Perfect Enough to Sleep? Perfectionism and Actigraphy-Determined Markers of Insomnia.

OBJECTIVES: Perfectionism is an important factor in insomnia development and maintenance. Previous studies exploring the relationship between perfectionism and insomnia have predominantly relied on self-reported sleep measures. Therefore, this study sought to assess whether actigraphy-measured sleep parameters were associated with perfectionism. METHODS: Sixty adults (85% females, mean age 30.18 ± 11.01 years) were sampled from the Australian general population. Actigraphy-derived objective sleep measures, subjective sleep diary measures, the Frost Multidimensional Perfectionism Scale (FMPS), Hewitt-Flett Multidimensional Perfectionism Scale (HFMPS) and Depression, Anxiety and Stress Scale 21 (DASS-21) were collected. RESULTS: High perfectionism levels were associated with poor sleep, but these relationships differed between objective and subjective measures. Perfectionism via FMPS total score and subscales of Concern over Mistakes, Doubts about Actions, Personal Standards and Self-oriented Perfectionism correlated with subjective sleep onset latency and sleep efficiency with moderate effects (r = .26 to .88). In contrast, perfectionism via HFMPS total score and subscales of Socially Prescribed Perfectionism and Parental Expectations predicted objective sleep onset latency and sleep efficiency. Additionally, stress mediated the relationships between objective sleep efficiency and Concern over Mistakes and Doubts about Actions. CONCLUSIONS: Perfectionism demonstrated stronger associations with subjective than objective sleep measures. Higher Parental Expectations and Socially Prescribed Perfectionism may increase one's vulnerability to objectively measured poor sleep. Therefore, perfectionism may be important in preventing and treating insomnia.

Cognitive strengths in first episode psychosis: a thematic analysis of clinicians' perspectives.

BACKGROUND: Cognitive deficits are associated with poor functional outcomes in individuals recovering from a first episode of psychosis (FEP). Existing treatments that target cognitive deficits in FEP may enhance cognitive function, but improvements to real-world functioning are less consistent. Furthermore, these treatments may not adequately address the personal recovery goals of young people attending FEP services. A novel cognitive strengths-based approach may overcome these shortcomings. METHODS: This qualitative study used semi-structured interviews to explore clinicians' (N = 12) perspectives toward the potential development of a cognitive strengths-based assessment or treatment in FEP. The interviews were analysed using thematic analysis. RESULTS: Five higher-order themes emerged: (1) pro-strengths attitude despite unfamiliarity and minimal use, (2) default to a cognitive deficit lens, (3) potential benefits of a cognitive strengths approach, (4) potential risks and barriers, and (5) considerations for successful implementation. While clinicians acknowledged their current deficit approach, they supported implementing a cognitive strengths assessment or treatment and highlighted their potential benefits for the personal recovery needs of young people with FEP. CONCLUSIONS: These findings suggest that a deficit-focused approach to cognitive function amongst clinicians may be common practice in FEP services. Nevertheless, a cognitive strengths approach was viewed favourably by clinicians and may represent a novel method of supporting personal recovery. Thus, the design and implementation of a cognitive strengths approach may be worthwhile. Future exploration of other stakeholder perspectives, such as young people with FEP, is essential.

Depressive psychopathology in first-episode schizophrenia spectrum disorders: a systematic review, meta-analysis and meta-regression.

BACKGROUND: Despite knowing for many decades that depressive psychopathology is common in first-episode schizophrenia spectrum disorders (FES), there is limited knowledge regarding the extent and nature of such psychopathology (degree of comorbidity, caseness, severity) and its demographic, clinical, functional and treatment correlates. This study aimed to determine the pooled prevalence of depressive disorder and caseness, and the pooled mean severity of depressive symptoms, as well as the demographic, illness, functional and treatment correlates of depressive psychopathology in FES. METHODS: This systematic review, meta-analysis and meta-regression was prospectively registered (CRD42018084856) and conducted in accordance with PRISMA and MOOSE guidelines. RESULTS: Forty studies comprising 4041 participants were included. The pooled prevalence of depressive disorder and caseness was 26.0% (seven samples, N = 855, 95% CI 22.1-30.3) and 43.9% (11 samples, N = 1312, 95% CI 30.3-58.4), respectively. The pooled mean percentage of maximum depressive symptom severity was 25.1 (38 samples, N = 3180, 95% CI 21.49-28.68). Correlates of depressive psychopathology were also found. CONCLUSIONS: At least one-quarter of individuals with FES will experience, and therefore require treatment for, a full-threshold depressive disorder. Nearly half will experience levels of depressive symptoms that are severe enough to warrant diagnostic investigation and therefore clinical intervention - regardless of whether they actually fulfil diagnostic criteria for a depressive disorder. Depressive psychopathology is prominent in FES, manifesting not only as superimposed comorbidity, but also as an inextricable symptom domain.

Subjective experiences of neurocognitive functioning in young people with major depression.

BACKGROUND: Research suggests that young people with major depressive disorder (MDD) experience neurocognitive deficits and that these are associated with poorer functional and clinical outcomes. However, we are yet to understand how young people experience such difficulties. The aim of the current study was to explore the subjective experiences of neurocognitive functioning among young people with MDD. METHODS: Semi-structured qualitative interviews were conducted with 11 young people (aged 17-24 years) attending a specialist clinic for youth experiencing moderate-severe depression. Interview transcripts were analysed via Thematic Analysis to identify patterns and themes representing how young people with MDD subjectively experience neurocognitive deficits. RESULTS: Five main themes were identified: (1) experience of neurocognitive complaints; (2) relationship between neurocognitive complaints and depression; (3) impact on functioning; (4) strategies and supports; and (5) neurocognitive complaints and treatment. Overall, young people with MDD commonly experienced a range of subjective neurocognitive complaints. These appeared to have a bidirectional relationship with depressive symptomatology and significantly disrupted vocational, social and independent functioning, and aspects of psychological well-being including self-esteem. Neurocognitive difficulties represented an experiential barrier to psychological therapeutic engagement and were perceived as variably responsive to psychotropic medications, highlighting the need for targeted intervention. DISCUSSION: Neurocognitive difficulties are a common and pervasive experience for young people with MDD, with perceived impacts on depressive symptoms, attitudinal beliefs, everyday functioning and therapeutic engagement. Subjective neurocognitive complaints may therefore contribute to or exacerbate personal challenges faced by young people with MDD and thus, require early identification, consideration in psychological formulation, and treatment. Further research into the mechanisms of neurocognitive impairment in MDD is also needed.

Ventricular volumes across stages of schizophrenia and other psychoses.

OBJECTIVE: Ventricular enlargement is common in established schizophrenia; however, data from ultra high-risk for psychosis and first-episode psychosis studies are inconclusive. This study aims to investigate ventricular volumes at different stages of psychosis. METHODS: Ventricular volumes were measured using a semi-automated and highly reliable method, for 89 established schizophrenia, 162 first-episode psychosis, 135 ultra high-risk for psychosis and 87 healthy controls using 1.5T magnetic resonance images. Clinical outcome diagnoses for ultra high-risk for psychosis were evaluated at long-term follow-up (mean: 7.5 years). RESULTS: Compared to controls, we identified significant ventricular enlargement of 36.2% in established schizophrenia ( p < 0.001). Ventricular enlargement was not significant in first-episode psychosis (6%) or ultra high-risk for psychosis (-3%). Examination across stages of schizophrenia-spectrum diagnoses subgroups revealed a significant linear trend ( p = 0.006; established schizophrenia = 36.2%, first-episode psychosis schizophrenia = 18.5%, first-episode psychosis schizophreniform = -4.2% and ultra high-risk for psychosis-schizophrenia converters = -18.5%). CONCLUSION: Ventricular enlargement is apparent in patients with established schizophrenia but is not a feature at the earliest stages of illness (ultra high-risk for psychosis and first-episode psychosis). Further research is needed to fully characterize the nature and timing of ventricular volume changes early in the course of illness and how these changes impact outcomes.

Antiglucocorticoid and related treatments for psychosis.

BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been implicated in the development and relapse of psychotic disorders. Elevated cortisol secretion has been positively linked with symptom severity in people with psychosis. Antiglucocorticoid and related drugs that target the HPA axis may be useful for the treatment of individuals with psychosis. OBJECTIVES: 1. To determine the effects of antiglucocorticoid and related drugs for the treatment of psychosis, when used alone or in combination with antipsychotic medication.2. To determine whether the effects of these medications differs between those in a prodromal phase or first episode of psychosis, and those with more established illness. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Trials Register (August 2009 and April 2014). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing antiglucocorticoid and related drugs compared to placebo (either as a sole treatment or as an adjunct to atypical antipsychotics, typical antipsychotics, antidepressants or other combination treatment) for people with a primary diagnosis of a psychotic disorder, or for individuals at high risk of developing a psychotic disorder. DATA COLLECTION AND ANALYSIS: Review authors independently selected trials, assessed methodological quality and extracted data. We used a fixed-effect meta-analysis. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes, and mean differences (MDs) and standardised mean differences (SMDs) with 95% CIs for continuous measures. We assessed risk of bias for included studies and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to create a 'Summary of findings' table. MAIN RESULTS: We included 11 studies that randomly assigned 509 people with schizophrenia, schizoaffective disorder or psychotic depression. No trials were conducted in patients at their first episode of psychotic illness and none included populations at high risk for developing psychosis. Our pre-stated outcomes of interest were mental state, global state, general functioning, adverse effects and quality of life.Two trials compared antiglucocorticoid drugs (mifepristone) versus placebo as sole treatment. Limited data from one trial showed no difference in the proportion responding to mifepristone when mental state was assessed immediately post intervention using the Brief Psychiatric Rating Scale (BPRS) (n = 5, 1 RCT, MD -5.20, 95% CI -17.91 to 7.51; very low-quality evidence); depressive symptoms (Hamilton Rating Scale for Depression (HAMD) total) were also similar between groups (n = 5, 1 RCT, MD 1.67, 95% CI -16.44 to 19.78; very low-quality evidence). However, a significant difference favoured treatment at short-term follow-up for global state (30% reduction in total BPRS, n = 221, 1 RCT, RR 0.58, 95% CI 0.38 to 0.89; low-grade quality evidence). This effect was also seen for short-term positive psychotic symptoms (50% reduction in BPRS positive symptom subscale, n = 221, 1 RCT, RR 0.60, 95% CI 0.43 to 0.84; low-grade quality evidence). Participants receiving mifepristone experienced a similar overall number of adverse effects as those receiving placebo (n = 226, 2 RCTs, RR 0.92, 95% CI 0.77 to 1.09; moderate-quality evidence). No data on general functioning or quality of life were available.One trial compared an antiglucocorticoid, dehydroepiandrosterone (DHEA), as an adjunct to atypical antipsychotic treatment to adjunctive placebo. Data for main outcomes of interest were of low quality, and analysis of useable data showed no significant effects of treatment on mental state or adverse effects. Data on global state, general functioning and quality of life were not available.Data from six trials comparing antiglucocorticoid drugs as an adjunct to combination treatment versus adjunctive placebo showed no significant differences between groups in mean endpoint scores for overall psychotic symptoms (n = 171, 6 RCTs, SMD 0.01, 95% CI - 0.29 to 0.32) or positive psychotic symptoms (n = 151, 5 RCTs, SMD -0.07, 95% CI - 0.40 to 0.25). Data from three trials showed no differences between groups in mean endpoint scores for negative symptoms (n = 94, 3 RCTs, MD 2.21, 95% CI -0.14 to 4.55). One study found improvements in global state that were similar between groups (n = 30, 1 RCT, RR 0.58, 95% CI 0.32 to 1.06; very low-quality evidence). In this comparison, pooled results showed that antiglucorticoids caused a greater overall number of adverse events (n = 199, 7 RCTs, RR 2.66, 95% CI 1.33 to 5.32; moderate quality evidence), but no quality of life data were available. AUTHORS' CONCLUSIONS: Good evidence is insufficient to conclude whether antiglucocorticoid drugs provide effective treatment for psychosis. Some global state findings suggest a favourable effect for mifepristone, and a few overall adverse effect findings favour placebo. Additional large randomised controlled trials are needed to justify findings.

Rumination, depressive symptoms and awareness of illness in schizophrenia.

BACKGROUND: Depressive symptoms are common in schizophrenia. Previous studies have observed that depressive symptoms are associated with both insight and negative appraisals of illness, suggesting that the way in which the person thinks about their illness may influence the occurrence of depressive responses. In affective disorders, one of the most well-established cognitive processes associated with depressive symptoms is rumination, a pattern of perseverative, self-focused negative thinking. AIMS: This study examined whether rumination focused on mental illness was predictive of depressive symptoms during the subacute phase of schizophrenia. METHOD: Forty participants with a diagnosis of schizophrenia and in a stable phase of illness completed measures of rumination, depressive symptoms, awareness of illness, and positive and negative symptoms. RESULTS: Depressive symptoms were correlated with rumination, including when controlling for positive and negative symptoms. The content of rumination frequently focused on mental illness and its causes and consequences, in particular social disability and disadvantage. Depressive symptoms were predicted by awareness of the social consequences of mental illness, an effect that was mediated by rumination. CONCLUSIONS: Results suggest that a process of perseveratively dwelling upon mental illness and its social consequences may be a factor contributing to depressive symptoms in people with chronic schizophrenia.

Development and validation of the positive evaluation core beliefs scale for social anxiety.

Fear of positive evaluation (FPE) is becoming recognised as an important component of social anxiety that is distinct from fear of negative evaluation (FNE). While core belief scales exist for fear of negative evaluation (FNE), none has been developed for FPE. Therefore, this paper describes the development and validation of a measure of core beliefs that is specific to FPE. An exploratory factor analysis was performed on 60 initial items with an Australian undergraduate sample, in which a confirmatory factor analysis was performed with an independent Australian general population sample. A series of further analyses were performed to test convergent and divergent validity. The Positive Evaluation Core Beliefs Scale (PECS) emerged as a 17-item two-factor psychometrically valid measure that correlates more strongly with measurement of FPE than FNE. The PECS measure offers a new opportunity for researchers and clinicians to better explore cognitions associated with social anxiety.

An open label pilot trial of low-dose lithium for young people at ultra-high risk for psychosis.

AIM: Lithium, even at low doses, appears to offer neuroprotection against a wide variety of insults. In this controlled pilot, we examined the safety (i.e., side-effect profile) of lithium in a sample of young people identified at ultra-high risk (UHR) for psychosis. The secondary aim was to explore whether lithium provided a signal of clinical efficacy in reducing transition to psychosis compared with treatment as usual (TAU). METHODS: Young people attending the PACE clinic at Orygen, Melbourne, were prescribed a fixed dose (450 mg) of lithium (n = 25) or received TAU (n = 78). The primary outcome examined side-effects, with transition to psychosis, functioning and measures of psychopathology assessed as secondary outcomes. RESULTS: Participants in both groups were functionally compromised (lithium group GAF = 56.6; monitoring group GAF = 56.9). Side-effect assessment indicated that lithium was well-tolerated. 64% (n = 16) of participants in the lithium group were lithium-adherent to week 12. Few cases transitioned to psychosis across the study period; lithium group 4% (n = 1); monitoring group 7.7% (n = 6). There was no difference in time to transition to psychosis between the groups. No group differences were observed in other functioning and symptom domains, although all outcomes improved over time. CONCLUSIONS: With a side-effect profile either comparable to, or better than UHR antipsychotic trials, lithium might be explored for further research with UHR young people. A definitive larger trial is needed to determine the efficacy of lithium in this cohort.

Enhanced cortisol suppression following administration of low-dose dexamethasone in first-episode psychosis patients.

OBJECTIVE: Impaired regulation of the hypothalamic-pituitary-adrenal (HPA) axis and hyper-activity of this system have been described in patients with psychosis. Conversely, some psychiatric disorders such as post-traumatic stress disorder (PTSD) are characterised by HPA hypo-activity, which could be related to prior exposure to trauma. This study examined the cortisol response to the administration of low-dose dexamethasone in first-episode psychosis (FEP) patients and its relationship to childhood trauma. METHOD: The low-dose (0.25 mg) Dexamethasone Suppression Test (DST) was performed in 21 neuroleptic-naïve or minimally treated FEP patients and 20 healthy control participants. Childhood traumatic events were assessed in all participants using the Childhood Trauma Questionnaire (CTQ) and psychiatric symptoms were assessed in patients using standard rating scales. RESULTS: FEP patients reported significantly higher rates of childhood trauma compared to controls (p = 0.001) and exhibited lower basal (a.m.) cortisol (p = 0.04) and an increased rate of cortisol hyper-suppression following dexamethasone administration compared to controls (33% (7/21) vs 5% (1/20), respectively; p = 0.04). There were no significant group differences in mean cortisol decline or percent cortisol suppression following the 0.25 mg DST. This study shows for the first time that a subset of patients experiencing their first episode of psychosis display enhanced cortisol suppression. CONCLUSIONS: These findings suggest there may be distinct profiles of HPA axis dysfunction in psychosis which should be further explored.

Relationship between vocational status and perceived stress and daily hassles in first-episode psychosis: an exploratory study.

PURPOSE: Vocational recovery is a primary treatment goal of young people with first-episode psychosis (FEP), yet treatment in this domain is often delayed due to concerns that it might be too stressful. This study aimed to examine whether a relationship exists between vocational status and level of perceived stress and daily hassles in FEP. METHODS: Forty-seven FEP participants were recruited upon admission to the Early Psychosis Prevention and Intervention Centre (EPPIC), Melbourne. Demographics, psychopathology, perceived stress (Perceived Stress Scale; PSS) and daily hassles (Hassles Scale; HS) were measured. RESULTS: Regarding vocational status, 19 participants were unemployed, 13 were employed, 14 were students, and 1 reported 'home duties'. ANOVAs and post hoc tests comparing the first three groups on perceived stress and daily hassles revealed that the mean PSS Total and mean PSS Distress scores of the employed group were significantly lower than those of the unemployed and student groups. Regarding hassles scores, the employed group had a significantly lower mean Hassles Intensity score than the unemployed group. Results were largely unchanged when covariates were included. There were no significant differences between the three groups in levels of anxiety, negative or positive symptoms. The employed group reported lower depression than the student group, but this finding disappeared after controlling for gender. CONCLUSIONS: These results provide preliminary evidence supporting the notion that working or studying is not associated with increased perceived stress or daily hassles in FEP. The findings require replication in larger samples and in different phases of psychosis.

Does prediction error during exposure relate to clinical outcomes in cognitive behavior therapy for social anxiety disorder? A study protocol.

Facing your fears, or exposure therapy, is an effective psychological intervention for anxiety disorders that is often thought to work through fear extinction learning. Fear extinction learning is a type of associative learning where fear reduces through repeated encounters with a feared situation or stimulus in the absence of aversive outcomes. Laboratory research suggests fear extinction learning is driven by threat prediction errors, defined as when fearful predictions do not eventuate. Threat prediction error and its relationship to exposure therapy outcomes haven't been studied enough in actual therapy settings. It remains unclear whether prediction error and extinction learning are central mechanisms of exposure therapy. We are conducting a longitudinal and observational study of how threat prediction error during exposure in social anxiety disorder (SAD) treatment relates to session-by-session symptom change and treatment outcome in addition to exposure surprise and learning outcome. We aim to recruit 65 adults with a primary diagnosis of SAD through an outpatient psychology clinic. Participants will receive 12 sessions of individual manualized cognitive behavioral therapy (CBT), adapted from an efficacious group protocol, that includes graded exposure. Exposure processes, including self-report measures of anxiety, threat prediction, threat outcomes, surprise, and learning outcome, will be measured with smartphone-based event-contingent ecological momentary assessments (EMAs) of all behavioral experiments completed during treatment. Clinical outcomes include self-reported social anxiety symptoms and social threat appraisals, at each session, post and 3-months after treatment. Prediction error will be operationalized as the mismatch between the threat prediction and threat outcome. The joint effect of threat prediction and threat outcome on session-by-session symptom change, treatment outcome, exposure surprise, and learning outcome will be explored using multilevel modeling. The present study will help determine whether threat prediction error during exposures in SAD treatment is related to theoretically implied clinical outcomes. This would contribute to the larger research aim of clarifying exposure therapy mechanisms.

The specific phenotype of depression in recent onset schizophrenia spectrum disorders: A symptom profile and network comparison to recent onset major depressive disorder without psychotic features.

The specific phenotype of depression in recent-onset schizophrenia spectrum disorders (SSD) and its relation to non-psychotic depression is unknown. Symptom profile and network analysis are complementary statistical techniques that may provide important insights into the presentation and relative importance of individual symptoms that give rise to depression. The aim of the current study was to characterise the profile and network of depressive symptoms in SSD and compare it to individuals with major depressive disorder (MDD) without psychotic features. This study involved analysis of baseline data pertaining to 109 individuals with comorbid SSD and depression and 283 with MDD without psychotic features. Study cohorts were the Psychosis Recent Onset GRoningen Survey (PROGR-S) and Youth Depression Alleviation (YoDA) trials, respectively. Profile and network analyses revealed that SSD and MDD differed in the profile and relative importance of individual depressive symptoms. While reported sadness was the primary hallmark of depression in both SSD and MDD, individuals with depression in SSD were more likely to sleep more, and have lower lassitude and pessimism. While sadness had great importance in MDD and SSD, in SSD but not MDD lassitude, sleep, appetite, concentration difficulties, and inability to feel were important in the network of depressive symptoms. The specific phenotype of depression might be different in SSD compared to MDD. Symptom inequivalence or underlying functional mechanisms in SSD might result in depression in SSD that is similar to MDD with atypical features.

Pineal morphology of the clinical high-risk state for psychosis and different psychotic disorders.

BACKGROUND: Pineal volume reductions have been reported in schizophrenia and clinical high-risk states for the development of psychosis, supporting the role of melatonin dysregulation in the pathophysiology of psychosis. However, it remains unclear whether pineal volume is associated with the later onset of psychosis in individuals at clinical high-risk (CHR) of psychosis or if pineal atrophy is specific to schizophrenia among different psychotic disorders. METHODS: This magnetic resonance imaging study examined the volume of and cyst prevalence in the pineal gland in 135 individuals at CHR of psychosis [52 (38.5%) subsequently developed psychosis], 162 with first-episode psychosis (FEP), 89 with chronic schizophrenia, and 87 healthy controls. The potential contribution of the pineal morphology to clinical characteristics was also examined in the CHR and FEP groups. RESULTS: Pineal volumes did not differ significantly between the CHR, FEP, and chronic schizophrenia groups, but were significantly smaller than that in healthy controls. However, pineal volumes were not associated with the later onset of psychosis in the CHR group or FEP sub-diagnosis (i.e., schizophrenia, schizophreniform disorder, affective psychosis, and other psychoses). No significant differences were observed in the prevalence of pineal cysts between the groups, and it also did not correlate with clinical characteristics in the CHR and FEP groups. CONCLUSION: These results suggest that pineal atrophy is a general vulnerability marker of psychosis, while pineal cysts do not appear to contribute to the pathophysiology of psychosis.

An investigation of the relationship between cortical connectivity and schizotypy in the general population.

Recent neuroimaging investigations have identified a relationship between psychotic symptoms in schizophrenia and abnormal brain connectivity. On the basis of the continuum model of psychosis, it was hypothesized that schizotypal traits in healthy control participants would be associated with relatively impaired frontotemporal white matter health as assessed using diffusion tensor imaging. Twenty-one participants (12 women and 9 men aged 18 to 58 years) completed the Schizotypal Personality Questionnaire (SPQ) and underwent diffusion-weighted magnetic resonance imaging scanning as part of a larger study. White matter integrity for the major association fibre tracts was assessed using standard measures of diffusivity, specifically fractional anisotropy (FA) and axial and radial diffusivity. A series of negative binomial regressions yielded significant relationships between reduced FA in seven white matter tracts and increased scores on the SPQ cognitive-perceptual factor. These findings are consistent with research relating brain connectivity to the positive symptoms of schizophrenia, suggesting that the neurobiological bases of schizotypal personality in healthy controls may be analogous to the neurobiological bases of schizophrenia spectrum disorders.

The psychometric validity of the Montgomery-Åsberg Depression Rating Scale (MADRS) in recent onset schizophrenia spectrum disorders.

Earlier recognition and accurate assessment of depressive symptoms is important to improving outcomes in individuals with recent-onset schizophrenia spectrum disorders (termed SSD hereafter)-regardless of whether positive psychotic symptoms are present or have resolved. The Montgomery-Åsberg Depression Rating Scale (MADRS) is frequently used to assess depressive symptoms in SSD, but no study has examined the psychometric validity of MADRS scores in individuals exclusively with SSD and sub-grouped by those with and without positive psychotic symptoms. This study involved baseline data from the Psychosis Recent Onset GRoningen Survey (PROGR-S). Measures used were: MADRS, depressive and negative subscales of Positive and Negative Syndrome Scale (PANSSD, PANSSN), and Schedules for Clinical Assessment in Neuropsychiatry (SCAN). The MADRS total score had sufficient concurrent validity with PANSSD (evidence by ρ≥0.70), and insufficient divergent validity with PANSSN (evidenced by ρ ≥0.30), in the full cohort and when sub-grouped by positive psychotic symptoms. In symptom networks, divergent communities comprising either MADRS or PANSSN items were found, except the MADRS item inability to feel overlapped with PANSSN items. The most divergent MADRS items were sadness, pessimism, and suicidal thoughts. The MADRS total score had sufficient predictive validity for determining caseness for MDD based on SCAN, but the optimal cut-off differed in those with and without positive psychotic symptoms (MADRS≥18 versus MADRS≥11). The MADRS has sufficient validity for assessing depressive symptoms in SSD. Since scores might depend upon symptoms of SSD, MADRS≥11 and the presence of sadness, pessimism, or suicidal ideation might be the best indicator of MDD in SSD.

Interrelationships between depressive symptoms and positive and negative symptoms of recent onset schizophrenia spectrum disorders: A network analytical approach.

OBJECTIVE: There is a need to better understand the interrelationships between positive and negative symptoms of recent-onset schizophrenia spectrum disorders (SSD) and co-occurring depressive symptoms. Aims were to determine: (1) whether depressive symptoms are best conceptualised as distinct from, or intrinsic to, positive and negative symptoms; and (2) bridging symptoms. METHODS: Network analysis was applied to data from 198 individuals with depressive and psychotic symptoms in SSD from the Psychosis Recent Onset GRoningen Survey (PROGR-S). Measures were: Montgomery-Åsberg Depression Rating Scale and Positive and Negative Syndrome Scale. RESULTS: Positive symptoms were just as likely to be associated with depressive and negative symptoms, and had more strong associations with depressive than negative symptoms. Negative symptoms were more likely to be associated with depressive than positive symptoms, and had more strong associations with depressive than positive symptoms. Suspiciousness and stereotyped thinking bridged between positive and depressive symptoms, and apparent sadness and lassitude between negative and depressive symptoms. CONCLUSIONS: Depressive symptoms might be best conceptualised as intrinsic to positive and negative symptoms pertaining to deficits in motivation and interest in the psychotic phase of SSD. Treatments targeting bridges between depressive and positive symptoms, and depressive and such negative symptoms, might prevent or improve co-occurring depressive symptoms, or vice-versa, in the psychotic phase of SSD.

Hippocampal pathology in individuals at ultra-high risk for psychosis: a multi-modal magnetic resonance study.

Although the hippocampus is a key brain region in the pathophysiology of schizophrenia, it is unclear whether structural or biochemical abnormalities predate illness onset. In this study, we used magnetic resonance imaging and spectroscopy data acquired prior to both the onset of psychosis and treatment with antipsychotics to determine this. Sixty-six young people clinically at ultra high-risk of development of psychosis were recruited, 59 of whom did not later develop a psychotic disorder and 7 who had done so after at least 24 months follow-up. These participants were compared with 29 healthy comparison subjects on multiple independent magnetic resonance measures: hippocampal volume, hippocampal T2 relaxation time, and medial temporal lobe metabolite concentrations (including N-acetylaspartate). We found similar reductions in left hippocampal volume in the at-risk group compared to comparison subjects regardless of later transition status; on the right this only reached significance for the at-risk group who did not transition to psychosis. T2 relaxation time in the left hippocampal head was significantly elevated in the later-psychotic group, and this elevation positively correlated with total positive symptoms in the UHR group as a whole. Medial temporal lobe metabolite concentrations did not differ. These findings suggest that there are subtle pathological changes in the hippocampus prior to the development of psychosis, but that they are limited to the left hippocampal head. However, standard measures of neuroanatomical disturbance do not appear to be predictive of later transition, and instead are likely to be non-specific and common in cases that later develop a non-psychotic disorder.

Superior temporal gyrus volume in antipsychotic-naive people at risk of psychosis.

BACKGROUND: Morphological abnormalities of the superior temporal gyrus have been consistently reported in schizophrenia, but the timing of their occurrence remains unclear. AIMS: To determine whether individuals exhibit superior temporal gyral changes before the onset of psychosis. METHOD: We used magnetic resonance imaging to examine grey matter volumes of the superior temporal gyrus and its subregions (planum polare, Heschl's gyrus, planum temporale, and rostral and caudal regions) in 97 antipsychotic-naive individuals at ultra-high risk of psychosis, of whom 31 subsequently developed psychosis and 66 did not, and 42 controls. RESULTS: Those at risk of psychosis had significantly smaller superior temporal gyri at baseline compared with controls bilaterally, without any prominent subregional effect; however, there was no difference between those who did and did not subsequently develop psychosis. CONCLUSIONS: Our findings indicate that grey matter reductions of the superior temporal gyrus are present before psychosis onset, and are not due to medication, but these baseline changes are not predictive of transition to psychosis.

Caudate nucleus volume in individuals at ultra-high risk of psychosis: a cross-sectional magnetic resonance imaging study.

The aim of the present study was to investigate whether volumetric abnormalities of the caudate nuclei predate the onset of psychotic illness. Caudate nuclei volume (CNVs), excluding the tail, were measured using region-of-interest (ROI) tracing of magnetic resonance imaging (MRI) scans acquired on a 1.5T scanner. Subjects included 39 individuals deemed at ultra-high risk of psychosis who converted to psychosis (UHR-P) after initial MRI scanning; 39 matched individuals at ultra-high risk who did not convert to psychosis (UHR-NP); and 39 matched healthy controls. All subjects were neuroleptic-naïve. After adjusting CNVs for intracranial volume (ICV), univariate analyses of variance and repeated measures analyses of variance were undertaken to examine the relationship of CNVs to psychosis transition and to family history of psychosis. Pearson's correlations were used to investigate the relationship of psychopathological scores to CNVs. CNVs did not differ significantly between UHR individuals and healthy controls, and there was no significant difference between converters and non-converters to psychosis. In the UHR group, presence of family history of psychosis was not related to CNVs. There was no correlation between CNVs and either positive or negative symptoms of schizophrenia. Significant associations were found between larger CNV and increased errors on a spatial working memory task but better verbal fluency performance. These data suggest that the caudate is macroscopically normal prior to illness onset, while the relationship to tasks of executive function may implicate the caudate together with its connections to prefrontal regions. Future research should examine changes longitudinally together with analysis of shape to assess subregions of the caudate that connect with prefrontal cortex.