Symptoms and lifetime treatment experiences in psychotic patients with and without substance abuse

The main objective of this study was to compare symptom load and lifetime treatment experiences between psychotic patients with substance abuse problems and psychotic patients without substance abuse problems. This is a cross-sectional study of 48 patients (26 inpatients and 22 outpatients) in a clinic for early intervention in psychosis. Patients’ were grouped into two categories based on whether they had a substance abuse problem or not. Twenty-one (43.8%) had a substance abuse problem and 27 (56.2%) had not. We used the Positive and Negative Symptom Scale (PANSS) scale to measure symptoms and several scales to measure substance abuse. Parametric tests (independent t-tests) were used to compare continuous variables, and chi-square tests were used to compare frequencies. Positive symptoms, negative symptoms, general psychopathology symptoms and the total score of psychotic symptoms did not differ significantly between the groups with psychosis alone and psychosis with substance abuse. The delusion subscore was significantly higher in the group with psychosis alone (t=?2.3, df=41, P<0.05), and the anxiety subscore was significantly higher in the group with psychosis with substance abuse (t=?2.3, df=41, P<0.05). There were no significant differences in the subscores for negative symptoms. The absence of differences in psychotic symptoms between the two groups with psychosis does not imply a strong relationship between psychotic symptoms and substance abuse. These results do not support the self-medication hypothesis. The higher rates of institutionalization among substance abusers may be explained by mechanisms other than exacerbations of psychotic symptoms, as there are few differences in symptoms among abusers and non-abusers.     

Sensation/novelty seeking in psychotic disorders: A review of the literature

The evaluation of personality traits is important for the better understanding of the person suffering from psychosis and for treatment individualization. However literature on patients’ personality and character in such disorders is limited. The aim of this review was to summarize the literature on sensation/novelty seeking (SNS), a trait which is biologically based and highly heritable and is associated with dopamine activity, and refers to a person’s tendency to seek varied, novel, complex, and intense sensations and experiences. A total of 38 studies were included in this review, involving 2808 patients and 2039 healthy controls. There is consistent evidence that this trait is independently associated with alcohol and substance abuse in patients with schizophrenia and related disorders. The estimation of SNS would help clinicians to identify patients at risk for abuse. There is also some evidence that higher SNS levels may relate to medication non-adherence and seem to increase the risk of patients’ aggressive and violent behavior, but studies are scarce. SNS was found not to be related to suicidality, whereas in the fields of patients’ quality of life and psychopathology results are contradictory, but most studies show no possible association. Several studies suggest that SNS is lower in psychotic patients compared to controls, whereas most yield no differences. The evidence for this trait as a potential endophenotype of schizophrenia is weak. SNS may be implicated in psychotic disorders’ course and prognosis in several ways and should be always inquired for. This trait can be reliably measured with the use of easily applicable self-rated instruments, and patients’ accounts could inform clinicians when planning management and delivering individualized treatment.     

Efficacy and safety of anti-inflammatory agents in treatment of psychotic disorders – A comprehensive systematic review and meta-analysis

ObjectiveAntipsychotic effects of immunomodulating drugs have been suggested; however, a thorough, comprehensive meta-analysis on the effect and safety of anti-inflammatory add-on treatment on psychotic disorders is lacking.MethodMultiple databases were searched up until February 2020. Only double-blinded, randomized, placebo-controlled clinical trials (RCTs) were included. Primary outcomes were change in total psychopathology and adverse events. Secondary outcomes included, amongst others, positive and negative symptoms, general psychopathology and cognitive domains. We performed random-effects meta-analyses estimating mean differences (MD) and standardized mean differences (SMD) for effect sizes.ResultsSeventy RCTs (N = 4104) were included, investigating either primarily anti-inflammatory drugs, i.e. drugs developed for immunomodulation, such as NSAIDs, minocycline and monoclonal antibodies (k = 15), or drugs with potential anti-inflammatory properties (k = 55), e.g. neurosteroids, N-acetyl cysteine, estrogens, fatty acids, statins, and glitazones. Antipsychotics plus anti-inflammatory treatment, compared to antipsychotics plus placebo, was associated with a PANSS scale MD improvement of -4.57 (95%CI = -5.93 to -3.20) points, corresponding to a SMD effect size of -0.29 (95%CI = -0.40 to -0.19). Trials on schizophrenia (MD = -6.80; 95%CI, -9.08 to -4.52) showed greater improvement (p < 0.01) than trials also including other psychotic disorders. However, primarily anti-inflammatory drugs (MD = 4.00; 95%CI = -7.19 to -0.80) were not superior (p = 0.69) to potential anti-inflammatory drugs (MD = 4.71; 95%CI = -6.26 to -3.17). Furthermore, meta-regression found that smaller studies showed significantly larger effect sizes than the larger studies (p = 0.0085), and only 2 studies had low risk of bias on all domains. Small but significant effects were found on negative symptoms (MD = -1.29), positive symptoms (MD = -0.53), general psychopathology (MD = -1.50) and working memory (SMD = 0.21). No differences were found regarding adverse events, but only 26 studies reported hereon.ConclusionsAnti-inflammatory add-on treatment to antipsychotics showed improvement of psychotic disorders; however, no superiority was found in primarily anti-inflammatory drugs, raising the question of the mechanism behind the effect, and treatment effect might be overestimated due to the large number of small studies.     

Altered relationships between age and functional brain activation in adolescents at clinical high risk for psychosis

Schizophrenia is considered a neurodevelopmental disorder, but whether the adolescent period, proximal to onset, is associated with aberrant development in individuals at clinical high risk (CHR) for psychosis is incompletely understood. While abnormal gray and white matter development has been observed, alterations in functional neuroimaging (fMRI) parameters during adolescence as related to conversion to psychosis have not yet been investigated. Twenty CHR individuals and 19 typically developing controls (TDC), (ages 14–21), were recruited from the Center for Assessment and Prevention of Prodromal States (CAPPS) at UCLA. Participants performed a Sternberg-style verbal working memory (WMem) task during fMRI and data were analyzed using a cross-sectional design to test the hypothesis that there is a deviant developmental trajectory in WMem associated neural circuitry in those at risk for psychosis. Eight of the CHR adolescents converted to psychosis within 2 years of initial assessment. A voxel-wise regression examining the relationship between age and activation revealed a significant group-by-age interaction. TDC showed a negative association between age and functional activation in the WMem circuitry while CHR adolescents showed a positive association. Moreover, CHR patients who later converted to overt psychosis showed a distinct pattern of abnormal age-associated activation in the frontal cortex relative to controls, while non-converters showed a more diffuse posterior pattern. Finding that age related variation in baseline patterns of neural activity differentiate individuals who subsequently convert to psychosis from healthy subjects suggests that these differences are likely to be clinically relevant.     

Gender differences in symptoms, functioning and social support in patients at ultra-high risk for developing a psychotic disorder

Gender differences have been widely observed in the clinical presentation, psychosocial functioning and course of illness in first-episode and chronic patients suffering from schizophrenia. However, little is known about gender differences in the psychosis prodrome. This study investigated gender differences in symptoms, functioning and social support in individuals at ultra-high-risk for developing a psychotic disorder. Sixty-eight ultra-high-risk patients were assessed at baseline, and twenty-seven returned for follow-up assessments approximately 6 and 12 months later. Clinical symptoms and functioning were assessed by clinical interview; social support was measured using a self-report questionnaire. There were no gender differences in demographic variables, symptoms or functioning at baseline. Males were found to have significantly higher levels of negative symptoms and marginally lower levels of functioning when baseline and follow-up time points were considered collectively. Additionally, females reported higher levels of social support at baseline. Differences in negative symptoms were found to mediate differences in functioning between male and female patients. This study suggests that gender based differences in symptom presentation and functional outcome may predate conversion to psychosis. Follow-up studies should examine the relationship between symptoms, functioning and social support in this population.     

Risk factors for completed suicide in schizophrenia and other chronic psychotic disorders: a case-control study

OBJECTIVE: Despite an increased risk for suicide among individuals diagnosed with psychotic disorders, risk factors for completed suicide remain largely unexamined in this population. Using a case-control design, this study aimed to investigate clinical and behavioural risk factors for suicide completion in schizophrenia and other chronic psychotic disorders. METHOD: A total of 81 psychotic subjects were examined; of these, 45 died by suicide. Proxy-based interviews with, on average, 2 informants were conducted using the SCID I and II interviews and a series of personality trait assessments. RESULTS: Psychotic individuals at risk for suicide are most readily identified by the presence of depressive disorders NOS, moderate to severe psychotic symptoms and a family history of suicidal behaviour. They also exhibited fewer negative symptoms, had more comorbid diagnoses and, contrary to findings in other populations, we found that cluster A and C personality trait symptoms seem to have protective effects against suicide in schizophrenics and other chronic psychotic suicides. CONCLUSIONS: Our study suggests that behavioural mediators of suicide risk, such as impulsive-aggressive behaviours, do not play a role in schizophrenic and chronic psychotic suicide. This is contrary to findings in other diagnostic groups, thus implying heterogeneity in predisposing mechanisms involved in suicide.     

Early childhood and adolescent risk factors for psychotic depression in a general population birth cohort sample

Background and purpose

In the group of severe mental disorders, psychotic depression (PD) is essentially under-researched. Knowledge about the risk factors is scarce and this applies especially to early risk factors. Our aim was to study early childhood and adolescent risk factors of PD in a representative birth cohort sample with a follow-up of up to 50 years.

Methods

The study was carried out using the Northern Finland Birth Cohort 1966 (NFBC 1966). We used non-psychotic depression (NPD) (n = 746), schizophrenia (SZ) (n = 195), psychotic bipolar disorder (PBD) (n = 27), other psychoses (PNOS) (n = 136) and healthy controls (HC) (n = 8200) as comparison groups for PD (n = 58). We analysed several potential early risk factors from time of birth until the age of 16 years.

Results

The main finding was that parents’ psychiatric illness [HR 3.59 (1.84–7.04)] was a risk factor and a high sports grade in school was a protective factor [HR 0.29 (0.11–0.73)] for PD also after adjusting for covariates in the multivariate Cox regression model. Parental psychotic illness was an especially strong risk factor for PD. The PD subjects had a parent with psychiatric illness significantly more often (p < 0.05) than NPD subjects. Differences between PD and other disorder groups were otherwise small.

Conclusions

A low sports grade in school may be a risk factor for PD. Psychiatric illnesses, especially psychoses, are common in the parents of PD subjects. A surprisingly low number of statistically significant risk factors may have resulted from the size of the PD sample and the underlying heterogeneity of the etiology of PD.

     

Neurobiological underpinnings and modulating factors in schizophrenia spectrum disorders with a comorbid substance use disorder: A systematic review

Recently there is a growing interest in the interaction of schizophrenia spectrum disorders (SSD) and substance use disorders (SUD), a condition named dual schizophrenia spectrum disorders (SSD+). While previous research has focused on clinical and cognitive aspects, little is known about the impact of comorbidity in the brain structure and functions. Evidence suggests that dual diagnosis patients, including SSD+, show a better neurocognitive functioning during the first years of illness, followed by a serious long-term decline. The initial search retrieved 94 articles, 12 were excluded for being redundant and 49 for not fulfilling the selection criteria. Thirty-three structural and functional neuroimaging studies that compare SSD and SSD+ patients were included. Both groups exhibited more brain alterations, in comparison to only SUD patients and healthy controls. SSD+ patients are less cognitively and emotionally impaired than non-dual SSD, but worse than healthy controls. The neurobiological alterations are prominent in SSD+ after five years of illness or longer. Moreover, SUD characteristics are important modulating factors, contrary to clinical severity or specific SSD diagnosis.     

利培酮口服液合用氯硝西泮与氟哌啶醇针剂肌内注射治疗精神分裂症急性激越症状疗效和安全性的研究

目的 比较利培酮口服液合用氯硝西泮与氟哌啶醇针剂肌内注射(以下简称肌注)对精神分裂症急性激越症状的疗效和安全性,以及由氟哌啶醇肌注换利培酮口服(以下简称换药组)对急性期疗效的影响.方法 205例伴有急性激越症状的精神分裂症患者按随机数字表方法分为利培酮口服液组(104例)和氟哌啶醇肌注组(101例).研究分为急性激越症状疗效评价(治疗前5 d)和换药后急性期疗效评估(治疗6周)2个阶段.以阳性和阴性症状量表兴奋因子(PANSS-EC)及阳性和阴性症状量表(PANSS)总分作为主要疗效评价指标.安全性评估采用锥体外系副反应量表(Simpson-Angus Rating Scale,SAS)和静坐不能评定量表(Barnes Akathisia Scale,BAS)评定锥体外系症状、记录不良事件和实验室检查.结果 治疗前5 d利培酮口服液组和氟哌啶醇肌注组的急性激越症状都有明显改善(P＜0.01),2组间疗效差异无统计学意义(P＞0.05);利培酮口服液组合作程度好于氟哌啶醇肌注组(P＜0.05),锥体外系不良反应低于氟哌啶醇肌注组(P＜0.05).由氟哌啶醇肌注换利培酮口服后,治疗6周末口服组和换药组疗效及总体不良事件发生率比较差异均无统计学意义(P均＞0.05),但锥体外系不良反应换药组高于口服组,差异有统计学意义(P＜0.05).结论 利培酮口服液合用氯硝西泮口服治疗精神分裂症急性激越症状与氟哌啶醇肌注疗效相当,但利培酮口服液合作程度好,锥体外系不良反应发生率低.由氟哌啶醇肌注换利培酮口服对急性期疗效无明显影响.     

Nerve growth factor in never-medicated first-episode psychotic and medicated chronic schizophrenic patients: possible implications for treatment outcome

Nerve growth factor (NGF) has been found to play a crucial role in the neuroplasticity of predominantly cholinergic neurons in brain development, and neuronal survival following brain injury, which reflect in cognitive performance. Wide ranges of neurodevelopmental abnormalities have been reported in schizophrenic patients, who also show poor cognitive performance. We report plasma NGF levels in never-medicated first-episode psychotic (FEP; N=24) and chronic medicated schizophrenic patients (N=24). NGF levels were determined in plasma by Enzyme-Linked ImmunoSorbent Assay (ELISA). Plasma NGF levels were significantly lower in both FEP and medicated chronic patients as compared to normal subjects (P<0.001). However, NGF levels were significantly higher in chronic schizophrenic patients, which were treated with antipsychotics as compared to FEP (P<0.05). Moreover, NGF levels in chronic patients treated with atypical antipsychotics were markedly higher as compared to patients treated with typical antipsychotics (P<0.05). Lower NGF levels in FEP patients at the onset of psychosis may have implications for the neurodevelopmental abnormalities. However, higher NGF levels in chronic patients treated with atypical antipsychotics may have implications for the treatment outcome.     

Antiepileptic drugs in the treatment of psychiatric disorders

The clinical interface between psychiatry and neurology is epilepsy; the pharmacological expression of this interface is antiepileptic drugs (AEDs), as they are used to treat both epilepsy and psychiatric disorders, especially bipolar disorders. The prevalence of psychiatric comorbidity and the risk of suicidal behavior/ideation/suicide are markedly increased in patients with epilepsy (PWE). Though AEDs receive initial indications for the treatment of epilepsy, currently the majority of AEDs are used to treat pain and psychiatric disorders. Thus in selecting the appropriate AEDs for treatment of PWE, consideration should be given to which AEDs best treat the epileptic disorder and the psychiatric comorbidity. This review is an overview of 21 AEDs in which negative psychotropic properties, approved indications in psychiatry, off-label studied uses in psychiatry, and principal uses in psychiatry are presented with literature review. A total of 40 psychiatric uses have been identified. Of the 21 AEDs reviewed, only 5 have U.S. Food and Drug Administration and/or European Medicines Agency psychiatric approval for limited uses; the majority of AEDs are used off-label. Many of these off-label uses are based on case reports, open-label studies, and poorly controlled or small-sample-size studies. In some instances, off-label use persists in the face of negative pivotal trials. Further placebo-controlled (augmentation and monotherapy) parallel-arm research with active comparators is required in the complex field of AED treatment of psychiatric disorders to minimize the treatment gap not only for PWE with psychiatric disorders, but also for psychiatric patients who would benefit from properly studied AEDs while minimizing adverse effects.     

Cannabinoids and psychotic symptoms: A potential role for a genetic variant in the P2X purinoceptor 7 (P2RX7) gene

To investigate the biological mechanisms underlying the higher risk for psychosis in those that use cannabis, we conducted a genome-wide environment-interaction study (GWEIS). In a sample of individuals without a psychiatric disorder (N = 1262), we analyzed the interactions between regular cannabis use and genotype with psychotic-like experiences (PLE) as outcome. PLE were measured using the Community Assessment of Psychic Experiences (CAPE). The sample was enriched for those at the extremes of both cannabis use and PLE to increase power. A single nucleotide polymorphism in the P2RX7 gene (rs7958311) was associated with risk for a high level of psychotic experiences in regular cannabis users (p = 1.10 x10^-7) and in those with high levels of lifetime cannabis use (p = 4.5 × 10^-6). This interaction was replicated in individuals with high levels of lifetime cannabis use in the IMAGEN cohort (N = 1217, p = 0.020). Functional relevance of P2RX7 in cannabis users was suggested by in vitro experiments on activated monocytes. Exposure of these cells to tetrahydrocannabinol (THC) or cannabidiol (CBD) reduced the immunological response of the P2X7 receptor, which was dependent on the identified genetic variant. P2RX7 variants have been implicated in psychiatric disorders before and the P2X7 receptor is involved in pathways relevant to psychosis, such as neurotransmission, synaptic plasticity and immune regulation. We conclude that P2RX7 plays a role in vulnerability to develop psychotic symptoms when using cannabis and point to a new pathway that can potentially be targeted by newly developed P2X7 antagonists.     

Prevalence and risk factors for tardive dyskinesia: a study in an Italian population of chronic schizophrenics

Summary The aim of this study was to evaluate tardive dyskinesia (TD) (prevalence and possible risk factors, pharmacological and clinical), in a population of schizophrenic patients after prolonged institutionalization. A total of 148 patients (80 male, 68 female) aged between 28 and 87 years (mean 55, SD 11) diagnosed according to DSM III were included in the study and assessed for the presence and severity of TD using the Abbreviated Rockland Simpson Scale for TD. Of the examined population, 32% were found to be affected by TD. Patients over 55 years had a relative risk of TD that was 2.3 times higher than in subjects under 55 (P<0.05). The most frequent movements were orofacial (60%) and in the extremities (56.4%). No significant relationship between duration of neuroleptic treatments, illness or hospitalization, anticholinergic drugs and TD prevalence was found. Severity was related to age, since there was a positive linear relationship between age and Simpson Scale scores (r=0.45,P<0.01).     

Prevalence and risk factors for suicidal ideation in a multiple sclerosis population

Objective

To estimate the prevalence, incidence and determinants of suicidal ideation in the multiple sclerosis (MS) population.

Methods

A sample of 188 subjects were randomly selected from a community-based MS clinic registry and participated in as many as 13 interviews over 6 months. Thoughts of “being better off dead” or of “harming oneself” were assessed using item 9 on the Patient Health Questionnaire, Brief (PHQ-9).

Results

At baseline, the 2-week period prevalence of suicidal ideation was 8.3%. Over the course of 6 months, 22.1% of respondents reported having such thoughts at least once. Survival analysis incorporating baseline PHQ-8 scores as a covariate confirmed that being age 65 and over (HR = 4.3, 95% CI 1.7–11.3) and having lower quartile self-efficacy ratings (HR = 3.5, 95% CI 1.5–8.2) predicted suicidal ideation. Lower levels of task-oriented coping (treated as a continuous variable) also predicted suicidal ideation after adjustment for depressive symptoms (p = 0.015), as did self-reported bladder or bowel symptoms (HR = 2.6, 95% CI 1.1–6.0) and difficulties with speaking and swallowing (HR = 2.9, 95% CI 1.3–6.8). Associations with MS symptoms were not confounded by depressive symptoms.

Conclusion

This study identified several potentially modifiable factors that may be useful for preventing suicide in people with MS.     

A 12-month comparison of brief psychodynamic psychotherapy and pharmacotherapy treatment in subjects with generalised anxiety disorders in a community setting

Little information is available on the use of brief psychotherapy among subjects with generalised anxiety disorder (GAD) within community mental health services. This study compared results among subjects treated with brief Adlerian psychodynamic psychotherapy (B-APP), those treated with medication (MED), or those who experienced combined treatment (COM). Symptomatology and occupational functioning were assessed using the Hamilton Anxiety and Depression scales (HAM-A; HAM-D), Clinical Global Impression (CGI), and Social and Occupational Functioning Assessment Scale (SOFAS) at intake (T1) and at 3, 6, and 12 months later (T3, T6, T12). The study sample included 87 patients with GAD (B-APP 34; MED 33; COM 20), and an ANOVA was applied for analysing repeated measures while controlling for personality disorder. After 6 months, CGI, HAM-A, HAM-D, and SOFAS scores significantly improved independently from the type of treatment. Subjects with personality disorders treated with B-APP exhibited superior results to those treated using other methods only in SOFAS scores at T6. These results were generally maintained at T12. Remission rates among subjects (HAM-A scores <7) varied between 55% (MED) and 74% (B-APP) at T6 and between 63% (MED) and 78% (COM) at T12; no significant differences appeared between the three treatment groups. A logistic regression model predicted anxiety remission only by CGI at T1. This paper discusses these results in relation to the use of brief psychotherapy within community mental health services.