“Getting physical”: the management of neuropsychiatric disorders using novel physical treatments

Objective

To summarize and review the utility of physical interventions in the treatment of psychiatric disorders.

Methods

A systematic review of the literature pertaining to novel physical interventions, namely, transcranial magnetic stimulation, deep brain stimulation, vagus nerve stimulation, and neurosurgery, was conducted using MEDLINE, EMBASE, and PSYCHLIT. Bibliographies of papers were scrutinized for further relevant references along with literature known to the authors.

Results

Currently available physical interventions worldwide are reviewed with respect to efficacy, applications, and putative indications. Physical interventions have experienced a resurgence of interest for both the investigation of brain function and the treatment of neuropsychiatric disorders. The widespread availability of neuroimaging technology has advanced our understanding of brain function and allowed closer examination of the effects of physical treatments. Clinically, transcranial magnetic stimulation seems likely to have a role in the management of depression, and its use in other neuropsychiatric disorders appears promising. Following on from its success in the management of intractable epilepsy, vagus nerve stimulation is undergoing evaluation in the treatment of depression with some success in refractory cases. Deep brain stimulation has improved mood in patients with Parkinson’s disease and may also relieve symptoms of obsessive-compulsive disorder. Neurosurgery has re-invented itself by way of increased technical sophistication, and although further assessment of its efficacy and clinical utility is still needed, its widespread practice reflects its increasing acceptance as a viable treatment of last resort.

Conclusion

It is clear that physical treatments are here to stay and “getting physical” offers a useful addition to the neuropsychiatrist’s therapeutic armamentarium. However, like all new treatments these interventions need to remain under rigorous scientific scrutiny to determine accurately their immediate and long-term effects.     

Regression in Children with Autism Spectrum Disorders

Objectives  

To understand the characteristics of autistic regression and to compare the clinical and developmental profile of children with autism spectrum disorders (ASD) in whom parents report developmental regression with age matched ASD children in whom no regression is reported.     

Multiple courses of antenatal steroids

The benefits and risks of multiple courses of antenatal steroids (ANS) are still unresolved issues. This was a prospective cohort study in a level III neonatal unit. Preterm babies ≤35 wk gestation were included. Malformations, chronic maternal steroid intake, exchange transfusions prior to cortisol sampling and incomplete ANS courses were exclusion criteria. Subjects were classified into: No course (Group 0), 1 course (group 1), 2 courses (Group 2), >2 courses (Group 3) of antenatal dexamethasone. The key outcome was adrenal function assessed by basal and post-ACTH cortisol on day 3. Other outcomes were neonatal morbidity, mortality, growth parameters at birth, long term growth and neuro-development. Of 210 eligible babies, 124 were enrolled. 38, 51, 10 and 25 babies belonged to groups 0, 1, 2 and 3 respectively. Basal and post-ACTH serum cortisol did not show any significant difference between groups (p=0.5 and p=0.9 respectively). Incidence of severe HMD requiring ventilation was significantly lower (p=0.02) in multiple course group (combined groups 2 and 3) compared to single course group. There were no differences in other neonatal morbidity, birth OFC and weight between single and multiple ANS groups. Follow up data at a mean age of 22 mth was available in 59 subjects (69%) belonging to groups 1–3. No differences were noted in the proportion of patients with abnormal neurological examination (p=0.1), abnormal PDI (p=0.9), abnormal MDI (p=0.9) and physical growth between multiple and single course groups. Multiple courses of antenatal dexamethasone resulted in a significant decrease in severe forms of RDS and they did not cause adrenal suppression, decreased growth or impaired neurodevelopment.     

Predisposition to uterine microbial contamination in the guinea-pig following administration of mucolytic drugs and steroid hormones.

Using guinea-pigs as a mammalian model, the effects of bromhexine hydrochloride, ethinyloestradiol, norethisterone acetate and prednisolone acetate on uterine microbial status were determined. Those drugs known to decrease mucus viscoelasticity predisposed to the entry of vaginal bacteria into the uterus, probably due to reduction of the cervical mucus barrier. Norethisterone acetate, which increases cervical mucus viscoelasticity, reduced these effects. The effects produced by the steroid hormones were independent of their immunosuppressive effects. The results also suggest that prednisolone acetate may exert oestrogen-like actions on cervical mucus.     

The effects of bromhexine hydrochloride and S-carboxymethyl-L-cysteine on guinea-pig uterine microflora

This study used guinea-pigs as a mammalian model to investigate the effects of bromhexine hydrochloride and S-carboxymethyl-L-cysteine on the integrity of the cervical mucus plug. It was shown that under normal circumstances the uterus is sterile, but following drug administration microorganisms began to appear in the uterus with no significant effect on the vaginal microbial population. It therefore appears that these two mucolytic agents may reduce cervical mucus viscoelasticity. After the animals had been mated, microorganisms were isolated from the uterus even in the absence of drug treatment.     

Schizoaffective disorder: diagnostic issues and future recommendations

Objective:  Difficulties surrounding the classification of mixed psychotic and affective syndromes continue to plague psychiatric nosology. This paper addresses the controversy regarding the diagnostic validity of schizoaffective disorder (SAD), a diagnosis that is used in both DSM-IV and ICD-10 and one that encroaches on both schizophrenia (SCZ) and bipolar disorder (BD).
Methods:  A systematic synthesis of clinical and empirical literature, including evidence from cognitive, neurobiological, genetic, and epidemiological research, was undertaken with the aim of evaluating the utility of the SAD classification.
Results:  Distinctions between the diagnostic categories of SCZ, SAD and BD are not clearly demarcated by findings from neuropsychological, neuroimaging, molecular neurobiology, or genetic epidemiology studies. On the contrary, convergent evidence purports overlap across current diagnostic boundaries in the heritability and pathophysiology of psychotic and affective disorders. However, there are some disorder-specific findings.
Conclusions:  Schizoaffective disorder is a prototypic boundary condition that epitomizes the pitfalls of the current categorical classification system. Future revisions to the DSM should consider the implementation of one of two alternative models to account for individuals presenting with mixed psychotic and affective symptoms. These include the views that (i) SAD is a comorbid set of symptoms that occur as a by-product of two separate disorders (SCZ and BD) or, that (ii) SAD exists as the mid-point on a continuum between SCZ and BD, such that the incorporation of these two disorders onto one dimension may be a suitable alternative. Hence the category SAD should be omitted in future revisions of DSM, allowing the development of meaningful nomenclature that rests upon further rigorous investigation of differences and similarities between disorders.     

Ancient and modern genomics of the Ohlone Indigenous population of California

Traditional knowledge, along with archaeological and linguistic evidence, documents that California supports cultural and linguistically diverse Indigenous populations. Studies that have included ancient genomes in this region, however, have focused primarily on broad-scale migration history of the North American continent, with relatively little attention to local population dynamics. Here, in a partnership involving researchers and the Muwekma Ohlone tribe, we analyze genomic data from ancient and present-day individuals from the San Francisco Bay Area in California: 12 ancient individuals dated to 1905 to 1826 and 601 to 184 calibrated years before the present (cal BP) from two archaeological sites and eight present-day members of the Muwekma Ohlone tribe, whose ancestral lands include these two sites. We find that when compared to other ancient and modern individuals throughout the Americas, the 12 ancient individuals from the San Francisco Bay Area cluster with ancient individuals from Southern California. At a finer scale of analysis, we find that the 12 ancient individuals from the San Francisco Bay Area have distinct ancestry from the other groups and that this ancestry has a component of continuity over time with the eight present-day Muwekma Ohlone individuals. These results add to our understanding of Indigenous population history in the San Francisco Bay Area, in California, and in western North America more broadly.

Among the geographic regions of North America, California is one of the areas with the greatest cultural and linguistic diversity of Indigenous peoples (1–3). With significant coastal and terrestrial ecological productivity, the region supported large precontact populations with the highest population density in North America (4–6). The geographic, cultural, and linguistic complexity of California at European contact contributed to considerable structuring among the Indigenous groups speaking more than 78 mutually unintelligible languages within six major linguistic families (3, 7). Today, California is home to 109 federally recognized sovereign tribal nations and more than 40 non–federally recognized tribal groups.Considering regions within California, the area surrounding San Francisco Bay in Northern California supported some of the highest regional population densities at the start of European colonization in 1776 (8, 9). Indeed, the 21 Spanish mission locations in California, which were situated in a manner that correlated with Indigenous population density, included five missions located near San Francisco Bay. Population reconstructions using Spanish mission baptismal recruitment records reveal that at contact, more than 15,000 Native Americans from five distinct language groups were residing in sedentary villages within 45 territorial communities (land-controlling autonomous polities) within 20 km of the bay (9–11). Extensive investigation of the region''s dense archaeology has produced a trans-Holocene record, revealing that intensive sedentary or semisedentary habitation extends back >5,000 y (11–14).With a rich regional archaeological record spanning >11,000 y of Indigenous habitation (14), much potential exists for coproduction of knowledge by recovering ancient DNA from Indigenous ancestors and jointly analyzing genetic and archaeological data. To date, however, California and the San Francisco Bay Area have seen little attention in paleogenomic studies. The most detailed study of ancient human genomic data in California has focused on Southern California, considering populations from the Channel Islands (15); additional significant studies of nearby regions have examined Lovelock Cave and Spirit Cave in Nevada (16), as well as the Pacific Northwest (16–18) and Northern Mexico (15, 19).With generally sparse geographic coverage and relatively few ancient individuals from North America investigated using genomics, studies in the region have often focused on questions concerning initial entry of Indigenous populations into the Americas and broad-scale migration history of early Indigenous groups (15, 16, 19, 20). Studies have often focused on the information revealed about broad-scale population history from a small number of individuals (21–24), with relatively few studies focusing on a specific geographic area and considering multiple sampled individuals (17, 18); another limitation has been the use of genetic sites in mitochondrial DNA rather than genome-wide (25).In this study, in partnership of researchers with the Muwekma Ohlone tribe of the San Francisco Bay Area, we examine a time transect of a single region of Indigenous habitation, centered on Sunol on the southeast side of San Francisco Bay. The Muwekma Ohlone are one of the descendant communities of Ohlone who originally occupied ∼4.3 million acres from San Francisco to Monterey and from the coast to the upland edge of the Central Valley. The Muwekma Ohlone comprise all the lineages who trace their ancestry through the Bay Area Missions of San Francisco, Santa Clara, and San Jose and who were also members of the historic previously federally recognized Verona Band of Alameda County who resided on the Pleasanton (Alisal), Sunol, Livermore (Del Mocho), and Niles (El Molino) rancherias from post-Spanish mission secularization (1834) to the early 1900s.We consider human paleogenomic analysis from burials at two adjacent ancestral Ohlone settlements set away from the bay margin near Sunol, one dated to 2,440 to 175 cal BP, the other to 605 to 100 cal BP (26, 27). We also present information derived from living members of the Muwekma Ohlone tribe, considering that their ancestral lands include this locality and noting their strong historical ties to this region in particular that persist to the present day (SI Appendix, Table S1). Tribal members trace familial connections to the Sunol region (a 5-mile radius around Sunol includes the historic rancherias listed above and Mission San Jose) over many generations, as reported in interviews with tribal elders and genealogical analysis (28–30). This investigation, considering multiple groups across a range of time periods, provides a case example of joint ancient and modern DNA analysis in a single regional setting.We combine information from traditional knowledge, genetics, and archaeology to examine the three sets of individuals. First, we investigate the ancient Bay Area individuals in relation to other ancient persons from the Americas, focusing attention on California and surrounding regions. Next, we examine the relationships of individuals between the two sites as well as between the ancient individuals and the modern tribal members, assessing the possibility of genetic continuity among these groups. The analysis reveals that genetic links between ancient and modern populations are evident despite the extreme disruption to the Ohlone that occurred during Spanish occupation and subsequent incorporation of the region into Mexico and then the United States—including forced migration to the missions and reductions in lifespan due to new diseases and the conditions of mission life (9, 31–33). The broader genetic context inferred for the three sets of individuals deepens understanding of Indigenous population history of California and the San Francisco Bay Area.     

Increased pituitary volume in patients with established bipolar affective disorder

Hypothalamic-pituitary-adrenal (HPA) axis dysfunction has been demonstrated in bipolar disorder (BD), but previous magnetic resonance imaging (MRI) studies of pituitary gland volume in BD have reported variable findings. In this MRI study we investigated pituitary volume in 26 patients with established bipolar I disorder (8 males and 18 females, mean age = 38.4 years) and 24 matched controls (7 males and 17 females, mean age = 38.7 years). The BD patients had a significantly larger pituitary volume as compared with controls, but there was no association between pituitary volume and illness duration, number of manic/depressive episodes, daily medication dosage, family history, or clinical subtype (i.e., psychotic and nonpsychotic). Pituitary volume was larger in females than in males for both groups. These results support previous neuroendocrine findings that implicate HPA axis dysfunction in the core pathophysiological process of BD.