Large-scale analysis of structural brain asymmetries during neurodevelopment: Associations with age and sex in 4265 children and adolescents.

Only a small number of studies have assessed structural differences between the two hemispheres during childhood and adolescence. However, the existing findings lack consistency or are restricted to a particular brain region, a specific brain feature, or a relatively narrow age range. Here, we investigated associations between brain asymmetry and age as well as sex in one of the largest pediatric samples to date (n = 4265), aged 1-18 years, scanned at 69 sites participating in the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. Our study revealed that significant brain asymmetries already exist in childhood, but their magnitude and direction depend on the brain region examined and the morphometric measurement used (cortical volume or thickness, regional surface area, or subcortical volume). With respect to effects of age, some asymmetries became weaker over time while others became stronger; sometimes they even reversed direction. With respect to sex differences, the total number of regions exhibiting significant asymmetries was larger in females than in males, while the total number of measurements indicating significant asymmetries was larger in males (as we obtained more than one measurement per cortical region). The magnitude of the significant asymmetries was also greater in males. However, effect sizes for both age effects and sex differences were small. Taken together, these findings suggest that cerebral asymmetries are an inherent organizational pattern of the brain that manifests early in life. Overall, brain asymmetry appears to be relatively stable throughout childhood and adolescence, with some differential effects in males and females.

Psychiatric vulnerability and the risk for unintended pregnancies, a systematic review and meta-analysis.

BACKGROUND: Unintended pregnancies (UPs) are a global health problem as they contribute to adverse maternal and offspring outcomes, which underscores the need for prevention. As psychiatric vulnerability has previously been linked to sexual risk behavior, planning capacities and compliance with contraception methods, we aim to explore whether it is a risk factor for UPs. METHODS: Electronic databases were searched in November 2020. All articles in English language with data on women with age ≥ 18 with a psychiatric diagnosis at time of conception and reported pregnancy intention were included, irrespective of obstetric outcome (fetal loss, livebirth, or abortion). Studies on women with intellectual disabilities were excluded. We used the National Institutes of Health tool for assessment of bias in individual studies and the Grading of Recommendations Assessment, Development and Evaluation method for assessment of quality of the primary outcome. FINDINGS: Eleven studies reporting on psychiatric vulnerability and UPs were included. The participants of these studies were diagnosed with mood, anxiety, psychotic, substance use, conduct and eating disorders. The studies that have been conducted show that women with a psychiatric vulnerability (n = 2650) have an overall higher risk of UPs compared to women without a psychiatric vulnerability (n = 16,031) (OR 1.34, CI 1.08-1.67) and an overall weighed prevalence of UPs of 65% (CI 0.43-0.82) (n = 3881). INTERPRETATION: Studies conducted on psychiatric vulnerability and UPs are sparse and many (common) psychiatric vulnerabilities have not yet been studied in relation to UPs. The quality of the included studies was rated fair to poor due to difficulties with measuring the outcome pregnancy intention (use of various methods of assessment and use of retrospective study designs with risk of bias) and absence of a control group in most of the studies. The findings suggest an increased risk of UPs in women with psychiatric vulnerability. As UPs have important consequences for mother and child, discussing family planning in women with psychiatric vulnerabilities is of utmost importance.

[Anxiety, depression and sleep disorders in Parkinson's disease: a complex interaction between body and mind]. / Angst, depressie en slaapproblemen bij de ziekte van Parkinson: een complexe interactie tussen lichaam en geest.

BACKGROUND: Anxiety and depression in Parkinson's disease (PD) are often unrecognized, partially due to a complex relationship with sleep disorders and other PD-related symptoms.
AIM: To gain more insight in anxiety, depression and sleep disorders in PD, their reciprocal interaction and relationship with other (non)motor symptoms.
METHOD: With three epidemiological studies in this thesis article we describe: the symptom dimensions of anxiety, motor symptoms and autonomic failure; predictors of the course of anxiety; and the temporal relationship between anxiety, depression and insomnia in PD.
RESULTS: Anxiety in PD has one affective and various somatic symptom dimensions. There is a symptomatic overlap between anxiety and symptoms of motor and autonomic dysfunctions. Anxiety, depression and impulsive-compulsive behaviors in de novo PD show a parallel course. Cognitive dysfunctions and REM-sleep behaviour disorder are risk factors for anxiety in PD patients. The relationship between insomnia and anxiety and depression is bi-directional.
CONCLUSION: There is an overlap, co-morbidity and interaction between anxiety, depression, sleep disorders and (non)motor symptoms, which warrants a multi-disciplinary approach to PD. Sleep disorders and cognitive dysfunctions may provide starting points for treatment and preventions of anxiety in PD.

[Consensus statement on the application of rTMS in depression in the Netherlands and Belgium]. / Consensusverklaring voor de toepassing van rTMS bij depressie in Nederland en België.

BACKGROUND: Since 2017, repetitive transcranial magnetic stimulation (rTMS) has become eligible for reimbursement for the treatment of therapy-resistant depression in the Dutch healthcare system.
AIM: To initiate a guideline in the Netherlands and Belgium for the safe and effective application of rTMS for the treatment of depression.
METHOD: Based on literature review, existing guidelines and consensus among Dutch rTMS experts, recommendations were developed regarding the implementation of rTMS as a treatment of depression. All available evidence was weighed and discussed among all co-authors and recommendations were reached by consensus among the group.
RESULTS: rTMS targeting the dorsolateral prefrontal cortex (DLPFC) should be seen as a first choice in the treatment of depression using high-frequency rTMS (left) or, as an alternative, low-frequency rTMS (right). Stimulation protocols should use more than 1000 pulses per session for an average of 20-30 sessions, offered in 2-5 sessions per week. Contraindications for rTMS include epilepsy, intracranial presence of (magnetisable) metals, pacemaker and cochlear implant.
CONCLUSION: rTMS, performed by competent professionals is an effective and safe treatment for depression.

Predictors and consequences of health anxiety symptoms: a novel twin modeling study.

OBJECTIVE: The question of how to best conceptualize health anxiety (HA) from a diagnostic and etiological perspective remains debated. The aim was to examine the relationship between HA and the symptoms of anxiety and obsessive-compulsive-related disorders in a normative twin population. METHOD: Four hundred and ninety-six monozygotic adult twin pairs from the Australian Twin Registry participated in the study (age, 34.4 ± 7.72 years; 59% females). Validated scales were used to assess each domain. We applied a twin regression methodology-ICE FALCON-to determine whether there was evidence consistent with 'causal' relationships between HA and other symptoms by fitting and comparing model estimates. RESULTS: Estimates were consistent with higher levels of obsessing ('unwanted thoughts') (P = 0.008), social anxiety (P = 0.03), and body dysmorphic symptoms (P = 0.008) causing higher levels of HA symptoms, and with higher levels of HA symptoms causing higher levels of physical/somatic anxiety symptoms (P = 0.001). CONCLUSION: Obsessional thoughts, body dysmorphic concerns, and social anxiety symptoms may have a causal influence on HA. To report physical/somatic anxiety appears to be a consequence of the underlying presence of HA-related fears. Should our results be confirmed by longitudinal studies, the evaluation and treatment of HA may benefit from the consideration of these identified risk factors.

[Transdiagnostic psychiatry: work in progress]. / Transdiagnostische psychiatrie: concept in ontwikkeling.

BACKGROUND: There is an increasing awareness that the current approach to clinical thought and work in psychiatry in relation to psychiatric diagnosis, treatment and research has its limitations. This necessitates a process to reform both the clinical practice and future scientific research. One way to reform this is the transdiagnostic approach. AIM: To clarify the psychological, biological and therapeutic aspects of a transdiagnostic approach in psychiatry. METHOD: An analysis of new approaches based on recent findings from the recent literature. RESULTS: Transdiagnostic psychiatry is a relatively new concept which is still under development. The examples extracted from the reviewed literature on developmental psychology, neurobiology and treatment demonstrate that this approach may lead to improvements in clinical care and generate new etiological insights. CONCLUSION: A transdiagnostic approach in psychiatry may lead to new insights that are relevant for clinical practice and future scientific research.

rTMS affects working memory performance, brain activation and functional connectivity in patients with multiple sclerosis.

OBJECTIVE: To investigate the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the right dorsolateral prefrontal cortex (DLPFC) on working memory performance, while measuring task-related brain activation and task-related brain connectivity in patients with multiple sclerosis (MS). METHODS: 17 patients with MS and 11 healthy controls (HCs) underwent 3 experimental sessions (baseline, real-rTMS, sham-rTMS), all including an N-back task (3 task loads: N1, N2, N3; control condition: N0) inside the MR scanner. Prior to imaging, real-rTMS (10 Hz) was applied to the right DLPFC. The stimulation site was defined based on individually assessed N-back task activation at baseline and located using neuronavigation. Changes in whole brain functional activation and functional connectivity with the right DLPFC were calculated. RESULTS: N-back task accuracy (N2 and N3) improved after real-rTMS (and not after sham-rTMS) compared with baseline (p=0.029 and p=0.015, respectively), only in patients. At baseline, patients with MS, compared with HCs, showed higher task-related frontal activation (left DLPFC, N2>N0), which disappeared after real-rTMS. Task-related (N1>N0) functional connectivity between the right DLPFC and the right caudate nucleus and bilateral (para)cingulate gyrus increased in patients after real-rTMS when compared with sham stimulation. CONCLUSIONS: In patients with MS, N-back accuracy improved while frontal hyperactivation (seen at baseline relative to HCs) disappeared after real-rTMS. Together with the changes in functional connectivity after real-rTMS in patients, these findings may represent an rTMS-induced change in network efficiency in patients with MS, shifting patients' brain function towards the healthy situation. This implicates a potentially relevant role for rTMS in cognitive rehabilitation in MS.

[ResPECT - a decade of Flemish-Dutch ECT research]. / ResPECT ­ een decennium Vlaams-Nederlands onderzoek naar elektroconvulsietherapie.

BACKGROUND: There is increasing clinical and scientific interest in electroconvulsive therapy (ECT). AIM: To provide an overview of the main research findings of the Flemish-Dutch research consortium ResPECT. METHOD: We report on our review of the relevant literature. RESULTS: Our studies confirm that ECT is one of the most efficient treatments for depression in later life and for depression with psychotic features. Older people with age-related brain pathology can respond well to ECT. It is still preferable to apply a standard pulse-width because this increases the efficacy of the treatment and minimises the cognitive impact. Even vulnerable older people can react favourably to ECT. CONCLUSION: Recent findings of the ResPECT consortium are providing new insights that are applicable in daily clinical practice. Research into mechanisms of action can also increase our understanding of the pathophysiology of severe depression.

Emotion regulation before and after transcranial magnetic stimulation in obsessive compulsive disorder.

BACKGROUND: Impaired emotion regulation may underlie exaggerated emotional reactivity in patients with obsessive compulsive disorder (OCD), yet instructed emotion regulation has never been studied in the disorder. METHOD: This study aimed to assess the neural correlates of emotion processing and regulation in 43 medication-free OCD patients and 38 matched healthy controls, and additionally test if these can be modulated by stimulatory (patients) and inhibitory (controls) repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (dlPFC). Participants performed an emotion regulation task during functional magnetic resonance imaging before and after a single session of randomly assigned real or sham rTMS. Effect of group and rTMS were assessed on self-reported distress ratings and brain activity in frontal-limbic regions of interest. RESULTS: Patients had higher distress ratings than controls during emotion provocation, but similar rates of distress reduction after voluntary emotion regulation. OCD patients compared with controls showed altered amygdala responsiveness during symptom provocation and diminished left dlPFC activity and frontal-amygdala connectivity during emotion regulation. Real v. sham dlPFC stimulation differentially modulated frontal-amygdala connectivity during emotion regulation in OCD patients. CONCLUSIONS: We propose that the increased emotional reactivity in OCD may be due to a deficit in emotion regulation caused by a failure of cognitive control exerted by the dorsal frontal cortex. Modulatory rTMS over the left dlPFC may influence automatic emotion regulation capabilities by influencing frontal-limbic connectivity.

[Dilemmas in the treatment of psychiatric symptoms in patients with Parkinson's disease]. / Dilemma's bij de behandeling van psychiatrische symptomen bij patiënten met de ziekte van Parkinson.

BACKGROUND: Psychiatric symptoms are common in Parkinson's disease (PD) and may complicate treatment. AIM: To review the prevalence and treatment options of psychiatric symptoms in PD patients and discuss the dilemmas that may arise. METHOD: Literature review. RESULTS: Psychiatric complaints, including depression, anxiety, apathy, impulse control disorders, hallucinations, delusions, sleep disturbances, and cognitive symptoms, frequently occur in PD patients. These symptoms have a great influence on the general functioning and quality of life of the patient. When treating these symptoms, adjusting neurological treatment and starting or adjusting psychotherapeutic or psychopharmacological treatment may be necessary. Even if individual symptoms can often be treated adequately, unwanted side effects in other symptom domains have to be taken into consideration. CONCLUSION: Adequate treatment of neuropsychiatric symptoms in PD patients is complex, and requires close multidisciplinary collaboration, especially in more advanced disease stages.

Gray matter differences contribute to variation in cognitive performance in Parkinson's disease.

BACKGROUND AND PURPOSE: A substantial proportion of patients with Parkinson's disease (PD) suffer from cognitive deficits, although there is a large variability in the severity of these impairments. Whilst the cognitive deficits are often attributed to monoaminergic changes, there is evidence that alterations in structural brain volume also play a role. The aim of our study was to gain more insight into the variability of cognitive performance amongst PD patients by examining the relation between regional gray matter (GM) volume and cognitive performance. METHODS: Linear regression analyses were performed between task performance and GM volume for six neuropsychological tasks within a group of 93 PD patients; they were additionally compared at a group level with matched healthy controls, using voxel-based morphometry. RESULTS: Our most important findings were positive correlations between GM volume and cognitive performance for (i) parahippocampal gyrus and verbal memory, (ii) medial temporal lobe and putamen and visuospatial memory, and (iii) middle temporal gyrus and frontal lobe and verbal fluency. In addition, decreased GM volume was found in the frontal, parietal and temporal cortices of PD patients compared with matched healthy controls. CONCLUSIONS: It is argued that the large variability in cognitive function across PD patients is partly mediated by GM volume differences in the implicated areas. Volume differences in these brain regions do not discriminate between patients and controls but explain cognitive variation within the patient population.

[Anxiety, obsessive-compulsive disorder and trauma in the DSM-5]. / Angst, obsessieve-compulsieve stoornis en trauma in de DSM-5.

BACKGROUND: The 12 anxiety disorders which were defined in the DSM-IV, have been increased to 27 disorders in the DSM-5. These 27 disorders have been subdivided into three chapters: 1. anxiety disorders, 2. obsessive-compulsive and related disorders (OCRD) and 3. trauma and stressor-related disorders. AIM: To describe the most important differences between the DSM-IV and DSM-5 classifications of the above-mentioned disorders. METHOD: Survey of the relevant literature. RESULTS: Within the chapter on anxiety disorders in DSM-5 the classifications of 'panic disorder' and 'agoraphobia' have been separated. In addition, DSM-5 allows the specification 'with panic attacks' to be applied to all psychiatric disorders. New additions to the group ocrd are: 'trichotillomania' and 'body dysmorphic disorder'. Also newly added to the group are the new classifications 'excoriation disorder' and 'hoarding disorder'. The DSM-IV group of adjustment disorders has been merged with the group of stress disorders. In accordance with the system adopted elsewhere in DSM-5, the disorders which are 'usually first diagnosed in infancy, childhood and adolescence' and which resemble the disorders defined in the three chapters have been added to these chapters. Two extra categories are defined in each of the three chapters. CONCLUSION: The three chapters in DSM-5 are little more than a re-arrangement of the disorders defined in DSM-IV. The revision has not led to any clarification of or insight into the relationship between and the etiology of these disorders.

Effects of psychotherapy on brain activation during negative emotional processing in patients with posttraumatic stress disorder: a systematic review and meta-analysis.

Post-traumatic stress disorder (PTSD) is a debilitating condition which has been related to problems in emotional regulation, memory and cognitive control. Psychotherapy has a non-response rate of around 50% and understanding the neurobiological working mechanisms might help improve treatment. To integrate findings from multiple smaller studies, we performed the first meta-analysis of changes in brain activation with a specific focus on emotional processing after psychotherapy in PTSD patients. We performed a meta-analysis of brain activation changes after treatment during emotional processing for PTSD with seed-based d mapping using a pre-registered protocol (PROSPERO CRD42020211039). We analyzed twelve studies with 191 PTSD patients after screening 3700 studies. We performed systematic quality assessment both for the therapeutic interventions and neuroimaging methods. Analyses were done in the full sample and in a subset of studies that reported whole-brain results. We found decreased activation after psychotherapy in the left amygdala, (para)hippocampus, medial temporal lobe, inferior frontal gyrus, ventrolateral prefrontal cortex, right pallidum, anterior cingulate cortex, bilateral putamen, and insula. Decreased activation in the left amygdala and left ventrolateral PFC was also found in eight studies that reported whole-brain findings. Results did not survive correction for multiple comparisons. There is tentative support for decreased activation in the fear and cognitive control networks during emotional processing after psychotherapy for PTSD. Future studies would benefit from adopting a larger sample size, using designs that control for confounding variables, and investigating heterogeneity in symptom profiles and treatment response.

Sleep as a window to target traumatic memories.

Post-traumatic stress disorder (PTSD) is a severe psychiatric disorder in which traumatic memories result in flashbacks and nightmares. With one-third of patients not responding to standard exposure-based psychotherapy, new treatment strategies are needed. Sleep offers a unique time window to enhance therapeutic efficacy. Traumatic memories that are neutralized in therapy need to be stored back into memory (consolidated) during sleep to solidify the treatment effect. New basic research shows that memory consolidation can be enhanced by presenting sounds or scents that were linked to the memory at encoding, again during sleep. This procedure, termed targeted memory reactivation (TMR), has, despite its clinical potential, not been tested in (PTSD) patients. In this narrative review, we explore the potential of TMR as a new sleep-based treatment for PTSD. First we provide the necessary background on the memory and sleep principles underlying PTSD as well as the present applications and conditional factors of TMR. Then, we will discuss the outstanding questions and most promising experimental avenues when testing TMR to treat traumatic memories.

Coordinated cortical thickness alterations across six neurodevelopmental and psychiatric disorders.

Neuropsychiatric disorders are increasingly conceptualized as overlapping spectra sharing multi-level neurobiological alterations. However, whether transdiagnostic cortical alterations covary in a biologically meaningful way is currently unknown. Here, we studied co-alteration networks across six neurodevelopmental and psychiatric disorders, reflecting pathological structural covariance. In 12,024 patients and 18,969 controls from the ENIGMA consortium, we observed that co-alteration patterns followed normative connectome organization and were anchored to prefrontal and temporal disease epicenters. Manifold learning revealed frontal-to-temporal and sensory/limbic-to-occipitoparietal transdiagnostic gradients, differentiating shared illness effects on cortical thickness along these axes. The principal gradient aligned with a normative cortical thickness covariance gradient and established a transcriptomic link to cortico-cerebello-thalamic circuits. Moreover, transdiagnostic gradients segregated functional networks involved in basic sensory, attentional/perceptual, and domain-general cognitive processes, and distinguished between regional cytoarchitectonic profiles. Together, our findings indicate that shared illness effects occur in a synchronized fashion and along multiple levels of hierarchical cortical organization.

Common limbic and frontal-striatal disturbances in patients with obsessive compulsive disorder, panic disorder and hypochondriasis.

BACKGROUND: Direct comparisons of brain function between obsessive compulsive disorder (OCD) and other anxiety or OCD spectrum disorders are rare. This study aimed to investigate the specificity of altered frontal-striatal and limbic activations during planning in OCD, a prototypical anxiety disorder (panic disorder) and a putative OCD spectrum disorder (hypochondriasis). METHOD: The Tower of London task, a 'frontal-striatal' task, was used during functional magnetic resonance imaging measurements in 50 unmedicated patients, diagnosed with OCD (n=22), panic disorder (n=14) or hypochondriasis (n=14), and in 22 healthy subjects. Blood oxygen level-dependent (BOLD) signal changes were calculated for contrasts of interest (planning versus baseline and task load effects). Moreover, correlations between BOLD responses and both task performance and state anxiety were analysed. RESULTS: Overall, patients showed a decreased recruitment of the precuneus, caudate nucleus, globus pallidus and thalamus, compared with healthy controls. There were no statistically significant differences in brain activation between the three patient groups. State anxiety was negatively correlated with dorsal frontal-striatal activation. Task performance was positively correlated with dorsal frontal-striatal recruitment and negatively correlated with limbic and ventral frontal-striatal recruitment. Multiple regression models showed that adequate task performance was best explained by independent contributions from dorsolateral prefrontal cortex (positive correlation) and amygdala (negative correlation), even after controlling for state anxiety. CONCLUSIONS: Patients with OCD, panic disorder and hypochondriasis share similar alterations in frontal-striatal brain regions during a planning task, presumably partly related to increased limbic activation.

[Impulse control disorders in Parkinson's disease]. / Impulscontrolestoornissen bij de ziekte van Parkinson en de relatie tot andere stoornissen binnen het impulsieve-compulsieve spectrum.

BACKGROUND: Parkinson's disease is characterised not only by the classic triad of bradykinesia, rigidity and tremor, but also by the frequent occurrence of various non-motor symptoms such as the impulse control disorders (pathological gambling, hypersexuality, compulsive buying, binge eating, punding and dopamine dependency). AIM: To increase insight into the clinical presentation, risk factors, treatment and the underlying pathophysiological mechanisms of impulse control disorders in Parkinson's disease. METHOD: Relevant literature was reviewed. RESULTS: Impulse control disorders belong to an important group of neuropsychiatric disorders that occur at some point in 5-10% of patients with Parkinson's disease. They generally occur in conjunction with dopaminergic medication and can have a marked social, relational and/ or financial impact. CONCLUSION: Early recognition of impulse control disorders in Parkinson's disease is important and a close collaboration between the neurologist and the psychiatrist is essential in order to ensure correct diagnosis and the best possible treatment. Impulse control disorders in Parkinson's disease show considerable phenomenological overlap with other repetitive behaviours within the impulsive-compulsive spectrum of disorders to which the obsessive-compulsive disorders and addiction disorders belong. The overlap can possibly be explained by a shared pathophysiological mechanism involving an imbalance between the direct and indirect pathways of the dorsal and ventral frontal-striatal circuits.

Associations between sex hormones, sleep problems and depression: A systematic review.

Sleep problems and depression are both common and have a high impact on quality of life. They are also strongly associated and commonly occur together. During the reproductive age, both sleep problems and depression are almost twice as common in women than men. Epidemiological studies show that women experience more sleep problems and depressive symptoms around times when sex hormones change, such as puberty and menopause, but it is unclear what effect sex hormones have on sleep problems and depression. This systematic review aims to summarize and evaluate studies that investigated the relationship between sex hormones, sleep and depression. Systematic search resulted in 2895 articles, of which 13 met inclusion criteria. Depressed patients showed worse sleep than controls, but no significant difference in endogenous hormone levels was found. Additionally, higher endogenous estrogen was associated with better sleep in controls, but associations between endogenous sex hormones and depressive symptoms were inconclusive. More research on the effect of sex hormones on sleep and depression is necessary.