Mitochondrial myopathy and comorbid major depressive disorder. effectiveness of dTMS on gait and mood symptoms

Background: Mitochondrial myopathies (MMs) often present with leukoencephalopathy and psychiatric symptoms, which do not respond to or worsen with psychiatric drugs. Case report: A 67-year-old woman with a 10-year history of probable chronic progressive external ophthalmoplegia, an MM, had drug-resistant, anxious-depressive symptoms. Since she had never had seizures, we proposed 20 sessions of deep transcranial magnetic stimulation (dTMS) for her depression. Surprisingly, besides the expected improvement of depression, we observed marked improvement of movement disorder that lasted as long as the patient was undergoing dTMS. She also improved her performance on neuropsychological tests of executive function and cognitive speed. Depressive symptom improvement was persistent, while anxiety symptoms recurred after the end of the sessions. Conclusions: dTMSmay be an alternative antidepressant strategy in patients withMMs, provided that they are free from seizures. The mechanism of improvement of motor disturbance may relate to dorsolateral prefrontal cortex stimulation and improved executive function and needs further investigation

STRUCTURAL NEUROIMAGING IN PATIENTS WITH PANIC DISORDER: FINDINGS AND LIMITATIONS OF RECENT STUDIES

Background: Panic disorder, a relatively common anxiety disorder, is often associated to agoraphobia and may be disabling. Its neurobiological underpinnings are unknown, despite the proliferation of models and hypotheses concerning it; investigating its correlates could provide the means for better understanding its pathophysiology. Recent structural neuroimaging techniques may contribute to the identification of possible brain morphological alterations that could be possibly related to the clinical expression of panic disorder. Methods: Through careful major database searches, using terms keen to panic, agoraphobia, structural magnetic neuroimaging and the like, we identified papers published in peer-review journals and reporting data on the brain structure of patients with panic disorder. Included papers were used comparatively to speculate about the nature of reported brain structural alterations. Results: Anxiety, which is the core feature of the disorder, correlates with the function of the amygdala, which showed a smaller volume in patients, as compared to healthy subjects. Data also showed a volumetric decrease of the anterior cingulate along with increased fractional anisotropy, and increase of some brainstem nuclei, particularly of the rostral pons. Other structures with reported volumetric correlates of panic disorder are the hippocampus and the parahippocampal cortices, the insula, the putamen, and the pituitary gland. Volumetric changes in the anterior cingulate, frontal, orbitofrontal, insular, and temporal cortices have also been described in structural neuroimaging studies. Major methodological limitations are considered in context. Conclusions: Several data point to the existence of structural neuroanatomical alterations in panic disorder, consisting in significant volumetric reductions or increases in different brain areas. White matter alterations were shown also in the only diffusion tensor imaging study performed to date. Available data do not allow us to conclude about the possible progression of these alterations

Parasomnias

Parasomnias are defined undesirable physical events or experiences that occur during entry into sleep, within sleep or during arousals from sleep. Parasomnias occur more frequently in children than in adults. All parasomnias can be diagnosed based on subjective reports from the patient, parent or caregiver, except for REM sleep behavior disorder where diagnosis requires polysomnographic investigation. This chapter also addresses the main clinical features and most recent treatments of parasomnias

Sleep disturbance in anxiety disorders

Anxiety disorders are the most frequent psychiatric disorder with a lifetime prevalence of 29% in the general population. Anxiety-related hyperarousal can often lead to persistent circadian rhythm and sleep disturbances. Patients affected by anxiety disorders, including post-traumatic stress disorder, panic disorder, obsessive compulsive disorder, generalized anxiety disorder, and phobias, often manifest sleep disturbances or complaints. Sleep disorders/disturbances are commonly associated with anxiety: impaired sleep can damage neurocognitive performance and increase daily anxiety. Restoring a correct circadian rhythm is essential and basic. The study of multiple relationships between sleep disturbances and anxiety symptoms is of considerable importance in medical practice

Circadian rhythm sleep disorders

Circadian rhythm sleep disorders, according to the ICSD-2, comprise a list of complaints sharing a common pathophysiological basis of misalignment between internal circadian rhythms and the desired or required time for sleep. The sleep disturbance produces sleep and wake periods that occur at inappropriate times, resulting in a complaint of insomnia or excessive sleepiness for patients. Diagnostic criteria include social or occupational impairment, and a diagnosis of CRSDs is appropriate only in the absence of other primary sleep disorders. The CRSDs recognized by ICSD-2 are: 1) Delayed sleep phase syndrome; 2) Advanced sleep-phase syndrome; 3) Non-24 hours sleepwake syndrome; 4) Jet lag syndrome; 5) Shift work disorder; 6) Irregular sleep-wake pattern; 7) Circadian rhythm sleep disorder due to medical condition; 8) Circadian rhythm sleep disorder due to drug or substance; 9) Circadian rhythm sleep disorder, not otherwise specified

Neuroimaging in sleep medicine

Functional and structural neuroimaging provide a means to understand brain function in patients affected by sleep disorders. Herein, we describe neuroimaging findings of primary sleep disorders, including types of dyssomnia related to intrinsic sleep impairments (i.e., idiopathic insomnia, narcolepsy, and obstructive sleep apnea) and abnormal motor behaviors during sleep (i.e., periodic limb movement disorder, restless legs syndrome and rapid-eye-movement sleep behavior disorder). We also include functional neuroimaging studies in sleep complaints secondary to specific psychiatric disorders. Functional neuroimaging may address different kinds of issues in sleep medicine. Functional and structural neural changes can have a causal role in the pathophysiology of sleep disorders. Other changes in brain structure or regional activity can be considered as secondary consequences of long-term sleep disruption. Neuroimaging studies can help to better understand the cognitive and neural responses to various therapeutic approaches. In the future, neuroimaging studies will probably lead to modify the nosography of sleep disorders on the basis of their underlying and characteristic neural correlates

Sleep disturbances and related psychopathologies

Clinical and neurophysiopathological correlates of sleep disorders/disturbances often precede and predispose to psychiatric disorders or psychological distress. Sleep disturbances can constitute, for each psychiatric disorder, a genuine worsening factor and a motor for illness. For this reason, it is useful to consider clinical intervention aimed at restoring normal sleep as a preventive intervention, both on sleep alterations as well as on mental disorders and psychological distress. The mutual relationships between the patient's personal aspects, sleep habits, and manifested sleep disturbances require further clarification. This chapter will analyze the prominent clinical impact of sleep disturbances and circadian rhythm alterations in major psychiatric disorders

Fundamentals of human chronobiology

Chronobiology is the study of biological temporal rhythms, including the circadian, weekly, seasonal, and annual rhythms. The term “circadian” comes from the Latin words “circa”, meaning “around”, and “dies [-ēi]”, meaning "day". A circadian rhythm can be defined as any biological process that manifests an endogenous entrainable oscillation of about 24 hours. Circadian rhythm affects physiology, behavior, cognition, and the sleep-wake cycle in mammalians and humans. The master clock located in the suprachiasmatic nuclei (SCN) of the hypothalamus has a central role in circadian rhythm preservation. The human circadian time-keeping system is characterized by a composite architecture, with the central brain’s SCN pacemaker and subsidiary clocks in nearly every cell. The sleep-wake cycle is a complex and dynamic phenomenon involving numerous cerebral structures, neuronal network, and neurotransmitters. Sleep is generally divided into non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. NREM and REM phases occur in the course of the sleep with cyclicity. Each phase has typical characteristics, including variations in brain wave patterns, eye movement type, and muscle tone. This chapter provides a general overview of the human circadian-generating systems and sleep physiology

Psychoeducation in sleep medicine

Insomnia is a frequent complaint that involves one-third of the adult population and is associated with a reduction in the quality of life, increased risk of medical and psychiatric comorbidities, and abuse of hypnotic medications. Psychological and behavioral therapies are increasingly used in the last decades as they have been recognized to be valid and effective options in the treatment of chronic primary and secondary insomnia, with many advantages over pharmacological interventions, including fewer side effects and better maintenance of clinical progress over time. Several non-pharmacological strategies, comprising the most widely known educational, behavioral and cognitive interventions, are described in terms of their effectiveness and recommendations. These therapies are suitable for adults of all ages and should be considered as first line intervention in the treatment of chronic insomnia