Psychedelic therapy in depression and substance use disorders.

Psychoactive substances obtained from botanicals have been applied for a wide variety of purposes in the rituals of different cultures for thousands of years. Classical psychedelics from N,N'-dimethyltryptamine, psilocybin, mescaline and various lysergamides cause specific alterations in perception, emotion and cognition by acting through serotonin 5-HT2A receptor activation. Lysergic acid diethylamide, the first famous breakthrough in the field, was discovered by chance by Albert Hoffman in the Zurich Sandoz laboratory in 1943, and studies on its psychoactive effects began to take place in the literature. Studies in this area were blocked after the legislation controlling the use and research of psychedelic drugs came into force in 1967, but since the 1990s, it has started to be a matter of scientific curiosity again by various research groups. In particular, with the crucial reports of psychotherapy-assisted psilocybin applications for life-threatening cancer-related anxiety and depression, a new avenues have been opened in the treatment of psychiatric diseases such as treatment-resistant depression and substance addictions. An increasing number of studies show that psychedelics have a very promising potential in the treatment of neuropsychiatric diseases where the desired efficiency cannot be achieved with conventional treatment methods. In this context, we discuss psychedelic therapy, encompassing its historical development, therapeutic applications and potential treatment effects-especially in depression, trauma disorders and substance use disorders-within the framework of ethical considerations.

Forcibly displaced persons and mental health: A survey of the experiences of Europe-wide psychiatry trainees during their training.

Many European countries have seen increasing refugee populations and asylum applications over the past decade. Forcibly displaced persons (FDPs) are known to be at higher risk of developing mental disorders and are in need of specific care. Thus, specific training for mental health professionals is recommended by international health organizations. The aim of this exploratory study was to assess the experience of clinical work with FDPs among psychiatric trainees in Europe and Central Asia as well as their interest and specific training received on this topic. An online questionnaire was designed by the Psychiatry Across Borders working group of the European Federation of Psychiatric Trainees (EFPT) and was distributed via email through local networks among European trainees from 47 countries between March 2017 and April 2019. Answers of 342 psychiatric trainees from 15 countries were included in the survey analysis. A majority of trainees (71%) had had contact with FDPs in the last year of their clinical work. Although three-quarters expressed a strong interest in the mental health of FDPs, only 35% felt confident in assessing and treating them. Specific training was provided to 25% of trainees; of this subset, only a quarter felt this training prepared them adequately. Skills training on transcultural competencies, post-traumatic stress disorder, and trauma management was regarded as essential to caring for refugees with confidence. Although psychiatric trainees are motivated to improve their skills in treating FDPs, a lack of adequate specific training has been identified. The development of practical skills training is essential. International online training courses could help meet this pressing need.

Relationship of negative symptom severity with cognitive symptoms and functioning in subjects at ultra-high risk for psychosis.

AIM: Negative symptoms and cognition are related with functioning in schizophrenia. However, it is not clear whether they have a similar effect in individuals at ultra-high risk (UHR) for psychosis. In this study, we aimed to explore relationship of negative symptoms with cognition and functioning cross-sectionally in people with UHR for psychosis. METHODS: In total, 107 people participated in this study. We assessed negative symptoms with Scale for Negative Symptoms (SANS). We applied a cognitive battery including seven tests. We evaluated functioning by using Global Assessment of Functioning Scale and work/study status as an indicator of role functioning. RESULTS: SANS scores were correlated to global functioning cross-sectionally. SANS total score was correlated to cognitive test scores related to cognitive flexibility and attention. Only Trail Making Test B (TMT B) was negatively correlated to global functioning. SANS-affective blunting and SANS-avolition scores were independently related to global functioning. There was a significant indirect effect of the TMT B and composite attention scores on global functioning through negative symptoms indicating a complete mediation. CONCLUSION: Our findings suggest that negative symptoms, particularly avolition have an impact on functioning and the association of cognition with functioning was mediated by negative symptoms in UHR.

Lower prepulse inhibition in clinical high-risk groups but not in familial risk groups for psychosis compared with healthy controls.

AIM: Although the lower level of prepulse inhibition (PPI) of the startle response is well known in schizophrenia, the onset of this difference is not clear. The aim of the present study was to compare PPI in individuals with clinical and familial high risk for psychosis, and healthy controls. METHODS: We studied PPI in individuals within three groups: ultra-high risk for psychosis (UHR, n = 29), familial high risk for psychosis (FHR, n = 24) and healthy controls (HC, n = 28). The FHR group was chosen among siblings of patients with schizophrenia, whereas UHR was defined based on the Comprehensive Assessment of At-Risk Mental States (CAARMS). We collected clinical data using the BPRS-E, SANS and SAPS when individuals with UHR were antipsychotic-naïve. A cognitive battery that assessed attention, cognitive flexibility, working memory, verbal learning and memory domains was applied to all participants. RESULTS: PPI was lower in the UHR group compared with both the FHR and HC groups. Those with a positive family history for schizophrenia had lower PPI than others in the UHR group. There was no difference in PPI between the FHR and HC groups. We found no relationship between PPI and cognitive performance in the three groups. Startle reactivity was not different among the three groups. Positive and negative symptoms were not related to PPI and startle reactivity in the UHR group. CONCLUSIONS: Our findings suggest that clinical and familial high-risk groups for psychosis have different patterns of PPI.

Dopamine Agonist-Induced Impulse Control Disorders in Patients With Prolactinoma: A Cross-Sectional Multicenter Study.

CONTEXT: Dopamine agonist (DA)-induced impulse control disorder (ICD) in patients with prolactinomas is not sufficiently known. OBJECTIVE: To evaluate the prevalence of DA-induced ICDs and possible risk factors related to these disorders in patients with prolactinoma. DESIGN, SETTING, AND PARTICIPANTS: This is a cross-sectional multicenter study involving 308 patients with prolactinoma followed up in tertiary referral centers who received at least three months of DA therapy. DA-induced ICDs (pathological gambling, hypersexuality, compulsive shopping, and compulsive eating) and impulsivity were assessed using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson Disease and the Barratt Impulsiveness Scale-11, respectively. Patients were evaluated in terms of parameters related to ICD development. RESULTS: Any ICD prevalence was 17% (n = 51). Hypersexuality was most common (6.5%). Although any ICD and hypersexuality were more common in male patients (P = 0.009, P < 0.001, respectively), compulsive eating was more common in female patients (P = 0.046). Current smoking, alcohol use, and gambling history were more frequent (P = 0.033, P = 0.002, P = 0.008, respectively) in patients with any ICD. In Barratt Impulsiveness Scale-11 total, attentional, motor, and nonplanning scores were higher in patients with any ICD (P < 0.001). Current smoking and alcohol use were more frequent (P = 0.007, P = 0.003, respectively) and percentage increase of testosterone levels at last visit was higher (P = 0.021) in male patients with prolactinomas with hypersexuality. CONCLUSION: Any ICD may be seen in one of six patients with prolactinoma who are receiving DA therapy. Endocrinology specialists should be aware of this side effect, particularly in male patients with a history of gambling, smoking, or alcohol use.

Investigation of the Video-EEG Findings and Clinical Data in Patients Diagnosed With Epilepsy and Psychosis.

BACKGROUND: Studies on electrophysiological characteristics of patients with epilepsy and concomitant psychosis are limited. We aimed to investigate the clinical and video-electroencephalography (EEG) findings of patients with epilepsy-related psychosis (EP). MATERIALS AND METHODS: Fifteen patients diagnosed with EP, assessed at the video-EEG monitoring unit and were under follow-up at both epilepsy and psychiatry clinics, were included. A total of 67 nonpsychotic epilepsy patients, investigated at the video-EEG monitoring unit were randomly selected as the control group and compared statistically with the EP group. RESULTS: In medical history, patients with EP had experienced significantly higher level of status epilepticus (P=0.002) and perinatal cerebral injury (P=0.04), whereas drug-resistant epilepsy was detected at a lower level (P=0.015). With respect to seizure onset zone, the EP group had significantly more seizures of unknown foci, whereas the control group had mostly temporal lobe origin (P=0.0004). EEG findings showed that slow background activity was significantly common among patients with EP (P=0.009). Although only 5 of 15 patients with EP had been operated, 43 of 67 patients had undergone epilepsy surgery (P=0.04) in the control group. However, there was no significant difference between the 2 groups with respect to postoperative seizure control as per Engel classification. CONCLUSIONS: Although our sample size could be considered small, slowed EEG background activity, and the marked frequency of initial precipitant factors such as status epilepticus, perinatal cerebral injury, and detected neuronal autoantibodies suggested that EP is associated with more extensive involvement. EP is not a contraindication for epilepsy surgery, when appropriately investigated preoperatively.

Correlates of Clozapine Use after a First Episode of Schizophrenia: Results From a Long-term Prospective Study.

BACKGROUND: Earlier commencement of clozapine has been related to a better response in treatment-resistant schizophrenia. OBJECTIVES: To identify variables that predict clozapine use after a first episode of schizophrenia (FES). METHODS: Patients with FES and ≤15 days of lifetime antipsychotic treatment were followed up during naturalistic treatment, and the patients who were initiated on clozapine were compared with those receiving non-clozapine antipsychotics for ≥24 months regarding demographic and clinical baseline characteristics, adherence, and relapse patterns during follow-up. Treatment-resistant schizophrenia was defined as two or more antipsychotic trials of adequate dose for ≥6 weeks. RESULTS: Twenty-eight patients who used clozapine and 77 non-clozapine antipsychotic users were included. Clozapine was initiated after a mean of 2.5 ± 1.1 adequate antipsychotic trials. Eight of the 28 clozapine-treated patients (28.6 %) began their clozapine treatment during the first 12 months of follow-up (mean 7.1 ± 3.3 months) and their premorbid childhood adjustment was significantly worse than those who started clozapine later (mean 78.5 ± 43.0 months). Compared with non-clozapine users, patients who started clozapine had significantly more relapses in the first 6 months of follow-up prior to clozapine use (35.7 vs. 11.7 %, p = 0.005), and were significantly more likely to have a first relapse despite treatment adherence (38.1 vs. 73.3 %, p = 0.01). In the multivariate analyses, antipsychotic polypharmacy and first relapse despite adherence to antipsychotic treatment independently predicted subsequent clozapine use. CONCLUSIONS: Clozapine use after a FES was predicted by a first relapse while being adherent to non-clozapine antipsychotics, especially if the first relapse occurred within the first 6 months. Developmental childhood difficulties predicted significantly earlier clozapine use.

History of childhood physical trauma is related to cognitive decline in individuals with ultra-high risk for psychosis.

The aim of this study was to investigate the relationship between childhood trauma (CT) and cognitive functioning in individuals with ultra-high risk for psychosis (UHR). Fifty-three individuals at UHR for psychosis were administered a neurocognitive battery that assessed attention, processing speed, verbal learning, memory, working memory, interference inhibition, and sustained attention. The CT was assessed using the short-version Childhood Trauma Questionnaire (CTQ). We dichotomized the sample by using cut-off scores for the presence of emotional, physical and sexual trauma, and physical and emotional neglect. Those with a history of physical trauma performed worse on the Digit Span Forward test, Trail making B (time), Stroop test (difference between color and word reading times), and completed categories of the Wisconsin Card Sorting Test (WCST). Physical trauma scores were correlated with WCST-completed categories, Digit Span Forward and Stroop test scores. Physical neglect scores were negatively correlated with Digit Span Forward Test scores. Most of the significant dose­response relationships between cognitive impairment and different subtypes of CT were found only in men. There was no difference between those with and without other kinds of childhood abuse or neglect in terms of cognitive impairment. Our findings suggest that a history of physical trauma has a negative impact on cognitive function in individuals at UHR for psychosis.

Delayed initiation of clozapine may be related to poor response in treatment-resistant schizophrenia.

The aim of this retrospective chart-review study was to investigate the relationship between delayed commencement of clozapine and the level of response in treatment-resistant schizophrenia (TRS). We included 162 patients with schizophrenia who used clozapine. The mean delay until starting clozapine after fulfillment of the TRS criteria was 29 months. The delay was shorter in those who gained benefit from clozapine (P=0.04), those who were treated in a specialized psychosis outpatient unit (P=0.01), and in men (P=0.009), and it correlated with age (P<0.001). The delay in starting clozapine and the maximum clozapine dose were independent contributors toward the response to clozapine in the logistic regression analysis. Moreover, of those who gained considerable benefit from clozapine, the patients were younger (P=0.01), the duration of illness before clozapine treatment was shorter (P=0.001), and the numbers of adequate antipsychotic trials before the use of clozapine were fewer (P=0.05). Our findings suggest that efforts aimed at reducing the delay for starting clozapine may increase the effectiveness of clozapine in TRS.

Non-convulsive status epilepticus associated with glutamic acid decarboxylase antibody.

Autoimmune encephalitis associated with glutamic acid decarboxylase antibodies (GAD-Ab) often presents with treatment-resistant partial seizures, as well as other central nervous system symptoms. In contrast to several other well-characterized autoantibodies, GAD-Ab has very rarely been associated with status epilepticus. We report a 63-year-old woman initially admitted with somnolence and psychiatric findings. The EEG findings, of generalized and rhythmical slow spike-wave activity over the posterior regions of both hemispheres, together with the clinical deterioration in responsiveness, led to the diagnosis of non-convulsive status epilepticus. Investigation of a broad panel of autoantibodies, revealed only increased serum GAD-Ab levels. Following methylprednisolone and intravenous immunoglobulin treatments, the patient's neurological symptoms improved, EEG findings disappeared and GAD-Ab levels significantly decreased. GAD-Ab should be added to the list of anti-neuronal antibodies associated with non-convulsive status epilepticus. Disappearance of clinical findings and seroreversion after immunotherapy suggest that GAD-Ab might be involved in seizure pathogenesis.