Poor Premorbid Social Adjustment Research Articles

Associations of psychotic symptom dimensions with clinical and developmental variables in twin and general clinical samples.

Positive, negative and disorganised psychotic symptom dimensions are associated with clinical and developmental variables, but differing definitions complicate interpretation. Additionally, some variables have had little investigation. To investigate associations of psychotic symptom dimensions with clinical and developmental variables, and familial aggregation of symptom dimensions, in multiple samples employing the same definitions. We investigated associations between lifetime symptom dimensions and clinical and developmental variables in two twin and two general psychosis samples. Dimension symptom scores and most other variables were from the Operational Criteria Checklist. We used logistic regression in generalised linear mixed models for combined sample analysis (n = 875 probands). We also investigated correlations of dimensions within monozygotic (MZ) twin pairs concordant for psychosis (n = 96 pairs). Higher symptom scores on all three dimensions were associated with poor premorbid social adjustment, never marrying/cohabiting and earlier age at onset, and with a chronic course, most strongly for the negative dimension. The positive dimension was also associated with Black and minority ethnicity and lifetime cannabis use; the negative dimension with male gender; and the disorganised dimension with gradual onset, lower premorbid IQ and substantial within twin-pair correlation. In secondary analysis, disorganised symptoms in MZ twin probands were associated with lower premorbid IQ in their co-twins. These results confirm associations that dimensions share in common and strengthen the evidence for distinct associations of co-occurring positive symptoms with ethnic minority status, negative symptoms with male gender and disorganised symptoms with substantial familial influences, which may overlap with influences on premorbid IQ.

Premorbid functioning in adolescence associates with comorbid disorders in individuals at ultra-high risk for psychosis: A brief report.

This study examines associations between premorbid adjustment and comorbid disorders in individuals at ultra-high risk (UHR) for psychosis. Premorbid social and academic adjustment data were collected from 146 UHR individuals using the Premorbid Adjustment Scale. Comorbid disorders were determined by the Structural Clinical Interview for DSM-IV. Logistic regressions showed lower premorbid social adjustment associated with personality disorders. Lower premorbid academic adjustment associated with affective disorders. More specifically, poor premorbid social adjustment in early and late adolescence associated with personality disorders. Lower premorbid social adjustment in late adolescence and lower premorbid academic adjustment in early adolescence associated with affective disorders. Partly corroborating evidence from schizophrenia samples, our findings suggest that poor premorbid adjustment relate to distinct comorbid disorders in UHR individuals. If replicated, it indicates that premorbid adjustment deficits may be a key area for targeted interventions improving the clinical prognosis of UHR individuals.

Clinical Indicators of Symptom Dimensions and Cognitive Ability in Schizophrenia

IntroductionSchizophrenia is a heterogeneous disorder and it is unknown what causes individual variability in symptoms and cognitive ability.Objectives To examine the association between nine clinical predictors measurable at the onset of schizophrenia and five phenotype dimensions: positive, negative (diminished expressivity), negative (motivation and pleasure), disorganised symptoms and cognitive ability.Methods852 participants (mean age 49 years old) with a diagnosis of schizophrenia or schizoaffective depression were included from the CardiffCOGS cross-sectional sample. Phenotype dimensions were created using confirmatory factor analysis and a 5-factor model. Associations were tested using linear regression, adjusting for age and sex. A Bonferroni correction was applied for (p<1.1x10-3) for multiple testing.ResultsAge of onset of psychosis was significantly associated with positive symptoms (β=-0.18, p=4.0 x10-6). Lower premorbid IQ was associated with diminished expressivity (β=-0.25, p= 7.0x10-13), reduced motivation and pleasure (β=-0.23, p= 4.3x10-11), disorganised symptoms (β=-0.14, p= 7.6x10-5) and reduced cognition (β=0.54, p= 4.8x10-77). Poor premorbid social adjustment held associations with all except positive. Developmental delay was associated with reduced cognition (β=-0.35, p= 4.3x10-5). Cannabis use (year before onset), psychosocial stressors (within 6 months), childhood abuse and family history of schizophrenia held no associations.ConclusionsClinical indicators measurable at schizophrenia onset are associated with lifetime symptom variability. A younger psychosis onset is associated with more severe positive symptoms, suggesting possible age-targeted management. Pre-established links of lower premorbid IQ with poor premorbid social adjustment and negative symptom severity with cognition are strengthened. Further investigation could potentially improve diagnosis and guide treatment choice for aspects of schizophrenia with poor outcomes.DisclosureNo significant relationships.

Examining which factors influence age of onset in males and females with schizophrenia

ObjectiveData from the 2010 Australian National Survey of High Impact Psychosis (SHIP) was used to examine (1) what variables influence age of onset (AOO) for males and females, and (2) whether influencing variables were different between the sexes. MethodData from 622 schizophrenia patients in the SHIP sample was used. These included early life factors, encompassing family psychiatric history, childhood development, trauma and parental loss. Factors occurring within 12 months of diagnosis were also used, including drug/alcohol abuse and premorbid work and social adjustment. Based on the recognised differences in symptom profiles and AOO between the sexes, these factors were regressed separately for males and females. ResultsStepwise linear regressions showed that a family history of psychiatric disorders was significantly associated with earlier AOO in both sexes. Other variables differed between males and females. Specifically, for females, an earlier AOO was associated with poor premorbid social adjustment and the loss of a family member in childhood. Older AOO was associated with immigrant status. For males, a younger AOO was associated with unemployment at onset, poor premorbid work adjustment, parental divorce in childhood, and lifetime cannabis use. A higher premorbid IQ was associated with an older AOO. ConclusionFamilial predisposition to psychiatric illness is related to earlier AOO of schizophrenia independent of sex. Males appear to have more individual-based predictive factors while females seem to have more community/social-based influences. Future directions for research in schizophrenia are suggested.

Clinical indicators of treatment-resistant psychosis.

Around 30% of individuals with schizophrenia remain symptomatic and significantly impaired despite antipsychotic treatment and are considered to be treatment resistant. Clinicians are currently unable to predict which patients are at higher risk of treatment resistance. To determine whether genetic liability for schizophrenia and/or clinical characteristics measurable at illness onset can prospectively indicate a higher risk of treatment-resistant psychosis (TRP). In 1070 individuals with schizophrenia or related psychotic disorders, schizophrenia polygenic risk scores (PRS) and large copy number variations (CNVs) were assessed for enrichment in TRP. Regression and machine-learning approaches were used to investigate the association of phenotypes related to demographics, family history, premorbid factors and illness onset with TRP. Younger age at onset (odds ratio 0.94, P = 7.79 × 10-13) and poor premorbid social adjustment (odds ratio 1.64, P = 2.41 × 10-4) increased risk of TRP in univariate regression analyses. These factors remained associated in multivariate regression analyses, which also found lower premorbid IQ (odds ratio 0.98, P = 7.76 × 10-3), younger father's age at birth (odds ratio 0.97, P = 0.015) and cannabis use (odds ratio 1.60, P = 0.025) increased the risk of TRP. Machine-learning approaches found age at onset to be the most important predictor and also identified premorbid IQ and poor social adjustment as predictors of TRP, mirroring findings from regression analyses. Genetic liability for schizophrenia was not associated with TRP. People with an earlier age at onset of psychosis and poor premorbid functioning are more likely to be treatment resistant. The genetic architecture of susceptibility to schizophrenia may be distinct from that of treatment outcomes.

F128. THE AGE OF ONSET OF SCHIZOPHRENIA SPECTRUM DISORDERS

BackgroundThis study characterizes the age of onset of schizophrenia spectrum disorders and summarizes findings regarding a range of clinical and social outcomes, cognition, brain structure, and mortality.MethodsThe review is based on series of systematic and nonsystematic literature searches. We included original articles and systematic reviews looking associations between age of onset and incidence, risk factors, suicides, brain structure and cognition.ResultsThe peak age of onset for schizophrenia spectrum disorders is between 20 to 29 years, in where the incidence estimate was among males 4.15 and among females 1.71 per 10,000 person-years. Male gender has been linked with earlier onset age, although among those with family history and cannabis use corresponding gender difference do not exist. Early onset schizophrenia has been linked e.g. with higher familial risk, poor premorbid social adjustment and cannabis use. In adult samples, earlier age of onset associated with worse outcome, regarding hospitalisations, negative symptoms, relapses, social and occupational functioning, and global outcome. Also in childhood and adolescence schizophrenia, earlier onset has been linked with more severe outcomes. Early age of onset has been linked also with larger cognitive deficits and brain alterations. In the few existing studies, later AOO has been linked with a higher suicide rate. In all, the current study found various differences between patients with different age of onset. However, the studies on age of onset are relative heterogeneous on methodology and have given varying results. More good quality studies are needed including patients without restriction due to the onset age.DiscussionAge of onset is an important characteristic of schizophrenia that could help when examining the origin, genetic mechanism and care of schizophrenia. Understanding factors that influence age of onset in schizophrenia may offer clues to prevent or delay the onset of this debilitating group of disorders.

Premorbid social adjustment and association with attenuated psychotic symptoms in clinical high-risk and help-seeking youth.

Attenuated positive symptom syndrome (APSS), characterized by 'putatively prodromal' attenuated psychotic-like pathology, indicates increased risk for psychosis. Poor premorbid social adjustment predicts severity of APSS symptoms and predicts subsequent psychosis in APSS-diagnosed individuals, suggesting application for improving detection of 'true' prodromal youth who will transition to psychosis. However, these predictive associations have not been tested in controls and therefore may be independent of the APSS diagnosis, negating utility for improving prediction in APSS-diagnosed individuals. Association between premorbid social maladjustment and severity of positive, negative, disorganized, and general APSS symptoms was tested in 156 individuals diagnosed with APSS and 76 help-seeking (non-APSS) controls enrolled in the Enhancing the Prospective Prediction of Psychosis (PREDICT) study using prediction analysis. Premorbid social maladjustment was associated with social anhedonia, reduced expression of emotion, restricted ideational richness, and deficits in occupational functioning, independent of the APSS diagnosis. Associations between social maladjustment and suspiciousness, unusual thought content, avolition, dysphoric mood, and impaired tolerance to normal stress were uniquely present in participants meeting APSS criteria. Social maladjustment was associated with odd behavior/appearance and diminished experience of emotions and self only in participants who did not meet APSS criteria. Predictive associations between poor premorbid social adjustment and attenuated psychotic-like pathology were identified, a subset of which were indicative of high risk for psychosis. This study offers a method for improving risk identification while ruling out low-risk individuals.

M42 - Using Polygenic Scores Based on Schneiderian First Rank Symptoms To Characterize Disease Trajectories In Severe Mental Illnesses

Background Mental illnesses such as bipolar disorder (BD), schizoaffective disorder (SA) and schizophrenia (SZ) have a huge impact on people’s lives and due to expensive treatments also on our health systems. Despite our advances in genetic and clinical research, it is still unknown what determines the highly variable courses of illness. Recent studies have focused on determining phenotypes more suitable for genetic analyses. Most analyses use diagnostic criteria based on DSM or ICD, however, the question arises whether it may be useful to classify subgroups of patients based on domains of psychopathology across diagnostic classification systems. To date, few studies exist that examine phenotypes based on such domains. We examined the presence/absence of Schneiderian first-rank symptoms (FRS) as a potential phenotype in a genome-wide association study (GWAS) analysis. The results of this analysis were used to calculate polygenic risk scores in an independent sample in which longitudinal clusters of psychopathology have been defined. We aim to explore the association of cluster membership with the individual load on first-rank polygenic risk scores (FR-PRS). Methods Discovery sample: Individuals with SZ, SA and BD (n=1621) were selected from a large multi-site study (BoMA) in Germany and phenotyped using a comprehensive inventory for phenotype characterization (IPGS), including the SCID-I, the OPCRIT and the GAF. Presence/ absence of FRS served to identify diagnostically heterogeneous subgroups. GWAS was carried out with PLINK 1.07 using as covariates: age, age of onset, mode of onset, poor premorbid social adjustment, gender, course of illness and 4 population structure PCs. Test sample: A subsample of individuals (n=198) with SZ, SA and BD from a longitudinal, multi-site cohort study (www.kfo241.de; www.PsyCourse.de) comprehensively phenotyped at 4 time points over 18 months. DNA samples were genotyped and imputed using the 1KG Phase3. 67 longitudinally measured variables derived from clinical symptom scales entered the cluster analyses. FAMD was applied to compute abstract data dimensions, which were used to derive longitudinal trajectories. Based on these trajectories, k-mean clustering for longitudinal data yielded 2 distinct subgroups. Identified clusters served as predictors for FR-PRS at 11 thresholds. Results Two clusters of longitudinal trajectories were identified: i) consistently low psychopathology scores and ii) consistently high psychopathology scores. Cluster membership was not significantly associated with the FR-PRS in either cluster. Discussion Although the results are preliminary and thus need to be interpreted with caution, the approach of longitudinal clustering to identify cross-diagnostic homogeneous subgroups of individuals appears feasible. The fact that more severe psychopathological features were not associated with increased genetic risk burden should be explored further. One possible explanation is a lack of power, another is that maybe psychopathology may be more influenced to a larger degree by other factors than genetics that may be easier to modify for future treatment options.

The relevance of cognitive, clinical and premorbid variables in predicting functional outcome for individuals with first-episode psychosis: A 3 year longitudinal study

Real-world functional deficits are common and persistent in individuals with psychosis. Cognitive deficits have been shown to compromise functioning. We aimed to study the predictive values of premorbid, sociodemographic, and baseline clinical and neurocognitive factors on long-term functional outcome for individuals with first episode non-affective psychosis. We failed to demonstrate a significant relationship between cognitive deficits at baseline and functional disability at 3 year follow-up. Diagnosis of schizophrenia (OR=2.457, p=0.011), shorter education (OR=1.177, p=0.005) and poor premorbid social adjustment (OR=1.628, p=0.013) emerged as the strongest predictors for the 114 subjects (56%) that exhibited functional disability at 3-year follow-up. A considerable proportion of the variance in functioning (74% at 1 year and 77% at 3 year) remained unexplained by baseline variables. The set of variables that predicted functional outcome at medium- (1 year) and long-term (3 years) differed. In conclusion, the length of follow-up influenced the relationship between baseline variables and functional outcome. A substantial proportion of the variance in function was not explained by these variables and therefore the influence of other factors warrants further investigation. The data support the notion that premorbid social adjustment is an important aspect in functional outcome over the course of the illness.

Attachment style predicts 6‐month improvement in psychoticism in persons with at‐risk mental states for psychosis

Insecure attachment may influence vulnerability to and outcome of psychotic symptomatology. The present study examined whether attachment style predicted symptoms and functioning of at-risk mental state (ARMS) patients after 6 months of psychosocial intervention, over and above the effects of initial clinical severity and premorbid social adjustment (PSA). Symptoms and functioning were assessed at baseline and 6 months later in 31 ARMS patients (mean age = 15.7). No patient received antipsychotic medication, but all engaged in intense psychosocial needs-adapted treatment. Clinicians (unaware of the aims of the study) rated attachment, PSA, symptoms, and functioning. Attachment was not related to baseline clinical severity. However, improvement in psychoticism was predicted by attachment (in particular by secure, preoccupied and dismissing) beyond the effects of baseline clinical severity and PSA. Secure attachment also predicted improvements in disorganization and functioning. Poor PSA predicted less improvement in disorganization and negative symptoms but did not impact psychoticism. The three attachment prototypes that predicted improvement in psychoticism (secure, preoccupied and dismissing) share the existence of at least one positive psychological model (either about self or about others). It may be that the psychosocial intervention helped ARMS patients to disconfirm negative models and/or reinforce positive ones. Patients' attachment styles were not related to baseline clinical severity but impacted improvement of positive symptoms. These findings appear consistent with evidence that impaired self-esteem and dysfunctional self and others schemas constitute risk factors for reality distortion.

Differential patterns of premorbid social and academic deterioration in deficit and nondeficit schizophrenia

Numerous studies indicate that social dysfunction is associated with negative symptoms of schizophrenia during the chronic phase of illness. However, it is unclear whether social abnormalities exist during the premorbid phase in people who later develop schizophrenia with prominent negative symptoms, or whether social functioning becomes progressively worse in these individuals from childhood to late adolescence. The current study examined differences in academic and social premorbid functioning in people with schizophrenia meeting criteria for deficit (i.e., primary and enduring negative symptoms) (DS: n=74) and non-deficit forms of schizophrenia (ND: n=271). Premorbid social and academic functioning was assessed for childhood, early adolescence, and late adolescence developmental periods on the Premorbid Adjustment Scale (PAS). Results indicated that both DS and ND participants showed deterioration in social and academic functioning from childhood to late adolescence. However, while ND schizophrenia demonstrated greater deterioration of academic compared to social premorbid functioning from childhood to late adolescence, the DS group exhibited comparable deterioration across both premorbid domains, with more severe social deterioration than the ND group. Findings suggest that people with DS show poorer social premorbid adjustment than those with ND as early as childhood, and are particularly susceptible to accelerated deterioration as the onset of schizophrenia becomes imminent. Thus, poor premorbid social adjustment and significant social deterioration from childhood to adolescence may be a hallmark feature of people who later go on to develop prominent negative symptoms and a unique marker for the DS subtype of schizophrenia.

Measuring quality of life in first-episode psychosis

Quality of life (QoL) measures are increasingly recognized as necessary parts of outcome assessments in psychosis. The present paper is a comprehensive study of patients with first-episode psychosis where QoL is measured by the commonly used Lehman Quality of Life Interview (L-QoLI). The aim is to examine if the L-QoLI maintain its original structure when used in a group of patients with first-episode psychosis, and to investigate what determines global subjective QoL with a specific emphasis on premorbid adjustment, duration of untreated psychosis (DUP) and clinical symptoms. The study indicates that the psychometric properties of the L-QoLI do not change significantly when used in first-episode samples. The patients report subjective and objective QoL in the fair to good range, with only a moderate association between the objective and subjective measures. Poor global satisfaction is predicted by being single, abusing drugs, being depressed, having a diagnosis of psychotic affective disorder, having poor premorbid social adjustment and DUP over 10 weeks. The study supports the notion that patients with first-episode psychosis construct QoL in the same way as other groups, and that longer durations of compromised function at this stage produces poor satisfaction with life rather than a downward readjustment of expectations.

Suicide attempts in schizophrenia and affective disorders with relation to some specific demographical and clinical characteristics

Demographical and clinical characteristics have been reported to modulate the risk for suicide. This study analysed demographical and clinical characteristics with respect to lifetime suicide attempts in 500 individuals affected with schizophrenic or affective disorders. Suicide attempts were associated with poor premorbid social adjustment, low age at onset, low scores on the “Global Assessment Scale” and childlessness in females.

The subtyping of schizophrenia in men and women: a latent class analysis

Latent class analysis on an epidemiologically based series of 447 first contact patients with a broad diagnosis of schizophrenia revealed evidence for two subtypes: a 'neurodevelopmental' type characterized by early onset, poor pre-morbid social adjustment, restricted affect and a male:female ratio of 7:3; and a 'paranoid' type characterized by later onset, persecutory delusions and an almost equal sex ratio. A third 'schizoaffective' subtype, whose existence was less clear cut, was almost entirely confined to females and characterized by dysphoria and persecutory delusions, and had negligible familial risk of schizophrenia. The aetiological, biological and clinical significance of this typology remains to be tested.