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Early interventions in high-risk population for psychotic disorder target both conversion rates and functional impairments. Existing guidelines (European Psychiatric Association, NICE, Canadian) do not consider drug treatment as the first-line choice, pharmaceuticals mostly complement least restrictive, non-pharmacological approaches (e.g., CBT). Pharmacotherapy can address existing specific symptoms (mood fluctuations, anxiety, subclinical brief or attenuated psychotic symptoms); it is reserved mainly for individuals with more severe symptoms, those that do not respond to psychological treatments or are escalating. There are only a few randomized controlled trials with antipsychotics (olanzapine, risperidone, aripiprazole, ziprasidone, amisulpride), either as a monotherapy or in combination with other interventions. The results did not show a superiority of drug therapy in prevention of transition to psychosis over alternative strategies; long-term antipsychotic treatment with a primarily preventive aim is not generally recommended. Other pharmacological interventions also include experimental drugs or food supplements (omega-3 polyunsaturated fatty acids, cannabidiol, D-serine).
Catatonia is a syndrome of primarily psychomotor disturbances associated with typical abnormalities of muscle tone. It is characterized by the co-occurrence of several symptoms of decreased, increased, or abnormal psychomotor activity. Catatonia is a neuropsychiatric syndrome, not an independent nosological entity. Historically associated mainly with schizophrenia (e.g., catatonic subtype), ICD-11, similarly to DSM-5, now recognizes catatonia under a separate classification category, apart from psychotic disorders. In addition to schizophrenia and other primary psychotic disorders, it can occur in the context of other mental disorders, such as mood disorders, or neurodevelopmental disorders, especially autism spectrum disorder. Catatonia can also develop during or immediately after intoxication or withdrawal from psychoactive substances, including phencyclidine, cannabis, hallucinogens such as mescaline or LSD, cocaine and MDMA or related drugs, or during the use of some psychoactive and non-psychoactive medications (e.g. antipsychotic medications, benzodiazepines, steroids, disulfiram, ciprofloxacin). Moreover, catatonia can occur as a direct pathophysiological consequence of various nonpsychiatric medical conditions, e.g., diabetic ketoacidosis, hypercalcemia, hepatic encephalopathy, homocystinuria, neoplasms head trauma, cerebrovascular disease, or encephalitis. Due to the fact that catatonia was mostly associated witch schizophrenia, many cases were not diagnosed and thus did not receive indicated treatment. There are no specific “anti-catatonic” drugs, first-line treatment are benzodiazepines and ECT, in addition to the symptomatic and supportive therapy. The recognition of catatonia as an independent category in ICD-11 can improve medical care for catatonic patients in clinical practice.
In addition to the global negative impact on mental health of general population, as well as psychiatric patients, Covid-19 pandemic affected significantly research. Initially, lockdowns and restrictions of human contacts temporarily disrupted clinical research activities, but the unprecedented health crisis also provided unique opportunity to study epidemiology of mental disorders, direct and indirect effects of the pandemic on psychiatric disorders, underlying pathophysiological mechanisms, or long-term neuropsychiatric consequences. Research has refocused now on better understanding of the causes, presentations, outcome trajectories, and therapy of mental illnesses. New research topics are followed by the surge in publications covering Covid-19 and mental health and/or psychiatric disorders and treatments. The impact of the pandemic on research and publications is also evidenced by the results of a survey among psychiatric researchers.
Major Depressive Disorder (MDD) is prevalent, often chronic, and requires ongoing monitoring of symptoms to track response to treatment and identify early indicators of relapse. Remote Measurement Technologies (RMT) provide an exciting opportunity to transform the measurement and management of MDD, via data collected from inbuilt smartphone sensors and wearable devices alongside app-based questionnaires and tasks.
To describe the amount of data collected during a multimodal longitudinal RMT study, in an MDD population.
RADAR-MDD is a multi-centre, prospective observational cohort study. People with a history of MDD were provided with a wrist-worn wearable, and several apps designed to: a) collect data from smartphone sensors; and b) deliver questionnaires, speech tasks and cognitive assessments and followed-up for a maximum of 2 years.
A total of 623 individuals with a history of MDD were enrolled in the study with 80% completion rates for primary outcome assessments across all timepoints. 79.8% of people participated for the maximum amount of time available and 20.2% withdrew prematurely. Data availability across all RMT data types varied depending on the source of data and the participant-burden for each data type. We found no evidence of an association between the severity of depression symptoms at baseline and the availability of data. 110 participants had > 50% data available across all data types, and thus able to contribute to multiparametric analyses.
RADAR-MDD is the largest multimodal RMT study in the field of mental health. Here, we have shown that collecting RMT data from a clinical population is feasible.
Maintenance treatment with antipsychotics remains the key principle in the long-term management of psychotic disorders. For some patients, it means life-long use of medication. Continuous drug administration helps to prevent relapses, maintain remission, and achieve functional recovery. Moreover, epidemiological data suggest that antipsychotic treatment significantly reduces mortality rates of schizophrenia patients. On the other hand, some authors argue that antipsychotic drugs may lose its efficacy over time, their long-term exposure results in more harm than benefit. Especially elderly patients are more sensitive to side effects. Several studies which followed-up patient cohorts over the span of several decades found that there are schizophrenia patients who can achieve good functional outcome and full recovery without antipsychotic treatment. Therefore, it is paramount to identify those individuals, particularly among elderly psychotic patients, who can thrive and benefit from timely antipsychotic discontinuation.
The global SARS-CoV-2 pandemic with subsequently imposed restrictions and lockdowns also radically disrupted academic life. Many research projects involving recruitment of human subjects were abruptly put on hold, educational activities have moved into online trainings, scientific meetings have been transformed into virtual events. Social distancing does not restrict only everyday human contact but also limits direct exchange of clinical, educational, and research experiences, professional and academic networking, sharing ideas. Besides all the drawbacks, does the current situation also bring any advantages? Every challenge results in new opportunities. Although the online congresses will most likely never fully replace real-life experience, it was found that many work meetings can be held more efficiently via online communication. Saving time, cutting costs of travel and accommodation, plus other expenses, may help to allocate limited resources where needed. Similarly, while practical medical education and training cannot be substituted for remote broadcasting, many theoretical presentations can. More importantly, epidemic of COVID-19 is a unique opportunity for mental health research, to study individual and population consequences of the virus, its impact on psychiatric patients. It is still early to predict whether and when research, training, meetings, and other academic activities return back to “normal”, but appears that some changes are here to stay.
The United Nations warned of COVID-19-related mental health crisis; however, it is unknown whether there is an increase in the prevalence of mental disorders as existing studies lack a reliable baseline analysis or they did not use a diagnostic measure. We aimed to analyse trends in the prevalence of mental disorders prior to and during the COVID-19 pandemic.
We analysed data from repeated cross-sectional surveys on a representative sample of non-institutionalised Czech adults (18+ years) from both November 2017 (n = 3306; 54% females) and May 2020 (n = 3021; 52% females). We used Mini International Neuropsychiatric Interview (MINI) as the main screening instrument. We calculated descriptive statistics and compared the prevalence of current mood and anxiety disorders, suicide risk and alcohol-related disorders at baseline and right after the first peak of COVID-19 when related lockdown was still in place in CZ. In addition, using logistic regression, we assessed the association between COVID-19-related worries and the presence of mental disorders.
The prevalence of those experiencing symptoms of at least one current mental disorder rose from a baseline of 20.02 (95% CI = 18.64; 21.39) in 2017 to 29.63 (95% CI = 27.9; 31.37) in 2020 during the COVID-19 pandemic. The prevalence of both major depressive disorder (3.96, 95% CI = 3.28; 4.62 v. 11.77, 95% CI = 10.56; 12.99); and suicide risk (3.88, 95% CI = 3.21; 4.52 v. 11.88, 95% CI = 10.64; 13.07) tripled and current anxiety disorders almost doubled (7.79, 95% CI = 6.87; 8.7 v. 12.84, 95% CI = 11.6; 14.05). The prevalence of alcohol use disorders in 2020 was approximately the same as in 2017 (10.84, 95% CI = 9.78; 11.89 v. 9.88, 95% CI = 8.74; 10.98); however, there was a significant increase in weekly binge drinking behaviours (4.07% v. 6.39%). Strong worries about both, health or economic consequences of COVID-19, were associated with an increased odds of having a mental disorder (1.63, 95% CI = 1.4; 1.89 and 1.42, 95% CI = 1.23; 1.63 respectively).
This study provides evidence matching concerns that COVID-19-related mental health problems pose a major threat to populations, particularly considering the barriers in service provision posed during lockdown. This finding emphasises an urgent need to scale up mental health promotion and prevention globally.
Compulsory admission procedures of patients with mental disorders vary between countries in Europe. The Ethics Committee of the European Psychiatric Association (EPA) launched a survey on involuntary admission procedures of patients with mental disorders in 40 countries to gather information from all National Psychiatric Associations that are members of the EPA to develop recommendations for improving involuntary admission processes and promote voluntary care.
The survey focused on legislation of involuntary admissions and key actors involved in the admission procedure as well as most common reasons for involuntary admissions.
We analyzed the survey categorical data in themes, which highlight that both medical and legal actors are involved in involuntary admission procedures.
We conclude that legal reasons for compulsory admission should be reworded in order to remove stigmatization of the patient, that raising awareness about involuntary admission procedures and patient rights with both patients and family advocacy groups is paramount, that communication about procedures should be widely available in lay-language for the general population, and that training sessions and guidance should be available for legal and medical practitioners. Finally, people working in the field need to be constantly aware about the ethical challenges surrounding compulsory admissions.
Investigation of the occurrence of psychotic symptoms in non-psychiatric population may help to identify population at risk of psychosis. The aim of our study was to find out lifetime and current prevalence of psychotic symptoms in the general population of the Czech Republic. Study sample consisted of a stratified population. All participants were administered the Psychosis Screening Questionnaire and the data on psychiatric treatment and diagnosis according to the M.I.N.I. were recorded. In total, 3244 subjects responded (48.1% males and 51.9% females). The most frequently reported symptom was paranoia (7.7%), followed by hypomania (6.2%), strange experiences (5.2%), thought insertion (3.8%), and hallucinations (1.7%). Lifetime prevalence of minimum 1 psychotic symptom was 17.9%. The highest proportion of responders reported only one symptom (13.5%). Significantly more males than females experienced paranoia (p=0.002). In the subset of individuals with a history of at least one psychotic symptom, 70.6% never visited a psychiatrist, 78.9% did not meet diagnostic criteria of psychotic disorder according to the M.I.N.I., and 67.0% failed to have any psychiatric diagnosis at all. The results suggest a high frequency of psychotic experience among the ethnically homogeneous Czech population. Only the longitudinal follow-up could confirm whether the symptomatic subjects are at risk of development of psychotic disorder. More likely, our findings support a hypothesis of the presence of psychiatric symptoms in the general population as a continuum of psychotic spectrum, from normality and sanity through unique psychotic experiences to fully expressed illness.
In the clinical practice, physicians are routinely asked to make decisions whether to initiate or continue antidepressant treatment in a situation where no safety data are available. As an example can serve pregnancy and breast-feeding, where controlled clinical trials provide little guidance. Females of fertile age are rarely included in the early phases of clinical testing, the Phase IIb and III trials have a standard provision to use a reliable contraception. Pregnancy during drug trial is considered as a ‘serious adverse event’ with subsequent study discontinuation. The reasons are not just ethical and legal but also marketing, the drug manufacturers fear to have their products associated with potentially grave side effects, such as malformations. Drug treatment in pregnancy and lactation thus pose a highly relevant clinical problem that cannot be addressed in controlled trials. Excessive concerns of negative consequences could erroneously result in generalizing recommendation not to get pregnant or to abort existing pregnancy. However, fetus may be already exposed to drugs early in the first trimester during frequently unplanned pregnancies; in addition, recent epidemiological data indicate increasing consumption of psychotropics, including antidepressants, by pregnant women. Psychiatrists have to weigh the known risks of treatment discontinuation versus potential risks for the fetus and infant. They should also consider whether alternative non-pharmacological interventions (psychotherapy, ECT, rTMS) are accessible or effective. The only available safety data on antidepressants come from animal studies, epidemiological trials, drug registries, case series, anecdotal case vignettes and clinical observations.
Computer programs are used in rehabilitation of cognitive deficit in schizophrenia. Repetitive transcranial magnetic stimulation (rTMS) can directly affect cortical excitability and metabolism of prefrontal lobe and subsequently affect cognition. The objective of our study was to investigate augmentation of cognitive rehabilitation in schizophrenia with rTMS. Study subjects were stabilized patients with DSM-IV diagnosis of schizophrenia, treated with second-generation antipsychotics, except for clozapine (total N=34). Study with rTMS was double-blind, randomized, placebo-controlled, with 2 parallel arms. All subjects participated in eight-week computer-assisted cognitive training, during first 2 weeks Group 1 (N=8) received rTMS and Group 2 (N=8) inactive sham stimulation. Patients who refused stimulation participated in rehabilitation program only. Data were assessed fo the totatl study sample and for each group separately. The results showed that computer-assisted cognitive training significantly improved severity of cognitive deficit in schizophrenia in many domains, especially executive functions: attention shift – flexibility, attention control, and working memory. The output was faster, more precise, and more reliable. We did not detect to effect of rTMS on the change of cognition, there was no significant difference between active and sham stimulation. This finding can be explained by a significantly lower initial score in Raven test found in actively stimulated group or by a smaller sample size in a double-blind study. The study confirmed efficacy of computer-assisted rehabilitation in remediation of cognitive deficit in schizophrenia.
Supported by the projects IGA MZ CR NF7571-3 and MSMT CR CNS 1M0517
The Czech law related to compulsory hospitalization dates back to 1966, but it has been revised several times. Besides having mental illness as a criterion for compulsory admission, the law requires the criterion that the patient may only be committed to the hospital, if he is an acute danger to himself and/or others. The Czech law does not accept the criterion that patient may be committed, if there is a danger to his health or if his behavior is not accepted to the community. The law does not specify the type of psychiatric illness required for a person to be committed. A patient admitted voluntarily to a psychiatric ward can be subsequently detained if he fulfilled the criteria of the law. The psychiatrist must examine the patient, decide and apply for commitment. The court has to be notified of compulsory admission in period of 24 hours. The detention is decided by judge in seven days. The detention could last up to 3 months then should be reevaluated by court. Appeals or complaints regarding compulsory acts are referred to the court by guardian or patient himself. A competence proceeding and the appointment of a guardian is considered in the case of demented, retarded, and in some cases of psychotic people. At issue is whether such people are capable of managing their own affairs, to make sound judgment-to weigh, to reason, and to make reasonable decision. Incompetence is decided by judge. Expert psychiatric witnesses play a role in determining the level of incompetence. The court appoints a guardian.
Since the introduction of antipsychotic drugs into schizophrenia treatment patients complained feeling ‘fuzzy or dull’, of being ‘unable to think straight’, feeling ‘like a zombie’. All these feelings were labeled as a syndrome of ‘neuroleptic dysphoria’. Patients may even fail to distinguish adverse events from symptoms of illness; they simply classify drugs as ‘good’ or ‘bad’, or alternatively they believe that medication makes their condition worse. Negative impact of side-effects on quality of life was repeatedly confirmed in various studies. The subjective acceptance of medication is becoming increasingly important outcome measure of tolerability in trials of new drugs, naturalistic observational studies and switch studies. Similarly to the quality of life assessment, impact of drugs on patients' well-being, subjective response to treatment, attitude towards medication, or preference of medication can be measured. Variety of side-effects is associated with antipsychotic treatment. Traditionally, most of the attention is being paid to EPS, akathisia, tardive dyskinesia, and lately weight gain, metabolic, endocrinological, or ECG abnormities. However, beyond the usual list, largely overlooked adverse events, such as sedation and somnolence, orthostatic hypotension, sexual side-effects may have more severe and direct impact on patient's well-being. The outcome of illness, including treatment compliance, can be negatively affected by the group of clinically highly relevant but mostly ignored side-effects, including sexual dysfunction. Their incidence in clinical trials and everyday practice, together with their consequences, thus deserve closer scrutiny.
Dysfunction of the serotonin system has been implicated in schizophrenia. 5-HT1A and 5-HT2A serotonin receptors are involved in the action of antipsychotic drugs. A common functional polymorphism (rs6295) in the promoter region of the human 5-HT1A receptor gene has been reported. This polymorphism may be useful in identifying psychopathology and phenotypic characteristics associated with altered function of the human 5-HT1A receptor.
The aim of this study was to determine whether genetic variants for these receptor influence the functional morphological characteristics of brain in schizophrenia.
63 patients with schizophrenia were genotyped for the functional variant in the promoter region of 5-HT1A receptor (rs6295) and for polymorphisms for 5-HT2A (rs6313) and serotonin transporter-SERT (rs4795541). The subjects were investigated by 18fluoro-deoxyglucose (18FDG) positron emission tomography (PET) in the resting state, magnetic resonance imaging (MR) and functional magnetic resonance (fMR) with 2-back test activation paradigm. Voxel-based-morphometry (VBM) was used to detect the differences in the density of grey and white matter. The neuroimaging data were treated by the use Statistical Parametric Mapping (SPM5) with genetic variants as the factor.
The polymorphism in 5-HT1A receptor was associated with the functional morphometric characteristics in cortical regions in projection areas of serotonergic system.
Our findings identify an important genetic factor predicting functional and structural characteristics in schizophrenia. Future research would test the role of HT1A polymorphism in the interaction with 5HT2A and SERT on morphological characteristics within the context of antipsychotic effects.
This research was supported by grant NR9324 (IGA MZCR) and by the project 1M0517 (MSMT).
Progress in neuroimaging contributed greatly to the schizophrenia research, including investigation of the etiological factors. We tested the hypothesis that lack of the normal asymmetry of language activation is familial and that it can be found in both schizophrenic and non-schizophrenic family members. In particular, we wanted to know whether relatives who are supposed to be transmitting liability to the illness also demonstrate the loss of asymmetry of language activation. We studied 5 families with at least two members affected with schizophrenia. Functional imaging (fMRI) was used to study cortical activation during a verbal task in Broca's area and its contralateral homologue in subjects with schizophrenia and their both parents who never manifested any psychotic symptoms but one of them had mother or father with schizophrenia. Schizophrenia patients showed lack of asymmetry of language activation. Parents without schizophrenia among their elderly relatives showed normal asymmetry of language activation. Three of parents who supposedly transmit liability to the illness demonstrated the loss of asymmetry of language activation. Our results suggest that lack of the normal asymmetry of language activation could be one of the inherited etiological factors of schizophrenia.
This work was supported by the research project of the Czech Ministry of Education, CNS 1M0517.
(1) to assess social and functional impairment in schizophrenia outpatients from the Czech and Slovak Republics, and
(2) to examine a relationship between functional impairment and antipsychotic treatment and demographic variables.
Enrolled were schizophrenia outpatients in a stable phase of illness, treated with current antipsychotic medication for a minimum of one month. Recorded were demographic and medication data, administered were Personal and Social Performance Scale (PSP), Subjective Well-being Under Neuroleptics (SWN), and CGI scale.
The total number of study subjects was 926. Most PSP values were within the interval of moderate impairment. Functional performance correlated positively with subjective satisfaction with medication and negatively with symptom severity. Higher education predicted better functioning on PSP. The best performance was associated with a stable relationship and a useful work role. The patients who showed the best level of functioning were more likely to be treated with antipsychotic monotherapy. No difference among drugs in monotherapy was found in subjective satisfaction.
The PSP values of stable schizophrenia outpatients indicated moderate degree of impairment. Improvement of functional capacity remains one of the unmet needs of schizophrenia patients.