antipsychotics used: risperidone (n=8;61.54%), olanzapine (n=4;30.8%). Five patients received antidepressants. Most patients had previously been seen by other medical specialties (internal medicine, dermatology and hematology). ‘’Match box sign’’: 7 patients (53.8%). Cerebral atrophy was present on brain scan in 4 patients. After discharge: acute psychiatric unit (n=7), outpatient appointments (n=4), day hospital (n=1) and 1 to a psychogeriatric unit.

Delusions of parasitosis are rare in our emergency department. The typical patient is a postmenopausal woman, a visitor or immigrant to Spain. Effective treatment requires a focus on cultural, gender, and age aspects, with close cooperation between psychiatry and other relevant specialties.

Current definitions for delusional disorder (DD) state that no cognitive or functional impairment is present. However, this assumption lacks empirical validation and has been questioned by numerous authors over the years. Through systematic search we collected articles that compare patients with DD with either healthy controls or patients with schizophrenia on the basis of their cognitive symptoms and their functional outcomes.

Our aim is to draw conclusions from the available evidence on neurocognitive and functional affectation of DD.

Systematic electronic search was performed using Pubmed and Embase databases. Inclusion criteria included that selected articles must be original studies, must be published in peer-reviewed journals, must contain a sample of DD patients that is compared with a sample of healthy controls and/or patients with schizophrenia and that samples must be compared on the basis of cognitive and/or functionality parameters. A qualitative synthesis was performed due to heterogeneity in data.

According to the information collected through our systematic review, DD patients tend to perform worse than healthy control in tests assessing cognitive functions. Results are not as conclusive regarding comparison between DD and schizophrenia, with mixed outcomes. When it comes to functionality, results are not conclusive either, with some degree of evidence pointing towards a better functioning in patients with DD in comparison to patients with schizophrenia.

Results agree with many authors who consider both conditions as part of a psychosis spectrum. Cognitive interventions, such as cognitive remediation, must be studied for their potential role in the treatment of patients with DD.

Paranoia querulans is a type of persistent delusional disorder of the persecutory subtype, recognized under ICD-10 and DSM-IV. Being a classically described entity, evidence is lacking from its conceptualization as a nosological entity to diagnosis and treatment. Furthermore, controversy still exists regarding its interplay between the judicial and mental health systems.

To summarize current evidence and knowledge regarding Paranoia querulans on its conceptualization, ethiopathological explanations, therapeutical management and interface between psychiatry and the law.

A systematic review was undertaken between June and October 2020 in the PubMed, Web of Science and Scopus databases according to PRISMA directive. Key-terms: ((querul* OR vexatious) AND (paranoia OR delusio* OR neuros* OR behavi* OR complai*) OR litig*) AND psychiatry. No language or time restrictions were established.

A total of 1648 studies were initially identified (PubMed: 679; WOS: 945; Scopus: 24; other: 0); after duplicates were removed, n=1381 studies remained. After screening title and abstract, 56 studies were included. Their main content was categorized into: 1. Conceptualization (n=26): Neurosis (n=5), psychosis (n=9), behavioral disorder (n=5); no psychiatric diagnosis (n=7). 2. Descriptive psychopathology (n=8) 3. Etiopathogenesis (n=9): Social or personality basis (n=3), culture (n=4), trauma (n=1), cognitive decline (n=1) 4. Management (n=1) 5. Psychiatry and Law: same object, different objectives (n=12)

There is controversy regarding the nosological entity of querulousness, from psychosis to neurosis or behavioral disorders. Some authors consider this behavior to not be a psychiatric diagnosis. Furthermore, most papers dealt with a social or nurture-based origin. There is a dearth of information regarding treatment.

JPE has received CME-related fees from Lundbeck.

Over the last decades, antipsychotic plasma levels have been used to evaluate therapeutic response, adherence and safety of antipsychotics in schizophrenia. Their clinical utility in delusional disorder (DD) has been poorly studied.

To investigate the relationship between plasma concentrations of risperidone (R), 9-OH-risperidone (9-OH-R) and olanzapine (OLZ), and clinical outcomes in DD.

Case-series of inpatients and outpatients with DD receiving treatment with risperidone (n=19) or olanzapine (n=2). Determination of R, 9-OH-R (active metabolite) and OLZ levels were obtained by high-performance liquid chromatography with electrochemical detection. Clinical variables such as treatment response or adverse events were recorded for all patients. These variables were correlated with two plasmatic ratios in patients treated with R: R:9-OH-R concentration ratio and total concentration-to-dose (C: D) ratio, indicating CYP2D6 activity and R elimination respectively.

Twenty-one patients were included: inpatients (n=10) and outpatients (n=11). Dose range: R, 1-6 mg/day; OLZ, 5-10 mg/day. Three outpatients (R, n=2; OLZ, n=1) presented antipsychotic levels under the detection limit (non-adherence). All R patients showed CYP2D6 activity (R: 9-OH-R ratio <1). Eight patients presented C: D > 14, indicating a reduction of R elimination, which was associated with poor clinical response (n=3), adverse events (n=3) and no clinical relevance (n=2). OLZ (n=2), no association between levels and clinical outcomes.

The determination of antipsychotic plasma levels may be of clinical utility in the assessment of treatment resistance, antipsychotic-adverse events or non-adherence in inpatients or outpatients with DD. Therapeutic drug monitoring should be further studied in future works.

AGR has received honoraria, registration for congresses and/or travel costs from Janssen, Lundbeck-Otsuka and Angelini.

Prevalence rates of panic attacks have been reported to be around 24-63% in psychotic patients. Common underlying biological substrates for panic and paranoia have been proposed, suggesting that delusional disorder (DD) may be preceded by the development of anxiety disorders.

The main objective of this study was to investigate anxiety comorbidity in DD. As a second objective, we set ourselves to know prescription rates for the use of antidepressants and benzodiazepines in anxiety disorders in the context of DD.

A systematic literature search was performed using PubMed (1980- September 2020) according to the PRISMA guidelines. The following search terms were used: (delusional disorder) AND (anxiety OR anxiety disorder OR anxi*). Research studies and case reports were included if they met the following criteria: DD diagnosis (DSM, ICD), publication in peer-review journal and investigations containing information on anxiety comorbidity in DD.

Four studies fulfilled our criteria, including 155 patients: 65 (42%) women, mean age 42.7 years (SD:14.96). Thirty-three of the 155 patients (21.29%) presented at least one comorbid anxiety disorder: 14 specific phobias, 9 panic attacks, 5 social phobias and 2 agoraphobias. Treatment was not reported for many patients (n= 28). Four patients received fluoxetine and 1 patient benzodiazepines. All of them showed partial improvement of symptoms.

Less than a third of DD patients showed an anxiety disorder. The effectiveness of antidepressant and benzodiazepine treatment has been poorly described. Future studies may be focused on the investigation of preceding comorbid anxiety disorders in patients with DD.

Several neuroimaging studies on psychosis spectrum have been published in the last decades, most of them based on schizophrenia. In the context of neuroanatomical dysfunctions, clinical and prognosis implications have been reported. Nevertheless, only a few studies have been focused on delusional disorder (DD).

To present the case of a patient diagnosed with DD who suffered from two cerebrovascular events after the onset of the psychiatric disease. Our aim is to elucidate potential implications of those lesions on the course of DD. We also reviewed the literature to assess evidence for specific changes in DD on brain structures and functions.

Case report and non-systematic narrative review in PubMed (2000-2020).

Case report: A 66-year-old female with DD presenting, during the course of the disease, general atrophy and consecutive ischemic lesions on parietal, occipital and cerebellar areas. Clinical stabilization was achieved 12-16 months after risperidone 1.5mg/day treatment. Review: 19 studies were included: Structural brain data (n=15), Functional data (n=13). Most of the structural neuroimaging studies reported white and gray matter abnormalities, particularly in temporal, parietal and frontal lobes, and in limbic structures. Functional neuroimaging studies pointed to temporal and parietal lobes, as well as basal ganglia and limbic related structures.

Temporal, parietal, frontal, basal ganglia and limbic-related structures, as well as dysfunctions in other specific brain regions, may be implicated in the core symptoms of DD. These findings might be further investigated as potential neuroimaging markers of prognosis, such as partial or delayed response to antipsychotic treatment, as presented in our case.