What clinical features precede the onset of bipolar disorder?

Despite a growing number of reports, there is still limited knowledge of the clinical features that precede the onset of bipolar disorder (BD). To explore this, we investigated baseline data from a prospectively evaluated longitudinal cohort of subjects aged 12–30 years to compare: first, lifetime rates of clinical features between a) subjects at increased genetic risk for developing BD (‘AR’), b) participants from families without mental illness (‘controls’), and c) those with established BD; and, second, prior clinical features that predict the later onset of affective disorders in these same three groups. This is the first study to report such comparisons between these three groups (though certainly not the first to compare AR and control samples). 118 AR participants with a parent or sibling with BD (including 102 with a BD parent), 110 controls, and 44 BD subjects were assessed using semi-structured interviews. AR subjects had significantly increased lifetime risks for depressive, anxiety and behavioural disorders compared to controls. Unlike prior reports, preceding anxiety and behavioural disorders were not found to increase risk for later onset of affective disorders in the AR sample, perhaps due to limited sample size. However, preceding behavioural disorders did predict later onset of affective disorders in the BD sample. The findings that i) AR subjects had higher rates of depressive, anxiety and behavioural disorders compared to controls, and ii) prior behavioural disorders increased the risk to later development of affective disorders in the BD group, suggest the possibility of therapeutic targeting for these disorders in those at high genetic risk for BD.     

Does auditory attention shift in the direction of an upcoming saccade?

In a series of experiments, we examined whether auditory attention shifts in the direction of an upcoming saccade, as recently reported for visual attention. Normal listeners made speeded discriminations for the elevation (up versus down) of abrupt sounds, regardless of their laterality. Each sound was presented around the time that a lateral saccade was made. Auditory elevation discriminations were reliably faster when the saccade was made towards the side of the auditory probe rather than away. Furthermore, an auditory probe on one side speeded up centrally-cued saccades made in that direction, although sounds did not influence saccades to peripheral visual events. The latter visual events were insufficient to affect hearing unless a saccade was made towards them. A further study showed that fixating towards or away from sounds, rather than saccading, could also affect elevation judgements, with poorer performance when fixating away. However, the influence of an upcoming saccade upon hearing could not be reduced to this fixation effect, since the saccade influence was found even for sounds which terminated before any shift in fixation began. Taken together, our results imply that the direction of an upcoming saccade can affect hearing, as can eye-position.     

Does urbanicity shift the population expression of psychosis?

Growing up in an urban area has been shown to be associated with an increased risk of psychotic disorder in later life. While it is commonly held that a only a tiny fraction of exposed individuals will develop schizophrenia, recent evidence suggests that expression of psychosis in exposed individuals may be much more common, albeit at attenuated levels. Findings are based on a population sample of 2548 adolescents and young adults aged originally 14–24 years, and followed up over almost 5 years up to ages 17–28 years. Trained psychologists assessed all these subjects with the core psychosis sections on delusions and hallucinations of the Munich-Composite International Diagnostic Interview. Growing up in an urban area was associated with an increased risk of expression of psychosis in the adolescents and young adults (adjusted OR 1.31, 95% CI 1.03–1.66). The proxy environmental risk factor that urbanicity represents may shift a relatively large section of the adolescent population along a continuum of expression of psychosis. Other causal influences may be required to make the transition to schizophrenia in adult life.     

Does the Modified Fatigue Impact Scale offer a more comprehensive assessment of fatigue in MS?

BACKGROUND: As a symptom of multiple sclerosis (MS), fatigue is difficult to manage because of its unknown etiology, the lack of efficacy of the drugs tested to date and the absence of consensus about which would be the ideal measure to assess fatigue. OBJECTIVE: Our aim was to assess the frequency of fatigue in a sample of MS patients and healthy controls (HC) using two fatigue scales, the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS) with physical, cognitive and psychosocial subscales. We also studied the relationship fatigue has with depression, disability and interferon beta. METHODS: Three hundred and fifty-four individuals (231 MS patients and 123 HC) were included in this cross-sectional study. Fatigue was assessed using the FSS and MFIS. Depression was measured by the Beck Depression Inventory (BDI), and disability by the Expanded Disability Status Scale (EDSS). A status of fatigue was considered when the FSS > or =5, of non-fatigue when the FSS < or =4, and scores between 4.1 and 4.9 were considered doubtful fatigue cases. RESULTS: Fifty-five percent of MS patients and 13% of HC were fatigued. The global MFIS score positively correlated with the FSS in MS and HC (r =0.68 for MS and r =0.59 for HC, p <0.0001). Nonetheless, the MFIS physical subscale showed the strongest correlation score with the FSS (r =0.75, p <0.0001). In addition, a prediction analysis showed the physical MFIS subscale to be the only independent predictor of FSS score (p <0.0001), suggesting other aspects of fatigue, as cognition and psychosocial functions, may be explored by the FSS to a lesser extent. Depression also correlated with fatigue (r =0.48 for the FSS and r =0.7 for the MFIS, p <0.0001) and, although EDSS correlated with fatigue as well, the scores decreased after correcting for depression. Interferon beta showed no relationship with fatigue. CONCLUSIONS: Fatigue is a frequent symptom found in MS patients and clearly related with depression. Each fatigue scale correlates with one another, indicating that they are measuring similar constructs. Nevertheless, spheres of fatigue as cognition and psychosocial functions are probably better measured by the MFIS, although this hypothesis will need to be confirmed with appropriate psychometrical testing.     

Does age at the onset of narcolepsy influence the course and severity of the disease?

ObjectiveThe aim of the study is to compare the course and severity of narcolepsy in relation to different ages at the disease onset.MethodsClinical interviews with the completion of the Stanford questionnaire, Epworth Sleepiness Scale (ESS) and Multiple Sleep Latency Test (MSLT) were evaluated in 105 patients (44 males, 61 females, mean age 45.4 ± 19.2, BMI 29.2 ± 5.8) suffering from narcolepsy.ResultsThe severity of the disease was judged by clinical complaints, ESS value and MSLT results. No relations with the age at onset and clinical tetrad were found, however, smoking may be associated with an increased risk of hypnagogic hallucinations. There was no correlation between the number of sleep and cataplectic attacks and the age at onset, nor did subjective ESS show any significant dependence. However, earlier onset of the disease correlated with shorter MSLT mean latency. A correlation was found between the BMI and narcolepsy sleepiness rating in the elderly and between degree of education attained and subjective complaints.ConclusionsThe clinical severity of narcolepsy does not depend on the age at onset.     

Is the poor sleep of shift workers a disorder?

OBJECTIVE: The purpose of this article is to describe the impact of shift work on sleep, as recently acknowledged in official nosologies of sleep disorders, and to discuss whether sleep altered by shift work actually constitutes a disorder. METHOD: The authors review subjective responses to recent survey questions about sleep and polygraphic measurements of sleep in shift workers and describe sleep clinic experiences with complaints related to shift work. FINDINGS: Shift work entails wide variation in work schedules, sleep quality, and worker tolerance and a high prevalence of night-shift sleepiness. It probably affects rates of drug use, health status, and family organization. Clinical presentations were rare, highly varied, and empirically treated. The United States, unlike other countries, has no legal restrictions on shift work. CONCLUSIONS: As a clinical phenomenon, sleep altered by shift work is common and varied, probably expresses nonphysiological sleep-wake scheduling, and is little treated. Further study of its health effects and consideration of whether it is a "disorder" or a "problem" seem warranted.     

Does Dynorphin Play a Role in the Onset of Puberty in Female Sheep?

Puberty onset involves increased gonadotrophin‐release (GnRH) release as a result of decreased sensitivity to oestrogen (E₂)‐negative feedback. Because GnRH neurones lack E₂ receptor α, this pathway must contain interneurones. One likely candidate is KNDy neurones (kisspeptin, neurokinin B, dynorphin). The overarching hypothesis of the present study was that the prepubertal hiatus in luteinising hormone (LH) release involves reduced kisspeptin and/or heightened dynorphin input. We first tested the specific hypothesis that E₂ would reduce kisspeptin‐immunopositive cell numbers and increase dynorphin‐immunopositive cell numbers. We found that kisspeptin cell numbers were higher in ovariectomised (OVX) lambs than OVX lambs treated with E₂ (OVX+ E₂) or those left ovary‐intact. Very few arcuate dynorphin cells were identified in any group. Next, we hypothesised that central blockade of κ‐opioid receptor (KOR) would increase LH secretion at a prepubertal (6 months) but not postpubertal (10 months) age. Luteinising hormone pulse frequency and mean LH increased during infusion of a KOR antagonist, norbinaltorphimine, in OVX + E₂ lambs at the prepubertal age but not in the same lambs at the postpubertal age. We next hypothesised that E₂ would increase KOR expression in GnRH neurones or alter synaptic input to KNDy neurones in prepubertal ewes. Oestrogen treatment decreased the percentage of GnRH neurones coexpressing KOR (approximately 68%) compared to OVX alone (approximately 78%). No significant differences in synaptic contacts per cell between OVX and OVX + E₂ groups were observed. Although these initial data are consistent with dynorphin inhibiting pulsatile LH release prepubertally, additional work will be necessary to define the source and mechanisms of this inhibition.     

Does a pro-inflammatory process precede Alzheimer's disease and mild cognitive impairment?

The occurrence of a plaque-dependent inflammation in Alzheimer's disease has been extensively documented in both human specimens and transgenic models of the disease. Since insoluble plaques are present in AD patients from early preclinical stages of the pathology, the point at which neuroinflammation first occurs in the progression of the AD pathology is still unknown. In this review we discuss the clinical and experimental evidence for the occurrence of inflammation in preclinical, asymptomatic phases of the progression of the AD pathology. In particular, we discuss the evidence from different transgenic models suggesting that a pro-inflammatory process might even be initiated prior to plaque deposition. The factors responsible for the early, pre-plaque inflammation are reviewed, with particular emphasis on the role of soluble Aβ oligomers. Furthermore, we analyze the consequences of the microglial activation and the deregulation of NGF metabolism, in the context of the earliest amyloid pathology. Finally, we propose MMP-9 as a promising biomarker for signalling early stages of an ongoing CNS inflammation.     

Does catatonia influence the phenomenology of childhood onset schizophrenia beyond motor symptoms?

Childhood onset schizophrenia (COS) and catatonia (C) are rare and severe psychiatric disorders. The aim of this study was to compare the phenomenology of COS with and without catatonia. We examined 33 cases consecutively referred to two major public university hospitals in Paris. There were 18 cases of COS (age=15.9+/-0.8 years) and 15 of COS+C (age=15.4+/-1.4 years). Patients were referred over the course of 3 and 9 years, respectively. Psychiatric assessment included socio-demographic, clinical and psychometric variables: the Brief Psychiatric Rating Scale (BPRS), the Scales for the Assessment of Positive (SAPS) and Negative Symptoms (SANS), and a catatonia rating scale. Patients with COS+C appeared to be more severely ill at admission and discharge compared with COS in nearly all clinical scores. They also exhibited significantly longer episode duration (50.8 weeks+/-4.8 vs 20.6+/-19.5). On the basis of multivariate logistic regression, the only clinical measure which significantly predicted group membership was the SANS Affective Flattening score (odds ratio=1.24; 95% CI=1.06-1.43). Our findings strongly suggest that catatonic COS differs from COS in ways that extend beyond motor symptoms. The SANS and SAPS scales, commonly used in schizophrenia, are not detailed enough to accurately describe catatonia in COS. The use of a catatonia rating scale is recommended to enhance recognition of and research into COS with catatonia.     

What causes the onset of psychosis?

It has become increasingly clear that the simple neurodevelopmental model fails to explain many aspects of schizophrenia including the timing of the onset, and the nature of the abnormal perceptions. Furthermore, we do not know why some members of the general population have anomalous experiences but remain well, while others enter the prodrome of psychosis, and a minority progress to frank schizophrenia. We suggest that genes or developmental damage result in individuals vulnerable to dopamine deregulation. In contemporary society, this is often compounded by abuse of drugs such as amphetamines and cannabis, which then propel the individual into a state of dopamine-induced misinterpretation of the environment. Certain types of social adversity such as migration and social isolation, as well as affective change can also contribute to this. Thereafter, biased cognitive appraisal processes result in delusional interpretation of the abnormal perceptual experiences. Thus, a plausible model of the onset of psychosis needs to draw not only on neuroscience, but also on the insights of social psychiatry and cognitive psychology.     

Does mirtazapine have a more rapid onset than SSRIs?

BACKGROUND: A single study utilizing a cross-sectional analysis of scores on the Hamilton Rating Scale for Depression (HAM-D) suggested that mirtazapine has a more rapid onset than selective serotonin reuptake inhibitors (SSRIs). Analysis based on the HAM-D may favor drugs with sleep-producing effects. The purpose of the present study was to determine if a review of all studies comparing an SSRI with mirtazapine, utilizing persistent improvement as the dependent variable, would suggest that mirtazapine had a more rapid onset than SSRIs. METHOD: All double-blind studies comparing mirtazapine with SSRIs were analyzed. Included in the analysis to determine speed of onset were 298 patients taking mirtazapine and 285 taking an SSRI. Pattern analysis, which has been described and used by other researchers, was employed to study speed of onset. RESULTS: At the end of each of the 3 studies, the total number of responders for each of the drugs did not differ. However, the proportion of responders with onset of persistent improvement in week 1 was greater for mirtazapine (13%, 38/298) than for the SSRIs (6%, 18/285; chi2 = 6.95, df = 1, p = .008). CONCLUSION: These data support the possibility that mirtazapine may have a more rapid onset than SSRIs. This observation should be considered preliminary because of the retrospective nature of the analysis and the absence of a placebo group.     

CDR3 spectratyping analysis of the T cell receptor repertoire in Guillain-Barré and Fisher syndromes

Several autoimmune and infectious disorders show oligoclonal expansion of particular T cell phenotypes. The extent of T cell involvement in the pathogenesis of Guillain-Barré syndrome (GBS), a post-infectious autoimmune neuropathy, however, is not clear. To identify the pathogenic T cell phenotypes in GBS and Fisher syndrome (FS), variations in T cell receptor use of the V beta 1-24 and V delta 1-5 chain genes were analyzed at complementarity-determining region 3 level in 119 patients with GBS or FS. Overall, V beta and V delta spectratypes were expanded more frequently in patients with GBS (V beta in 77%, V delta in 53%) or FS (V beta in 75%, V delta in 65%) than in the healthy controls (V beta in 59%, V delta in 38%). No particular spectratype was significantly associated with GBS or FS. Subgrouping the patients by Campylobacter jejuni serology and anti-ganglioside IgG antibodies also failed to detect particular spectratype gene use. The frequency of V beta 5.2 expansion tended to be higher in patients with positive Haemophilus influenzae serology (50%) than in the controls (7%), but the difference was not significant. Our findings show that oligoclonal expansion of T cells bearing particular type T cell receptor V beta and V delta genes frequently occurs in GBS and FS, suggestive that T cells mediate the development of these neuropathies. The predominant phenotypes vary, even within subgroups of patients with a syndrome of single etiological origin or those with uniform serological features.     

Does the presence of anxiety affect the validity of a screening test for depression in the elderly?

INTRODUCTION: Depression in the elderly is frequently detected by screening instruments and often accompanied by anxiety. We set out to study if anxiety will affect the ability to detect depression by a screening instrument. OBJECTIVE: To validate the short Zung depression rating scale in Israeli elderly and to study the affect of anxiety on its validity. DESIGN: The short Zung was validated against a psychiatric evaluation, in a geriatric inpatient and outpatient service. The overall validity was determined, as well as for subgroups of sufferers and non-sufferers of anxiety. SETTING: An urban geriatric service in Israel. PATIENTS: 150 medical inpatients and outpatients, aged 70 years and older.MEASURES: Psychiatric evaluation of modified Anxiety Disorders Interview Schedule for DSM-IV as criterion standard for anxiety and depression and short Zung instrument for depression. RESULTS: By criterion validity, 60% suffered from depression. The overall validity of the short Zung was high (sensitivity 71.1%, specificity 88.3%, PPV 90.1%, NPV 67.1%). The validity for those not suffering from anxiety was good (sensitivity 71.1%, specificity 90.2%, PPV 84.4%, NPV 80.7%). In those with anxiety, sensitivity, specificity and PPV were high (71.2%, 77.8%, 94.9% respectively), although the specificity was less than in non-suffers. However major difference was in the NPV rate being much lower (31.8%). CONCLUSION: The short Zung, an easily administered instrument for detecting depression, is also valid in the Israeli elderly. However, anxiety limits the usefulness of this instrument in correctly ruling out depression. The clinician must be aware, therefore, that those suffering from anxiety may score negatively for depression on a screening instrument, such as the short Zung.