Forensically relevant challenging behaviors and the genetics domain.

Impulsive and aggressive behaviors along with intellectual disabilities often manifest in the context of genetic disorders and are a persisting challenge to professionals in the forensic psychiatric and psychological setting. The following chapter comprises an overview of relevant factors in the gene-context-behavior interaction such as monoamine oxidase A activity and specific epileptic phenomena. It presents several examples of monogenetic disorders with behaviors from the aggression spectrum and summarizes emerging strategies for treatment and clinical management thereof.

A Patient with Moderate Intellectual Disability and 49, XXXYY Karyotype.

Klinefelter syndrome is a chromosomal disorder in which one extra X chromosome is present (47,XXY). Several other numeric variants of this syndrome are described that comprise one or more additional sex chromosomes such as 48,XXXY, 48,XXYY and 49,XXXXY. These rare conditions are often associated with increased risk for congenital malformations, additional medical problems, and a more complex psychological phenotype.

Adult male patient with severe intellectual disability caused by a homozygous mutation in the HNMT gene.

Histamine is involved in various physiological functions like sleep-wake cycle and stress regulation. The histamine N-methyltransferase (HNMT) enzyme is the only pathway for termination of histamine neurotransmission in the central nervous system. Experiments with HNMT knockout mice generated aggressive behaviours and dysregulation of sleep-wake cycles.

A de novo Novel Splice Variant in an Adult Female with Severe Intellectual Disability.

The catenin beta-1 () gene, encoding a sub-unit of the cadherin/catenin protein complex that is involved in the Wnt signalling pathway important for proper interneuron development, is considered to be causative for the rare autosomal dominant mental retardation syndrome, formerly called MRD19 but later renamed neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV). Its main characteristics are moderate to severe intellectual disability (ID), disruptive autistic behaviours, microcephaly, absent or limited speech, facial dysmorphisms, peripheral hypertonia/spasticity, motor delay and visual defects. So far, 35 patients have been reported with a de novo loss-of-function variant in .

Neurosyphilis Mimicking Autoimmune Encephalitis: A Case Report and Review of the Literature.

Neurosyphilis may imitate a wide range of neurological and psychiatric diseases, including autoimmune encephalitis. To avoid further cognitive decline and morbidity, early recognition and adequate treatment are of particular importance in both neurosyphilis and autoimmune encephalitis. In case of a strong clinical suspicion of a diagnosis of autoimmune encephalitis, guidelines recommend initiating immunotherapy even in the absence of immunological confirmation.

A longitudinal perspective on the pharmacotherapy of 24 adult patients with Phelan McDermid syndrome.

Over the past years, 24 patients with Phelan-McDermid syndrome were carefully investigated with respect to history, somatic and neurologic antecedents, treatment history, behavioural issues, and psychiatric symptoms including possible catatonic features and regression phenomena. Patients were originally referred for specialized diagnosis and treatment advice because of recurrent challenging behaviours along with instable mood. In all, standardized neuropsychiatric examination was performed including assessment of intellectual and adaptive functioning as well as communication and behaviour concerns.

Clinical Presentation of Laboratory Confirmed Neurosyphilis in a Recent Cases Series.

Objective: The worldwide increase in the incidence of syphilis necessitates alertness to the occurrence of neurosyphilis. Early recognition of neurosyphilis allows for timely treatment, leading to a better treatment outcome. This retrospective study aims to describe the clinical presentation of neurosyphilis in a recent series of neurosyphilis patients.

Phelan-McDermid syndrome due to mutation in an intellectually disabled adult male: successful treatment with lithium.

For 30 years, Phelan and co-workers described a syndrome characterised by neonatal hypotonia, global developmental delay, strongly impaired speech, sleep disturbances and hyperreactivity to sensory stimuli. This Phelan-McDermid syndrome (PMS), also presenting with symptoms from the autism spectrum and a higher risk of developing seizure disorders, may be caused by a deletion of chromosome 22q13 or by a mutation in the gene. Its core psychopathological phenotype comprises symptoms from the bipolar spectrum for which generally treatment with a mood-stabilising anticonvulsant in combination with an atypical antipsychotic seems to be most effective.

Malaria Fever Therapy for General Paralysis of the Insane: A Historical Cohort Study.

Background/aims: This year marks the 100th anniversary of the first malaria fever treatment (MFT) given to patients with general paralysis of the insane (GPI) by the Austrian psychiatrist and later Nobel laureate, Julius Wagner-Jauregg. In 1921 Wagner-Jauregg reported an impressive therapeutic success of MFT and it became the standard treatment for GPI worldwide. In this study, MFT practice in the Dutch Vincent van Gogh psychiatric hospital in GPI patients who had been admitted in the period 1924-1954 is explored.

Relationship between plasma homovanillic acid and outcome in patients with psychosis spectrum disorders.

Background: Psychosis spectrum disorders, especially schizophrenia, have been linked to disturbed dopaminergic activity in the brain. Plasma homovanillic acid (pHVA) levels partly represent dopaminergic metabolism in the central nervous system. In the present study associations between (changes in) pHVA levels, symptom severity and symptomatic improvement in patients with psychoses were investigated.

Clinical Presentation of General Paralysis of the Insane in a Dutch Psychiatric Hospital, 1924-1954.

General paralysis of the insane (GPI) or dementia paralytica was once a fatal complication of syphilitic infection and a major reason for psychiatric hospitalization. Nowadays, physicians consider GPI to be exceptional. It should be noted, however, that syphilis re-emerged worldwide at the turn of the 20th to 21st century and a revival of GPI can, therefore, be expected.

A 12q24.31 interstitial deletion in an adult male with MODY3: neuropsychiatric and neuropsychological characteristics.

A 39-year-old male patient with a disharmonic intelligence profile and juvenile diabetes mellitus is described. At 14 months of age, minor facial dysmorphisms were noticed. He had delayed motor development, obesity at early age, and a diagnosis of insulin-dependent diabetes at the age of 10 years.

BDNF and S100B in psychotic disorders: evidence for an association with treatment responsiveness.

Objective: Brain-derived neurotrophic factor (BDNF) and S100B are involved in brain plasticity processes and their serum levels have been demonstrated to be altered in patients with psychoses. This study aimed to identify subgroups of patients with psychotic disorders across diagnostic boundaries that show a specific symptom profile or response to treatment with antipsychotics, by measuring serum levels of BDNF and S100B.

Methods: The study sample consisted of 58 patients with DSM-IV psychotic disorders.

Neurosyphilis in the mixed urban-rural community of the Netherlands.

Objective: Neurosyphilis is caused by dissemination into the central nervous system of Treponema pallidum. Although the incidence of syphilis in the Netherlands has declined since the mid-1980s, syphilis has re-emerged, mainly in the urban centres. It is not known whether this also holds true for neurosyphilis.

Neuropsychological phenotype of a patient with a de novo 970 kb interstitial deletion in the distal 16p11.2 region.

The 16p11.2 microdeletion syndrome is characterized by a wide range of phenotypic expressions and is frequently associated with developmental delay, symptoms from the autism spectrum, epilepsy, congenital anomalies, and obesity. These phenotypes are often related to a proximal 16p11.

Beta-propeller protein-associated neurodegeneration (BPAN), a rare form of NBIA: novel mutations and neuropsychiatric phenotype in three adult patients.

Neurodegeneration with brain iron accumulation (NBIA) comprises a group of rare neuropsychiatric syndromes characterized by iron accumulation in the basal ganglia. The pantothenate kinase-associated neurodegeneration (PKAN) was the first NBIA form to be genetically identified almost 15 years ago. Nowadays, eight types can be genetically distinguished.

Behavioural phenotype of a patient with a de novo 1.2 Mb chromosome 4q25 microdeletion.

A female patient, 20 years of age, is reported with a history characterized by developmental and psychomotor delay, and during grammar-school period increasing learning problems, ritualistic behaviours and social withdrawal. Subsequently, challenging and autistic-like behaviours became prominent. The patient showed mild facial dysmorphisms, long thin fingers with bilateral mild short V metacarpals, and hyperlaxity of the joints.

Cardiometabolic comorbidity in antipsychotic treated patients: need for systematic evaluation and treatment.

Objective: The aim of the study was to determine the prevalence of cardiometabolic dysregulations and their somatic treatment regimens in a group of psychiatric patients treated with antipsychotics.

Methods: In a naturalistic cohort study, baseline cardiometabolic parameters were measured in 543 outpatients. After one year, a second assessment was performed in 220 patients out of the total sample.

Kallmann syndrome and paranoid schizophrenia: a rare combination.

Kallmann syndrome (KS) is a genetically heterogeneous and rare disorder characterised by the combination of hypothalamic hypogonadism and anosmia/hyposmia, a variable degree of intellectual disability and several somatic anomalies. In about one-third of the patients, mutations have been identified in at least seven different genes. Virtually no data are available about possible neuropsychiatric symptoms in KS.

Neuropsychiatric adverse events of varenicline: a systematic review of published reports.

Introduction: Over the past years, the impact of varenicline in patients with mental illness has been debated as serious neuropsychiatric adverse events (AEs) have been reported with varenicline use.

Aim: To identify and summarize published case reports of neuropsychiatric AEs ascribed to varenicline and to determine potential risk factors for these AEs.

Methods: A literature search of MEDLINE, the Cochrane Library, EMBASE, and PsychInfo database was conducted for case reports concerning the neuropsychiatric AEs of varenicline published in English from 2006 (approval year by the US Food and Drug Administration and the Dutch Medicines Evaluation Board) to January 1, 2012.

Hypersociability in the behavioral phenotype of 17q21.31 microdeletion syndrome.

The 17q21.31 microdeletion syndrome with its characteristic features including developmental delay, moderate intellectual disability, facial dysmorphisms, and anomalies of the brain and multiple organ systems was recently described. As to its behavioral profile, scarce data from clinical observations have suggested a remarkably amiable, friendly disposition, to some extent comparable to that observed in Angelman and Williams syndromes.

Phelan-McDermid syndrome: clinical report of a 70-year-old woman.

Phelan-McDermid or 22q13.3 deletion syndrome is characterized by global intellectual disability, childhood hypotonia, severely delayed or absent speech, features of autism spectrum disorder, without any major dysmorphisms or somatic anomalies. It is typically diagnosed before adolescence and data about adult patients are virtually absent.

The neurocognition of alexithymia: evidence from neuropsychological and neuroimaging studies.

Objective: Alexithymia refers to an ineffective regulation and expression of emotions. It constitutes a major risk factor for a range of medical and psychiatric problems, including chronic pain, somatisation, anxiety and depression. Alexithymia is a multi-faceted concept, described in terms of cognitive and affective aspects.

Cerebellar cognitive affective syndrome and autosomal recessive spastic ataxia of charlevoix-saguenay: a report of two male sibs.

Background: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare neurodegenerative disorder caused by mutations in the SACS gene (13q12) encoding the protein sacsin. It is characterized by early-onset cerebellar ataxia, lower limb spasticity, sensorimotor axonal polyneuropathy, and atrophy of the superior cerebellar vermis. Cerebellar disorders in general may be accompanied by the cerebellar cognitive affective syndrome (CCAS) which presents with disturbances of executive functioning, spatial cognition, linguistic capacities, and affect.

A de novo 3.57 Mb microdeletion in 8q12.3q13.2 in a patient with mild intellectual disability and epilepsy.

A female patient, nine years of age, is reported with a history characterized by delay of psychomotor and speech development, mild to moderate intellectual disability and persistent sleep disturbances since the age of two. The patient showed facial dysmorphisms, a pectus excavatum and a sandal gap. Apart from lowered intelligence, neuropsychological functioning disclosed impaired attentional capacities and executive control as well as weak motor skills.