Course Of Schizophrenia Spectrum Disorders Research Articles

The association of childhood trauma with depressive and negative symptoms in recent onset psychosis: a sex-specific analysis.

Childhood trauma may impact the course of schizophrenia spectrum disorders (SSD), specifically in relation to the increased severity of depressive or negative symptoms. The type and impact of trauma may differ between sexes. In a large sample of recent-onset patients, we investigated the associations of depressive and negative symptoms with childhood trauma and whether these are sex-specific. A total of 187 first-episode psychosis patients in remission (Handling Antipsychotic Medication: Long-term Evaluation of Targeted Treatment study) and 115 recent-onset SSD patients (Simvastatin study) were included in this cross-sectional study (men: n = 218; women: n = 84). Total trauma score and trauma subtypes were assessed using the Childhood Trauma Questionnaire Short Form; depressive and negative symptoms were rated using the Positive And Negative Symptoms Scale. Sex-specific regression analyses were performed. Women reported higher rates of sexual abuse than men (23.5% v. 7.8%). Depressive symptoms were associated with total trauma scores and emotional abuse ratings in men (β: 0.219-0.295; p ≤ 0.001). In women, depressive symptoms were associated with sexual abuse ratings (β: 0.271; p = 0.011). Negative symptoms were associated with total trauma score and emotional neglect ratings in men (β: 0.166-0.232; p ≤ 0.001). Negative symptoms in women were not linked to childhood trauma, potentially due to lack of statistical power. Depressive symptom severity was associated with different types of trauma in men and women with recent-onset SSD. Specifically, in women, depressive symptom severity was associated with childhood sexual abuse, which was reported three times as often as in men. Our results emphasize the importance of sex-specific analyses in SSD research.

Antipsychotic medication for women with schizophrenia spectrum disorders.

There are significant differences between men and women in the efficacy and tolerability of antipsychotic drugs. Here, we provide a comprehensive overview of what is currently known about the pharmacokinetics and pharmacodynamics of antipsychotics in women with schizophrenia spectrum disorders (SSDs) and translate these insights into considerations for clinical practice. Slower drug absorption, metabolism and excretion in women all lead to higher plasma levels, which increase the risk for side-effects. Moreover, women reach higher dopamine receptor occupancy compared to men at similar serum levels, since oestrogens increase dopamine sensitivity. As current treatment guidelines are based on studies predominantly conducted in men, women are likely to be overmedicated by default. The risk of overmedicating generally increases when sex hormone levels are high (e.g. during ovulation and gestation), whereas higher doses may be required during low-hormonal phases (e.g. during menstruation and menopause). For premenopausal women, with the exceptions of quetiapine and lurasidone, doses of antipsychotics should be lower with largest adjustments required for olanzapine. Clinicians should be wary of side-effects that are particularly harmful in women, such as hyperprolactinaemia which can cause oestrogen deficiency and metabolic symptoms that may cause cardiovascular diseases. Given the protective effects of oestrogens on the course of SSD, oestrogen replacement therapy should be considered for postmenopausal patients, who are more vulnerable to side-effects and yet require higher dosages of most antipsychotics to reach similar efficacy. In conclusion, there is a need for tailored, female-specific prescription guidelines, which take into account adjustments required across different phases of life.

Abnormal Brain Bioenergetics in First-Episode Psychosis.

BackgroundConverging evidence indicates impaired brain energy metabolism in schizophrenia and other psychotic disorders. Creatine kinase (CK) is pivotal in providing adenosine triphosphate in the cell and maintaining its levels when energy demand is increased. However, the activity of CK has not been investigated in patients with first-episode schizophrenia spectrum disorders. MethodsUsing in vivo phosphorus magnetization transfer spectroscopy, we measured CK first-order forward rate constant (kf) in the frontal lobe, in patients with first-episode psychosis (FEP; n = 16) and healthy controls (n = 34), at rest. ResultsCK kf was significantly reduced in FEP compared to healthy controls. There were no differences in other energy metabolism-related measures, including phosphocreatine (PCr) or ATP, between groups. We also found increase in glycerol-3-phosphorylcholine, a putative membrane breakdown product, in patients. ConclusionsThe results of this study indicate that brain bioenergetic abnormalities are already present early in the course of schizophrenia spectrum disorders. Future research is needed to identify the relationship of reduced CK kf with psychotic symptoms and to test treatment alternatives targeting this pathway. Increased glycerol-3-phosphorylcholine is consistent with earlier studies in medication-naïve patients and later studies in first-episode schizophrenia, and suggest enhanced synaptic pruning.

Retinal structural alterations in chronic versus first episode schizophrenia spectrum disorders

Recent studies have found evidence of retinal thinning in schizophrenia spectrum disorder patients; however, it is not known whether retinal thinning is present at the first episode of psychosis or whether it is a result of the progression of the disease or related factors (e.g., emergence of medical comorbidities). We hypothesized that first episode patients (FEP) would not differ on any retinal variables when compared to age matched controls, while chronically ill patients would show evidence of retinal thinning compared to age matched controls. 15 first episode patients, 20 control subjects age-matched to the FEP group, 18 chronically ill patients, and 18 control subjects age-matched to the chronically ill group participated in Spectral Domain OCT scans. We collected data on retinal nerve fiber layer (RNFL) thickness, macula thickness and volume, and ganglion cell-inner plexiform layer (GCL-IPL) thickness as well as cup-to-disc ratio at the optic nerve head. No evidence of retinal structural change was found in the first episode group. In contrast, chronic schizophrenia and schizoaffective disorder patients were characterized by GCL-IPL thinning and overall macula thinning and volume reduction. No evidence of RNFL thinning was observed in the chronic group, however. These data suggest that retinal structure is unaffected very early in the course of schizophrenia spectrum disorders but that thinning is an aspect of illness progression, medical comorbidity, and/or long-term antipsychotic medication use in schizophrenia spectrum disorders. Among retinal indices, macula thickness and volume appear to be the most sensitive to the changes associated with illness chronicity.

Impact of emotion dysregulation and cognitive insight on psychotic and depressive symptoms during the early course of schizophrenia spectrum disorders.

Emotion dysregulation is relevant to the aetiology of schizophrenia spectrum disorders (SSD). While most studies have focused on the chronic phase of SSD, little is known about the effects of emotion dysregulation and associated cognitive risk factors during the early phase of the illness, with negative implications for early intervention. The purpose of this study is to examine the impact of maladaptive cognitive emotion regulation strategies, global emotion dysregulation, and cognitive insight on psychotic and comorbid depressive symptoms in patients with early SSD. Participants included 150 newly diagnosed outpatients with SSD who were seeking treatment at the Early Psychosis Intervention Program. All participants completed the Cognitive Emotion Regulation Questionnaire, Difficulties with Emotion Regulation Scale, and Beck Cognitive Insight Scale. Severity of psychotic and depressive symptoms were rated on the Brief Psychiatric Rating Scale. Multivariate regression adjusting for gender and psychiatric comorbidity revealed that global emotion dysregulation was associated with more severe positive and depressive symptoms. Further moderation analyses revealed a significant interaction between global emotion dysregulation and cognitive insight (self-certainty) on depression such that for patients with high self-certainty, greater global emotion dysregulation was associated with increased severity of depressive symptoms. There was no interaction between global emotion dysregulation and cognitive insight on positive symptoms. Our findings provide preliminary support for the associations between emotion dysregulation and psychopathology in early SSD. Further research is needed to examine the transdiagnostic role of emotion dysregulation in the aetiology and treatment of a wider range of psychotic disorders.

The neuropsychology of emerging psychosis and the role of working memory in episodic memory encoding.

BackgroundEpisodic memory encoding and working memory (WM) deficits are among the first cognitive signs and symptoms in the course of schizophrenia spectrum disorders. However, it is not clear whether the deficit pattern is generalized or specific in nature. We hypothesized that encoding deficits at an early stage of the disease might be due to the more fundamental WM deficits.MethodsWe examined episodic memory encoding and WM by administering the California Verbal Learning Test, a 2-back task, and the Wisconsin Card Sorting Test in 90 first-episode psychosis (FE) patients and 116 individuals with an at-risk mental state for psychosis (ARMS) compared to 57 healthy subjects.ResultsLearning progress, but not span of apprehension, was diminished to a similar extent in both the ARMS and the FE. We showed that this was due to WM impairment by applying a structural equation approach.ConclusionThus, we conclude that verbal memory encoding deficits are secondary to primary WM impairment in emerging psychosis.

Genetic and environmental factors in the etiology of schizophrenia - towards mainstreaming

Abstract The prevalence of schizophrenia in a population is about 1%. Many efforts are constantly made to find the cause of this mental illness. Authors of this article provide groups of factors influencing the development of the disease. Among these factors, genetics seems to be an interesting and reasonable trend of exploration. GWAS research studies allow not only determining the point mutations in the genome, but also try to give an answer to the question about the biological mechanisms of disease. A microRNA MIR137, which is involved in neurogenesis and maturation of neurons may be an example. However, the genetic component may not always be sufficient to trigger symptoms. Definitely, a large group of environmental factors has an important role. Schizophrenia is a complex disease in which many genes interact with the environment. This article is a presentation of genes and the impact of various external environmental factors, leading to the onset of schizophrenia. Interrelationship between polygenic determinant of disease and the impact of both environmental and social factors in future will certainly become the field of interest for research concerning the etiology and course of schizophrenia-spectrum disorders.

The Burden of Mental Illness Beyond Clinical Symptoms: Impact of Stigma on the Onset and Course of Schizophrenia Spectrum Disorders

The Burden of Mental Illness Beyond Clinical Symptoms: Impact of Stigma on the Onset and Course of Schizophrenia Spectrum Disorders

Physical Activity in Schizophrenia is Higher in the First Episode than in Subsequent Ones.

Schizophrenia is frequently associated with abnormal motor behavior, particularly hypokinesia. The course of the illness tends to deteriorate in the first years. We aimed to assess gross motor activity in patients with a first episode (n = 33) and multiple episodes (n = 115) of schizophrenia spectrum disorders using wrist actigraphy. First episode patients were younger, had higher motor activity and reduced negative symptom severity. Covarying for age, chlorpromazine equivalents, and negative symptoms, first episode patients still had higher motor activity. This was also true after excluding patients with schizophreniform disorder from the analyses. In first episode patients, but not in patients with multiple episodes, motor activity was correlated with antipsychotic dosage. In conclusion, after controlling for variables related to disorder chronicity, patients with first episodes were still more active than patients with multiple episodes. Thus, reduced motor activity is a marker of deterioration in the course of schizophrenia spectrum disorders.

Maladaptive Personality Traits Increase Subjectively During the Course of Schizophrenia Spectrum Disorders

We assessed both current maladaptive personality traits (MPTs) and, retrospectively, premorbid MPTs in patients with schizophrenia spectrum disorders (SSDs). This was to examine whether the patients had the impression that their personality had changed and which traits were affected. We also wanted to determine whether the perceived changes could be explained by SSD psychopathology. MPTs were assessed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnoses, axis II disorders, screening questionnaire and interview, integrating questions on subjective estimation of premorbid MPTs in moderately ill SSD patients. Forty-five patients were included. Premorbid MPTs were remembered as significantly less pronounced than current MPTs for the whole spectrum of personality traits (p < 0.001). Antisocial traits had worsened significantly less (p < 0.001), and borderline and obsessive-compulsive traits had worsened significantly more (both p < 0.01) than the mean increase. Associations between MPT increase and SSD psychopathology were significant for schizotypal, avoidant, and depressive traits. According to the patients' retrospective assessment, MPTs increased through onset and course of SSDs. Memory bias, depressed mood, and SSD symptoms alone could not sufficiently explain these differences. Subjective MPT increase may play a role for the patients' concept of illness, quality of life, and adherence to therapeutic interventions. It should be addressed in SSD treatment.

Affecting coping: Does neurocognition predict approach and avoidant coping strategies within schizophrenia spectrum disorders?

According to various diathesis-stress models of schizophrenia, life stress plays a defining role in the onset and course of schizophrenia-spectrum disorders. In this regard, individual differences in coping strategies and affective traits, variables related to the management and experience of stress, may play a large role in susceptibility to the disorder and symptom exacerbation. Furthermore, it has been posited that cognitive deficits may limit an individuals' ability to effectively respond to stressful situations. We investigated the relationships between attention, immediate memory, trait negative affect (NA), trait positive affect (PA) and specific coping strategies within three groups: chronic schizophrenia patients (n=27), psychometrically-defined schizotypy (n=89), and schizotypy demographically-matched controls (n=26). As hypothesized affective traits displayed predictable relationships with specific coping strategies, such that NA was associated with the greater use of avoidant coping strategies within the schizophrenia and schizotypy group, while PA was associated with greater use of approach coping styles within all groups. The schizotypy group reported significantly higher levels of NA and also greater use of avoidant coping strategies than both the control and schizophrenia group. As expected group differences were found in trait affect, coping strategies, and cognitive functioning. Importantly, these group differences remained significant even when demographic variables were entered as covariates. Contrary to our expectations, cognitive functioning displayed only a few tenuous relationships with coping strategies within the schizophrenia and schizotypy groups. Overall, results support the notion that affective traits and not cognitive functioning is the best predictor of approach and avoidant coping strategies.

Cognitive functioning in the early course of first-episode schizophrenia spectrum disorders

The aim of this study was to examine possible cognitive changes throughout the early course of schizophrenia spectrum disorders. Forty-two patients, aged 15-50 years, admitted to a first episode psychosis program (PAFIP) serving to the community of Cantabria (Spain) and 43 healthy volunteers completed a brief battery of five neurocognitive tests at four time-points over 3 months. The cognitive testing comprise five domains: attention, visuomotor speed, declarative memory, working memory and executive function. Baseline assessment occurred within 72 hour after the initiation of standard pharmacological treatment, and after then parallel forms of the tests were applied at week-2, week-6, and month-3. Patient scores showed a significant impairment compared to healthy volunteers in the five cognitive domains at baseline and week-2 assessments. After the first 3 months of antipsychotic treatment, the patient group performance reached healthy volunteers level on executive function (Stroop interference) and immediate verbal memory tests. In contrast, performance on working memory, sustained attention, visuomotor speed, and verbal memory delayed recall domains still remained below healthy volunteers, although visuomotor processing speed showed a significant improvement. Schizophrenia spectrum patients show heterogeneous patterns and degrees of cognitive changes that contribute to stress the importance of when, what, and how neurocognitive functioning in the early phases of the illness is evaluated.

Cannabis and psychosis--a review

The present review focuses on articles dealing with clinical or epidemiological studies on the association between cannabis use and psychoses. Included are all articles published since 1990 that were located by a Medline or Psyclit data-base research and those earlier articles that are needed for a correct understanding of studies published during the index episode. The three main topics found are 1) is there evidence for a so called cannabis psychosis 2) do cannabis users exhibit a higher risk of developing a psychotic disorder or 3) does its use worsen the course in established schizophrenia spectrum disorders. The review concludes that very high doses of cannabis can induce a brief psychosis but that this condition is extremely rare. Therefore, such a diagnosis should only be made after careful exclusion of other etiologies. The actual evidence regarding the impact of cannabis use on persons vulnerable to psychosis is not conclusive. Cannabis use seems to worsen the course of schizophrenia spectrum disorders. Adolescents run a higher risk from using cannabis than older people. They should be strongly advised not to indulge in such behaviour.