Django White

Neuropsychological and socio-occupational functioning in young psychiatric outpatients: A longitudinal investigation

Background Clinical symptoms and neuropsychological deficits are longitudinally associated with functional outcome in chronic psychiatric cohorts. The current study extended these findings to young and early-course psychiatric outpatients, with the aim of identifying cognitive markers that predict later socio-occupational functioning. Methods At baseline, 183 young psychiatric outpatients were assessed. Ninety-three returned for follow-up (M = 21.6 years old; SD = 4.5) with an average re-assessment interval of 21.6 months (SD = 7.0), and primary diagnoses of major depressive disorder (n = 34), bipolar disorder (n = 29), or psychosis (n = 30). The primary outcome measure was cross-validated with various other functional measures and structural equation modelling was used to map out the interrelationships between predictors and later functional outcome. Results Good socio-occupational functioning at follow-up was associated with better quality of life, less disability, current employment and being in a romantic relationship. The final structural equation model explained 47.5% of the variability in functional outcome at follow-up, with baseline neuropsychological functioning (a composite of memory, working memory and attentional switching) the best independent predictor of later functional outcome. Notably, depressive and negative symptoms were only associated with functioning cross-sectionally. Diagnosis at follow-up was not associated with functional outcome. Conclusions Neuropsychological functioning was the single best predictor of later socio-occupational outcome among young psychiatric outpatients. Therefore, framing psychiatric disorders along a neuropsychological continuum is likely to be more useful in predicting functional trajectory than traditional symptom-based classification systems. The current findings also have implications for early intervention utilising cognitive remediation approaches.

Distinguishing young people with emerging bipolar disorders from those with unipolar depression.

BACKGROUND To facilitate early intervention, there is a need to distinguish unipolar versus bipolar illness trajectories in adolescents and young adults with adult-type mood disorders. METHODS Detailed clinical and neuropsychological evaluation of 308 young persons (aged 12 to 30 years) with moderately severe unipolar and bipolar affective disorders. RESULTS Almost 30% (90/308) of young people (mean age=19.4±4.4yr) presenting for care with affective disorders met criteria for a bipolar-type syndrome (26% with bipolar I). Subjects with bipolar- and unipolar-type syndromes were of similar age (19.8 vs. 19.2yr) and reported comparable ages of onset (14.5 vs. 14.3yr). Clinically, those subjects with unipolar and bipolar-type disorders reported similar levels of psychological distress, depressive symptoms, current role impairment, neuropsychological dysfunction and alcohol or other substance misuse. Subjects with unipolar disorders reported more social anxiety (p<0.01). Subjects with bipolar disorders were more likely to report a family history of bipolar (21% vs. 11%; [χ(2)=4.0, p<.05]) or psychotic (19% vs. 9%; [χ(2)=5.5, p<.05]), or substance misuse (35% vs. 23%; [χ(2)=3.9, p<.05]), but not depressive (48% vs. 53%; χ(2)=0.3, p=.582]) disorders. CONCLUSIONS Young subjects with bipolar disorders were best discriminated by a family history of bipolar, psychotic or substance use disorders. Early in the course of illness, clinical features of depression, or neuropsychological function, do not readily differentiate the two illness trajectories.

Sleep-wake cycle in young and older persons with a lifetime history of mood disorders.

Considering the marked changes in sleep and circadian rhythms across the lifespan, age may contribute to the heterogeneity in sleep-wake profiles linked to mood disorders. This study aimed to investigate the contributions of age and depression severity to sleep-wake disturbances. The Hamilton Depression Rating Scale (HDRS) was administered to assess current symptoms severity in 238 persons with a history of a mood disorder between 12 and 90 years of age (y.o.). Actigraphy was recorded over five to 22 days. Regression analyses and analyses of variance [age (12–19 y.o., 20–39 y.o., 40–59 y.o., and ≥60 y.o.) by depression severity (HDRS< and ≥8)] were conducted. The 12–19 y.o. and 20–39 y.o. groups had a delayed sleep schedule and acrophase compared to all other groups. The ≥60 y.o. group had a lower rhythmicity and amplitude (p≤.006) than the 12–19 y.o. group (p≤.046). Participants with a HDRS≥8 spent longer time in bed, had later sleep offset times and had lower circadian rhythmicity than those with a HDRS<8 (p≤.036). Younger age and higher HDRS score correlated with later sleep onset and offset times, longer time in bed, higher WASO, lower sleep efficiency and later acrophase (p≤.023). Age was a significant predictor of delayed sleep and activity schedules (p≤.001). The profile of sleep-wake cycle disturbances associated with mood disorders changes with age, with prominent sleep phase delay during youth and reduced circadian strength in older persons. Conversely, disruptions in sleep consolidation seem more stable across age.

In vivo glutathione levels in young persons with bipolar disorder: A magnetic resonance spectroscopy study

Oxidative stress has recently been reported to assume a significant role in the pathophysiology of bipolar disorder. Several studies have demonstrated the replenishment of glutathione (GSH) diminishes oxidative cellular damage and ameliorates depressive symptoms in this disorder. Whilst the mechanism by which GSH exerts any clinical effect is unknown it has been proposed that it involves the bolstering of antioxidant defences by increasing the bioavailability of GSH, which in turn reverses clinical symptoms of depression. Such a proposal is predicated on the implicit assumption that GSH is diminished in these patients prior to GSH supplementation. However hitherto no study has reported in vivo measures of GSH in patients with bipolar disorder. Using magnetic resonance spectroscopy we obtained in vivo measures of GSH in young people with bipolar disorder and contrasted these with matched healthy controls. Young people with bipolar disorder were found to have no diminution in baseline GSH concentration and, furthermore, no significant correlations were found between GSH and clinical scores of depression or mania. The results do not support the hypothesis that oxidative stress is involved in the primary pathophysiology of bipolar disorder.

Frequent alcohol, nicotine or cannabis use is common in young persons presenting for mental healthcare: a cross-sectional study

Objectives To determine the prevalence of recent alcohol, nicotine or cannabis use in young persons presenting for mental healthcare. Design A cross-sectional study of young people seeking mental healthcare completed self-report questionnaires regarding their use of alcohol, nicotine or cannabis. Setting Data were collected from two sites as part of the national headspace services programme. Participants 2122 young people aged 12–30 years provided information as part of a patient register; a subset of N=522 participants also provided more detailed information about their patterns of alcohol use. Outcome measures Prevalence levels of recent alcohol, nicotine or cannabis use within relevant age bands (12–17, 18–19 and 20–30) or primary diagnostic categories. Results The rates for use at least weekly of alcohol for the three age bands were 12%, 39% and 45%, and for cannabis 7%, 14% and 18%, respectively. The rates of daily nicotine use for the three age bands were 23%, 36% and 41%. The pattern of alcohol use was characterised by few abstainers as well as many risky drinkers. Age of onset across all three substances was approximately 15 years. Individuals who used any of the three substances more frequently were likely to be older, male or have psychotic or bipolar disorders. Conclusions Frequent use of alcohol, nicotine or cannabis in young people seeking mental healthcare is common. Given the restricted legal access, the patterns of use in those aged 12–17 years are particularly notable. Reductions in substance use needs to be prioritised within services for at-risk young people.

Functional impairment in adolescents and young adults with emerging mood disorders

BACKGROUND Between 30 and 60% of adults with unipolar or bipolar disorders exhibit impairments across multiple domains. However, little is known about impaired functioning in youth with mood disorders. AIMS To examine the prevalence of objective, subjective and observer-rated disability in a large, representative sample of young people with a primary mood disorder. METHOD Individuals aged 16-25 years presenting to youth mental health services for the first time with a primary mood disorder participated in a systematic diagnostic and clinical assessment. Impairment was assessed using objective (unemployment or disability payments), observer- (Social and Occupational Functioning Assessment Scale; SOFAS) and self-rated measures (role functioning according to the Brief Disability Questionnaire). RESULTS Of 1241 participants (83% unipolar; 56% female), at least 30% were functionally impaired on the objective, self-rated and/or observer-rated measures, with 16% impaired according to all three criteria. Even when current distress levels were taken into account, daily use of cannabis and/or nicotine were significantly associated with impairment, with odds ratios (OR) ranging from about 1.5 to 3.0. Comorbid anxiety disorders were related to lower SOFAS scores (OR = 2-5). CONCLUSIONS Levels of disability were significant, even in those presenting for mental healthcare for the first time. Functional impairment did not differ between unipolar and bipolar cases, but some evidence suggested that females with bipolar disorder were particularly disabled. The prevalence of comorbid disorders (50%) and polysubstance use (28%) and their association with disability indicate that more meaningful indicators of mood episode outcomes should focus on functional rather than symptom-specific measures. The association between functioning and nicotine use requires further exploration.

Clinical correlates of chronotypes in young persons with mental disorders.

While important changes in circadian rhythms take place during adolescence and young adulthood, it is unclear how circadian profiles during this period relate to emerging mental disorders. This study aimed to: (i) characterise morningness–eveningness preference in young people with primary anxiety, depression, bipolar or psychotic disorders as compared to healthy controls, and (ii) to investigate associations between morningness–eveningness preference and the severity of psychiatric symptoms. Four hundred and ninety-six males and females aged between 12 and 30 years were divided into five groups according to primary diagnosis. The Hamilton Depression Rating Scale and the Brief Psychiatric Rating Scale were administered by a research psychologist and participants completed the Kessler Psychological Distress Scale and the Horne–Östberg Morningness–Eveningness Questionnaire (ME). ME scores were significantly lower (i.e. higher levels of “eveningness”) in all patient diagnosis subgroups compared to the control group. The psychosis group had higher ME scores than the depression and anxiety groups. Compared to the control group, the anxiety, depression and bipolar subgroups had a significantly higher proportion of “moderate evening” types, with a similar trend for the psychosis group. The proportion of “extreme evening” types was significantly higher in the anxiety and depression subgroups than in the control group. Lower ME scores correlated with worse psychological distress in males from the bipolar group. Lower ME scores correlated with higher depression severity in females with depression and in males with bipolar disorder. These results suggest that young persons with various mental disorders, especially those with affective disorders, present with a stronger “eveningness” preference and higher rates of evening chronotypes than healthy controls from the same age group. Later chronotypes were generally associated with worse psychological distress and symptoms severity. These associations were modulated by sex and primary diagnosis.

Microstructural white matter changes are correlated with the stage of psychiatric illness

Microstructural white matter changes have been reported in the brains of patients across a range of psychiatric disorders. Evidence now demonstrates significant overlap in these regions in patients with affective and psychotic disorders, thus raising the possibility that these conditions share common neurobiological processes. If affective and psychotic disorders share these disruptions, it is unclear whether they occur early in the course or develop gradually with persistence or recurrence of illness. Utilisation of a clinical staging model, as an adjunct to traditional diagnostic practice, is a viable mechanism for measuring illness progression. It is particularly relevant in young people presenting early in their illness course. It also provides a suitable framework for determining the timing of emergent brain alterations, including disruptions of white matter tracts. Using diffusion tensor imaging, we investigated the integrity of white matter tracts in 74 patients with sub-syndromal psychiatric symptoms as well as in 69 patients diagnosed with established psychosis or affective disorder and contrasted these findings with those of 39 healthy controls. A significant disruption in white matter integrity was found in the left anterior corona radiata and in particular the anterior thalamic radiation for both the patients groups when separately contrasted with healthy controls. Our results suggest that patients with sub-syndromal symptoms exhibit discernable early white matter changes when compared with healthy control subjects and more significant disruptions are associated with clinical evidence of illness progression.

Thoughts of death or suicidal ideation are common in young people aged 12 to 30 years presenting for mental health care

BackgroundReducing suicidal behaviour is a major public health goal. Expanding access to care has been identified as a key strategy. In Australia, a national network of primary-care based services (headspace) has been established for young people with mental ill-health. This study determines the socio-demographic, psychopathological and illness-stage correlates of suicidal ideation in young persons attending headspace services.MethodsSuicidal ideation was recorded using the specific suicide item of the Hamilton Depression Rating Scale (HDRS) in a cohort of subjects aged 12-30 years (N = 494) attending headspace services.ResultsOf the 494 young persons assessed, 32% (158/494) had a positive response to any level of the HDRS suicide item, consisting of 16% (77/494) reporting that life was not worth living and a further 16% (81/494) reported thoughts of death or suicidal ideation. Young women (19%; 94/494) were more likely to report any positive response as compared with young men (13%; 64/494) [χ2(2,494) = 13.6, p < .01]. Those with ‘attenuated syndromes’ reported positive responses at rates comparable to those with more established disorders (35% vs. 34%; χ2(1,347) = 0.0, p = 0.87). However, more serious levels of suicidal ideation were more common in those with depressive disorders or later stages of illness. In multivariate analyses, the major predictors of the degree of suicidal ideation were increasing levels of clinician-rated depressive symptoms (beta = 0.595, p < .001), general psychopathology (beta = 0.198, p < .01), and self-reported distress (beta = 0.172, p < .05).ConclusionsFeelings that life is not worth living, thoughts of death or suicidal ideation are common in young people seeking mental health care. These at-risk cognitions are evident before many of these individuals develop severe or persistent mental disorders. Thoughts of death or suicidal ideation may well need to be a primary intervention target in these young people.

Cluster analysis reveals abnormal hippocampal neurometabolic profiles in young people with mood disorders

While numerous studies have employed magnetic resonance spectroscopy (MRS) to determine in vivo neurometabolite levels associated with mood disorders the findings in both unipolar depression and bipolar disorder have been mixed. Data-driven studies may shed new light on this literature by identifying distinct subgroups of patients who may benefit from different treatment strategies. The objective of the present study was to utilize hierarchical cluster analysis in order to generate new hypotheses with respect to neurometabolic profiling of mood disorder. Participants were 165 young persons (18-30 yrs) with a mood disorder and 40 healthy controls. Neurometabolite levels were recorded via proton-MRS ((1)H MRS). The ratios (relative to creatine) of glutamate (GLU), N-acetyl aspartate (NAA) and myo-inositol (MI) measured within the hippocampus. Self-reported and clinician rated symptoms as well as cognition were also measured. The unipolar depression (N=90) and bipolar disorder (N=75) groups did not significantly differ (from each other or controls) in their levels of GLU, NAA or MI. Cluster analyses derived four subgroups of patients who were distinguished by all three metabolites. There was a pattern of positive association between NAA and GLU, whereby clusters were abnormally increased (clusters 1, 2) or normal (cluster 4) or abnormally decreased (cluster 3) in these neurometabolites. These findings suggest that there are neurometabolic abnormalities in subgroups of young people with mood disorder, which may occur despite diagnostic similarities. Such evidence highlights that the underlying neurobiology of mood disorder is complex and MRS may have unique utility in delineating underlying neurobiology and targeting treatment strategies.