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Bipolar disorder (BD) is a psychiatric disorder associated with increased rates of obesity and inflammation. Leptin is an adipokine that is mainly produced by the white adipose tissue in response to insulin. It stimulates the immune system, increasing the production of pro-inflammatory cytokines. There is currently uncertainty regarding possible alterations in peripheral leptin levels across the mood states in BD.
Methods
This study comprises a between-group meta-analysis comparing serum and plasma leptin levels in people with BD in mania, depression or euthymia and healthy controls. We conducted a systematic search for all possibly eligible-English and non-English peer-reviewed articles. We calculated the effect size (ES) utilizing Hedges’ adjusted g using random effects.
Results
Eleven studies were included in the meta-analyses, providing data on 1118 participants. Serum and plasma leptin levels were not altered in subjects with BD when compared to healthy controls in mania (g = −0.99, 95% CI −2.43 to 0.43, P = 0.171), in depression (g = 0.17, 95% CI −0.45 to 0.79, P = 0.584), or in euthymia (g = 0.03, 95% CI −0.39 to 0.46, P = 0.882). However, we did observe a stronger association between leptin levels and both age and BMI in patients with BD in euthymia compared to healthy controls, such that the greater the age of the individuals, the greater the difference in leptin levels between BD and controls; and the higher the BMI, the greater the difference in leptin levels between BD and controls.
Conclusions
Our meta-analysis provides evidence that leptin levels are not altered in BD across the mood spectrum compared to healthy controls. The disproportionate increase of leptin levels with increase in BMI in BD speaks in favour of a potential inflammatory role of white adipose tissue in BD and a disproportionate increase of leptin levels with increase in age.
The evidence informing the management of cardiovascular risk in patients with psychiatric disorders is weak.
Methods
This cohort study used data from all patients, aged ≥ 30, registered in 140 primary care practices (n = 524,952) in London to estimate the risk of developing diabetes, hypertension, hyperlipidemia, tobacco consumption, obesity, and physical inactivity, between 2005 and 2015, for patients with a previous diagnosis of schizophrenia, depression, anxiety, bipolar or personality disorder. The role of antidepressants, antipsychotics and social deprivation in these associations was also investigated. The age at detection of cardiovascular risk factor was compared between patients with and without psychiatric disorders. Variables, for exposures and outcomes, defined from general practitioners records, were analysed using multivariate regression.
Results
Patients with psychiatric disorders had an increased risk for cardiovascular risk factors, especially diabetes, with hazard ratios: 2.42 (2.20–2.67) to 1.31 (1.25–1.37), hyperlipidemia, with hazard ratios: 1.78 (1.60–1.97) to 1.25 (1.23–1.28), and obesity. Antidepressants, antipsychotics and social deprivation did not change these associations, except for smoking and physical inactivity. Antidepressants were associated with higher risk of diabetes, hypertension and hyperlipidemia. Antipsychotics were associated with a higher risk of diabetes. Antidepressants and antipsychotics were associated with lower risk of other risk factors. Patients with psychiatric conditions have later detection of cardiovascular risk factors. The interpretation of these results should acknowledge the lower rates of detection of risk factors in mentally ill patients.
Conclusions
Cardiovascular risk factors require special clinical attention among patients with psychiatric disorders. Further research could study the effect of antidepressants and antipsychotics on cardiovascular risk factors.
To validate the diagnosis of hyperkinetic disorders (HD) in the Danish Psychiatric Central Research Registry (DPCRR) for children and adolescents aged 4 to 15 given in the years 1995 to 2005.
Method
From a total of 4568 participants, a representative random subsample of n = 387 patients were used to validate the diagnosis. Patient files were systematically scored for the presence of ICD-10 criteria for HD and oppositional defiant disorder/conduct disorder (ODD/CD; F91). Further to this, an inter-rater reliability study was also conducted, whereby two experienced child and adolescent psychiatrists who were blind to patients discharge diagnoses, rated a random subsample of n = 101 participants.
Results
Information was available for 372 out of 387 patients. Out of n = 372 available files, n = 324 (86.8%) were evaluated to fulfil diagnostic criteria for HD. Due to missing information it was not possible to reach a conclusion for 5.1% of the cases, 3.8% of the diagnoses were registration errors, and in 4.3% of the files the diagnosis had to be rejected. Inter-rater agreement was high (κ = 0.83, z = 10.9, P < .001). The validity of hyperkinetic disorders, unspecified (F90.9) was lower and comorbid CD/ODD were under-diagnosed in the sample. All participants fulfilling HD criteria also fulfilled DSM-5-criteria for ADHD.
Conclusion
The risk of misclassification of patients with HD in the DPCRR is relatively low, with the exception of the diagnosis of hyperkinetic disorders, unspecified (F90.9).
Reduced gray matter volumes in the superior temporal gyrus (STG) have been reported in patients with schizophrenia. Such volumetric abnormalities might denote alterations in cortical thickness, surface area, local gyrification or all of these factors. The STG can be anatomically divided into five subregions using automatic parcellation in FreeSurfer: lateral aspect of the STG, anterior transverse temporal gyrus of Heschl gyrus (HG), planum polare (PP) of the STG, planum temporale (PT) of the STG and transverse temporal sulcus.
Methods
We acquired magnetic resonance imaging (MRI) 3T scans from 40 age- and sex-matched patients with schizophrenia and 40 healthy subjects, and the scans were automatically processed using FreeSurfer. General linear models were used to assess group differences in regional volumes and detailed thickness, surface area and local gyrification.
Results
As expected, patients with schizophrenia had significantly smaller bilateral STG volumes than healthy subjects. Of the five subregions in the STG, patients with schizophrenia showed significantly and marginally reduced volumes in the lateral aspect of the STG and PT of the STG bilaterally compared with healthy subjects. The volumetric alteration in bilateral lateral STG was derived from both the cortical thickness and surface area but not local gyrification. There was no significant laterality of the alteration in the lateral STG between patients and controls and no correlation among the structures and clinical characteristics.
Conclusions
These findings suggest that of five anatomical subregions in the STG, the lateral STG is one of the most meaningful regions for brain pathophysiology in schizophrenia.
Adolescent-onset schizophrenia (AOS) is associated with cognitive impairment and poor clinical outcome. Cognitive dysfunction is hypothesised, in part, to reflect functional dysconnectivity between the frontal cortex and the striatum, although structural abnormalities consistent with this hypothesis have not yet been demonstrated in adolescence.
Objective
To characterise frontostriatal white matter (WM) tracts in relation to cognition in AOS.
Design
A MRI volumetric and diffusion tensor imaging study.
Participants
Thirty-seven AOS subjects and 24 age and sex-matched healthy subjects.
Outcome measures
Using probabilistic tractography, cortical regions with the highest connection probability for each striatal voxel were determined, and correlated with IQ and specific cognitive functions after co-varying for age and sex. Fractional anisotropy (FA) from individual tracts was a secondary measure.
Results
Bayesian Structural Equation modeling of FA from 12 frontostriatal tracts showed processing speed to be an intermediary variable for cognition. AOS patients demonstrated generalised cognitive impairment with specific deficits in verbal learning and memory and in processing speed after correction for IQ. Dorsolateral prefrontal cortex connectivity with the striatum correlated positively with these measures and with IQ. DTI voxel-wise comparisons showed lower connectivity between striatum and the motor and lateral orbitofrontal cortices bilaterally, the left amygdalohippocampal complex, right anterior cingulate cortex, left medial orbitofrontal cortex and right dorsolateral prefrontal cortex.
Conclusions
Frontostriatal dysconnectivity in large WM tracts that can explain core cognitive deficits are evident during adolescence. Processing speed, which is affected by alterations in WM connectivity, appears an intermediary variable in the cognitive deficits seen in schizophrenia.
The purpose of this paper was to examine national differences in the desire to participate in decision-making of people with severe mental illness in six European countries.
Methods
The data was taken from a European longitudinal observational study (CEDAR; ISRCTN75841675). A sample of 514 patients with severe mental illness from the study centers in Ulm, Germany, London, England, Naples, Italy, Debrecen, Hungary, Aalborg, Denmark and Zurich, Switzerland were assessed as to desire to participate in medical decision-making. Associations between desire for participation in decision-making and center location were analyzed with generalized estimating equations.
Results
We found large cross-national differences in patients’ desire to participate in decision-making, with the center explaining 47.2% of total variance in the desire for participation (P < 0.001). Averaged over time and independent of patient characteristics, London (mean = 2.27), Ulm (mean = 2.13) and Zurich (mean = 2.14) showed significantly higher scores in desire for participation, followed by Aalborg (mean = 1.97), where scores were in turn significantly higher than in Debrecen (mean = 1.56). The lowest scores were reported in Naples (mean = 1.14). Over time, the desire for participation in decision-making increased significantly in Zurich (b = 0.23) and decreased in Naples (b = −0.14). In all other centers, values remained stable.
Conclusions
This study demonstrates that patients’ desire for participation in decision-making varies by location. We suggest that more research attention be focused on identifying specific cultural and social factors in each country to further explain observed differences across Europe.
ADHD in childhood is associated with development of negative psychosocial and behavioural outcomes in adults. Yet, relatively little is known about which childhood and adulthood factors are predictive of these outcomes and could be targets for effective interventions. To date follow-up studies have largely used clinical samples from the United States with children ascertained at baseline using broad criteria for ADHD including all clinical subtypes or the use of DSM III criteria.
Aims
To identify child and adult predictors of comorbid and psychosocial comorbid outcomes in ADHD in a UK sample of children with DSM-IV combined type ADHD.
Method
One hundred and eighteen adolescents and young adults diagnosed with DSM-IV combined type ADHD in childhood were followed for an average of 6 years. Comorbid mental health problems, drug and alcohol use and police contact were compared for those with persistent ADHD, sub-threshold ADHD and population norms taken from the Adult Psychiatric Morbidity Study 2007. Predictors included ADHD symptomology and gender.
Results
Persistent ADHD was associated with greater levels of anger, fatigue, sleep problems and anxiety compared to sub-threshold ADHD. Comorbid mental health problems were predicted by current symptoms of hyperactivity-impulsivity, but not by childhood ADHD severity. Both persistent and sub-threshold ADHD was associated with higher levels of drug use and police contact compared to population norms.
Conclusions
Young adults with a childhood diagnosis of ADHD showed increased rates of comorbid mental health problems, which were predicted by current levels of ADHD symptoms. This suggests the importance of the continuing treatment of ADHD throughout the transitional years and into adulthood. Drug use and police contact were more common in ADHD but were not predicted by ADHD severity in this sample.
Parenting dimensions are associated with depressive symptoms in adolescents. We investigated the role of perceived parenting dimensions and gene-environment interactions between these perceived parenting dimensions and five well-known variable number of tandem repeats (VNTRs): 5-HTTLPR, STin2, DAT1, DRD4, and MAO-A, in depressive symptoms.
Methods
From a non-clinical sample of 1111 Belgian adolescents (mean age: 13.79 years, SD = .94; 51% boys), 1103 adolescents consented for genetic research. Five VNTRs were analyzed using DNA from saliva samples. Perceived parenting dimensions (i.e., support, proactive control, psychological control, punishment, and harsh punishment) were examined using self-report scales completed by adolescents and their parents. Depressive symptoms were investigated using the CES-D self-report scale. Statistical analyses were performed in R using linear regression.
Results
Parental support, as perceived by the adolescent, was negatively associated with depressive symptoms (CES-D) and psychological control was positively associated with these symptoms. The only interaction effect withstanding correction for multiple testing was observed for 5-HTTLPR and the difference in proactive control as perceived by adolescents in comparison to parents. Short-allele carriers showed more depressive symptoms when there was a higher discrepancy in proactive control as perceived by adolescents versus parents.
Conclusions
Our results suggest that perceived parenting dimensions are associated with depressive symptoms, as measured by the CES-D. We only found modest evidence for 5-HTTLPR as a moderator in the association between the difference in perception of proactive control (adolescents vs. parents) and depressive symptoms.